Exploiting the σ-phylic properties of cationic gold(I) catalysts in the ring opening reactions of aziridines with indoles

Abstract

A study on the S_N2-type ring opening reactions of aziridines with indoles as nucleophiles is reported. Under gold(I) catalysis a great variety of tryptamine derivatives were prepared in good to excellent yields with complete stereocontrol when chiral aziridines were used. We demonstrated that cationic gold(I) catalysts are superior Lewis acids to the previously reported group 3, 12 and 13 metals in terms of catalyst loading and reaction yields. Moreover, complete regioselectivity was observed for 2-phenyl-N-tosylaziridine; whereas, regioselectivity up to 10 : 1 ratio was observed with 2-methyl-N-tosylaziridine. Finally, a preliminary study on the dearomatization reactions giving rise to pyrroloindolines is also reported.

---

Introduction

Aziridine nucleophilic ring-opening reactions have been recognized for a long time as a precious and reliable tool to introduce a CCN motif in a huge number of substrates.¹ In the specific case of the indole nucleus, regioselective nucleophilic ring-opening of aziridines led to the formation of tryptamine derivatives, chemically synthesized or naturally occurring drugs/alkaloids with well-defined and significant biological effects.² However, reported examples with indoles as nucleophiles are relatively rare and involve aziridines bearing an electron withdrawing group at nitrogen (activated aziridines) under (Lewis) acidic catalysis.³ In particular, the regiochemical outcome for reactions involving C2 monosubstituted aziridines largely depends on the substitution pattern (Scheme 1).

Scheme 1 Previously reported results on the ring opening reactions of aziridines with indoles.

For example, indoles add regioselectively at the benzylic position of C2 aryl substituted aziridines under LiClO₄,^3h and Sc(OTf)₃/Zn(OTf)₂ catalysis,^3a or in the presence of an excess of BF₃ ³ⁱ (Scheme 1, eqn (1)). Moving to alkyl substituted aziridines, mixtures of both conceivable regioisomers are isolated using Zn(OTf)₂ ^3c as a catalyst, and only one report of regioselective reaction in the presence of an excess of BF₃ has been reported until now³ⁱ (Scheme 1, eqn (2)). Besides, aziridines 2-carboxylate have been involved in the synthesis of tryptophan derivatives using 1 equivalent of Sc(ClO₄)₃,^3j Sc(OTf)₃ ^3b or Y(OTf)₃ ^3d as a promoter (Scheme 1, eqn (3)). From the data reported in Scheme 1, it should be noted that working with chiral C2 substituted aziridines, enantiomeric pure compounds can be obtained, suggesting the involvement of a S_N2-type mechanism for the ring-opening reaction.^3i,c Clearly, enantiomeric pure derivatives have been obtained in C3 selective ring opening reactions of enantiomeric pure C2 substituted aziridines.^3b,d,j Furthermore, several of the reported reactions suffer from some drawbacks, i.e., they are performed in the presence of at least a stoichiometric amount of Lewis acids, require an excess of aziridine/indole substrates and/or are limited in scope.

On the other hand, indole is one of the most extensively explored heterocyclic nuclei. A plethora of synthetic methodologies have been developed for the assembly of the indole core⁴ as well as for the functionalization of the preformed nucleus.⁵ This latter goal has been mainly achieved on the pyrrole moiety with electrophiles, exploiting the enamine-type reactivity at the C3 carbon atom and the nucleophilic properties of the nitrogen atom, and, to a lesser extent, with nucleophiles, reversing the natural reactivity by the insertion of suitable substituents at nitrogen or at C2/C3 positions.

Other interconnected and fascinating research areas encompass the dearomative manipulation of the preformed indole ring⁶ for the synthesis of the indolenine core and the cyclization/cycloaddition reactions for the synthesis of polycyclic indole derivatives,^4e,h,k,7 either common scaffolds in naturally occurring and bioactive compounds. Over the last few years, the effectiveness of all these transformations has been notably enhanced through the development of new catalytic and organocatalytic processes.

Considering these results and in step with our latest research reports on the synthesis of polycyclic indoles⁸ and indole derivatives⁹ under gold catalysis, we recognized gold-activated aziridines as suitable electrophiles for the simple functionalization and the dearomative reactions of indoles for the synthesis of β-indolylamines and fused pyrrolo[2,3-b]indoles, respectively (Scheme 2).

Scheme 2 Planned gold(I) catalyzed reactions.

Formation of stable complexes via N-coordination of aziridines with in situ generated triphenylphosphine gold(I) triflate (AuPPh₃OTf) has been recently described by Lorenz and co-workers.¹⁰ These complexes are quite stable and can be isolated and characterized under standard laboratory conditions. Moreover, in 2007 Wu and co-workers published a gold(III) chloride/silver triflate catalyzed ring-opening reaction of aziridines with furan and electron-rich arenes.¹¹ Thus, in the presence of 1–5% of AuCl₃ and 3–15% of AgOTf in nitromethane at room temperature, the reaction affords the corresponding β-aryl(furyl)amines in good to excellent yields. Moreover, several papers dealing with the σ-phylic properties of gold species have been recently published.^8a,12

Results

We started our investigations testing the reactivity of indoles 1a and 1h with racemic 2-phenyl-N-tosylaziridine (2a), under conventional Lewis acid, organic acid and gold catalyses. A comprehensive review of the reaction conditions we tested is summarized in Table 1.

Table 1 Optimization studies for the formation of tryptamine derivatives 3a and 3h

Entry^a	Indole	Eq. of 2a	Catalyst (mol%)	Solvent	T, °C	Time, h	Yield, %
a Entries 1–3, 5–14: reaction conditions: to a solution of indole (0.3 mmol) and aziridine (n equiv.) in the appropriate solvent (2 mL, 0.15 M), a catalyst was added and the mixture was stirred for the stated time and temperature. Entry 4, see ref. 3i. b BDHP = 1,1′-binaphthyl-2,2′-diyl hydrogenphosphate.
1	1a	1.1	In(OTf)3 (15 mol%)	DCM	rt, 40	20	42
2	1a	1.1	Sc(OTf)3 (15 mol%)	DCM	rt, 40	20	21
3	1h	1.5	Zn(NTf2)2 (15 mol%)	DCE	rt, 60	20	48
4	1a	0.6	BF3·OEt2 (1.5 eq.)	DCM	−20	0.2	54
5	1h	1.5	TfOH (5 mol%)	DCE	rt	1.5	51
6	1h	1.5	BDHP (5 mol%)^b	DCE	80	20	Traces
7	1a	1.1	AuCl3 (5 mol%), AgOTf (15 mol%)	CH3NO2	rt	24	23
8	1h	1.5	AgOTf (5 mol%)	DCM	rt, 40	20	50
9	1a	1.5	AgNTf2 (5 mol%)	DCE	80	24	45
10	1h	1.5	[Au(PPh3)OTf] (5 mol%)	DCE	80	0.5	61
11	1h	1.5	[Au(IPr)SbF6] (5 mol%)	DCE	80	0.5	79
12	1h	1.5	[Au(JohnPhos)NTf2] (5 mol%)	DCE	80	0.5	87
13	1h	1.5	[Au(PPh3)NTf2] (5 mol%)	DCE	80	0.5	80
14	1a	1.1	[Au(JohnPhos)NTf 2 ] (5 mol%)	DCE	80	4.5	98

---

We choose to survey the reactivity of 2-alkynylindole 1h, besides simple and commercially available 1a, to verify the feasibility of a domino process involving nucleophilic addition of an indole to an aziridine and subsequent hydroamination of the triple bond (Table 1, compound in brackets). However, under the tested reaction conditions, this compound has never been isolated or detected in the crude reaction mixtures. When the reaction works toward the formation of the desired compounds 3, the isolated regioisomers arose from the C2 selective ring-opening of the aziridine, compounds 3a and 3h. The structure of 3a was elucidated via 1D and 2D NMR experiments.¹³ Initially, for comparison, we tested several conventional Lewis acids under catalytic conditions (15 mol%, entries 1–3). Instead, boron trifluoride was used under the conditions reported in ref. 3i (entry 4). These first attempts, however, led to the formation of the desired product in poor or moderate yields. Similar results were obtained in the presence of trifluoroacetic acid as the catalyst, whereas phosphoric acid (1,1′-binaphthyl-2,2′-diyl hydrogenphosphate) proved essentially ineffective, entries 5 and 6. Thus, gold(III) chloride, in the presence of silver triflate as an activating agent, was tested under the reaction conditions reported by Wu,¹¹ entry 7. In this case, 3a was obtained in 23% yield. 5 mol% silver triflate, silver triflimidate or cationic gold(I) species proved more effective, entries 8–14, and compounds 3a and 3h were isolated in 45–98% yields, with [Au(JohnPhos)NTf₂] as the catalyst of choice.

With these results in hand, we initially choose to test the scope of the reaction under the conditions reported in Table 1, entry 14, changing the substituent array on the indole nucleus (Scheme 3).

Scheme 3 Reaction scope with 2-phenyl-N-tosylaziridines 2a and (R)2a.

Product yields ranged from very good to excellent when the reaction was performed with 2-aryl, 2-alkyl, 2-vinyl, 2-alkynyl and 2-allyl indoles (1a, 1c–f, 1h–j), with N-Me protected indoles 1b and 1g and with indole itself (1k). The introduction of an EWG on the indole phenyl moiety is well tolerated (1l), whereas in the presence of an EDG, indole 1m, or when an ethoxycarbonyl group is linked at C2 of the indole nucleus, indoles 1n and 1o, the corresponding tryptamine derivatives 3m–o were obtained in moderate yields. Moreover, the reactions of indoles 1a,c–e,k were repeated in the presence of (R)-2-phenyl-N-tosylaziridine ((R)2a) yielding the corresponding optically active compounds (S)3a,c–e,k in enantiomeric excesses comparable to that of the starting aziridine.

Next, we turned our attention to the aziridine nucleus testing the reactivity of N-tosylaziridine (2b) (Scheme 4).

Scheme 4 Reaction scope with N-tosylaziridine 2b.

The reaction works well also with the unsubstituted N-tosylaziridine (2b). Tryptamines 3p–t were obtained in 62–71% yield using a slight excess (1.2 equivalents) of thermally fragile 2b. Working with a larger excess of 2b (1.5 or 2.0 equivalents) resulted in the isolation of dirty reaction products, contaminated by inseparable tarry decomposition compounds arising from 2b.

Then, we focused on the ring opening reactions of racemic 2-methyl-N-tosylaziridine (2c) with indoles 1 (Table 2).

Table 2 Ring-opening reactions of 2-methyl-N-tosylaziridine (2c) with indoles 1

Entry^a	Indole	Catalyst (mol%)	Solvent	T, °C	Overall yield, %	Ratio 3/3′
a Entries 1–3, 5–9: reaction conditions: to a solution of indole (0.3 mmol) and aziridine (1.1 equiv.) in DCE (2 mL, 0.15 M), a catalyst was added and the mixture was stirred for the stated time and temperature. Entry 4: see ref. 3i. Entries 10–13: reaction conditions: to a solution of indole (0.3 mmol) and aziridine (0.15 equiv.) in DCE (2 mL, 0.15 M), a catalyst was added and the mixture was stirred at 80 °C for 24 h.
1	1a	[Au(JohnPhos)(NTf2)] (5 mol%)	DCE	80	98	2 : 1
2	1c	[Au(JohnPhos)(NTf2)] (5 mol%)	DCE	80	86	2 : 1
3	1e	[Au(JohnPhos)(NTf2)] (5 mol%)	DCE	80	92	2 : 1
4	1a	BF3·OEt2 (1.5 equiv.)	DCM	20	55	12 : 1
5	1a	[Au(JohnPhos)(SbF6)(CH3CN)] (5 mol%)	DCE	80	91	1.5 : 1
6	1a	[Au(PPh3)(NTf2)] (5 mol%)	DCE	80	31	1.5 : 1
7	1a	[Au(IPr)(NTf2)] (5 mol%)	DCE	80	99	2 : 1
8	1a	[Au(IPr)(SbF6)(CH3CN)] (5 mol%)	DCE	80	96	2 : 1
9	1a	AuCl/AgOTf (5 mol%)	DCE	80	27	7 : 1
10	1a	AuCl/AgOTf (5 mol%)	DCE	80	46	10 : 1
11	1a	AuCl/AgNTf2 (5 mol%)	DCE	80	70	7 : 1
12	1a	AuCl/AgSbF6 (5 mol%)	DCE	80	70	7 : 1
13	1a	AgOTf (5 mol%)	DCE	80	—	—

---

Generally, quite unsatisfactory results were obtained working with 2-methyl-N-tosylaziridine 2c. The first three experiments (entries 1–3), performed with indoles 1a,c,e under standard reaction conditions, resulted in the isolation in excellent overall yields of an inseparable mixture of both conceivable regioisomeric tryptamines 3u–w and 3′u–w in 2 : 1 ratios. As reported in the Introduction, regioselectivity in the ring-opening reaction of activated 2-alkylaziridines, using indoles as nucleophiles, is still a challenging objective and only one example of a regioselective reaction has been reported until now in the presence of an excess (1.5 equiv.) of boron trifluoride etherate.³ⁱ Thus, we performed the reaction between 1a and 2c under the conditions reported by Farr and co-workers (entry 4) attaining 3u and 3′u in a 12 : 1 ratio. Next, with the aim to improve the regioisomeric ratios between 3 and 3′ under catalytic conditions, we tested several cationic gold(I) complexes varying both the ligands and the counterions (entries 5–8) achieving quite disappointing results. Better results could be obtained in the presence of simple gold(I) salts such as gold(I) triflate, generated in situ by mixing equimolecular amounts of gold(I) chloride and silver triflate. Thus, the reaction gave rise to compounds 3u and 3′u in a 7 : 1 ratio (entry 9). The yield and regioisomeric ratio comparable to those obtained with boron trifluoride could be obtained working in the presence of 2 equivalents of indole 1a (entry 10). A brief screening on the nature of silver salts was then performed revealing that AuCl/AgSbF₆ and AuCl/AgNTf₂ were the catalysts of choice to achieve 3u and 3′u in 70% yield and 7 : 1 ratio (entries 11 and 12). A control experiment performed with silver triflate as the catalyst failed to give the desired compound (entry 13). Structures and ratios between the two regioisomers were assigned via NMR analysis.¹³ A control reaction between indole 1a and aziridine (S)2c under the reaction conditions reported in Table 2, entry 12 resulted in the isolation of a mixture of (R)3u (94% ee) and 3′u in 68% overall yield (10 : 1 ratio) (Scheme 5).

Scheme 5 Gold(I) catalyzed reaction of indole 1a and aziridine (S)2c.

Moreover, several additional experiments were performed with indole 1a and aziridines 2d–f (Scheme 6).

Scheme 6 Gold(I) catalyzed reaction of indole 1a and aziridines 2d–f.

Under standard reaction conditions indole 1a reacts with aziridines 2d and 2e giving rise to tryptamines 3x,y in low to moderate yields, besides unreacted 1a. Moreover, the same reaction performed in the presence of aziridine 2f resulted in the isolation of unreacted 1a (45%) alongside a mixture of unidentified compounds.

Finally, we want to report our preliminary results on the dearomative domino addition/annulation reactions between N,3-dimethylindole 1p, N-benzyl-3-methylindole 1q, 2,3-dimethylindole 1r and 3-allyl-N-methylindole 1s with aziridines 2a and 2b, under cationic [Au(JohnPhos)(NTf₂)] gold(I) catalysis (Scheme 7).

Scheme 7 Dearomative domino addition/annulation reactions.

Excellent results on related dearomative reactions, involving unsubstituted aziridines,¹⁴ symmetrically C2/C3 substituted aziridines¹⁵ or C2 substituted aziridines,¹⁶ have been recently reported.

Under cationic gold(I) catalysis, the dearomatization reactions of indoles 1p–r with aziridine 2a proceeded in moderate yields giving rise to the corresponding diastereoisomeric dihydropyrroloindolines (±)4a–c and (±)4′a–c as racemic mixtures. Diastereoisomers (±)4a/(±)4′a and (±)4c/(±)4′c could be separated by column chromatography and the structures were established by comparison with the reported data¹⁶ for (±)4a and (±)4′a and by 2D NOESY experiments for (±)4c and (±)4′c. Diastereoisomers (±)4b/(±)4′b were characterized as a mixture via NMR and by comparison with the reported data.¹⁶ Reactions with indoles 1p,q were repeated also in the presence of chiral aziridine (R)2a giving rise to enantiomeric enriched diastereoisomers 4a (96% ee), 4′a (96% ee)/4b (99% ee) and 4′b (99% ee). 4a/4′a and 4b/4′b were evaluated as mixtures via chiral HPLC analysis, after chromatographic purification.^13,17

Working with indole 1p and aziridine 2b, the indoline 4d was obtained in 55% yield after optimization of the reaction conditions. In particular, the reactions performed under standard conditions (ratio indole/aziridine 1 : 1.2, 0.15 M solution in dichloroethane) at 80 and at 120 °C under conventional heating or at temperatures ranging from 120 to 150 °C under microwave irradiation gave unsatisfactory results (yields 18–39%, Scheme 7, entries 1–4). A brief optimization study on the reagent ratios and reaction concentrations revealed that doubling the equivalents of 2b has no effect on the product yield (Scheme 7, entry 5). On the other hand, working with two equivalents of indole 1p, at 0.3 M and 0.6 M concentrations, the desired compound could be isolated in 45% and 55% yields, respectively (Scheme 7, entries 6 and 7). Under optimized reaction conditions, 3-allyl-N-methylindole (1s) was tested in the dearomative reaction giving rise to indoline 4e in 45% yield.

Discussion

As a general remark it can be stated that cationic gold(I) complexes are active catalysts in the ring-opening reactions of activated aziridine with indoles as nucleophiles. In particular, [Au(JohnPhos)NTf₂] is the catalyst of choice for the ring-opening reactions performed with 2-phenyl-N-tosylaziridine 2a. Thus, the nucleophilic attack of indoles 1a–o, through the C3 carbon atom, occurs regioselectively at the C2 of the aziridine ring, yielding the corresponding tryptamine derivatives 3a–o in excellent yields with a catalyst loading of only 5 mol%. Moreover, the ring-opening reactions provide racemic mixtures when performed with achiral aziridine 2a and is stereospecific employing the chiral aziridine (R)2a as the starting material. Based on these experimental results and literature reports, a reaction mechanism can be postulated for the ring-opening reactions of 2a and (R)2a with indoles 1 (Scheme 8). Therefore, azaphilic^10,18 activation of aziridine by a cationic gold(I) catalyst produces an activated complex (I). Then indole 1 attacks regioselectively at the benzylic carbon of I producing a new intermediate IIvia a Friedel–Crafts-type reaction. Rearomatization and protodeauration steps conclude the catalytic cycle affording 3 and restoring the catalyst.

Scheme 8 Proposed reaction mechanism.

The stereospecificity attained with (R)2a accounts for the intermediacy of a strongly polarized species like I, reacting with 1via the S_N2-type mechanism. Besides, the intermediacy of a zwitterionic species III, Scheme 8, can be disregarded as it would provide racemic 3 by S_N1-type mechanism. Unfortunately, the same regioselectivity was not observed in the ring-opening reactions involving 2-methyl-N-tosylaziridine (2b) under [Au(JohnPhos)NTf₂] catalysis. As reported in the literature and confirmed by our experiments (see Table 2), boron trifluoride is able to almost regioselectively address the nucleophilic attack at the more hindered carbon atom of the aziridine ring. It seems that an excess of a hard Lewis acid like boron trifluoride is essential to establish a strong interaction within both reacting substrates and to trigger the reaction toward the C2 selective ring-opening reaction path.^3i,19 Instead, cationic gold(I) complexes in a catalytic amount weakly interact with the aziridine nitrogen, and in the absence of a strong directing group like a phenyl ring in aziridine 2a, the reaction outcomes are driven by steric and electronic issues making possible two opposite reaction paths. Both of them involve the ring-opening reaction of aziridine 2b, respectively, at C2 and C3, affording mixtures of both conceivable tryptamines 3 and 3′. In line with these observations, it is worth noting that using 5 mol% of more electrophilic naked cationic gold salts improves the regioisomeric ratio between 3u and 3′u. Importantly, the [Au(JohnPhos)NTf₂] catalyst proves effective also in the dearomative reactions of C3 substituted indoles. In this latter case, a reaction intermediate analogous to II, Scheme 8, evolves by intramolecular amination reaction and regeneration of the catalyst.

Conclusions

In this work we established the high efficiency of a cationic gold(I) catalyst [Au(JohnPhos)(NTf₂)] in the ring opening reactions of 2-phenyl-N-tosylaziridine 2a and (R)2a with indoles as nucleophiles. In particular, we gathered a large collection of tryptamine derivatives in high yields, with complete stereochemical control and at a catalyst loading of only 5 mol%. To the best of our knowledge, only sporadic examples of related Lewis acid catalyzed reactions have been reported until now.^3h,a,i Furthermore, it should be pointed out that, depending on the nature of the Lewis acid employed, previously reported reactions could suffer from lack of stereocontrol due to racemization of the starting aziridine during the reaction course.^16a The results obtained with 2a, besides those obtained with N-tosylaziridine itself (2b), represent the key strength of our work. In contrast, less exciting results have been achieved with 2-methyl-N-tosylaziridine (2c) and in the dearomative domino addition/annulation reactions. In the first case, we observed a lack of regiochemical control even if nearly quantitative reaction yields could be obtained. Dearomative reactions giving rise to pyrroloindoline derivatives, besides excellent stereocontrol, present several drawbacks. Moderate yields and low diastereoselection are the main weak points that must be addressed and further efforts in these directions are ongoing in our laboratory. Also the results reported for aziridines 2d–f in Scheme 6 could represent a good starting point for further investigations.

Experimental

General experimental details

All chemicals and solvents are commercially available and were used after distillation or treatment with drying agents. Silica gel F254 thin-layer plates were employed for thin-layer chromatography (TLC). Silica gel 40–63 micron per 60 Å was employed for flash column chromatography. Melting points were measured with a Perkin-Elmer DSC 6 calorimeter at a heating rate of 5 °C min⁻¹ and are uncorrected. ¹H and ¹³C-NMR spectra were determined with a Varian-Gemini 200, a Bruker 300 or 500 Avance spectrometer at room temperature in CDCl₃, CD₂Cl₂ or d₆-acetone with residual solvent peaks as the internal reference. The APT sequence was used to distinguish the methine and methyl carbon signals from those arising from methylene and quaternary carbon atoms. Two-dimensional NMR experiments were performed, where appropriate, to aid the assignment of structures. Low-resolution MS spectra were recorded with a Thermo-Finnigan LCQ advantage AP electrospray/ion trap equipped instrument using a syringe pump device to directly inject sample solutions. Microwave promoted reactions were performed with a single-mode Personal Chemistry microwave synthesizer “Emrys Creator,” using sealed glass vessels. The temperature was detected with an infrared sensor. Indoles 1a, 1e, 1k, 1n, 1o, 1p, 1r are commercially available and were used without any further purification. Indoles 1b–d, and 1l are known compounds and were prepared as reported in the literature.^9,20 Indoles 1q and 1s are known compounds and were prepared according to literature procedures.²¹ Indole 1h ²² and indoles 1i and 1j ²³ were prepared according to the procedures reported in ref. 9 and 20 (see below). Indoles 1f and 1g were prepared as reported in ref. 24 and 8b, respectively.^24,8b Indole 1m is a new compound and was prepared as reported below. Aziridines 2a–f are known compounds and were prepared according to standard procedures.²⁵ AuCl₃, AuCl[Au(PPh₃)Cl], [Au(JohnPhos)Cl], [Au(IPr)Cl], AgNTf₂, AgOTf, In(OTf)₃, Zn(NTf)₂ and TfOH were purchased from commercial suppliers and used as received, the rest of the gold catalysts were prepared according to literature procedures.²⁶

Preparation and characterization data for compounds 1h–j,m

2-(Phenylethynyl)-1H-indole (1h)²². Ethyl 2-(phenylethynyl)-1H-indole-1-carboxylate²⁰ (0.84 g, 2.9 mmol) was dissolved in MeOH (20 mL). Solid K₂CO₃ (0.40 g, 2.9 mmol) was added and the mixture stirred for 2 h at 40 °C. Then the solvent was removed in vacuum and the residue was dissolved in H₂O/EtOAc 1 : 1 (50 mL). The two phases were separated and the aqueous layer was extracted with EtOAc (2 × 15 mL). The combined organic layers were dried over Na₂SO₄, filtered and concentrated in vacuum to yield 2-(phenylethynyl)-1H-indole (1h) (0.59 g, 94%) as a yellow solid. ¹H-NMR (200 MHz, CD₂Cl₂): δ 8.39 (s, 1H), 7.59 (m, 3H), 7.40 (m, 4H), 7.27 (t, J = 6.9 Hz, 1H), 7.15 (t, J = 7.3 Hz, 1H), 6.87 (s, 1H). ¹³C-NMR (50 MHz, CD₂Cl₂): δ 136.5 (C), 131.6 (2 × CH), 128.9 (CH), 128.7 (2 × CH), 128.0 (C), 123.8 (CH), 122.8 (C), 120.9(CH), 120.7 (CH), 119.0 (C), 111.0 (CH), 108.8 (CH), 92.6 (C), 81.8 (C). ESI-MSm/z 218 (M + H⁺, 100). Data are in agreement with those reported in ref. 22.

2-(Pent-1-yn-1-yl)-1H-indole (1i). To a well stirred solution of ethyl 2-(((trifluoromethyl)sulfonyl)oxy)-1H-indole-1-carboxylate²⁰ (1.0 g, 2.96 mmol) and pent-1-yne (0.24 g, 3.55 mmol) in dry DMF (12 mL), Pd(PPh₃)₄ (4 mol%, 132 mg, 0.12 mmol), CuI (2 mol%, 11.3 mg, 0.06 mmol) and Et₃N (8.25 mL, 59.2 mmol) were added. The mixture was then stirred at room temperature until the disappearance of starting materials (ca. 1 h) and then diluted with 0.1 M HCl (100 mL). The aqueous phase was extracted with EtOAc (3 × 50 mL); the combined organic phases were washed with brine (1 × 50 mL), dried over Na₂SO₄, filtered and concentrated in vacuum. Purification by column chromatography (Hex/EtOAc 98 : 2) yielded ethyl 2-(pent-1-yn-1-yl)-1H-indole-1-carboxylate (0.72 g, 95%) as a yellow oil. ¹H-NMR (200 MHz, CDCl₃): δ 8.13 (d, J = 8.2 Hz, 1H), 7.48 (m, 1H), 7.37–7.17 (m, 2H), 6.82 (s, 1H), 4.51 (q, J = 7.1 Hz, 2H), 2.48 (t, J = 7.1 Hz, 2H), 1.68 (sextet, J = 7.1 Hz, 2H), 1.49 (t, J = 7.1 Hz, 3H), 1.08 (t, J = 7.3 Hz, 3H). Ethyl 2-(pent-1-yn-1-yl)-1H-indole-1-carboxylate (0.72 g, 2.82 mmol) was dissolved in MeOH (19 mL). Solid K₂CO₃ (0.39 g, 2.82 mmol) was added and the mixture was stirred for 2 h at 40 °C. After that time, the solvent was removed in vacuum and the residue was dissolved in H₂O/EtOAc 1 : 1 (50 mL). The two phases were separated and the aqueous layer was extracted with EtOAc (2 × 15 mL). The combined organic layers were dried over Na₂SO₄, filtered and concentrated in vacuum to yield 2-(pent-1-yn-1-yl)-1H-indole (1i) (0.49 g, 94%) as a brown wax. ¹H-NMR (200 MHz, CDCl₃): δ 8.09 (s, 1H), 7.56 (m, 1H), 7.35–7.02 (m, 3H), 6.66 (d, J = 1.3 Hz, 1H), 2.44 (t, J = 7.0 Hz, 2H), 1.63 (sextet, J = 7.1 Hz, 2H), 1.07 (t, J = 7.3 Hz, 3H). ¹³C-NMR (50 MHz, CDCl₃): δ 136.0 (C), 128.1 (C), 123.2 (CH), 120.8 (CH), 120.5 (CH), 119.8 (C), 110.8 (CH), 107.7 (CH), 93.9 (C), 73.4 (C), 22.3 (CH₂), 21.8 (CH₂), 13.8 (CH₃). ESI-MSm/z 182 (M − H⁺, 100).

2-Allyl-1H-indole (1j)²³. Ethyl 2-allyl-1H-indole-1-carboxylate²⁰ (0.25 g, 1.11 mmol) was dissolved in MeOH (8 mL) and K₂CO₃ (0.15 g, 1.11 mmol) was added. The mixture was stirred for 30 min at 40 °C. After that time, the solvent was removed in vacuum and the residue was dissolved in H₂O/EtOAc 1 : 1 (15 mL). The two phases were separated and the aqueous layer was extracted with EtOAc (2 × 5 mL). The combined organic layers were dried over Na₂SO₄, filtered and concentrated in a vacuum to yield 2-allyl-1H-indole (1j) (0.11 g, 60%) as a white solid. ¹H-NMR (200 MHz, CDCl₃): δ 7.89 (s, 1H), 7.54 (d, J = 6.8 Hz, 1H), 7.36–7.00 (m, 3H), 6.28 (s, 1H), 6.00 (m, 1H), 5.21 (m, 2H), 3.55 (d, J = 6.3 Hz, 2H). Data are in agreement with those reported in ref. 23.

N,N-Diethyl-1H-indol-6-amine (1m). A solution of 2 M NaOH (3.7 mL, 7.49 mmol) was added to a stirring solution of 6-(N,N-diethylamino)-1-(phenylsulfonyl)-1H-indole²⁷ (200 mg, 0.61 mmol) in 7 mL of MeOH and heated at 85 °C under a nitrogen atmosphere. The reaction mixture was stirred for 24 h until no more starting product was detectable by TLC analysis. Methanol was removed under reduced pressure and the crude product was poured into H₂O (25 mL) and extracted with EtOAc (4 × 20 mL), washed with brine and dried over Na₂SO₄. The solvent was removed under reduced pressure and then the residue was purified by flash chromatography over a silica gel column using Hex/EtOAc (7 : 3) to afford N,N-diethyl-1H-indol-6-amine (1m) (95 mg, 83%) as pale brown oil. ¹H-NMR (200 MHz, CDCl₃): δ 7.87 (s, 1H), 7.47 (d, J = 9.1 Hz, 1H), 7.01 (m, 1H), 6.78 (m, 2H), 6.42 (m, 1H), 3.36 (q, J = 7.0 Hz, 4H), 1.16 (t, J = 7.0 Hz, 6H). ¹³C-NMR (C₆D₆, 50 MHz): δ 145.2 (C), 138.0 (C), 121.7 (CH), 121.3 (CH), 120.9 (C), 110.7 (CH), 102.4 (CH), 96.3 (CH), 45.7 (2 × CH₂), 12.7 (2 × CH₃). ESI-MSm/z 189 (M + H⁺, 100).

Preparation and characterization data for compounds 3a–t, (S)3a, (S)3c–e, (S)3k, 3x,y

Representative procedure for gold(I)-catalyzed ring opening of N-tosyl aziridines (procedure A). To a N₂-flushed solution of indoles 1a–o (1.0 equiv.) and N-tosyl aziridine 2a, (R)2a or 2b (1.1 or 1.2 equiv.) in DCE (0.15 M), [Au(JohnPhos)(NTf₂)] (5 mol%) was added and the mixture was stirred at 80 °C for 0.5–5 h. The solvent was then removed in vacuum and the residue was purified by column chromatography (SiO₂) to yield the corresponding products 3a–t, (S)3a, (S)3c–e, (S)3k.

4-Methyl-N-(2-phenyl-2-(2-phenyl-1H-indol-3-yl)ethyl)benzenesulfonamide (3a). Procedure A was followed using 2-phenyl-1H-indole (1a) (58 mg, 0.3 mmol), 2-phenyl-1-tosylaziridine (2a) (90.2 mg, 0.33 mmol) and [Au(JohnPhos)(NTf₂)] (11.6 mg, 0.015 mmol) in DCE (2 mL). Purification of the crude product by column chromatography (Hex/EtOAc 8 : 2) yielded 3a (137 mg, 98%) as a white solid (m.p.: 165–167 °C). ¹H NMR (300 MHz, CDCl₃): δ 8.27 (s, 1H), 7.54–7.38 (m, 8H), 7.32–7.09 (m, 9H), 6.97 (t, J = 7.5 Hz, 1H), 4.49 (dd, J = 10.7, 6.1 Hz, 1H), 4.24 (dd, J = 9.1, 2.8 Hz, 1H), 3.84–3.62 (m, 2H), 2.42 (s, 3H). ¹H NMR (300 MHz, CDCl₃ + D₂O): δ 7.54–7.38 (m, 8H), 7.32–7.09 (m, 9H), 6.97 (t, J = 7.5 Hz, 1H), 4.49 (dd, J = 10.7, 6.1 Hz, 1H), 3.80 (dd, J = 12.2, 6.1 Hz, 1H), 3.70 (dd, J = 10.9, 12.0 Hz, 1H), 2.41 (s, 3H). ¹³C NMR (50 MHz, CDCl₃): δ 143.4 (C), 141.9 (C), 138.0 (C), 136.5 (C), 136.4 (C), 132.4 (C), 129.8 (2 × CH), 129.1 (2 × CH), 128.9 (2 × CH), 128.8 (2 × CH), 128.6 (CH), 127.9 (2 × CH), 127.3 (C), 127.2 (2 × CH), 126.9 (CH), 122.7 (CH), 120.4 (CH), 120.3 (CH), 111.8 (CH), 109.7 (C), 46.9 (CH₂), 42.5 (CH), 21.8 (CH₃). ESI-MSm/z 465 (M − H⁺, 100). Calcd for C₂₉H₂₆N₂O₂S [466.59]: C 74.65, H 5.62, N 6.00; found C 74.38, H 5.78, N 5.86.

(S)-4-Methyl-N-(2-phenyl-2-(2-phenyl-1H-indol-3-yl)ethyl)benzenesulfonamide ((S)3a). Procedure A was followed using (R)-2-phenyl-1-tosylaziridine ((R)2a). (S)3a was obtained in 98% yield and 97% ee. (S)3a was analyzed via chiral-HPLC in comparison with racemic 3a, see the ESI† (HPLC section) for details.

4-Methyl-N-(2-(1-methyl-2-phenyl-1H-indol-3-yl)-2-phenylethyl)benzenesulfonamide (3b). Procedure A was followed using 1-methyl-2-phenyl-1H-indole (1b) (62 mg, 0.3 mmol), 2-phenyl-1-tosylaziridine (2a) (90.2 mg, 0.33 mmol) and [Au(JohnPhos)(NTf₂)] (11.6 mg, 0.015 mmol) in DCE (2 mL). Purification of the crude product by column chromatography (Hex/EtOAc 8 : 2) yielded 3b (137 mg, 95%) as a white thick oil. ¹H-NMR (300 MHz, CDCl₃): δ 7.55–7.12 (m, 17H), 6.95 (t, J = 7.0 Hz, 1H), 4.25 (dd, J = 10.6, 6.6 Hz, 1H), 3.72–3.51 (m, 5H), 2.44 (s, 3H). ¹³C-NMR (75 MHz, CDCl₃): δ 143.6 (C), 142.2 (C), 140.9 (C), 137.8 (C), 136.6 (C) 131.5 (C), 131.2 (2 × CH), 130.0 (2 × CH), 129.0 (CH), 128.9 (2 × CH), 128.8 (2 × CH), 128.0 (2 × CH), 127.5 (2 × CH), 126.9 (CH), 126.2 (C), 122.3 (CH), 120.2 (CH), 120.1 (CH), 110.3 (C), 110.2 (CH), 46.9 (CH₂), 42.8 (CH), 31.3 (CH₃), 21.9 (CH₃). ESI-MSm/z 503 [M + Na⁺, 100]. Calcd for C₃₀H₂₈N₂O₂S [480.63]: C 74.97, H 5.87, N 5.83; found C 75.29, H 5.71, N 5.97.

N-(2-(2-(4-Isopropoxyphenyl)-1H-indol-3-yl)-2-phenylethyl)-4-methylbenzenesulfonamide (3c). Procedure A was followed using 2-(4-isopropoxyphenyl)-1H-indole (1c) (75.4 mg, 0.3 mmol), 2-phenyl-1-tosylaziridine (2a) (90.2 mg, 0.33 mmol) and [Au(JohnPhos)(NTf₂)] (11.6 mg, 0.015 mmol) in DCE (2 mL). Purification of the crude product by column chromatography (Hex/EtOAc 8 : 2) yielded 3c (142 mg, 90%) as a white solid (m.p.: 75–78 °C). ¹H-NMR (200 MHz, CDCl₃): δ 8.18 (s, 1H), 7.50–7.36 (m, 3H), 7.32–7.08 (m, 11H), 6.97–6.85 (m, 3H), 4.59 (hept, J = 6.0 Hz, 1H), 4.45 (dd, J = 10.7, 6.2 Hz, 1H), 4.22 (dd, J = 9.0, 2.9 Hz, 1H), 3.84–3.55 (m, 2H), 2.40 (s, 3H), 1.39 (d, J = 6.2 Hz, 3H), 1.37 (d, J = 6.0 Hz, 3H). ¹³C-NMR (50 MHz, CDCl₃): δ 158.5 (C), 143.3 (C), 142.0 (C), 138.0 (C), 136.5 (C), 136.3 (C), 130.1 (2 × CH), 129.8 (2 × CH), 128.8 (2 × CH), 127.9 (2 × CH), 127.4 (C), 127.2 (2 × CH), 126.9 (CH), 124.4 (C), 122.4 (CH), 120.3 (CH), 120.1 (CH), 116.3 (2 × CH), 111.4 (CH), 109.1 (C), 70.3 (CH), 46.8 (CH₂), 42.4 (CH), 22.3 (CH₃), 22.2 (CH₃), 21.7 (CH₃). ESI-MSm/z 523 [M − H⁺, 100]. Calcd for C₃₂H₃₂N₂O₃S [524.67]: C 73.25, H 6.15, N 5.34; found: C 73.02, H 6.27, N 5.49.

(S)-N-(2-(2-(4-Isopropoxyphenyl)-1H-indol-3-yl)-2-phenylethyl)-4-methylbenzenesulfonamide ((S)3c). Procedure A was followed using (R)-2-phenyl-1-tosylaziridine ((R)2a). (S)3c was obtained in 89% yield and 98% ee. (S)3c was analyzed via chiral-HPLC in comparison with racemic 3c, see the ESI† (HPLC section) for details.

N-(2-(2-(3-Acetylphenyl)-1H-indol-3-yl)-2-phenylethyl)-4-methylbenzenesulfonamide (3d). Procedure A was followed using 1-(3-(1H-indol-2-yl)phenyl)ethanone (1d) (70.6 mg, 0.3 mmol), 2-phenyl-1-tosylaziridine (2a) (90.2 mg, 0.33 mmol) and [Au(JohnPhos)(NTf₂)] (11.6 mg, 0.015 mmol) in DCE (2 mL). Purification of the crude product by column chromatography (Hex/EtOAc 7 : 3) yielded 3d (148 mg, 97%) as a yellowish solid (m.p.: 77–79 °C). ¹H-NMR (200 MHz, CDCl₃): δ 8.92 (s, 1H), 7.89 (m, 2H), 7.64–7.05 (m, 14H), 6.96 (t, J = 7.2, 1H), 4.48 (m, 2H), 3.75 (m, 2H), 2.42 (s, 3H), 2.37 (s, 3H). ¹³C NMR (50 MHz, CDCl₃): δ 198.2 (C), 143.5 (C), 141.8 (C), 137.7 (C), 136.8 (C), 136.7 (C), 136.6 (C), 133.3 (CH), 133.0 (C), 129.8 (2 × CH), 129.3 (CH), 128.9 (2 × CH), 128.9 (CH), 128.0 (2 × CH), 127.3 (C), 127.2 (2 × CH), 127.1 (CH), 122.9 (CH), 120.5 (CH), 120.3 (CH), 112.0 (CH), 110.4 (C), 47.1 (CH₂), 43.0 (CH), 26.8 (CH₃), 21.7 (CH₃). 1 CH_ar is overlapping probably with 2 × CH at 128.0. ESI-MSm/z 507 [M − H⁺, 100]. Calcd for C₃₁H₂₈N₂O₃S [508.63]: C 73.20, H 5.55, N 5.51; found: C 73.58, H 5.41, N 5.62.

(S)-N-(2-(2-(3-Acetylphenyl)-1H-indol-3-yl)-2-phenylethyl)-4-methylbenzenesulfonamide ((S)3d). Procedure A was followed using (R)-2-phenyl-1-tosylaziridine ((R)2a). (S)3d was obtained in 97% yield and 97% ee. (S)3d was analyzed via chiral-HPLC in comparison with racemic 3d, see the ESI† (HPLC section) for details.

4-Methyl-N-(2-(2-methyl-1H-indol-3-yl)-2-phenylethyl)benzenesulfonamide (3e). Procedure A was followed using 2-methyl-1H-indole (1e) (39.4 mg, 0.3 mmol), 2-phenyl-1-tosylaziridine (2a) (90.2 mg, 0.33 mmol) and [Au(JohnPhos)(NTf₂)] (11.6 mg, 0.015 mmol) in DCE (2 mL). Purification of the crude product by column chromatography (Hex/EtOAc 8 : 2) yielded 3e (112 mg, 92%) as a white solid (m.p.: 147–150 °C). ¹H-NMR (200 MHz, CDCl₃): δ 7.97 (s, 1H), 7.62 (d, J = 8.3 Hz, 2H), 7.31–7.08 (m, 9H), 6.90 (t, J = 7.4 Hz, 1H), 4.41 (dd, J = 10.4, 6.1 Hz, 1H), 4.33 (dd, J = 8.9, 2.9 Hz, 1H), 3.84 (ddd, J = 12.1, 9.1, 6.2, 1H), 3.61 (ddd, J = 12.1, 10.6, 3.2, 1H), 2.45 (s, 3H), 2.33 (s, 3H). ¹H-NMR (200 MHz, CDCl₃ + D₂O): δ 7.62 (d, J = 8.3 Hz, 2H), 7.31–7.08 (m, 9H), 6.90 (t, J = 7.4 Hz, 1H), 4.41 (dd, J = 10.5, 6.1 Hz, 1H), 4.33 (dd, J = 8.9, 2.9 Hz, 1H), 3.83 (dd, J = 12.1, 6.1, 1H), 3.60 (dd, J = 12.1, 10.6, 1H), 2.45 (s, 3H), 2.32 (s, 3H). ¹³C NMR (50 MHz, CDCl₃): δ 143.7 (C), 141.7 (C), 136.7 (C), 135.8 (C), 133.9 (C), 130.0 (2 × CH), 128.8 (2 × CH), 127.9 (2 × CH), 127.3 (2 × CH), 127.2 (C), 126.8 (CH), 121.4 (CH), 119.8 (CH), 118.9 (CH), 111.1 (CH), 109.2 (C), 46.6 (CH₂), 42.3 (CH), 21.8 (CH₃), 12.2 (CH₃). ESI-MSm/z 403 [M − H⁺, 100]. Calcd for C₂₄H₂₄N₂O₂S [404.52]: C 71.26, H 5.98, N 6.93; found: C 71.48, H 6.02, N 6.80.

4-Methyl-N-(2-phenyl-2-(2-vinyl-1H-indol-3-yl)ethyl)benzenesulfonamide (3f). Procedure A was followed using ethyl 2-vinyl-1H-indole (1f) (42.9 mg, 0.3 mmol), 2-phenyl-1-tosylaziridine (2a) (90.2 mg, 0.33 mmol) and [Au(JohnPhos)(NTf₂)] (11.6 mg, 0.015 mmol) in DCE (2 mL). Purification of the crude product by column chromatography (Hex/EtOAc 3 : 1) yielded 3f (112 mg, 90%) as a white solid (m.p.: 130–132 °C). ¹H-NMR (200 MHz, CDCl₃): δ 8.23 (s, 1H), 7.60 (d, J = 8.3 Hz, 2H), 7.32–7.14 (m, 10H), 6.88 (ddd, J = 8.2, 6.9, 1.1 Hz, 1H), 6.69 (dd, J = 17.5, 11.3 Hz, 1H), 5.52 (d, J = 17.6 Hz, 1H), 5.28 (d, J = 11.3 Hz, 1H), 4.49 (dd, J = 10.3, 6.1 Hz, 1H), 4.30 (dd, J = 8.7, 3.4 Hz, 1H), 3.87 (m, 1H), 3.62 (m, 1H), 2.43 (s, 3H). ¹³C-NMR (50 MHz, CDCl₃): δ 143.6 (C), 141.1 (C), 136.9 (C), 136.7 (C), 134.3 (C), 129.9 (2 × CH), 128.8 (2 × CH), 127.8 (2 × CH), 127.3 (2 × CH), 127.2 (C), 126.9 (CH), 125.3 (CH), 123.4 (CH), 120.3 (CH), 120.1 (CH), 113.6 (CH₂), 113.0 (C), 111.3 (CH), 46.5 (CH₂), 41.8 (CH), 21.8 (CH₃). ESI-MSm/z 439 [M + Na⁺, 100]. Calcd for C₂₅H₂₄N₂O₂S [416.54]: C 72.09, H 5.81, N 6.73; C 72.37, H 5.88, N 6.72.

(E)-4-Methyl-N-(2-(1-methyl-2-(4-methylstyryl)-1H-indol-3-yl)-2-phenylethyl)benzenesulfonamide (3g). Procedure A was followed using ethyl (E)-1-methyl-2-(4-methylstyryl)-1H-indole (1g) (74.2 mg, 0.3 mmol), 2-phenyl-1-tosylaziridine (2a) (90.2 mg, 0.33 mmol) and [Au(JohnPhos)(NTf₂)] (11.6 mg, 0.015 mmol) in DCE (2 mL). Purification of the crude product by column chromatography (Hex/EtOAc 8 : 2) yielded 3g (108 mg, 69%) as a yellow wax. ¹H-NMR (200 MHz, CDCl₃): δ 7.55 (d, J = 8.3 Hz, 2H), 7.37–7.10 (m, 14H), 6.94 (m, 2H), 6.64 (d, J = 16.5 Hz, 1H), 4.58 (dd, J = 10.5, 6.3 Hz, 1H), 4.30 (dd, J = 8.8, 3.1 Hz, 1H), 3.84–3.59 (m, 5H), 2.39 (s, 3H), 2.34 (s, 3H). ¹³C-NMR (50 MHz, CDCl₃): δ 143.4 (C), 142.2 (C), 138.6 (C), 138.1 (C), 137.7 (C), 136.7 (C), 135.7 (CH), 134.1 (C), 129.8 (2 × CH), 129.7 (2 × CH), 128.9 (2 × CH), 128.0 (2 × CH), 127.3 (2 × CH), 126.9 (CH), 126.8 (2 × CH), 126.6 (C), 122.4 (CH), 120.1 (CH), 119.8 (CH), 115.7 (CH), 110.7 (C), 109.8 (CH), 47.0 (CH₂), 43.2 (CH), 31.1 (CH₃), 21.6 (CH₃), 21.5 (CH₃). ESI-MS m/z 519 [M − H⁺, 100]. Calcd for C₃₃H₃₂N₂O₂S [520.68]: C 76.12, H 6.19, N 5.38; found C 76.23, H 6.02, N 5.49.

4-Methyl-N-(2-phenyl-2-(2-(phenylethynyl)-1H-indol-3-yl)ethyl)benzenesulfonamide (3h). Procedure A was followed using 2-(phenylethynyl)-1H-indole (1h) (65.2 mg, 0.3 mmol), 2-phenyl-1-tosylaziridine (2a) (90.2 mg, 0.33 mmol) and [Au(JohnPhos)(NTf₂)] (11.6 mg, 0.015 mmol) in DCE (2 mL). Purification of the crude product by column chromatography (Hex/EtOAc 8 : 2) yielded 3h (128 mg, 87%) as a yellowish solid (m.p.: 190–192 °C). ¹H-NMR (200 MHz, d₆-Acetone): δ 10.59 (s, 1H), 7.70 (d, J = 8.3 Hz, 2H), 7.57–7.41 (m, 8H), 7.39–7.09 (m, 7H), 6.99 (t, J = 7.0 Hz, 1H), 6.49 (t, J = 5.5 Hz, 1H), 4.74 (t, J = 8.0 Hz, 1H), 4.08–3.80 (m, 2H), 2.34 (s, 3H). ¹³C-NMR (50 MHz, d₆-Acetone): δ 143.0 (C), 142.6 (C), 138.4 (C), 136.9 (C), 131.3 (2 × CH), 129.7 (2 × CH), 128.9 (2 × CH), 128.5 (2 × CH), 128.2 (2 × CH), 127.1 (2 × CH), 126.8 (C), 126.6 (CH), 123.5 (CH), 123.0 (C), 121.4 (C), 119.9 (CH), 119.5 (CH), 116.8 (C), 111.5 (CH), 95.0 (C), 82.3 (C), 46.8 (CH₂), 43.5 (CH), 20.7 (CH₃). 1 CH_ar is missing, probably overlapping. ESI-MSm/z 489 [M − H⁺, 100]. Calcd for C₃₁H₂₆N₂O₂S [490.62]: C 75.89, H 5.34, N 5.71; found: C 76.22, H 5.28, N 5.93.

4-Methyl-N-(2-(2-(pent-1-yn-1-yl)-1H-indol-3-yl)-2-phenylethyl)benzenesulfonamide (3i). Procedure A was followed using 2-(pent-1-yn-1-yl)-1H-indole (1i) (55 mg, 0.3 mmol), 2-phenyl-1-tosylaziridine (2a) (90.2 mg, 0.33 mmol) and [Au(JohnPhos)(NTf₂)] (11.6 mg, 0.015 mmol) in DCE (2 mL). Purification of the crude product by column chromatography (Hex/EtOAc 5 : 1) yielded 3i (127 mg, 93%) as a white solid (m.p.: 126–128 °C). ¹H-NMR (200 MHz, CDCl₃): δ 8.06 (s, 1H), 7.60 (d, J = 8.3 Hz, 2H), 7.31–7.07 (m, 9H), 6.92 (t, J = 6.7 Hz, 2H), 4.48 (m, 2H), 3.80 (dd, J = 8.1, 6.3 Hz, 2H), 2.47–2.29 (m, 5H), 1.71–1.53 (m, 2H), 1.02 (t, J = 7.3 Hz, 3H). ¹³C-NMR (50 MHz, CDCl₃): δ 143.4 (C), 141.4 (C), 137.2 (C), 135.9 (C), 129.8 (2 × CH), 128.8 (2 × CH), 128.0 (2 × CH), 127.3 (2 × CH), 127.0 (CH), 126.5 (C), 123.6 (CH), 120.3 (CH), 119.3 (CH), 118.4 (C), 118.0 (C), 111.1 (CH), 97.4 (C), 72.7 (C), 46.5 (CH₂), 43.0 (CH), 22.2 (CH₂), 21.8 (CH₃), 21.7 (CH₂), 13.9 (CH₃). ESI-MSm/z 455 [M − H⁺, 100]. Calcd for C₂₈H₂₈N₂O₂S [456.60]: C 73.65, H 6.18, N 6.14; C 73.37, H 6.12, N 6.26.

N-(2-(2-Allyl-1H-indol-3-yl)-2-phenylethyl)-4-methylbenzenesulfonamide (3j). Procedure A was followed using ethyl 2-allyl-1H-indole (1j) (47.2 mg, 0.3 mmol), 2-phenyl-1-tosylaziridine (2a) (90.2 mg, 0.33 mmol) and [Au(JohnPhos)(NTf₂)] (11.6 mg, 0.015 mmol) in DCE (2 mL). Purification of the crude product by column chromatography (Hex/EtOAc 7 : 3) yielded 3j (103 mg, 80%) as a white wax. ¹H NMR (200 MHz, CDCl₃): δ 7.99 (s, 1H), 7.60 (d, J = 8.2, 2H), 7.37–7.03 (m, 10H), 6.89 (t, J = 7.5, 1H), 5.87 (m, 1H), 5.2–5.05 (m, 2H), 4.42 (dd, J = 10.4, 6.2 Hz, 1H), 4.31 (dd, J = 9.0, 3.4 Hz, 1H), 3.82 (m, 1H), 3.59 (m, 1H), 3.42 (d, J = 6.4 Hz, 2H), 2.43 (s, 3H). ¹³C NMR (50 MHz, CDCl₃): δ 143.6 (C), 141.5 (C), 136.9 (C), 136.0 (C), 135.2 (C), 134.7 (CH), 129.9 (2 × CH), 128.7 (2 × CH), 127.9 (2 × CH), 127.3 (2 × CH), 127.2 (C), 126.8 (CH), 121.7 (CH), 119.9 (CH), 119.3 (CH), 117.9 (C), 111.2 (CH), 109.7 (CH), 46.6 (CH₂), 42.2 (CH), 31.0 (CH₂), 21.7 (CH₃). ESI-MSm/z 429 [M − H⁺, 100]. Calcd for C₂₆H₂₆N₂O₂S [430.57]: C 72.53, H 6.09, N 6.51; found: C 72.87, H 5.99, N 6.61.

N-(2-(1H-Indol-3-yl)-2-phenylethyl)-4-methylbenzenesulfonamide (3k). Procedure A was followed using 1H-indole (1k) (51.4 mg, 0.3 mmol), 2-phenyl-1-tosylaziridine (2a) (90.2 mg, 0.33 mmol) and [Au(JohnPhos)(NTf₂)] (11.6 mg, 0.015 mmol) in DCE (2 mL). Purification of the crude product by column chromatography (Hex/EtOAc 8 : 2) yielded 3k (100 mg, 83%) as a white solid (m.p.: 185–188 °C). ¹H-NMR (200 MHz, DMSO-d₆): δ 10.86 (s, 1H), 7.62 (dd, J = 8.1, 1.5 Hz, 2H), 7.39–7.05 (m, 10H), 7.00 (t, J = 8.2 Hz, 1H), 6.85 (t, J = 7.9 Hz, 1H), 4.27 (t, J = 7.7 Hz, 1H), 3.35–3.19 (m, 2H), 2.32 (s, 3H). ¹³C-NMR (50 MHz, DMSO-d₆): δ 143.6 (C), 143.1 (C), 138.3 (C), 136.9 (C), 130.2 (2 × CH), 128.9 (2 × CH), 128.7 (2 × CH), 127.2 (2 × CH), 127.1 (C), 126.8 (CH), 122.8 (CH), 121.7 (CH), 119.0 (CH), 116.1 (C), 112.1 (CH), 48.2 (CH₂), 43.3 (CH), 21.6 (CH₃). ESI-MSm/z 391 [M − H⁺, 100]. Calcd for C₂₃H₂₂N₂O₂S [390.50]: C 70.74, H 5.68, N 7.17; found C 70.99, H 5.75, N 7.01.

(S)-N-(2-(1H-Indol-3-yl)-2-phenylethyl)-4-methylbenzenesulfonamide ((S)3k). Procedure A was followed using (R)-2-phenyl-1-tosylaziridine ((R)2a). (S)3k was obtained in 85% yield and 97% ee. (S)3k was analyzed via chiral-HPLC in comparison with racemic 3k, see the ESI† (HPLC section) for details.

4-Methyl-N-(2-phenyl-2-(2-phenyl-6-(trifluoromethyl)-1H-indol-3-yl)ethyl)benzenesulfonamide (3l). Procedure A was followed using 2-phenyl-6-(trifluoromethyl)-1H-indole (1l) (78.4 mg, 0.3 mmol), 2-phenyl-1-tosylaziridine (2a) (90.2 mg, 0.33 mmol) and [Au(JohnPhos)(NTf₂)] (11.6 mg, 0.015 mmol) in DCE (2 mL). Purification of the crude product by column chromatography (Hex/EtOAc 8 : 2) yielded 3l (156 mg, 97%) as a white solid (m.p.: 201–203 °C). ¹H-NMR (200 MHz, CDCl₃): δ 8.64 (s, 1H), 7.68 (s, 1H), 7.46–7.34 (m, 7H), 7.32–6.99 (m, 9H), 4.49 (dd, J = 10.7, 6.0 Hz, 1H), 4.13 (m, 1H), 3.69 (m, 2H), 2.40 (s, 3H). ¹³C-NMR (50 MHz, CDCl₃): δ 143.6 (C), 141.2 (C), 140.6 (C), 136.4 (C), 135.3 (C), 131.6 (C), 129.8 (2 × CH), 129.5 (C), 129.2 (2 × CH), 129.1 (CH), 129.0 (2 × CH), 128.9 (2 × CH), 127.8 (2 × CH), 127.1 (2 × CH), 125.2 (q, J = 271 Hz, C), 124.6 (q, J = 32 Hz, C), 120.4 (CH), 116.9 (q, J = 3.5 Hz, CH), 110.5 (C), 109.1 (q, J = 4.3 Hz, CH), 46.8 (CH₂), 42.2 (CH), 21.6 (CH₃). ESI-MSm/z 533 [M − H⁺, 100]. Calcd for C₃₀H₂₅F₃N₂O₂S [534.60]: C 67.40, H 4.71, N 5.24; found: C 67.76; H 4.80, N 5.31.

N-(2-(6-(Diethylamino)-1H-indol-3-yl)ethyl)-4-methylbenzenesulfonamide (3m). Procedure A was followed using N,N-diethyl-1H-indol-6-amine (1m) (56.50 mg, 0.3 mmol), 2-phenyl-1-tosylaziridine (90.2 mg, 0.33 mmol) (2a) and [Au(JohnPhos)(NTf₂)] (11.6 mg, 0.015 mmol) in DCE (2 mL). Purification of the crude product by column chromatography (Hex/EtOAc 8 : 2) yielded 3m (41 mg, 30%) as a white solid (m.p.: 54–56 °C). ¹H NMR (C₆D₆, 200 MHz): δ 7.45 (d, J = 8.4 Hz, 1H), 7.36 (d, J = 8.1 Hz, 2H), 7.19–7.12 (m, 3H), 6.98–6.89 (m, 4H), 6.58 (d, J = 8.1 Hz, 2H), 6.26–6.22 (m, 2H), 5.41 (t, J = 7.0 Hz, 1H), 4.73 (bs, 1H), 3.94–3.84 (m, 1H), 3.47–3.36 (m, 1H), 2.77 (q, J = 7.0 Hz, 4H), 1.83 (s, 3H), 0.86 (t, J = 7.0 Hz, 6H). ¹³C NMR (C₆D₆, 50 MHz): δ 145.0 (C), 142.3 (C), 140.9 (C), 137.3 (C), 135.1 (C), 129.3 (2 × CH), 129.0 (2 × CH), 127.1 (2 × CH), 126.8 (C), 126.7 (2 × CH), 124.6 (CH), 121.6 (C), 120.4 (CH), 116.1 (CH), 102.3 (CH), 49.5 (CH₂), 45.8 (2 × CH₂), 40.7 (CH), 20.9 (CH₃), 12.8 (2 × CH₃). 1 CH_ar is missing, probably overlapping. ESI-MSm/z 484 [M + Na⁺, 100], 462 [M + H⁺, 60]. Calcd for C₂₇H₃₁N₃O₂S: C 70.25, H 6.77, N 9.10; found C 70.15, H 6.53, N 9.07.

Ethyl 3-(2-(4-methylphenylsulfonamido)-1-phenylethyl)-1H-indole-2-carboxylate (3n). Procedure A was followed using ethyl 1H-indole-2-carboxylate (1n) (56.7 mg, 0.3 mmol), 2-phenyl-1-tosylaziridine (2a) (90.2 mg, 0.33 mmol) and [Au(JohnPhos)(NTf₂)] (11.6 mg, 0.015 mmol) in DCE (2 mL). Purification of the crude product by column chromatography (Hex/EtOAc 8 : 2) yielded 3n (75 mg, 54%) as a white solid (m.p.: 175–177 °C). ¹H-NMR (200 MHz, CDCl₃): δ 9.19 (s, 1H), 7.58 (d, J = 8.3 Hz, 2H), 7.38 (d, J = 8.2 Hz, 1H), 7.32–7.10 (m, 9H), 6.91 (t, J = 7.0 Hz, 1H), 5.39 (dd, J = 10.0, 6.1 Hz, 1H), 4.88 (m, 1H), 4.28 (q, J = 7.1 Hz, 2H), 4.00–3.70 (m, 2H), 2.39 (s, 3H), 1.37 (t, J = 7.1 Hz, 3H). ¹³C-NMR (50 MHz, CDCl₃): δ 162.3 (C), 143.4 (C), 141.1 (C), 136.9 (C), 136.4 (C), 129.7 (2 × CH), 128.7 (2 × CH), 127.9 (2 × CH), 127.2 (2 × CH), 126.9 (CH), 126.5 (C), 125.7 (CH), 124.8 (C), 122.0 (CH), 121.9 (C), 120.8 (CH), 112.5 (CH), 61.6 (CH₂), 46.6 (CH₂), 41.6 (CH), 21.7 (CH₃), 14.5 (CH₃). ESI-MSm/z 461 [M − H⁺, 100]. Calcd for C₂₆H₂₆N₂O₄S [462.56]: C 67.51, H 5.67, N 6.06; found: 67.88, H. 5.52, N. 6.19.

Ethyl 5-fluoro-3-(2-(4-methylphenylsulfonamido)-1-phenylethyl)-1H-indole-2-carboxylate (3o). Procedure A was followed using ethyl 5-fluoro-1H-indole-2-carboxylate (1o) (62.2 mg, 0.3 mmol), 2-phenyl-1-tosylaziridine (2a) (90.2 mg, 0.33 mmol) and [Au(JohnPhos)(NTf₂)] (11.6 mg, 0.015 mmol) in DCE (2 mL). Purification of the crude product by column chromatography (Hex/EtOAc 8 : 2) yielded 3o (75 mg, 54%) as a white solid (m.p.: 125–127 °C). ¹H-NMR (200 MHz, CDCl₃): δ 9.27 (s, 1H), 7.79 (d, J = 8.3 Hz, 1H), 7.57 (d, J = 8.3 Hz, 2H), 7.35–7.12 (m, 7H), 6.99 (td, J = 9.0, 2.4 Hz, 1H), 6.78 (dd, J = 9.9, 2.3 Hz, 1H), 5.33 (dd, J = 5.9, 10.4 Hz, 1H), 4.90 (m, 1H), 4.29 (q, J = 7.1 Hz, 2H), 3.89 (dt, J = 12.7, 6.4 Hz, 1H), 3.69 (td, J = 11.8, 4.6 Hz, 1H), 2.40 (s, 3H), 1.37 (t, J = 7.1 Hz, 3H). ¹³C NMR (50 MHz, CDCl₃): δ 162.0 (C), 157.8 (d, J_C–F = 237 Hz, C), 143.5 (C), 140.7 (C), 136.7 (C), 133.0 (C), 129.8 (2 × CH), 128.8 (2 × CH), 127.8 (2 × CH), 127.1 (2 × CH), 127.0 (CH), 126.4 (C), 121.7 (d, J_C–F = 5.5 Hz, C), 114.9 (d, J_C–F = 27 Hz, CH), 113.5 (d, J_C–F = 9.4 Hz, CH), 106.3 (d, J_C–F = 24 Hz, CH), 61.7 (CH₂), 46.2 (CH₂), 41.3 (CH), 21.7 (CH₃), 14.5 (CH₃). ESI-MSm/z 479 [M − H⁺, 100]. Calcd for C₂₆H₂₅FN₂O₄S [480.55]: C 64.98, H 5.24, N 5.83; found: C 64.72, H 5.38, N 5.91.

4-Methyl-N-(2-(2-phenyl-1H-indol-3-yl)ethyl)benzenesulfonamide (3p). Procedure A was followed using 2-phenyl-1H-indole (1a) (58 mg, 0.3 mmol), 1-tosylaziridine (2b) (71 mg, 0.36 mmol, 1.2 equiv.) and [Au(JohnPhos)(NTf₂)] (11.6 mg, 0.015 mmol) in DCE (2 mL). Purification of the crude product by column chromatography (Hex/EtOAc 8 : 2) yielded 3p (77 mg, 66%) as a white solid (m.p.: 129–130 °C). ¹H-NMR (200 MHz, CDCl₃): δ 8.16 (s, 1H), 7.58 (d, J = 8.3 Hz, 2H), 7.51–7.33 (m, 7H), 7.27–7.03 (m, 4H), 4.40 (t, J = 6.0 Hz, 1H), 3.26 (m, 2H), 3.07 (m, 2H), 2.39 (s, 3H). ¹³C-NMR (50 MHz, CDCl₃): δ 143.4 (C), 137.1 (C), 136.1(C), 135.9 (C), 132.8 (C), 129.8 (2 × CH), 129.2 (2 × CH), 128.8 (C), 128.4 (2 × CH), 128.2 (CH), 127.2 (2 × CH), 122.8 (CH), 120.2 (CH), 119.0 (CH), 111.2 (CH), 108.6 (C), 43.4 (CH₂), 25.2 (CH₂), 21.7 (CH₃). ESI-MSm/z 389 [M − H⁺, 100]. Calcd for C₂₃H₂₂N₂O₂S [390.50]: C 70.74, H 5.68, N 7.17; found C 70.95, H 5.56, N 7.01.

N-(2-(2-(4-Isopropoxyphenyl)-1H-indol-3-yl)ethyl)-4-methylbenzenesulfonamide (3q). Procedure A was followed using 2-(4-isopropoxyphenyl)-1H-indole (1c) (75.3 mg, 0.3 mmol), 1-tosylaziridine (2b) (71 mg, 0.36 mmol, 1.2 equiv.) and [Au(JohnPhos)(NTf₂)] (11.6 mg, 0.015 mmol) in DCE (2 mL). Purification of the crude product by column chromatography (Hex/EtOAc 8 : 2) yielded 3q (96 mg, 71%) as a white solid (m.p.: 54–55 °C). ¹H-NMR (200 MHz, CDCl₃): δ 8.12 (s, 1H), 7.57 (d, J = 8.4 Hz, 2H), 7.44–7.31 (m, 4H), 7.22–7.01 (m, 4H), 6.93 (d, J = 8.9 Hz, 2H), 4.59 (hept, J = 6.0 Hz, 1H), 4.41 (t, J = 6.1 Hz, 1H), 3.26 (m, 2H), 3.04 (m, 2H), 2.39 (s, 3H), 1.38 (d, J = 6.1 Hz, 6H). ¹³C-NMR (50 MHz, CDCl₃): δ 158.1 (C), 143.3 (C), 137.1 (C), 136.1 (C), 135.9 (C), 129.8 (2 × CH), 129.6 (2 × CH), 128.9 (C), 127.2 (2 × CH), 124.8 (C), 122.4 (CH), 120.1 (CH), 118.7 (CH), 116.4 (2 × CH), 111.1 (CH), 107.7 (C), 70.3 (CH), 43.4 (CH₂), 25.2 (CH₂), 22.3 (CH₃), 21.7 (CH₃). ESI-MSm/z 447 [M − H⁺, 100]. Calcd for C₂₆H₂₈N₂O₃S [448.58]: C 69.62, H 6.29, N 6.25; found C 69.86, H 6.32, N 6.18.

N-(2-(2-(3-Acetylphenyl)-1H-indol-3-yl)ethyl)-4-methylbenzenesulfonamide (3r). Procedure A was followed using 1-(3-(1H-indol-2-yl)phenyl)ethanone (1d) (70.6 mg, 0.3 mmol), 1-tosylaziridine (2b) (71 mg, 0.36 mmol, 1.2 equiv.) and [Au(JohnPhos)(NTf₂)] (11.6 mg, 0.015 mmol) in DCE (2 mL). Purification of the crude product by column chromatography (Hex/EtOAc 7 : 3) yielded 3r (80 mg, 62%) as a yellowish solid (m.p.: 52.5–54 °C). ¹H-NMR (200 MHz, CDCl₃): δ 8.59 (s, 1H), 8.06 (m, 1H), 7.86 (d, J = 7.5 Hz, 1H), 7.73 (d, J = 7.8 Hz, 1H), 7.62–7.30 (m, 5H), 7.27–7.01 (m, 4H), 4.80 (t, J = 6.1 Hz, 1H), 3.27 (m, 2H), 3.08 (m, 2H), 2.58 (s, 3H), 2.37 (s, 3H). ¹³C-NMR (50 MHz, CDCl₃): δ 198.4 (C), 143.5 (C), 137.8 (C), 137.1 (C), 136.3 (C), 134.7 (C), 133.3 (C), 132.8 (CH), 129.8 (2 × CH), 129.5 (CH), 128.7 (C), 127.9 (CH), 127.8 (CH), 127.2 (2 × CH), 123.1 (CH), 120.3 (CH), 119.1 (CH), 111.5 (CH), 109.3 (C), 43.5 (CH₂), 26.9 (CH₃), 25.5 (CH₂), 21.7 (CH₃). ESI-MSm/z 431 [M − H⁺, 100]. Calcd for C₂₅H₂₄N₂O₃S [432.53]: C 69.42, H 5.59, N 6.48; found C 69.83, H 5.47, N 6.22.

4-Methyl-N-(2-(2-methyl-1H-indol-3-yl)ethyl)benzenesulfonamide (3s). Procedure A was followed using 2-methyl-1H-indole (1e) (39.4 mg, 0.3 mmol), 1-tosylaziridine (2b) (71 mg, 0.36 mmol, 1.2 equiv.) and [Au(JohnPhos)(NTf₂)] (11.6 mg, 0.015 mmol) in DCE (2 mL). Purification of the crude product by column chromatography (Hex/EtOAc 8 : 2) yielded 3s (70 mg, 71%) as a white wax. ¹H-NMR (200 MHz, CDCl₃): δ 7.82 (s, 1H), 7.62 (d, J = 8.3 Hz, 2H), 7.33–7.16 (m, 4H), 7.14–6.96 (m, 2H), 4.31 (t, J = 6.2 Hz, 1H), 3.22 (m, 2H), 2.90 (m, 2H), 2.40 (s, 3H), 2.35 (s, 3H). ¹³C-NMR (50 MHz, CDCl₃): δ 143.5 (C), 137.1 (C), 135.6 (C), 132.7 (C), 129.8 (2 × CH), 128.4 (C), 127.2 (2 × CH), 121.4 (CH), 119.6 (CH), 117.8 (CH), 110.7(CH), 107.3 (C), 43.4 (CH₂), 24.9 (CH₂), 21.7 (CH₃), 11.8 (CH₃). ESI-MSm/z 327 [M − H⁺, 65]. Calcd for C₁₈H₂₀N₂O₂S [328.43]: C 65.83, H 6.14, N 8.53; found C 66.11, H 6.00, N 8.77.

N-(2-(1H-Indol-3-yl)ethyl)-4-methylbenzenesulfonamide (3t). Procedure A was followed using 1H-indole (1k) (35.1 mg, 0.3 mmol), 1-tosylaziridine (2b) (71 mg, 0.36 mmol, 1.2 equiv.) and [Au(JohnPhos)(NTf₂)] (11.6 mg, 0.015 mmol) in DCE (2 mL). Purification of the crude product by column chromatography (Hex/EtOAc 9 : 1) yielded 3t (65 mg, 69%) as a white wax. ¹H-NMR (200 MHz, CDCl₃): δ 8.03 (s, 1H), 7.64 (d, J = 8.3 Hz, 3H), 7.45–6.92 (m, 7H), 4.38 (t, J = 5.9 Hz, 1H), 3.28 (m, 2H), 2.93 (m, 2H), 2.40 (s, 3H). ¹³C-NMR (50 MHz, CDCl₃): δ 143.5 (C), 137.1 (C), 136.7 (C), 129.8 (2 × CH), 127.2 (2 × CH), 122.9 (CH), 122.4 (CH), 119.7 (CH), 118.7 (CH), 111.8 (C), 111.6 (CH), 43.3 (CH₂), 25.7 (CH₂), 21.7 (CH₃). ESI-MSm/z 313 [M − H⁺, 100]. Calcd for C₁₇H₁₈N₂O₂S [314.40]: C 64.94, H 5.77, N 8.91; found C 65.19, H 5.83, N 8.87.

Benzyl (2-(2-phenyl-1H-indol-3-yl)ethyl)carbamate (3x). Procedure A was followed using 2-phenyl-1H-indole (1a) (58 mg, 0.3 mmol), benzyl aziridine-1-carboxylate (2d) (64 mg, 0.36 mmol, 1.2 equiv.) and [Au(JohnPhos)(NTf₂)] (11.6 mg, 0.015 mmol) in DCE (2 mL). Purification of the crude product by column chromatography (Hex/EtOAc 9 : 1) yielded 3x (63 mg, 57%) as a white solid (m.p.: 46–48 °C). ¹H NMR (300 MHz, CDCl₃): δ 8.26 (s, 1H), 7.69–7.12 (m, 14H), 5.05 (s, 1H), 4.84 (t, J = 6.0 Hz, 1H), 3.53 (q, J = 6.8 Hz, 2H), 3.13 (t, J = 7.1 Hz, 2H). ¹³C NMR (75 MHz, CDCl₃): δ 156.6 (C), 136.9 (C), 136.1 (C), 135.7 (C), 133.1 (C), 129.2 (C), 129.2 (2 × CH), 128.7 (CH), 128.3 (4 × CH), 128.2 (2 × CH), 128.1 (CH), 122.7 (CH), 120.1 (CH), 119.3 (CH), 111.2 (CH), 109.8 (C), 66.7 (CH₂), 41.8 (CH₂), 25.3 (CH₂). ESI-MSm/z 393 [M + Na⁺, 75], 371 [M + H⁺, 100]. Calcd for C₂₄H₂₂N₂O₂ [370.44]: C 77.81, H 5.99, N 7.56; found C 77.69, H 5.87, N 7.68.

4-Methyl-N-(2-(2-phenyl-1H-indol-3-yl)cyclohexyl)benzenesulfonamide (3y). Procedure A was followed using 2-phenyl-1H-indole (1a) (58 mg, 0.3 mmol), 7-tosyl-7-azabicyclo[4.1.0]heptane (2e) (91 mg, 0.36 mmol, 1.2 equiv.) and [Au(JohnPhos)(NTf₂)] (11.6 mg, 0.015 mmol) in DCE (2 mL). Purification of the crude product by column chromatography (Hex/EtOAc 8 : 2) yielded 3y (35 mg, 26%) as a white wax. ¹H NMR (300 MHz, CDCl₃): δ 8.02 (s, 1H), 7.51–7.39 (m, 5H), 7.29–7.18 (m, 2H), 7.15–7.08 (m, 3H), 6.84–6.77 (m, 3H), 4.15 (m, 1H), 3.43 (m, 1H), 2.83 (ddd, J = 12.2, 10.8, 4.1, 1H), 2.52 (m, 1H), 2.30 (s, 3H), 1.88 (m, 3H), 1.30 (m, 4H). ¹³C NMR (75 MHz, CDCl₃): δ 142.6 (C), 136.4 (2 × C), 136.0 (C), 132.7 (C), 129.3 (2 × CH), 129.2 (2 × CH), 129.0 (2 × CH), 128.6 (CH), 126.6 (2 × CH), 122.1 (CH), 120.3 (CH), 119.7 (CH), 112.5 (C), 111.3 (CH), 56.3 (CH), 41.7 (CH), 35.0 (CH₂), 32.5 (CH₂), 26.2 (CH₂), 25.3 (CH₂), 21.8 (CH₃) (one quaternary carbon is missing, probably overlapped with one negative signal, CH). ESI-MSm/z 444 [M + H⁺, 100]. Calcd for C₂₇H₂₈N₂O₂S [444.59]: C 72.94, H 6.35, N 6.30; found C 72.86, H 6.12, N 6.41.

Representative procedures for the ring opening reactions of 2-methyl-N-tosyl aziridine (2c and (S)2c) – see Table 2 for details

Table 2, entries 1–3 general procedure. To a N₂-flushed solution of indoles 1a,c,e (1.0 equiv.) and 2-methyl-N-tosyl aziridine (2c) (1.1 equiv.) in DCE (0.15 M), [Au(JohnPhos)(NTf₂)] (5 mol%) was added and the mixture was stirred at 80 °C for 24 h. The solvent was then removed in vacuum and the residue was purified by column chromatography (SiO₂) to yield the corresponding products 3u–w/3′u–w as inseparable mixtures.

4-Methyl-N-(2-(2-phenyl-1H-indol-3-yl)propyl)benzenesulfonamide (3u) and 4-methyl-N-(1-(2-phenyl-1H-indol-3-yl)propan-2-yl)benzenesulfonamide (3′u). The general procedure was followed using 1H-indole 1a (39.0 mg, 0.2 mmol), aziridine 2c (46.5 mg, 0.22 mmol) and [Au(JohnPhos)(NTf₂)] (7.75 mg, 0.01 mmol) in DCE (2 mL). Purification of the crude product by column chromatography (Hex/EtOAc 8 : 2) yielded 3u/3′u (79.3 mg, 98%) in a 2 : 1 ratio as a white solid. The ratio and identity of the two regioisomers were established via 1D and 2D NMR analysis. See the copy of the original spectra enclosed in the ESI.† ESI-MS m/z 403 [M − H⁺, 100]. Reported data are in agreement with those reported in the literature.³ⁱ

N-(2-(2-(4-Isopropoxyphenyl)-1H-indol-3-yl)propyl)-4-methylbenzenesulfonamide (3v) and N-(1-(2-(4-isopropoxyphenyl)-1H-indol-3-yl)propan-2-yl)-4-methylbenzenesulfonamide (3′v). The general procedure was followed using 1H-indole 1c (75.4 mg, 0.3 mmol), aziridine 2c (69.7 mg, 0.33 mmol) and [Au(JohnPhos)(NTf₂)] (11.6 mg, 0.015 mmol) in DCE (2 mL). Purification of the crude product by column chromatography (Hex/EtOAc 8 : 2) yielded 3v/3′v (120 mg, 86%) in a 2 : 1 ratio as a pink solid. The ratio and identity of the two regioisomers were established by analogy with 3u/3′uvia¹H NMR analysis. See the copy of the original spectra enclosed in the ESI.† ESI-MS m/z 461 [M − H⁺, 100].

4-Methyl-N-(2-(2-methyl-1H-indol-3-yl)propyl)benzenesulfonamide (3w) and 4-methyl-N-(1-(2-methyl-1H-indol-3-yl)propan-2-yl)benzenesulfonamide (3′w). The general procedure was followed using 1H-indole 1e (39.5 mg, 0.3 mmol), aziridine 2c (69.7 mg, 0.33 mmol) and [Au(JohnPhos)(NTf₂)] (11.6 mg, 0.015 mmol) in DCE (2 mL). Purification of the crude product by column chromatography (Hex/EtOAc 8 : 2) yielded 3w/3′w (94.4 mg, 92%) in a 2 : 1 ratio as a pink thick oil. The ratio and identity of the two regioisomers were established by analogy with 3u/3′uvia¹H NMR analysis. See the copy of the original spectra enclosed in the ESI.† ESI-MS m/z 341 [M − H⁺, 100].

Table 2, entry 4. To a solution of 1H-indole 1a (58.0 mg, 0.3 mmol) and aziridine 2c (42.3 mg, 0.2 mmol) in DCM (1 mL) boron trifluoride etherate (0.04 mL, 0.3 mmol) was added at room temperature over a period of 10 min. The solution was stirred for 24 h and was quenched with 5% aqueous NaHCO₃ solution (1 mL). The two phases were separated and the aqueous layer was extracted with DCM (2 × 1 mL). The combined organic layers were dried over Na₂SO₄, filtered and concentrated in vacuum. Purification by column chromatography (Hex/EtOAc 8 : 2) yielded 3u and 3′u (43 mg, 55%) as inseparable mixture in a 12 : 1 ratio as a white solid. Reported data refer to major isomers and are in agreement with those reported in ref. 3i. ¹H-NMR (200 MHz, CDCl₃): δ 8.10 (s, 1H), 7.49–7.30 (m, 9H), 7.26–7.15 (m, 3H), 6.99 (t, J = 7.3 Hz, 1H), 4.18 (d, J = 7.1 Hz, 1H), 3.32 (m, 3H), 2.40 (s, 3H), 1.39 (d, J = 5.9 Hz, 3H). ¹³C NMR (50 MHz, CDCl₃): δ 143.2 (C), 136.7 (C), 136.5 (2 × C), 132.8 (C), 129.7 (2 × CH), 129.1 (2 × CH), 129.0 (2 × CH), 128.4 (CH), 127.1 (2 × CH), 126.7 (C), 122.5 (CH), 120.0 (CH), 119.9 (CH), 112.9 (C), 111.5 (CH), 48.1 (CH₂), 31.8 (CH), 21.7 (CH₃), 19.0 (CH₃). ESI-MSm/z 427 [M + Na⁺, 100].

Table 2, entry 12. To a N₂-flushed solution of AuCl (2.3 mg, 0.01 mmol) and AgSbF₆ (3.4 mg, 0.01 mmol) in DCE (1.33 mL), indole 1a (77.3 mg, 0.4 mmol) and aziridine 2c (42.3 mg, 0.20 mmol) were added and the mixture was stirred for 24 h at 80 °C. The solvent was then removed in vacuum and the residue was purified by column chromatography (Hex/EtOAc 8 : 2) yielding 3u/3′u (51 mg, 70%) as an inseparable mixture in a 7 : 1 ratio as a white solid. The ratio and identity of the two regioisomers were established via¹H NMR analysis and are in agreement with those reported in ref. 12. See the enclosed copy of the original spectra. The same reaction was performed using (S)-2-methyl-1-tosylaziridine ((S)2c). The purified reaction mixture was analyzed via chiral-HPLC, see the ESI† (HPLC section) for details.

Preparation and characterization data for compounds (±)4a–d and (±)4′a–c

(±)-3a,8-Dimethyl-3-phenyl-1-tosyl-1,2,3,3a,8,8a-hexahydropyrrolo[2,3-b]indole ((±)4a and (±)4′a). Procedure A was followed using 1,3-dimethyl-indole (1p) (87.1 mg, 0.6 mmol), aziridine 2a (197 mg, 0.72 mmol) and [Au(JohnPhos)(NTf₂)] (23.3 mg, 0.03 mmol) in DCE (4 mL). Purification of the crude product by column chromatography (Hex/DCM 1 : 1) yielded progressively (±)4a and (±)4′a (170 mg, overall yield 68%, ratio 60 : 40) as white solids (m.p.: (±)4a 115–117.2 °C; (±)4′a 173–176 °C). (±)4a:¹⁶¹H NMR (300 MHz, CDCl₃): δ 7.86 (d, J = 8.3 Hz, 2H), 7.42 (d, J = 8.0 Hz, 2H), 7.29–7.23 (m, 3H), 7.05 (dt, J = 7.7, 1.3 Hz, 1H), 6.85 (d, J = 6.2, 2H), 6.39 (d, J = 7.8 Hz, 1H), 6.31 (t, J = 7.4 Hz, 1H), 5.60 (d, J = 7.4 Hz, 1H), 5.40 (s, 1H), 3.80 (dd, J = 12.2, 6.5 Hz, 1H), 3.42 (t, J = 12.4 Hz, 1H), 3.07 (s, 3H), 2.76 (dd, J = 12.6, 6.5 Hz, 1H), 2.50 (s, 3H), 1.31 (s, 3H). ¹³C NMR (75 MHz, CDCl₃): δ 151.2 (C), 144.2 (C), 137.6 (C), 136.1 (C), 130.3 (2 × CH), 129.2 (2 × CH), 129.0 (C), 128.8 (CH), 128.3 (2 × CH), 127.9 (CH), 127.7 (2 × CH), 125.8 (CH), 116.8 (CH), 105.4 (CH), 91.5 (CH), 57.1 (C), 55.4 (CH), 51.6 (CH₂), 31.7 (CH₃), 26.4 (CH₃), 22.0 (CH₃). ESI(+)-MS (m/z %): 441 (100) [M + Na]⁺. Calcd for C₂₅H₂₆N₂O₂S [418.56]: C 71.74, H 6.26, N 6.69; found C.71.92, H 6.16, N 6.85. (±)4′a:^16b1H NMR (300 MHz, CDCl₃): δ 7.90 (d, J = 8.2 Hz, 2H), 7.42 (d, J = 8.1 Hz, 2H), 7.38–7.24 (m, 3H), 7.19 (t, J = 7.6 Hz, 1H), 6.96 (dd, J = 6.6, 2.9 Hz, 2H), 6.67 (t, J = 7.4 Hz, 1H), 6.56 (dd, J = 7.1, 3.5 Hz, 2H), 5.10 (s, 1H), 3.89–3.76 (m, 2H), 3.61 (dd, J = 11.0, 8.0 Hz, 1H), 3.06 (s, 3H), 2.50 (s, 3H), 0.53 (s, 3H). ¹³C NMR (75 MHz, CDCl₃): δ 149.5 (C), 144.4 (C), 135.7 (C), 135.5 (C), 133.0 (C), 130.2 (2 × CH), 129.1 (2 × CH), 129.0 (CH), 128.5 (2 × CH), 128.2 (2 × CH), 127.8 (CH), 122.7 (CH), 118.2 (CH), 107.9 (CH), 94.8 (CH), 54.5 (C), 52.9 (CH₂), 52.4 (CH), 33.2 (CH₃), 22.0 (CH₃), 16.9 (CH₃). ESI-MSm/z 419 [M + H⁺, 100]. Calcd for C₂₅H₂₆N₂O₂S [418.56]: C 71.74, H 6.26, N 6.69; found: C 71.88, H 6.02, N 6.98.

8-Benzyl-3a-methyl-3-phenyl-1-tosyl-1,2,3,3a,8,8a-hexahydropyrrolo[2,3-b]indole ((±)4b and (±)4′b). Procedure A was followed using indole 1p (132.7 mg, 0.6 mmol), aziridine 2a (196.8 mg, 0.72 mmol) and [Au(JohnPhos)(NTf₂)] (23.3 mg, 0.03 mmol) in DCE (4 mL). Purification of the crude product by column chromatography (Hex/EtOAc 9 : 1) yielded (±)4b and (±)4′b as an inseparable mixture (187 mg, overall yield 63%, ratio 60 : 40, white solid). (±)4b ^13,14/(±)4′b: ¹H-NMR (300 MHz, CDCl₃): by comparison with NMR data in ref 16b, signals marked in blue and red can be attributed to (±)4b and (±)4′b, respectively. Signals in black are superimposed hydrogens. δ 7.76 (m, 4H), 7.46–7.20 (m, 20H), , 7.03–6.94 ¹³C-NMR (75 MHz, CDCl₃): δ 150.3, 148.7, 144.2, 144.1, 139.2, 138.9, 137.3, 136.00, 135.7, 135.2, 132.9, 130.1, 130.0, 129.1 129.0, 128.8, 128.7, 128.7, 128.6, 128.4, 128.2, 128.0, 127.7, 127.6, 127.6, 127.4, 127.2, 127.0, 126.0, 122.5, 117.9, 116.7, 108.0, 105.6, 92.5, 90.1, 57.1, 55.5, 54.8, 52.8, 52.7, 51.4, 49.9, 48.3, 29.9, 26.66, 21.9, 17.0. ESI-MSm/z 495 [M + H⁺, 100].

(±)-3a,8a-Dimethyl-3-phenyl-1-tosyl-1,2,3,3a,8,8a-hexahydropyrrolo[2,3-b]indole ((±)4c and (±)4′c). Procedure A was followed using 2,3-dimethyl-1H-indole (1r) (43.6 mg, 0.3 mmol), aziridine 2a (90.2 mg, 0.33 mmol) and [Au(JohnPhos)(NTf₂)] (11.6 mg, 0.015 mmol) in DCE (2 mL). Purification of the crude product by column chromatography (Hex/EtOAc 98 : 2–9 : 1–8 : 2) yielded progressively (±)4′c and (±)4c (69 mg, overall yield 55%, ratio (±)4c/(±)4′c 70 : 30) as white solids (m.p.: (±)4c 177–179 °C; (±)4′c 145–147 °C). (±)4c: ¹H-NMR (300 MHz, CDCl₃): δ 7.72 (d, J = 8.1 Hz, 2H), 7.41–6.95 (m, 8H), 6.56 (t, J = 7.8 Hz, 1H), 6.46 (t, J = 7.3 Hz, 1H), 5.92 (d, J = 7.4 Hz, 1H), 5.42 (bs, 1H), 3.58–3.32 (m, 3H), 2.39 (s, 3H), 1.84 (s, 3H), 1.22 (s, 3H). ¹³C-NMR (75 MHz, CDCl₃): δ 148.2 (C), 143.3 (C), 139.1 (C), 137.6 (C), 135.6 (C), 129.7 (2 × CH), 129.6 (2 × CH), 128.3 (2 × CH), 127.9 (CH), 127.7 (CH), 127.3 (2 × CH), 126.1 (CH), 118.4 (CH), 109.2 (CH), 91.9 (C), 59.5 (C), 51.4 (CH), 50.6 (CH₂), 23.5 (CH₃), 22.7 (CH₃), 21.7 (CH₃). ESI-MSm/z 419 [M + H⁺, 100]. Calcd for C₂₅H₂₆N₂O₂S [418.56]: C 71.74, H 6.26, N 6.69; found: C 71.95, H 6.02, N 6.81. (±)4′c: ¹H-NMR (300 MHz, CDCl₃): δ 7.80 (d, J = 8.3 Hz, 2H), 7.32–7.23 (m, 5H), 7.15–7.08 (m, 2H), 7.06 (dd, J = 7.6, 1.1 Hz, 1H), 6.99 (d, J = 6.8 Hz, 1H), 6.76 (dt, J = 7.4, 0.8 Hz, 1H), 6.58 (d, J = 7.8 Hz, 1H), 5.26 (bs, 1H), 3.70 (dd, J = 7.5, 2.1 Hz, 1H), 3.47 (m, 2H), 2.43 (s, 3H), 1.72 (s, 3H), 0.93 (s, 3H). ¹³C-NMR (75 MHz, CDCl₃): δ 146.9 (C), 143.6 (C), 139.3 (C), 137.3 (C), 135.0 (C), 129.9 (2 × CH), 129.1 (2 × CH), 128.7 (CH), 128.5 (2 × CH), 127.9 (2 × CH), 127.5 (CH), 122.8 (CH), 119.4 (CH), 109.5 (CH), 92.3 (C), 59.8 (C), 52.6 (CH₂), 51.6 (CH), 24.1 (CH₃), 21.9 (CH₃), 19.7 (CH₃). ESI-MSm/z 419 [M + H⁺, 100]. Calcd for C₂₅H₂₆N₂O₂S [418.56]: C 71.74, H 6.26, N 6.69; found: C 71.90, H 6.11, N 6.58.

Reactions between indoles 1p,q and aziridine (R)2a. The reactions between indoles 1p,q and aziridine (R)2a were performed as reported above for the reactions with racemic 2a. The crude reaction mixtures were purified through a short pad of silica gel giving rise to pure mixtures of 4a/4′a and 4b/4′b which were evaluated via chiral HPLC analysis, in comparison with racemic (±)4a/(±)4′a and (±)4b/(±)4′b, respectively, see the ESI† (HPLC section) for details.

(±)-(3a,8a-cis)-3a,8-Dimethyl-1-tosyl-1,2,3,3a,8,8a-hexahydropyrrolo[2,3-b]indole ((±)4d). Entry 7, Scheme 7. In a nitrogen flushed vial a solution of aziridine 2b (39.5 mg, 0.2 mmol) and [Au(JohnPhos)(NTf₂)] (7.7 mg, 0.01 mmol) in DCE (0.6 mL) was prepared. Then a solution of indole 1p (58.1 mg, 0.4 mmol) in DCE (0.7 mL) was added and the mixture was stirred for 1 min under nitrogen. The vial was then sealed and heated at 150 °C for 1 h in a single-mode microwave synthesizer. The solvent was removed at reduced pressure and the resulting crude product was purified by flash column chromatography, affording indoline (±)4d (38 mg, 55%) as a white wax. ¹H-NMR (200 MHz, CDCl₃): δ 7.78 (d, J = 8.2 Hz, 2H), 7.34 (d, J = 7.9 Hz, 2H), 7.10 (t, J = 7.6 Hz, 1H), 6.92 (d, J = 7.2 Hz, 1H), 6.65 (t, J = 7.3 Hz, 1H), 6.40 (d, J = 7.8 Hz, 1H), 5.12 (s, 1H), 3.61–3.47 (m, 1H), 3.13–2.95 (m, 4H), 2.45 (s, 3H), 1.93 (ddd, J = 12.4, 5.8, 2.7 Hz, 1H), 1.39 (m, 1H), 1.14 (s, 3H). ¹³C-NMR (50 MHz, CDCl₃): δ 150.2 (C), 143.8 (C), 137.1 (C), 133.4 (C), 130.0 (2 × CH), 128.7 (CH), 127.5 (2 × CH), 122.1 (CH), 117.9 (CH), 106.2 (CH), 91.3 (CH), 53.3 (C), 48.7 (CH₂), 39.7 (CH₂), 31.6 (CH₃), 24.6 (CH₃), 21.7 (CH₃). ESI-MSm/z 365 [M + Na⁺, 38]. Calcd for C₁₉H₂₂N₂O₂S [342.46]: C 66.64, H 6.48, N 8.18; found: C 66.86, H 6.33, N 8.01.

(±)-(3a,8a-cis)-3a-Allyl-8-methyl-1-tosyl-1,2,3,3a,8,8a-hexahydropyrrolo[2,3-b]indole ((±)4e). Entry 8, Scheme 7. In a nitrogen flushed vial a solution of aziridine 2b (39.5 mg, 0.2 mmol) and [Au(JohnPhos)(NTf₂)] (7.7 mg, 0.01 mmol) in DCE (0.6 mL) was prepared. Then a solution of indole 1s (68.5 mg, 0.4 mmol) in DCE (0.7 mL) was added and the mixture was stirred for 1 min under nitrogen. The vial was then sealed and heated at 150 °C for 1 h in a single-mode microwave synthesizer. The solvent was removed at reduced pressure and the resulting crude product was purified by flash column chromatography, affording indoline (±)4e (33 mg, 45%) as a white wax. ¹H-NMR (300 MHz, CD₂Cl₂): δ 7.77 (d, J = 8.3 Hz, 2H), 7.39 (d, J = 7.9 Hz, 2H), 7.10 (td, J = 7.7, 1.3 Hz, 1H), 6.94 (dd, J = 7.3.1.3 Hz, 1H), 6.65 (td, J = 7.3, 1.0 Hz, 1H), 6.40 (dd, J = 7.9, 0.7 Hz, 1H), 5.42 (m, 1H), 5.16 (s, 1H), 4.97 (m, 1H), 4.92 (m, 1H), 3.60 (m, 1H), 2.96 (m, 4H), 2.47 (s, 3H), 2.30 (m, 1H), 2.06 (m, 1H), 1.87 (m, 1H), 1.42 (m, 1H). ¹³C-NMR (75 MHz, CD₂Cl₂): δ 151.1 (C), 144.1 (C), 137.1 (C), 134.1 (CH), 131.6 (C), 130.1 (2 × CH), 128.7 (CH), 127.4 (2 × CH), 122.8 (CH), 118.1 (C), 117.5 (CH), 105.8 (CH), 88.4 (CH), 57.3 (C), 48.4 (CH₂), 42.7 (CH₂), 37.8 (CH₂), 31.3 (CH₃), 21.5 (CH₃). ESI-MSm/z 391 [M + Na⁺, 100]. Calcd for C₂₁H₂₄N₂O₂S [368.49]: C 68.45, H 6.56, N 7.60; found: C 68.40, H 6.59, N 7.55.

Notes and references

1. (a) G. Callebaut, T. Meiresonne, N. De Kimpe and S. Mangelinckx, Chem. Rev., 2014, 114, 7954; (b) P.-A. Wang, Beilstein J. Org. Chem., 2013, 9, 1677; (c) R. Chawla, A. K. Singh and L. D. S. Yadav, RSC Adv., 2013, 3, 11385; (d) S. Stanković, M. D'hooghe, S. Catak, H. Eum, M. Waroquier, V. Van Speybroeck, N. De Kimpe and H.-J. Ha, Chem. Soc. Rev., 2012, 41, 643; (e) S. H. Krake and S. C. Bergmeier, Tetrahedron, 2010, 66, 7337; (f) P. Lu, Tetrahedron, 2010, 66, 2549; (g) G. S. Singh, M. D'hooghe and N. De Kimpe, Chem. Rev., 2007, 107, 2080.
2. (a) M. Ishikura, T. Abe, T. Choshi and S. Hibino, Nat. Prod. Rep., 2015, 32, 1389; (b) S. Lancianesi, A. Palmieri and M. Petrini, Chem. Rev., 2014, 114, 7108; (c) A. N. Da Silva and S. J. Tepper, CNS Drugs, 2012, 26, 823; (d) D. G. Barceloux, in Medical Toxicology of Drug Abuse, John Wiley & Sons, Inc., Hoboken, 2012, pp. 193–199; (e) D. Zhang, H. Song and Y. Qin, Acc. Chem. Res., 2011, 44, 447; (f) A. J. Kochanowska-Karamyan and M. T. Hamann, Chem. Rev., 2010, 110, 4489; (g) G. Blay, J. R. Pedro and C. Vila, in Catalytic Asymmetric Friedel-Crafts Alkylations, ed. M. Bandini and A. Umani-Ronchi, Wiley-VCH, Weinheim, 2009, pp. 223–270.
3. Selected recent examples: (a) M. K. Ghorai, D. P. Tiwari and N. Jain, J. Org. Chem., 2013, 78, 7121; (b) I. Tirotta, N. L. Fifer, J. Eakins and C. A. Hutton, Tetrahedron Lett., 2013, 54, 618; (c) J. Cockrell, C. Wilhelmsen, H. Rubin, A. Martin and J. B. Morgan, Angew. Chem., Int. Ed., 2012, 51, 9842; (d) Y. Li, E. Hayman, M. Plesescu and S. R. Prakash, Tetrahedron Lett., 2008, 49, 1480; (e) H. M. Kaiser, W. F. Lo, A. M. Riahi, A. Spannenberg, M. Beller and M. K. Tse, Org. Lett., 2006, 8, 5761; (f) T. Hudlicky, U. Rinner, K. J. Finn and I. Ghiviriga, J. Org. Chem., 2005, 70, 3490; (g) U. Rinner, T. Hudlicky, H. Gordon and G. R. Pettit, Angew. Chem., Int. Ed., 2004, 43, 5342; (h) J. S. Yadav, B. V. S. Reddy and G. Parimala, J. Chem. Res., Synop., 2003, 78; (i) R. N. Farr, R. J. Alabaster, J. Y. L. Chung, B. Craig, J. S. Edwards, H. W. Gibson, G.-J. Ho, G. R. Humphrey, S. A. Johnson and E. J. J. Grabowski, Tetrahedron: Asymmetry, 2003, 14, 3503; (j) T. Nishikawa, S. Kajii, K. Wada, M. Ishikawa and M. Isobe, Synthesis, 2002, 1658; (k) J. S. Yadav, B. V. S. Reddy, S. Abraham and G. Sabitha, Tetrahedron Lett., 2002, 43, 1565.
4. For selected recent reviews and books on indole synthesis see: (a) G. Bartoli, R. Dalpozzo and M. Nardi, Chem. Soc. Rev., 2014, 43, 4728; (b) G. Abbiati, F. Marinelli, E. Rossi and A. Arcadi, Isr. J. Chem., 2013, 53, 856; (c) M. Platon, R. Amardeil, L. Djakovitch and J.-C. Hierso, Chem. Soc. Rev., 2012, 41, 3929; (d) S. Cacchi and G. Fabrizi, Chem. Rev., 2011, 111, PR215; (e) R. Vicente, Org. Biomol. Chem., 2011, 9, 6469; (f) S. Cacchi, G. Fabrizi and A. Goggiamani, Org. Biomol. Chem., 2011, 9, 641; (g) S. A. Patil, R. Patil and D. D. Miller, Curr. Med. Chem., 2011, 18, 615; (h) J. Barluenga, F. Rodríguez and F. J. Fañanás, Chem. – Asian J., 2009, 4, 1036; (i) N. T. Patil and Y. Yamamoto, Chem. Rev., 2008, 108, 3395; (j) K. Krüger, A. Tillack and M. Beller, Adv. Synth. Catal., 2008, 350, 2153; (k) L. Ackermann, Synlett, 2007, 507; (l) G. R. Humphrey and J. T. Kuethe, Chem. Rev., 2006, 106, 2875; (m) S. Cacchi and G. Fabrizi, Chem. Rev., 2005, 105, 2873; (n) G. Zeni and R. C. Larock, Chem. Rev., 2004, 104, 2285; (o) Modern Heterocyclic Chemistry, ed. J. Barluenga and C. Valdés, Wiley-VCH Verlag GmbH & Co. KGaA, 2011, pp. 377–531.
5. For selected recent reviews and books on indole functionalization see: (a) R. Dalpozzo, Chem. Soc. Rev., 2015, 44, 742; (b) M. Shiri, Chem. Rev., 2012, 112, 3508; (c) M. Bandini, Org. Biomol. Chem., 2013, 11, 5206; (d) G. Broggini, E. M. Beccalli, A. Fasana and S. Gazzola, Beilstein J. Org. Chem., 2012, 8, 1730; (e) T. Lindel, N. Marsch and S. K. Adla, Top. Curr. Chem., 2012, 309, 67; (f) C. C. J. Loh and D. Enders, Angew. Chem., Int. Ed., 2012, 51, 46; (g) N. Batail, M. Genelot, V. Dufaud, L. Joucla and L. Djakovitch, Catal. Today, 2011, 173, 1; (h) M. Bandini, Chem. Soc. Rev., 2011, 40, 1358; (i) E. M. Beck and M. J. Gaunt, Top. Curr. Chem., 2010, 292, 85; (j) A. Palmieri, M. Petrini and R. R. Shaikh, Org. Biomol. Chem., 2010, 8, 1259; (k) G. Bartoli, G. Bencivenni and R. Dalpozzo, Chem. Soc. Rev., 2010, 39, 4449; (l) M. Bandini and A. Eichholzer, Angew. Chem., Int. Ed., 2009, 48, 9608; (m) L. Joucla and L. Djakovitch, Adv. Synth. Catal., 2009, 351, 673; (n) Catalytic Asymmetric Friedel–Crafts Alkylations, ed. M. Bandini and A. Umani-Ronchi, Wiley-VCH, Weinheim, 2009; (o) B. Thomas, T. B. Poulsen and K. A. Jørgensen, Chem. Rev., 2008, 108, 2903.
6. For selected recent reviews on indole dearomatization see: (a) W. Zi, Z. Zuo and D. Ma, Acc. Chem. Res., 2015, 48, 702; (b) Q. Ding, X. Zhou and R. Fan, Org. Biol. Chem., 2014, 12, 4807. For selected recent examples on indole dearomatization see: (c) W. Zi, H. Wu and F. D. Toste, J. Am. Chem. Soc., 2015, 137, 3225; (d) C. Liu, Q. Yin, L.-X. Dai and S.-L. You, Chem. Commun., 2015, 51, 5971; (e) M. Jia, M. Monari, Q.-Q. Yang and M. Bandini, Chem. Commun., 2015, 51, 2320; (f) Y.-C. Zhang, J.-J. Zhao, F. Jiang, S.-B. Sun and F. Shi, Angew. Chem., Int. Ed., 2014, 53, 13912; (g) M. Mari, S. Lucarini, F. Bartoccini, G. Piersanti and G. Spadoni, Beilstein J. Org. Chem., 2014, 10, 1991; (h) M. Jia, G. Cera, D. Perrotta, M. Monari and M. Bandini, Chem. – Eur. J., 2014, 20, 9875; (i) H. Li, R. P. Hughes and J. Wu, J. Am. Chem. Soc., 2014, 136, 6288; (j) H. Yin, T. Wang and N. Jiao, Org. Lett., 2014, 16, 2302; (k) L. Han, C. Liu, W. Zhang, X.-X. Shi and S.-L. You, Chem. Commun., 2014, 50, 1231.
7. For selected recent reviews on polycyclic indole synthesis see: (a) L.-Q. Lu, J.-R. Chen and W.-J. Xiao, Acc. Chem. Res., 2012, 45, 1278. For selected recent papers on polycyclic indole synthesis see: (b) C. N. Rao, D. Lentz and H.-U. Reissig, Angew. Chem., Int. Ed., 2015, 54, 2750; (c) J. Gao, Y. Shao, J. Zhu, J. Zhu, H. Mao, X. Wang and X. Lv, J. Org. Chem., 2014, 79, 9000; (d) R. K. Arigela, R. Kumar, S. Samala, S. Gupta and B. Kundu, Eur. J. Org. Chem., 2014, 6057; (e) C. R. Reddy, U. Dilipkumarand and M. D. Reddy, Org. Lett., 2014, 16, 3792; (f) S. Das, R. L. Harde, D. E. Shelke, N. Khairatkar-Joshi, M. Bajpai, R. S. Sapalya, H. V. Surve, G. S. Gudi, R. Pattem, D. B. Behera, B. J. Satyawan and A. Thomas, Bioorg. Med. Chem. Lett., 2014, 24, 2073; (g) S. He, R. P. Hsung, W. R. Presser, Z.-X. Ma and B. J. Haugen, Org. Lett., 2014, 16, 2180; (h) T. Wang, S. Shi, D. Pflaesterer, E. Rettenmeier, M. Rudolph, F. Rominger and A. S. K. Hashmi, Chem. – Eur. J., 2014, 20, 292.
8. (a) V. Pirovano, M. Dell'Acqua, D. Facoetti, S. Rizzato, G. Abbiati and E. Rossi, Eur. J. Org. Chem., 2013, 6267; (b) V. Pirovano, L. Decataldo, E. Rossi and R. Vicente, Chem. Commun., 2013, 49, 3594; (c) E. Rossi, V. Pirovano, M. Negrato, G. Abbiati and M. Dell'Acqua, Beilstein J. Org. Chem., 2015, 11, 1997; (d) V. Pirovano, E. Arpini, M. Dell'Acqua, R. Vicente, G. Abbiati and E. Rossi, Adv. Synth. Catal., 2016, 358, 403.
9. V. Pirovano, D. Facoetti, M. Dell'Acqua, E. Della Fontana, G. Abbiati and E. Rossi, Org. Lett., 2013, 15, 3812.
10. I.-P. Lorenz, C. Krinninger, R. Wilberger, R. Bobka, H. Piotrowski, M. Warchhold and H. Nöth, J. Organomet. Chem., 2005, 690, 1986.
11. X. Sun, W. Sun, R. Fan and J. Wu, Adv. Synth. Catal., 2007, 349, 2151.
12. (a) J. J. Hirner, K. E. Roth, Y. Shi and S. A. Blum, Organometallics, 2012, 31, 6843; (b) Y.-Q. Zhang, Z.-H. Chen, Y.-Q. Tu, C.-A. Fan, F.-M. Zhang, A.-X. Wang and D.-Y. Yuan, Chem. Commun., 2009, 2706; (c) S. Miaskiewicz, J.-M. Weibel, P. Pale and A. Blanc, Org. Lett., 2016, 18, 844; (d) M. Hoffmann, J.-M. Weibel, P. de Fremont, P. Pale and A. Blanc, Org. Lett., 2014, 16, 908; (e) N. Kern, M. Hoffmann, A. Blanc, J.-M. Weibel and P. Pale, Org. Lett., 2013, 15, 836; (f) N. Kern, A. Blanc, S. Miaskiewicz, M. Robinette, J.-M. Weibel and P. Pale, J. Org. Chem., 2012, 77, 4323; (g) N. Kern, A. Blanc, J.-M. Weibel and P. Pale, Chem. Commun., 2011, 47, 6665.
13. See the ESI† for details.
14. M. Nakagawa and M. Kawahara, Org. Lett., 2000, 2, 953.
15. (a) D. Yang, L. Wang, F. Han, D. Li, D. Zhao, Y. Cao, Y. Ma, W. Kong, Q. Sun and R. Wang, Chem. – Eur. J., 2014, 20, 16478; (b) L. Wang, D. Yang, F. Han, D. Li, D. Zhao and R. Wang, Org. Lett., 2015, 17, 176.
16. (a) Y.-M. Huang, C.-W. Zheng, L. Pan, Q.-W. Jin and G. Zhao, J. Org. Chem., 2015, 80, 10710; (b) Z. Chai, Y.-M. Zhu, P.-J. Yang, S. Wang, S. Wang, Z. Liu and G. Yang, J. Am. Chem. Soc., 2015, 137, 10088.
17. The stereochemistry of the indoline products was tentatively assigned by analogy with the results reported by Zhao et al. (ref. 16a). Thus, they synthesized almost pure (S,S,S)3a, (R,R,R)3a and (S,S,S)3b whose structures were established by single-crystal X-ray diffraction.
18. (a) J. J. Hirner, K. E. Roth, Y. Shi and S. A. Blum, Organometallics, 2012, 31, 6843; (b) N. Kern, A. Blanc, S. Miaskiewicz, M. Robinette, J.-M. Weibel and P. Pale, J. Org. Chem., 2012, 77, 4323.
19. M. K. Ghorai, A. Kumar and D. Prakash Tiwari, J. Org. Chem., 2010, 75, 137.
20. E. Rossi, G. Abbiati, V. Canevari, E. Magri and G. Celentano, Synthesis, 2006, 299.
21. (a) C. Shao, G. Shi, Y. Zhang, S. Pan and X. Guan, Org. Lett., 2015, 17, 2652; (b) J. S. Yadav, B. V. S. Reddy, P. Muralikrishna Reddy and Ch. Srinivas, Tetrahedron Lett., 2002, 43, 5185; (c) I. Usui, S. Schmidt, M. Keller and B. Breit, Org. Lett., 2008, 10, 1207.
22. M. Nagamochi, Y.-Q. Fang and M. Lautens, Org. Lett., 2007, 9, 2955.
23. T. Pei, Y.-C. Chen, P. G. Dormer and I. W. Davies, Angew. Chem., Int. Ed., 2008, 47, 4231.
24. J. Waser, B. Gaspar, H. Nambu and E. M. Carreira, J. Am. Chem. Soc., 2006, 128, 11693.
25. (a) R. A. Craig, N. R. O'Connor, A. F. G. Goldberg and B. M. Stoltz, Chem. – Eur. J., 2014, 20, 4806; (b) Y. Pei, K. Brade, E. Brule, L. Hagberg, F. Lake and C. Moberg, Eur. J. Org. Chem., 2005, 2835; (c) T. A. Moss, D. M. Barber, A. F. Kyle and D. J. Dixon, Chem. – Eur. J., 2013, 19, 3071; (d) M. Žinić, S. Alihodžić and V. Škarić, J. Chem. Soc., Perkin Trans. 1, 1993, 21; (e) H. Rubin, J. Cockrell and J. B. Morgan, J. Org. Chem., 2013, 78, 8865; (f) N. Hsueh, G. J. Clarkson and M. Shipman, Org. Lett., 2015, 17, 3632.
26. (a) N. Mézailles, L. Ricard and F. Gagosz, Org. Lett., 2005, 7, 4133; (b) L. Ricard and F. Gagosz, Organometallics, 2007, 26, 4704.
27. M. Dell'Acqua, L. Ronda, R. Piano, S. Pellegrino, F. Clerici, E. Rossi, A. Mozzarelli, M. L. Gelmi and G. Abbiati, J. Org. Chem., 2015, 80, 10939.

---

Footnote

† Electronic supplementary information (ESI) available. See DOI: 10.1039/c6ob00672h

---