On the understanding of BF₃·Et₂O-promoted intra- and intermolecular amination and oxygenation of unfunctionalized olefins

Abstract

BF₃·Et₂O was found to be effective for both intra- and intermolecular amination and oxygenation of unfunctionalized olefins. In the presence of 3 equiv. of BF₃·Et₂O, intramolecular hydroamination of N-(pent-4-enyl)-p-toluenesulfonamides, N-(hex-5-enyl)-p-toluenesulfonamides, intermolecular hydroamination between sulfonamides and cyclohexene, norbornene or styrene, lactonization of pent-4-enoic acid or hex-5-enoic acid compounds and esterification of cyclohexene with different carboxylic acids all proceeded readily, leading to the corresponding amination or oxygenation products in up to 99% isolated yields. Preliminary NMR experiments and DFT calculations suggested that the intramolecular hydroamination reactions proceeded via a sulfonimidic acid intermediate (N=S–OH), and formation of the corresponding Brønsted acid HF or HBF₄ was less likely.

---

Introduction

Heterocyclic compounds are privileged structures in medicinal chemistry.¹ Such moieties have also been frequently found as key skeletons in biologically active compounds.² For these reasons, significant efforts have been made to develop new methods for C–N or C–O bond formation and for heterocycle construction. In addition to the well-developed functional group transformation reactions,³ hydroamination is also one of the most efficient methods for the preparation of nitrogen-containing heterocyclic compounds,⁴ and tremendous efforts have been made in transition metal-catalyzed hydroamination reactions.⁵

In contrast to these achievements, Brønsted or Lewis acid-catalyzed intramolecular hydroamination reactions were relatively less successful possibly due to the overly strong interaction of the catalysts with the amino groups. Such interactions decreased both the reactivity of the amino groups and the catalytic activity of the Brønsted or Lewis acids, and high reaction temperature or longer reaction time was generally required.

This problem has been overcome by introducing sulfonyl groups into the amino groups to reduce the interaction between the nucleophiles and the catalysts. In their pioneer report, Hartwig et al. showed that in the presence of strong acids such as triflic acid, alkene sulfonamide substrates could be cyclized, leading to the corresponding 2-substituted piperidines and pyrrolidines in excellent isolated yields.⁶ Later, different Brønsted acids,⁷ heteropoly acids⁸ and Lewis acids⁹ were also reported to catalyze the hydroamination of different substrates.

It is our purpose to fully understand the important role of Lewis acids in the amination and oxygenation of unfunctionalized olefins. Herein, we wish to report our progress on BF₃·Et₂O-promoted amination and oxygenation of unfunctionalized olefins as a continuation to our program on the cyclization of alkene amine (amide) substrates.

Results and discussion

We have shown that zinc halides can be used to promote hydroamination of a variety of substrates,¹⁰ but the reactions would have to be carried out at high temperature. We reasoned that this was due to the high affinity of Lewis acids to the amino groups in the substrates,¹¹ rendering the latter less reactive. We assumed that Lewis acid would be a viable promoter for hydroamination of isolated unfunctionalized C=C double bonds if the Lewis acid was carefully chosen.

During our study of (diacetoxyiodo)benzene-promoted intramolecular haloamination of unfunctionalized olefins, we found that BF₃·Et₂O could be used as fluorine source, and several fluoroamination products could be obtained in satisfactory isolated yields.¹² However, small amount of hydroamination product was detected when a control experiment was carried out in the absence of (diacetoxyiodo)benzene. We therefore decided to study the reaction in details to get further understanding of BF₃-mediated reactions. BF₃ has been used to promote hydroamination–glycosylation reactions.¹³ However, to the best of our knowledge, this compound has not been used to promote hydroamination of unfunctionalized olefins.

On the basis of literature results⁶ and our understanding of Lewis acid-promoted hydroamination reactions, BF₃·Et₂O-promoted intramolecular hydroamination of N-(2,2-diphenylpent-4-enyl)-p-toluenesulfonamide (1a) was studied in details to get further information. The reactions were carried out in the presence of different amount of BF₃·Et₂O at different temperatures, and the results were summarized in Table 1.

Table 1 BF₃·Et₂O-promoted hydroamination of 1a under different conditions^a

Entry	BF3·Et2O (equiv.)	Temp (°C)	Time (h)	Solvent	2a : 1a^b
a The reactions were carried out with 0.25 mmol of 1a and 2.5 mL of solvent under argon atmosphere.b Determined by crude ^1H NMR analysis.c Under air atmosphere.d No hydroamination product was detected.
1	10	rt	48	DCM	31 : 69
2	10	40	24	DCM	40 : 60
3	10	50	24	DCE	78 : 22
4	10	60	24	DCE	>99 : 1
5	5	60	24	DCE	>99 : 1
6	3	60	24	DCE	98 : 2 (98 : 2)^c
7	1.5	60	24	DCE	94 : 6
8	1	60	24	DCE	30 : 70
9	0.3	80	48	DCE	89 : 11
10	0.3	70	48	DCE	63 : 37
11	0.2	80	48	DCE	52 : 48
12	0.2	70	48	DCE	51 : 49
13	0.1	80	48	DCE	38 : 62
14	3	60	24	THF	Trace
15	3	60	24	CH3CN	70 : 30
16	3	60	24	EA	30 : 70
17	3	60	24	Toluene	70 : 30
18	1 (BCl3)	30 °C	24	DCE	—^d
19	1 (BBr3)	30 °C	24	DCE	—^d

---

As shown in Table 1, both the amount of BF₃·Et₂O and the reaction temperature were very crucial for the reaction. Reaction proceeded sluggishly at low temperature even in the presence of 10 equiv. of BF₃·Et₂O (entries 1–3). However, fast reactions were observed when the reaction was carried out at elevated temperature, and reaction could be completed in 24 h at 60 °C in the presence of 3 equiv. of BF₃·Et₂O (entry 6) either under argon atmosphere or in open-air system. The use 1 equiv. of BF₃·Et₂O was not successful, and only one third of the substrate could be converted at 60 °C (entry 8). Further reducing the amount of BF₃·Et₂O led to significant drops of the conversion (entries 9–13). 1,2-Dichloroethane was the most suitable solvent among the reaction media tested (entry 6 vs. entries 14–17), and this reaction condition was used for the study of other substrates. Reactions in the presence of boron trichloride or boron tribromide were also tested. The substrate was consumed at 30 °C, but no desired hydroamination product was detected (entries 18 and 19).

N-Alkyl or N-carboxyamide substrates were unable to react possibly due to the strong interaction between BF₃·Et₂O and the amino/amido groups. When N-Boc substrate was used, deprotection occurred and 2,2-diphenyl-4-penten-1-amine was recovered. Different sulfonamide substrates showed different reactivity, and trifluoromethanesulfonamide substrate failed to react possibly due to the low reactivity of the nitrogen atom. Different substrates were tested to study the scope of the reaction, and the results were summarized in Table 2.

Table 2 BF₃·Et₂O-promoted intramolecular hydroamination of N-electron deficient substrates^a

a Reaction conditions: substrate: 1 mmol, BF₃·Et₂O: 3 mmol, reaction temperature = 60 °C, reaction time = 24 h, solvent = DCE (10 mL).b Reaction conditions: substrate: 1 mmol, BF₃·Et₂O (30 mol%), 80 °C, 48 h, DCE (10 mL).c Structure confirmed with X-ray diffraction experiment.d The total isolated yield for 2k and 2k′. The ratio was determined with ¹H NMR.

---

As shown in Table 2, p-toluene-, methane- or 2-nitrobenzenesulfonamide substrates gave good to excellent isolated yields, and the reactions were less dependent on the Thorpe–Ingold effect (2a, and 2d–2f).¹⁴ For substrates with substituents on the C=C double bond, the results depended on the substituents on the mainchain. For substrates with small substituents such as 2,2-dimethyl- (1g) or –(CH₂)₅– (1h) on the mainchain, substituents on C=C double bonds showed little effect on the reaction, and normal hydroamination products 2g and 2h could be isolated in excellent yields.¹⁵ For substrates with phenyl group on the mainchain (1i and 1j), the substituents on the C=C double bonds could have drastic effects on the course of the reactions. When 1i was used as the starting material, the desired product 2i was isolated in a rather low yield (34%). When substrate 1j was subjected to the same reaction, no hydroamination product was detected at all. In contrast, Friedel–Crafts alkylation product 2j was isolated in high yield (Scheme 1).¹⁵ Structures of both 2h and 2j were confirmed by X-ray diffraction experiments (Fig. 1).¹⁶

Scheme 1 Friedel–Crafts cyclization of substrate 1j.

Fig. 1 ORTEP drawings of 2h and 2j. Hydrogen atoms were omitted for clarity.

When N-(hex-5-en-1-yl)-p-toluenesulfonamide (1k) was subjected to the same reaction under otherwise identical conditions, both expected 1-tosyl-2-methylpiperidine (2k) and unexpected 1-tosyl-2-ethylpyrrolidine (2k′) were isolated with a ratio of 1 : 2. Other substituted 1-(p-toluenesulfonamido)-5-hexene substrates gave rather complicated results and the studies were not continued at this stage. The reaction of N-(2-allylphenyl)-p-toluenesulfonamide 1l produced the corresponding indoline compound 2l in moderate isolated yield. Substrates 1a, 1e, 1g and 1l were also tested for BF₃·Et₂O-catalyzed reactions. In the presence of 30 mol% of BF₃·Et₂O, hydroamination of these substrates could also be realized at elevated temperature and prolonged reaction time (80 °C/48 h vs. 60 °C/24 h), giving the corresponding cyclization products 2a, 2e, 2g and 2l in similar isolated yields.

After intramolecular hydroamination of different N-(pent-4-en-1-yl)sulfonamide substrates, intermolecular hydroamination of cyclohexene, norbornene and styrene were also studied, and the results were summarized in Table 3.

Table 3 BF₃·Et₂O-promoted intermolecular hydroamination of olefins^a

a Reaction conditions: olefin: 2 mmol, nucleophile: 4 mmol, BF₃·Et₂O: 6 mmol, DCE: 10 mL, 60 °C, 24 h.b Reaction conditions: olefin: 2 mmol, nucleophile: 4 mmol, BF₃·Et₂O: 30 mol%, 80 °C, 48 h, DCE (10 mL).c 1,4-Dioxane was used as solvent.

---

As shown in Table 3, sulfonamides were suitable nitrogen sources for the hydroamination of different substrates, and Markovnikov products were obtained for unsymmetrical substrates such as styrene. Substituents on nitrogen atom showed some impact on the results possibly due to the steric hindrance caused by the introduced substituents. Reactions of benzene- or p-toluenesulfonamide gave products in excellent isolated yields, and introducing substituents to nitrogen atoms caused a drop of isolated yields. Reactions using catalytic amount of BF₃·Et₂O were also tested, and hydroamination products 4a, 4b and 4f could be obtained in similar isolated yields when the reactions were carried out at elevated temperature (30 mol% of BF₃·Et₂O, 80 °C/48 h).

To further extend the scope of the reaction, intermolecular esterifications were carried out using cyclohexene (3) as the model substrates (Table 4). Both aromatic and aliphatic carboxylic acids could react with cyclohexene, and the corresponding cyclohexyl carboxylates were isolated in up to 95% isolated yields. No reaction was observed in the absence of BF₃·Et₂O.

Table 4 BF₃·Et₂O-promoted intermolecular esterification reactions^a

Entry	Acid	Product	5^b (%)
a The reactions were carried out with 2 mmol of cyclohexene, 4 mmol of acid and 6 mmol of BF3·Et2O in 5 mL of DCE.b Isolated yield based on cyclohexene.
1	PhCOOH	PhCOOCy (5a)	73
2	o-MePhCOOH	o-MePhCOOCy (5b)	73
3	m-MePhCOOH	m-MePhCOOCy (5c)	71
4	p-MePhCOOH	p-MePhCOOCy (5d)	73
5	p-tBuPhCOOH	p-tBuPhCOOCy (5e)	73
6	p-MeOPhCOOH	p-MeOPhCOOCy (5f)	53
7	p-ClPhCOOH	p-ClPhCOOCy (5g)	45
8	p-O2NPhCOOH	p-O2NPhCOOCy (5h)	36
9	CyCOOH	CyCOOCy (5i)	82
10	AcOH	AcOCy (5j)	95
11	iPrCOOH	iPrCOOCy (5k)	70

---

Similarly, lactonization of alkene carboxylic acids gave the corresponding lactone compounds in up to 91% isolated yields (Table 5).

Table 5 BF₃·Et₂O-promoted lactonization reactions^a,b

a Reaction conditions: substrate = 1 mmol, BF₃·Et₂O = 3 mmol, solvent = DCM (5 mL), 60 °C, 24 h.b Isolated yields.

---

Tilley et al. have studied triflate-catalyzed hydroamination of olefins with sulfonamides¹⁷ and concluded that the most possible reaction pathway would be the coordination of sulfonamide to metal and the subsequent generation of an acidic proton. Proton transfer to C=C double bond produced a carbenium cation intermediate which could be captured by the amide nitrogen to give the final hydroamination product. Using PhNH₃B(C₆F₅)₄ as catalyst, Bergman et al. were able to realize the hydroamination and hydroarylation of several alkenes with anilines. They pointed out the possible acid catalysis in many metal-catalyzed systems.¹⁸ Szolcsányi et al. studied the intramolecular hydroamination of N-tosylalkenylamines using different metal triflate as catalyst, and concluded that triflic acid, generated in situ by hydrolysis of metal triflate, could be the true hydroamination catalyst of the reaction.^9c Very recently, Sarpong et al. succeeded in the intramolecular hydroamination catalyzed by HI generated in situ via hydrolysis of iodotrimethylsilane.¹⁹

Several control experiments were carried out to study if the reaction was promoted by BF₃ or promoted by HF or HBF₄ formed during the reaction (Table 6). Given that interaction of HF with BF₃ gave HBF₄ as the final product,²⁰ reaction of 1a in the presence of HBF₄ was first carried out under otherwise identical conditions (entry 1). Preliminary results indicated that aqueous HBF₄ was unable to promote the reaction. Adding excess amount of water to generate HBF₄ in situ was also unable to give expected high yields (entries 2 to 5). But complete conversion was observed when the reaction was carried out at 60 °C for 24 h using 1 equiv. of HBF₄·Et₂O as the reaction promoter (entry 8).

Table 6 Control experiments for hydroamination of 1a^a

Entry	BF3·Et2O (equiv.)	Additive	2a : 1a^b
a The reactions were carried out with 0.5 mmol of 1a and 5 mL of DCE under argon atmosphere. Reaction temperature = 60 °C, reaction time = 24 h.b Determined by crude ^1H NMR analysis.
1	0	HBF4 (48 wt% in H2O, 3 equiv.)	NR
2	3	H2O (1 equiv.)	90 : 10
3	3	H2O (2.5 equiv.)	80 : 20
4	3	H2O (5 equiv.)	35 : 65
5	3	H2O (10 equiv.)	NR
6	0	HBF4·Et2O (3 equiv., rt)	91 : 9
7	0	HBF4·Et2O (1 equiv., rt)	73 : 27
8	0	HBF4·Et2O (1 equiv., 60 °C)	>99 : 1
9	0	HBF4·Et2O (20 mol%, 60 °C)	61 : 39

---

However, further experiments indicated that BF₃·Et₂O and HBF₄ behaved very differently in several reactions. In a side-by-side comparison, reaction of o-methylbenzoic acid with cyclohexene always gave lower substrate conversion when HBF₄ was used as the reaction promoter (Table 7, entry 1 vs. entry 2, and entry 3 vs. entry 4). Similar trends were observed for intermolecular hydroamination of cyclohexene with N-methyl p-toluenesulfonamide (entry 5 vs. 6).

Table 7 Side-by-side comparison for BF₃·Et₂O and HBF₄-promoted reactions^a,b

Entry	Promoter	Time (h)	o-MePhCOOH : 5c
a The reactions were carried out at 60 °C with 1 mmol of substrate and 1 mmol of o-MePhCOOH in DCE (2.5 mL). The ratios of o-MePhCOOH-to-5c were determined with crude NMR analysis of the reaction mixture.b The reactions were carried out at 60 °C with 1 mmol of substrate and 1 mmol of TsNHMe in DCE (2.5 mL). The ratios of TsNHMe-to-4b were determined with crude NMR analysis of the reaction mixture.
1	BF3·Et2O 20%	12	72 : 28
2	HBF4·Et2O 20%	12	84 : 16
3	BF3·Et2O 20%	24	54 : 46
4	HBF4·Et2O 20%	24	67 : 33

---

Entry	Promoter	Time (h)	TsNHMe : 4b
5	BF3·Et2O 20%	24	69 : 31
6	HBF4·Et2O 20%	24	82 : 18

---

Especially, when the reactions were carried out in the presence of base, the reaction with HBF₄ as the promoter was completely suppressed by triethylamine, and the reactions promoted by BF₃ were less affected by the addition of the same amount of base (Table 8).

Table 8 Effect of base on BF₃·Et₂O and HBF₄-promoted reactions^a

Entry	Promoter (equiv.)	Base (equiv.)	2a : 1a
a The reactions were carried out with 0.25 mmol of substrate in 2.5 mL of DCE. The ratios of 2a : 1a were determined with crude NMR analysis of the reaction mixture.
1	BF3·Et2O (3)	TEA (3)	NR
2	BF3·Et2O (3)	TEA (2)	38 : 62
3	BF3·Et2O (3)	TEA (1)	95 : 5
4	BF3·Et2O (3)	TEA (20%)	>95 : 5
6	HBF4·Et2O (1)	TEA (1)	NR

---

These results indicated that the BF₃-promoted hydroamination reactions were less affected by the addition of base, and the reaction pathway for BF₃-promoted heterocyclization reactions was different from the HBF₄-promoted ones.

NMR experiments were then carried out to study the possible interaction between BF₃·Et₂O and substrate 1e. While no significant chemical shift changes were observed for protons on C=C double bonds and protons adjacent to sulfonamido group, the signal splitting pattern changed significantly. A triplet peak for amide proton and a quartet peak for adjacent methylene peak were observed for 1e before the addition of BF₃ (Fig. 2a), but the triplet amide signal vanished and the quartet peak changed to triplet after the addition of BF₃ (Fig. 2b).

Fig. 2 NMR spectra of 1e before and after the addition of BF₃·Et₂O. (a) Upper: NMR spectrum of 1e. (b) Lower: NMR spectrum of 1e after the addition of BF₃·Et₂O. Signals at 1.4 and 4.2 ppm were from diethyl ether.

Similar phenomena were also observed when mixing p-toluenesulfonamide or N-methyl p-toluenesulfonamide with BF₃·Et₂O, and a very broad signal corresponding to amide proton was identified after careful examination of the NMR spectra of the mixture of N-methyl p-toluenesulfonamide and BF₃. The N-methyl group changed from doublet peak to a singlet peak after the addition of BF₃. These results indicated that a fast protonation–deprotonation occurred on the sulfonamide functional group after adding BF₃ to N-methyl p-toluenesulfonamide.

Hartwig et al. showed that significant downfield shift for the N-methyl signal was observed on proton NMR spectrum when triflic acid was allowed to mix with N-methyl p-toluenesulfonamide.⁶ Our own NMR study also showed a 0.4 ppm downfield shift for N-Me group after adding 1 equiv. of triflic acid to the CDCl₃ solution of the sample. However, after adding BF₃·Et₂O to 1e, the chemical shift change for adjacent proton signals were almost negligible. These results suggested that interaction between BF₃ and sulfonamide was weaker than the interaction between triflic acid and sulfonamide.

When BF₃ was allowed to mix with sulfonamide, it would interact with nitrogen or oxygen atom in the sulfonamide via an Lewis acid–base interaction. Such N⋯BF₃ or O⋯BF₃ interaction would increase the acidity of the sulfonamide proton, and the change of signal splitting pattern was caused by the fast deprotonation–reprotonation of the sulfonamide nitrogen atom.

Further, H–F coupling was observed on ¹⁹F NMR spectrum of HBF₄, and no H–F coupling could be observed when BF₃ was mixed with either N-methyl p-toluenesulfonamide or substrate 1e. These results suggested that HF or HBF₄ was not formed when BF₃ was mixed with sulfonamides. These results were also in agreement with different reaction behaviours observed for BF₃·Et₂O- and HBF₄-promoted reactions (Table 7).

Several modes of action could be proposed when BF₃·Et₂O was mixed with sulfonamides (Fig. 3) and structures b and e could be excluded based on the experimental results.

Fig. 3 Possible modes of interaction between BF₃ and sulfonamides.

Protonation of C=C double bond was initially proposed as the key step of hydroamination reaction (Fig. 4). However, DFT calculation on the carbenium cations g and h indicated that these were high energy species, and reactions through these intermediates were less likely.

Fig. 4 Possible carbenium cation structures.

Detailed DFT calculations were then performed to study the possible interactions between BF₃ and the sulfonamide functional group. Structures for intermediates (a–f) and two different carbenium cations (g) and (h) were optimized at ωB97XD/6-311++G(d,p) level using an implicit solvation model (SMD)²¹ with dichloroethane as the solvent, and the energies for these species were calculated.

The energy profiles were given in Fig. 5. The calculation results suggested that interaction between BF₃ and oxygen atom of the sulfonamide (d) was the most favorable one, but the formation of hydroamination product from this intermediate was difficult due to the high energy barriers (f and g). Alternatively, BF₃ could interact with sulfonamide through N⋯BF₃ Lewis pair (a). However, the energy for intermediate (a) was higher than the energy of (d), and elevated temperature was required in order for the intermediate (d) to overcome the energy barrier. The strong O⋯BF₃ interaction also accounted for the high amount of BF₃ used for the reaction. Reaction via sulfonimidic acid intermediate (c) was the most possible one.

Fig. 5 Energy profiles for different reaction pathways.

It was then reasonable to assume that after the interaction of BF₃ with sulfonamide, a sulfonimidic acid intermediate (c) was formed at elevated temperature. The hydroamination was made possible via this intermediate similar to the Cope-type hydroamination reactions (Fig. 6).²²

Fig. 6 A proposed reaction intermediate.

Results in Table 2 showed that Friedel–Crafts alkylation product 2j rather than the corresponding hydroamination product was isolated when trisubstituted substrate 1j was subjected to the reaction, and two products were obtained when substrate 1k was used as the starting material. These results indicated that formation of carbenium cation became easier when the thus formed carbenium cation intermediates exhibited enough stability.

Based on the literature results and our preliminary study, a tentative reaction pathway was proposed as shown in Scheme 2. When BF₃ was added to the reaction mixture, it would interact with amide to form an LA–NHRTs adduct (A). This was a stable structure and elevated temperature is needed for the conversion from structure A to LA–O adduct B (ΔG = 5.9 kcal mol⁻¹). Tautomerization of the LA–O adduct B produced sulfonimidic acid structure C. Hydroamination product was finally formed in a concerted manner similar to Cope-type hydroamination reactions. When olefins bearing carboxyamide groups were used as the substrates, tautomerization was difficult, and such substrates were difficult to undergo similar hydroamination reactions under current conditions. When substrate 1j was used, formation of a tertiary carbenium cation became possible, and 2j was formed as the final product via intramolecular Friedel–Crafts reaction. Excess amount of BF₃·Et₂O was necessary due to the strong interaction between BF₃·Et₂O and the oxygen atoms in both the substrates and the products.²³

Scheme 2 A tentative mechanism for BF₃-promoted hydroamination reaction.

Conclusions

In summary, we have shown that BF₃·Et₂O is able to promote intra- and intermolecular amination and oxygenation of unactivated C=C double bonds. The current method would be more desirable for medicinal chemistry due to its non-transition metal feature. Preliminary study indicated that the substrate activation was realized through Lewis acid–base adducts between BF₃ and the sulfonamides. The key step involved the formation of a sulfonimidic acid intermediate N=S–OH via tautomerization of the NH⋯BF₃ Lewis pair. HBF₄-promoted proton transfer was less likely based on the current control experiments and NMR studies. Further understanding the key role of sulfonimidic acid formation on the course of intramolecular hydroamination and further reducing the amount of reaction promoter are still underway, and the results will be reported in due time.

Experimental

General experimental information

Reactions were carried out using commercially available reagents in oven-dried apparatus. ¹H, ¹³C and ¹⁹F NMR spectra were recorded on a 400 MHz spectrometer at 298 K using deuterated chloroform as solvent and TMS as the internal reference. Column chromatography was performed employing 200–300 mesh silica gel unless otherwise noted. Thin layer chromatography (TLC) was performed on silica gel GF₂₅₄. Melting points were measured on a digital melting-point apparatus without correction of the thermometer. HRMS analyses were carried out with Varian FTICR-MS 7.0T. IR spectra were recorded with KBr pellet, and wavenumbers were given in cm⁻¹. Unless otherwise indicated, starting materials and reagents used in study were used as received without further purification. Substrates used were prepared according to our previous works.^10b,24

Method for DFT calculation

The structures were optimized at ωB97XD/6-311++G(d,p) level with Gaussian 09 Revision B. 01.²⁵ Implicit solvation model (SMD)²¹ was applied using dichloroethane as the reaction medium until a stationary point was found.

General procedure for intramolecular hydroamination

A sealed tube was charged with aminoalkene (1.0 mmol), 1,2-dichloroethane (10 mL) and BF₃·Et₂O (3.0 mmol), the tube was sealed and heated in an oil bath (60 °C). The reaction mixture was stirred at this temperature for 24 h and was then cooled to room temperature. The tube was opened with care. The mixture was poured into water, and organic layer was separated. The aqueous layer was extracted with dichloromethane. The organic phase was combined, dried (MgSO₄), and concentrated to give a crude product which was purified by flash column chromatography to give the corresponding product.

N-(p-Toluenesulfonyl)-2-methyl-4,4-diphenylpyrrolidine 2a. Compound 2a was prepared according to the general procedure and was isolated as a white solid (355 mg, 90% yield) after flash chromatography (EtOAc/petroleum 5%); mp 105–106 °C. ¹H NMR (400 MHz, CDCl₃) δ 7.53 (d, J = 8.2 Hz, 2H), 7.17–7.01 (m, 12H), 4.10 (d, J = 10.4 Hz, 1H), 3.86 (d, J = 10.3 Hz, 1H), 3.70 (dd, J = 13.2, 6.7 Hz, 1H), 2.70 (dd, J = 12.6, 7.4 Hz, 1H), 2.30 (s, 3H), 2.18 (dd, J = 12.6, 6.9 Hz, 1H), 1.17 (d, J = 6.2 Hz, 3H). ¹³C NMR (100 MHz, CDCl₃) δ 144.6, 143.8, 142.0, 134.4, 128.5, 127.5, 126.7, 126.2, 125.7, 125.5, 125.4, 125.3, 57.4, 54.5, 51.3, 45.0, 21.1, 20.3. Spectral data was consistent with the known N-(p-toluenesulfonyl)-2-methyl-4,4-diphenylpyrrolidine.¹⁵

1-Methanesulfonyl-2-methyl-4,4-diphenyl-pyrrolidine 2b. Compound 2b was prepared according to the general procedure and was isolated as a white solid (294 mg, 93% yield) after flash chromatography (EtOAc/petroleum 5%); mp 119–121 °C. ¹H NMR (400 MHz, CDCl₃) δ 7.33 (d, J = 7.7 Hz, 2H), 7.23 (dd, J = 19.6, 9.3 Hz, 4H), 7.13 (d, J = 7.3 Hz, 4H), 4.26 (d, J = 10.7 Hz, 1H), 3.99 (d, J = 11.0 Hz, 1H), 3.81 (dd, J = 14.3, 6.3 Hz, 1H), 3.07 (dd, J = 13.1, 6.9 Hz, 1H), 2.29 (s, 3H), 2.16 (dd, J = 12.9, 9.1 Hz, 1H), 1.31 (d, J = 6.0 Hz, 3H). ¹³C NMR (100 MHz, CDCl₃) δ 145.3, 144.4, 128.8, 128.6, 126.9, 126.8, 126.6, 126.5, 59.1, 55.4, 53.0, 46.0, 36.9, 22.2. IR: 3080, 3057, 2927, 2893, 2867, 1580, 1490, 1447, 1319, 1135, 964, 779, 704 cm⁻¹. HRMS-ESI (m/z): [M + H]⁺ calcd for C₁₈H₂₁NO₂S, 316.1371; found: 316.1369.

N-(2-Nitrobenzenesulfonyl)-2-methyl-4,4-diphenylpyrrolidine 2c. Compound 2c was prepared according to the general procedure and was isolated as a yellow solid (312 mg, 73% yield) after flash chromatography (EtOAc/petroleum 5%); mp 114–116 °C. ¹H NMR (400 MHz, CDCl₃) δ 7.75 (d, J = 7.8 Hz, 1H), 7.47–7.37 (m, 3H), 7.19–7.13 (m, 4H), 7.10–7.03 (m, 5H), 6.97 (t, J = 7.3 Hz, 1H), 4.49 (d, J = 10.8 Hz, 1H), 3.98–3.95 (m, 1H), 3.92 (d, J = 11.1 Hz, 1H), 2.87 (dd, J = 12.8, 6.2 Hz, 1H), 2.19 (dd, J = 12.6, 9.2 Hz, 1H), 1.15 (d, J = 6.1 Hz, 3H). ¹³C NMR (100 MHz, CDCl₃) δ 148.0, 145.2, 143.9, 133.9, 133.3, 131.7, 130.1, 128.7, 128.6, 126.7, 126.7, 126.6, 126.6, 123.9, 58.7, 56.3, 52.8, 46.8, 21.3. Spectral data was consistent with N-(2-nitrobenzensulfonyl)-2-methyl-4,4-diphenylpyrrolidine.¹⁵

N-(4-Toluenesulfonyl)-2,4,4-trimethylpyrrolidine 2d. Compound 2d was prepared according to the general procedure and was isolated as a yellow solid (260 mg, 97% yield) after flash chromatography (EtOAc/petroleum 5%); mp 80–81 °C, lit.^{26 1}H NMR (400 MHz, CDCl₃) δ 7.63 (d, J = 8.1 Hz, 2H), 7.22 (d, J = 8.0 Hz, 2H), 3.55 (dd, J = 14.4, 6.9 Hz, 1H), 3.08 (d, J = 10.4 Hz, 1H), 2.98 (d, J = 10.4 Hz, 1H), 2.33 (s, 3H), 1.64 (dd, J = 12.5, 7.2 Hz, 1H), 1.32 (d, J = 6.2 Hz, 3H), 1.28 (d, 1H), 0.94 (s, 3H), 0.44 (s, 3H). ¹³C NMR (100 MHz, CDCl₃) δ 143.2, 135.2, 129.5, 127.5, 61.5, 56.1, 48.9, 37.1, 26.5, 25.9, 22.8, 21.6. Spectral data was consistent with N-(4-toluenesulfonyl)-2,4,4-trimethyl-pyrrolidine.²⁷

N-(4-Toluenesulfonyl)-2-methylpyrrolidine 2e. Compound 2e was prepared according to the general procedure and was isolated as a white solid (226 mg, 94% yield) after flash chromatography (EtOAc/petroleum 5%); mp 93–94 °C, lit.^{28 1}H NMR (400 MHz, CDCl₃) δ 7.62 (d, J = 8.0 Hz, 2H), 7.22 (d, J = 8.0 Hz, 2H), 3.60 (dq, J = 13.0, 6.6 Hz, 1H), 3.36–3.31 (m, 1H), 3.08–3.02 (m, 1H), 2.33 (s, 3H), 1.72–1.71 (m, 1H), 1.57 (ddd, J = 19.9, 12.6, 7.5 Hz, 1H), 1.44–1.38 (m, 2H), 1.22 (d, J = 6.3 Hz, 3H). ¹³C NMR (100 MHz, CDCl₃) δ 143.2, 134.7, 129.6, 127.4, 56.0, 49.1, 33.4, 23.9, 22.9, 21.5. Spectral data was consistent with N-(4-toluenesulfonyl)-2-methylpyrrolidine.²⁹

N-(p-Toluenesulfonyl)-3-methyl-2-azaspiro[4.5]decane 2f. Compound 2f was prepared according to the general procedure and was isolated as a yellow oil (300 mg, 97% yield) after flash chromatography (EtOAc/petroleum 5%). ¹H NMR (400 MHz, CDCl₃) δ 7.64 (d, J = 8.1 Hz, 2H), 7.22 (d, J = 7.9 Hz, 2H), 3.51–3.43 (m, 1H), 3.16 (d, J = 10.6 Hz, 1H), 3.06 (d, J = 10.7 Hz, 1H), 2.33 (s, 3H), 1.71 (dd, J = 12.7, 7.1 Hz, 1H), 1.32 (d, J = 6.1 Hz, 3H), 1.26–1.04 (m, 8H), 0.79–0.70 (m, 2H), 0.61 (dd, J = 11.6, 5.4 Hz, 1H). ¹³C NMR (100 MHz, CDCl₃) δ 143.3, 135.0, 129.5, 127.3, 55.1, 40.9, 36.5, 34.2, 25.8, 23.7, 22.8, 22.7, 21.5. Spectral data was consistent with N-(p-toluenesulfonyl)-3-methyl-2-azaspiro[4.5]decane.¹⁵

2-Isopropyl-4,4-dimethyl-1-(toluene-4-sulfonyl)-pyrrolidine 2g. Compound 2g was prepared according to the general procedure and was isolated as a white solid (293 mg, 99% yield) after flash chromatography (EtOAc/petroleum 10%); mp 83–85 °C. ¹H NMR (400 MHz, CDCl₃) δ 7.65 (d, J = 8.1 Hz, 2H), 7.22 (d, J = 8.0 Hz, 2H), 3.63–3.58 (m, 1H), 3.19 (d, J = 10.8 Hz, 1H), 2.94 (d, J = 10.9 Hz, 1H), 2.45–2.43 (m, 1H), 2.35 (s, 3H), 1.43–1.36 (m, 2H), 0.92 (s, 3H), 0.75 (dd, J = 10.8, 6.9 Hz, 6H), 0.40 (s, 3H). ¹³C NMR (100 MHz, CDCl₃) δ 142.9, 136.2, 129.4, 127.2, 64.8, 61.8, 39.2, 37.1, 30.2, 26.1, 25.7, 21.5, 19.2, 14.5. HRMS-ESI (m/z): [M + H]⁺ calcd for C₁₆H₂₅NO₂S, 296.1684; found: 296.1674.

3-Isopropyl-2-(toluene-4-sulfonyl)-2-aza-spiro[4.5]decane 2h. Compound 2h was prepared according to the general procedure and was isolated as a white solid (310 mg, 92% yield) after flash chromatography (EtOAc/petroleum 10%); mp 103–105 °C. ¹H NMR (400 MHz, CDCl₃) δ 7.64 (d, J = 8.1 Hz, 2H), 7.21 (d, J = 8.0 Hz, 2H), 3.53–3.48 (m, 1H), 3.40 (d, J = 11.2 Hz, 1H), 2.86 (d, J = 11.2 Hz, 1H), 2.43–2.40 (m, 1H), 2.33 (s, 3H), 1.35–1.14 (m, 10H), 0.75 (dd, J = 14.2, 6.9 Hz, 6H), 0.68–0.62 (m, 1H), 0.57–0.53 (m, 1H). ¹³C NMR (100 MHz, CDCl₃) δ 142.8, 135.8, 129.3, 127.0, 63.8, 40.8, 36.3, 33.5, 30.2, 25.7, 23.7, 22.5, 21.3, 19.1, 14.4. IR: 3044, 2946, 2929, 2852, 2674, 2490, 1922, 1812, 1597, 1491, 1449, 1340, 1158, 1092, 1036, 816, 730, 660 cm⁻¹. HRMS-ESI (m/z): [M + H]⁺ calcd for C₁₉H₂₉NO₂S, 336.1997; found: 336.1998.
Crystal data for 2h. C₁₉H₂₉NO₂S, M = 335.49, orthorhombic, a = 9.2889(19) Å, b = 17.158(3) Å, c = 11.652(2) Å, α = 90.00°, β = 90.00°, γ = 90.00°, V = 1857.1(6) ų, T = 293(2) K, space group Pna2(1), Z = 4, μ(MoKα) = 0.184 mm⁻¹, 17 703 reflections measured, 4426 independent reflections (R_int = 0.0518). The final R₁ values were 0.0441 (I > 2σ(I)). The final wR(F²) values were 0.0986 (I > 2σ(I)). The final R₁ values were 0.0585 (all data). The final wR(F²) values were 0.1084 (all data). The goodness of fit on F² was 0.979. Flack parameter = 0.00(7).¹⁶

N-(p-Toluenesulfonyl)-2-ethyl-4,4-diphenylpyrrolidine 2i. Compound 2i was prepared according to the general procedure and was isolated as a thick paste (140 mg, 34% yield) after flash chromatography (EtOAc/petroleum 5%). ¹H NMR (400 MHz, CDCl₃) 7.50 (d, J = 8.2 Hz, 2H), 7.19–7.05 (m, 12H), 4.07 (d, J = 10.5 Hz, 1H), 3.96 (d, J = 10.5 Hz, 1H), 3.58–3.52 (m, 1H), 2.69 (dd, J = 12.7, 7.5 Hz, 1H), 2.31 (s, 3H), 2.26–2.21 (m, 1H), 2.00–1.94 (ddd, J = 13.4, 7.6, 3.2 Hz, 1H), 1.22 (dd, J = 15.4, 10.8 Hz, 1H), 0.75 (t, J = 7.4 Hz, 3H). ¹³C NMR (100 MHz, CDCl₃) δ 145.7, 144.7, 142.8, 135.6, 129.4, 128.4, 127.0, 126.6, 126.5, 126.5, 126.4, 126.2, 61.1, 58.6, 52.3, 42.4, 28.2, 21.4, 10.0. IR: 3056, 3025, 2946, 2929, 2879, 1949, 1806, 1598, 1494, 1448, 1334, 1262, 1093, 1026, 804 cm⁻¹. HRMS-ESI (m/z): [M + H]⁺ calcd for C₂₅H₂₇NO₂S, 406.1841; found: 406.1842.

N-(4,4-Dimethyl-1-phenyl-1,2,3,4-tetrahydro-naphthalen-1-ylmethyl)-4-methyl-benzenesulfonamide 2j. Compound 2j was prepared according to the general procedure and was isolated as a white solid (400 mg, 95% yield) after flash chromatography (EtOAc/petroleum 10%); mp 148–150 °C. ¹H NMR (400 MHz, CDCl₃) δ 7.61 (d, J = 8.2 Hz, 2H), 7.38 (d, J = 7.9 Hz, 1H), 7.24–7.06 (m, 6H), 6.99 (t, J = 7.1 Hz, 1H), 6.82 (d, J = 7.3 Hz, 2H), 6.64 (d, J = 7.8 Hz, 1H), 4.05 (d, J = 9.5 Hz, 1H), 3.64 (t, J = 11.2 Hz, 1H), 3.26 (dd, J = 11.9, 1.8 Hz, 1H), 2.42 (ddd, J = 13.6, 10.8, 5.4 Hz, 1H), 2.35 (s, 3H), 1.77 (dt, J = 7.5, 3.5 Hz, 1H), 1.36–1.33 (m, 2H), 1.22 (s, 3H), 1.17 (s, 3H). ¹³C NMR (100 MHz, CDCl₃) δ 148.7, 147.1, 143.4, 136.3, 136.0, 129.7, 128.1, 127.8, 127.4, 127.3, 127.2, 127.1, 126.4, 126.2, 51.7, 47.6, 34.1, 33.8, 31.9, 31.8, 31.5, 21.5. IR: 3296, 3057, 3019, 2959, 2916, 2860, 1931, 1807, 1598, 1490, 1424, 1328, 1162, 1093, 849, 757, 702, 669. IR: 3296, 3057, 3019, 2959, 2916, 2860, 1931, 1807, 1598, 1490, 1424, 1328, 1162, 1093, 849, 757, 702, 669. HRMS-ESI (m/z): [M + H]⁺ calcd for C₂₆H₂₉NO₂S, 420.1997; found: 420.1994.
Crystal data for 2j. C₂₆H₂₉NO₂S, M = 419.56, triclinic, a = 11.089(2) Å, b = 13.375(3) Å, c = 16.281(3) Å, α = 80.22(3)°, β = 77.60(3)°, γ = 77.15(3)°, V = 2280.3(8) ų, T = 293(2) K, space group P1̄, Z = 4, μ(MoKα) = 0.164 mm⁻¹, 28 896 reflections measured, 10 801 independent reflections (R_int = 0.0359). The final R₁ values were 0.0540 (I > 2σ(I)). The final wR(F²) values were 0.1309 (I > 2σ(I)). The final R₁ values were 0.0868 (all data). The final wR(F²) values were 0.1512 (all data). The goodness of fit on F² was 1.018.¹⁶

2-Methyl-1-(toluene-4-sulfonyl)-2,3-dihydro-1H-indole 2l. Compound 2l was prepared according to the general procedure and was isolated as a white solid (140 mg, 48% yield) after flash chromatography (EtOAc/petroleum 5%); mp 63–64 °C, lit.^{28 1}H NMR (400 MHz, CDCl₃) δ 7.56 (d, J = 8.1 Hz, 1H), 7.46 (d, J = 8.1 Hz, 2H), 7.10 (t, J = 7.6 Hz, 1H), 7.06 (d, J = 8.1 Hz, 2H), 6.93 (dt, J = 14.5, 7.2 Hz, 2H), 4.28–4.23 (m, 1H), 2.79 (dd, J = 16.0, 9.4 Hz, 1H), 2.33 (dt, J = 13.1, 6.5 Hz, 1H), 2.24 (s, 3H), 1.32 (d, J = 6.5 Hz, 3H). ¹³C NMR (100 MHz, CDCl₃) δ 143.6, 140.9, 135.1, 131.5, 129.4, 127.5, 126.8, 125.2, 124.4, 117.0, 58.3, 36.0, 23.3, 21.4. Spectral data was consistent with 2-methyl-1-(toluene-4-sulfonyl)-2,3-dihydro-1H-indole.³⁰

General procedure for intermolecular hydroamination

A sealed tube was charged dry with alkene (2.00 mmol), 1,2-dichloroethane (10 mL), sulfonamide (4.0 mmol) and BF₃·Et₂O (6.0 mmol). The tube was sealed and heated in an oil bath (60 °C). The reaction mixture was stirred at this temperature for 24 h and was then cooled to room temperature. The tube was then opened with care. The mixture was poured into water, and the organic layer was separated. The aqueous layer was extracted with dichloromethane. The organic layers were combined, dried (MgSO₄), and concentrated to give a crude product which was purified by flash column chromatography to give the corresponding product. The yield was calculated based on the corresponding alkene.

N-Cyclohexyl p-toluenesulfonamide 4a. Compound 4a was prepared according to the general procedure and was isolated as a white solid (450 mg, 88% yield) after flash chromatography (EtOAc/petroleum 10%); mp 84–85 °C, lit.^{31 1}H NMR (400 MHz, CDCl₃) δ 7.70 (d, J = 8.3 Hz, 2H), 7.22 (d, J = 8.0 Hz, 2H), 4.64 (s, 1H), 3.08–3.01 (m, 1H), 2.35 (s, 3H), 1.68–1.65 (m, 2H), 1.57–1.53 (m, 2H), 1.43 (dd, J = 8.7, 3.8 Hz, 1H), 1.16–1.01 (m, 5H). ¹³C NMR (100 MHz, CDCl₃) δ 142.8, 138.4, 129.4, 126.8, 52.4, 33.6, 25.0, 24.5, 21.3. Spectral data was consistent with N-cyclohexyl-p-toluenesulfonamide.¹⁵

N-Cyclohexyl-N-methyl-p-toluenesulfonamide 4b. Compound 4b was prepared according to the general procedure and was isolated as a white solid (280 mg, 52% yield) after flash chromatography (EtOAc/petroleum 5%); mp 74–75 °C. ¹H NMR (400 MHz, CDCl₃) δ 7.59 (d, J = 7.9 Hz, 2H), 7.19 (d, J = 7.9 Hz, 2H), 3.66 (s, 1H), 2.64 (s, 3H), 2.31 (s, 3H), 1.63 (d, J = 4.5 Hz, 2H), 1.49 (d, J = 12.9 Hz, 1H), 1.37 (s, 2H), 1.24–1.14 (m, 4H), 0.92–0.85 (m, 1H). ¹³C NMR (100 MHz, CDCl₃) δ 142.6, 137.1, 129.4, 126.6, 56.5, 30.0, 28.4, 25.5, 25.1, 21.2. Spectral data was consistent with N-cyclohexyl N-methyl p-toluenesulfonamide.¹⁵

N-Cyclohexyl-N-(n-butyl)-p-toluenesulfonamide 4c. Compound 4c was prepared according to the general procedure and was isolated as a yellow oil (260 mg, 42% yield) after flash chromatography (EtOAc/petroleum 5%). ¹H NMR (400 MHz, CDCl₃) δ 7.63 (d, J = 8.2 Hz, 2H), 7.19 (d, J = 8.2 Hz, 2H), 3.56–3.51 (m, 1H), 3.04–3.00 (t, 2H), 2.34 (s, 3H), 1.65 (d, J = 12.4 Hz, 2H), 1.55–1.51 (m, 5H), 1.27–1.13 (m, 6H), 0.99–0.89 (m, 1H), 0.86–0.83 (m, 3H). ¹³C NMR (100 MHz, CDCl₃) δ 142.5, 138.7, 129.4, 126.7, 57.7, 43.5, 34.0, 31.6, 26.0, 25.2, 21.3, 20.1, 13.6. Spectral data was consistent with N-cyclohexyl N-n-butyl-p-toluenesulfonamide.³²

N-Cyclohexyl-N-phenyl-p-toluenesulfonamide 4d. Compound 4d was prepared according to the general procedure and was isolated as a white solid (340 mg, 51% yield) after flash chromatography (EtOAc/petroleum 5%); mp 141–142 °C, lit.^{33 1}H NMR (400 MHz, CDCl₃) δ 7.55 (d, J = 8.1 Hz, 2H), 7.28–7.22 (m, 3H), 7.17 (d, J = 8.2 Hz, 2H), 6.95 (d, J = 7.0 Hz, 2H), 4.11–4.05 (m, 1H), 2.35 (s, 3H), 1.76 (d, J = 11.4 Hz, 2H), 1.62 (d, J = 13.5 Hz, 2H), 1.45 (d, J = 13.5 Hz, 1H), 1.32–1.18 (m, 2H), 0.97 (qd, J = 12.4, 3.2 Hz, 2H), 0.78–0.74 (m, 1H). ¹³C NMR (100 MHz, CDCl₃) δ 142.8, 138.8, 135.6, 132.5, 129.4, 128.6, 128.5, 127.3, 59.1, 32.7, 25.9, 25.0, 21.5. Spectral data was consistent with N-cyclohexyl-N-phenyl-p-toluenesulfonamide.³²

N-Cyclohexylbenzenesulfonamide 4e. Compound 4e was prepared according to the general procedure and was isolated as a white solid (460 mg, 96% yield) after flash chromatography (EtOAc/petroleum 10%); mp 88–89 °C, lit.^{34 1}H NMR (400 MHz, CDCl₃) δ 7.83 (d, J = 7.2 Hz, 2H), 7.46 (dt, J = 24.8, 7.2 Hz, 3H), 4.85 (d, J = 7.4 Hz, 1H), 3.07 (td, J = 13.5, 6.8 Hz, 1H), 1.66 (d, J = 7.8 Hz, 2H), 1.55 (dd, J = 9.1, 3.6 Hz, 2H), 1.44–1.41 (dd, J = 53.0, 11.4 Hz, 1H), 1.19–0.98 (m, 5H). ¹³C NMR (100 MHz, CDCl₃) δ 141.4, 132.3, 129.0, 126.8, 52.6, 33.8, 25.1, 24.5. Spectral data was consistent with N-cyclohexylbenzenesulfonamide.³⁴

N-Bicyclo[2.2.1]hept-2-yl-p-toluenesulfonamide 4f. Compound 4f was prepared according to the general procedure and was isolated as a white solid (390 mg, 73% yield) after flash chromatography (EtOAc/petroleum 10%); mp 129–131 °C, lit.^{34 1}H NMR (400 MHz, CDCl₃) δ 7.70 (d, J = 7.9 Hz, 2H), 7.23 (d, J = 7.9 Hz, 2H), 4.91 (s, 1H), 3.04 (t, 1H), 2.35 (s, 3H), 2.06 (d, 2H), 1.49–1.47 (m, 1H), 1.32–1.26 (m, 3H), 1.10 (d, J = 13.1 Hz, 1H), 1.02 (d, J = 10.3 Hz, 1H), 0.97–0.89 (m, 2H). ¹³C NMR (100 MHz, CDCl₃) δ 143.1, 137.9, 129.6, 127.0, 56.6, 42.4, 40.6, 35.5, 35.1, 28.0, 26.3, 21.5. Spectral data was consistent with N-bicyclo[2.2.1]hept-2-yl-p-toluenesulfonamide.¹⁵

N-Bicyclo[2.2.1]hept-2-yl-4′-N-dimethylbenzenesulfonamide 4g. Compound 4g was prepared according to the general procedure and was isolated as a yellow solid (545 mg, 97% yield) after flash chromatography (EtOAc/petroleum 5%); mp 67–68 °C, lit.^{35 1}H NMR (400 MHz, CDCl₃) δ 7.58 (d, J = 8.2 Hz, 2H), 7.21 (d, J = 8.1 Hz, 2H), 3.74 (dd, J = 8.2, 6.0 Hz, 1H), 2.63 (s, 3H), 2.33 (s, 3H), 2.11–2.09 (m, 1H), 1.81–1.75 (m, 1H), 1.49–1.43 (m, 1H), 1.32 (ddd, J = 22.1, 12.3, 6.7 Hz, 4H), 1.07–0.95 (m, 3H). ¹³C NMR (100 MHz, CDCl₃) δ 143.0, 136.2, 129.6, 127.2, 59.9, 39.1, 36.8, 36.6, 35.7, 29.9, 29.2, 27.3, 21.5. Spectral data was consistent with N-bicyclo[2.2.1]hept-2-yl-4′-N-dimethylbenzenesulfonamide.³⁵

N-Bicyclo[2.2.1]hept-2-ylbenzenesulfonamide 4h. Compound 4h was prepared according to the general procedure and was isolated as a white solid (190 mg, 39% yield) after flash chromatography (EtOAc/petroleum 10%); mp 92–94 °C, lit.^{34 1}H NMR (400 MHz, CDCl₃) δ 7.83 (d, J = 7.6 Hz, 2H), 7.50–7.40 (m, 3H), 5.35 (d, J = 7.2 Hz, 1H), 3.04 (td, J = 7.5, 3.2 Hz, 1H), 2.04 (d, J = 28.1 Hz, 2H), 1.46 (dd, J = 11.8, 8.4 Hz, 1H), 1.35–1.23 (m, 3H), 1.14–1.01 (m, 1H), 0.99–0.87 (m, 3H). ¹³C NMR (100 MHz, CDCl₃) δ 140.9, 132.5, 129.1, 127.0, 56.7, 42.5, 40.5, 35.6, 35.1, 28.0, 26.3. Spectral data was consistent with N-bicyclo[2.2.1]hept-2-ylbenzenesulfonamide.³⁴

4-Methyl-N-(1-phenyl-ethyl)-benzenesulfonamide 4i. Compound 4i was prepared according to the general procedure and was isolated as a white solid (340 mg, 61% yield) after flash chromatography (EtOAc/petroleum 10%); mp 69–71 °C, lit.^{36 1}H NMR (400 MHz, CDCl₃) δ 7.54 (d, J = 8.2 Hz, 2H), 7.13–7.08 (m, 5H), 7.03 (d, J = 7.6 Hz, 2H), 5.09 (d, J = 7.0 Hz, 1H), 4.38 (p, J = 6.9 Hz, 1H), 2.30 (s, 3H), 1.33 (d, J = 6.9 Hz, 3H). ¹³C NMR (100 MHz, CDCl₃) δ 143.1, 142.1, 137.7, 129.4, 128.5, 127.4, 127.1, 126.1, 53.7, 23.6, 21.5. Spectral data was consistent with 4-methyl-N-(1-phenyl-ethyl)benzenesulfonamide.³⁷

4′-N-Dimethyl-N-(1-phenyl-ethyl)benzenesulfonamide 4j. Compound 4j was prepared according to the general procedure and was isolated as a white solid (110 mg, 18% yield) after flash chromatography (EtOAc/petroleum 5%); mp 69–70 °C, lit.^{38 1}H NMR (400 MHz, CDCl₃) δ 7.65 (d, J = 7.8 Hz, 2H), 7.22–7.17 (m, 7H), 5.20 (q, J = 6.9 Hz, 1H), 2.48 (s, 3H), 2.34 (s, 3H), 1.20 (d, J = 7.0 Hz, 3H). ¹³C NMR (100 MHz, CDCl₃) δ 143.2, 139.9, 137.2, 129.7, 128.4, 127.5, 127.3, 127.1, 54.8, 28.4, 21.5, 15.2. Spectral data was consistent with 4′-N-dimethyl-N-(1-phenylethyl)benzenesulfonoamide.³⁸

N-[1-(4-Bromophenyl)ethyl]-4-methylbenzenesulfonamide 4k. Compound 4k was prepared according to the general procedure and was isolated as a white solid (320 mg, 45% yield) after flash chromatography (EtOAc/petroleum 5%); mp 135–137 °C, lit.^{39 1}H NMR (400 MHz, CDCl₃) δ 7.50 (d, J = 8.3 Hz, 2H), 7.23 (d, 2H), 7.11 (d, J = 8.1 Hz, 2H), 6.90 (d, J = 8.4 Hz, 2H), 4.77 (d, J = 6.8 Hz, 1H), 4.36 (p, J = 6.8 Hz, 1H), 2.33 (s, 3H), 1.32 (d, J = 6.9 Hz, 3H). ¹³C NMR (100 MHz, CDCl₃) δ 143.4, 141.1, 137.4, 131.5, 129.5, 128.0, 127.1, 121.2, 53.1, 23.4, 21.5. Spectral data was consistent with N-[1-(4-bromo-phenyl)-ethyl]-4-methyl-benzenesulfonamide.³⁹

General procedure for intermolecular esterification

A sealed tube was charged with olefin (2.0 mmol), carboxylic acid (4.0 mmol), 1,2-dichloroethane (5 mL) and BF₃·Et₂O (6.0 mmol). The tube was sealed and heated in an oil bath (60 °C). The reaction mixture was stirred at this temperature for 24 h and was then cooled to room temperature. The tube was then opened with care. The mixture was poured into water, and the organic layer was separated. The aqueous layer was extracted with dichloromethane. The organic layer was combined, dried (MgSO₄), and concentrated to give a crude product which was purified by flash column chromatography to give the corresponding product.

Cyclohexyl benzoate 5a. Compound 5a was prepared according to the general procedure and isolated as yellow oil (300 mg, 73% yield) after flash chromatography (petroleum). ¹H NMR (400 MHz, CDCl₃) δ 7.98–7.96 (m, 2H), 7.47–7.43 (m, 1H), 7.34 (t, J = 7.6 Hz, 2H), 4.98–4.92 (m, 1H), 1.88–1.84 (m, 2H), 1.74–1.69 (m, 2H), 1.55–1.46 (m, 3H), 1.41–1.23 (m, 3H). ¹³C NMR (100 MHz, CDCl₃) δ 166.1, 132.8, 131.1, 129.6, 128.3, 73.1, 31.7, 25.6, 23.7. Spectral data was consistent with the known benzoic acid cyclohexyl ester.⁴⁰

Cyclohexyl 2-methylbenzoate 5b. Compound 5b was prepared according to the general procedure and isolated as yellow oil (320 mg, 73% yield) after flash chromatography (petroleum). ¹H NMR (400 MHz, CDCl₃) δ 7.82 (d, J = 7.6 Hz, 1H), 7.30 (t, J = 7.4 Hz, 1H), 7.16 (t, J = 7.4 Hz, 2H), 4.97–4.91 (m, 1H), 2.52 (s, 3H), 1.89–1.86 (m, 2H), 1.72–1.69 (m, 2H), 1.52–1.46 (m, 3H), 1.38–1.24 (m, 3H). ¹³C NMR (100 MHz, CDCl₃) δ 167.3, 139.9, 131.8, 131.7, 130.6, 130.6, 125.8, 73.1, 31.8, 25.6, 23.9, 21.9. Spectral data was consistent with the known 2-methyl-benzoic acid cyclohexyl ester.⁴¹

Cyclohexyl 3-methylbenzoate 5c. Compound 5c was prepared according to the general procedure and isolated as yellow oil (310 mg, 71% yield) after flash chromatography (petroleum). ¹H NMR (400 MHz, CDCl₃) δ 7.78 (d, J = 6.7 Hz, 2H), 7.29–7.22 (m, 2H), 4.98–4.92 (m, 1H), 2.33 (s, 3H), 1.88–1.85 (m, 2H), 1.73–1.71 (m, 2H), 1.53–1.49 (m, 3H), 1.39–1.24 (m, 3H). ¹³C NMR (100 MHz, CDCl₃) δ 166.2, 137.9, 133.4, 130.9, 130.0, 128.1, 126.6, 72.9, 31.6, 25.5, 23.7, 21.3. Spectral data was consistent with the known 3-methyl-benzoic acid cyclohexyl ester.⁴²

Cyclohexyl 4-methylbenzoate 5d. Compound 5d was prepared according to the general procedure and isolated as yellow oil (320 mg, 73% yield) after flash chromatography (petroleum). ¹H NMR (400 MHz, CDCl₃) δ 7.85 (d, J = 8.1 Hz, 2H), 7.13 (d, J = 8.0 Hz, 2H), 4.96–4.90 (m, 1H), 2.30 (s, 3H), 1.88–1.83 (m, 2H), 1.70–1.68 (m, 2H), 1.51–1.47 (m, 3H), 1.37–1.23 (m, 3H). ¹³C NMR (100 MHz, CDCl₃) δ 166.2, 143.3, 129.6, 129.0, 128.4, 72.8, 31.7, 25.7, 23.9, 21.8. Spectral data was consistent with the known 4-methyl-benzoic acid cyclohexyl ester.⁴³

4-tert-Butyl-benzoic acid cyclohexyl ester 5e. Compound 5e was prepared according to the general procedure and isolated as yellow oil (380 mg, 73% yield) after flash chromatography (petroleum). ¹H NMR (400 MHz, CDCl₃) δ 7.89 (d, J = 8.3 Hz, 2H), 7.34 (d, J = 8.3 Hz, 2H), 4.95–4.89 (m, 1H), 1.84–1.80 (m, 2H), 1.69–1.65 (m, 2H), 1.49–1.43 (m, 3H), 1.35–1.26 (m, 3H), 1.22 (s, 9H). ¹³C NMR (100 MHz, CDCl₃) δ 165.9, 156.2, 129.4, 128.3, 125.2, 72.7, 35.0, 31.7, 31.1, 25.5, 23.7. Spectral data was consistent with the known 4-tert-butyl-benzoic acid cyclohexyl ester.⁴⁴

Cyclohexyl 4-methoxybenzate 5f. Compound 5f was prepared according to the general procedure and isolated as yellow oil (250 mg, 53% yield) after flash chromatography (petroleum). ¹H NMR (400 MHz, CDCl₃) δ 7.91 (d, J = 8.9 Hz, 2H), 6.82 (d, J = 8.9 Hz, 2H), 4.94–4.88 (m, 1H), 3.75 (s, 3H), 1.87–1.82 (m, 2H), 1.71–1.68 (m, 2H), 1.51–1.44 (m, 3H), 1.37–1.22 (m, 3H). ¹³C NMR (100 MHz, CDCl₃) δ 165.8, 163.2, 131.6, 123.5, 113.5, 72.7, 55.4, 31.8, 25.6, 23.8. Spectral data was consistent with the known 4-methoxy-benzoic acid cyclohexyl ester.⁴⁵

4-Chloro-benzoic acid cyclohexyl ester 5g. Compound 5g was prepared according to the general procedure and isolated as yellow oil (215 mg, 45% yield) after flash chromatography (petroleum). ¹H NMR (400 MHz, CDCl₃) δ 7.89 (d, J = 8.5 Hz, 2H), 7.31 (d, J = 8.5 Hz, 2H), 4.96–4.90 (m, 1H), 1.88–1.83 (m, 2H), 1.71–1.68 (m, 2H), 1.53–1.45 (m, 3H), 1.40–1.26 (m, 3H). ¹³C NMR (100 MHz, CDCl₃) δ 165.2, 139.1, 131.0, 129.5, 128.7, 73.5, 31.7, 25.5, 23.7. Spectral data was consistent with the known 4-chloro-benzoic acid cyclohexyl ester.⁴³

4-Nitro-benzoic acid cyclohexyl ester 5h. Compound 5h was prepared according to the general procedure and isolated as yellow oil (180 mg, 36% yield) after flash chromatography (petroleum). ¹H NMR (400 MHz, CDCl₃) δ 8.19 (d, J = 8.8 Hz, 2H), 8.12 (d, J = 8.8 Hz, 2H), 5.01–4.94 (m, 1H), 1.91–1.87 (m, 2H), 1.73–1.70 (m, 2H), 1.57–1.49 (m, 3H), 1.42–1.27 (m, 3H). ¹³C NMR (100 MHz, CDCl₃) δ 164.1, 150.4, 136.4, 130.7, 123.5, 74.4, 31.6, 25.4, 23.7. Spectral data was consistent with the known 4-nitro-benzoic acid cyclohexyl ester.⁴⁴

Cyclohexyl cyclohexanecarboxylate 5i. Compound 5i was prepared according to the general procedure and isolated as yellow oil (345 mg, 82% yield) after flash chromatography (petroleum). ¹H NMR (400 MHz, CDCl₃) δ 4.70–4.65 (m, 1H), 2.19–2.18 (m, 1H), 1.81 (d, J = 13.1 Hz, 2H), 1.71–1.57 (m, 7H), 1.44–1.40 (m, 1H), 1.38–1.11 (m, 10H). ¹³C NMR (100 MHz, CDCl₃) δ 175.5, 71.8, 43.5, 31.6, 29.1, 25.9, 25.5, 23.7. Spectral data was consistent with the known cyclohexyl cyclohexanecarboxylate.⁴⁶

Cyclohexyl acetate 5j. Compound 5j was prepared according to the general procedure and isolated as yellow oil (270 mg, 95% yield) after flash chromatography (petroleum). ¹H NMR (400 MHz, CDCl₃) δ 4.68–4.64 (m, 1H), 1.96 (s, 3H), 1.78 (d, J = 10.0 Hz, 2H), 1.66–1.64 (m, 2H), 1.49–1.47 (m, 1H), 1.37–1.16 (m, 5H). ¹³C NMR (100 MHz, CDCl₃) δ 170.7, 72.8, 31.8, 25.5, 23.9, 21.5. Spectral data was consistent with the known cyclohexyl acetate.⁴⁷

Cyclohexyl isobutyrate 5k. Compound 5k was prepared according to the general procedure and isolated as yellow oil (240 mg, 70% yield) after flash chromatography (petroleum). ¹H NMR (400 MHz, CDCl₃) δ 4.71–4.65 (m, 1H), 2.47–2.40 (m, 1H), 1.74–1.73 (m, 2H), 1.65–1.63 (m, 2H), 1.49–1.44 (m, 1H), 1.37–1.28 (m, 5H), 1.08 (d, J = 7.0 Hz, 6H). ¹³C NMR (100 MHz, CDCl₃) δ 176.7, 72.1, 34.3, 31.6, 25.5, 23.7, 19.1. Spectral data was consistent with the known cyclohexyl isobutyrate.⁴⁸

General procedure for lactonization

A sealed tube was charged with substrate (1.0 mmol), 1,2-dichloroethane (5 mL) and BF₃·Et₂O (3.0 mmol). The tube was sealed and heated in an oil bath (60 °C). The reaction mixture was stirred at this temperature for 24 h and was then cooled to room temperature. The tube was then opened with care. The mixture was poured into water, and the organic layer was separated. The aqueous layer was extracted with dichloromethane. The organic layer was combined, dried (MgSO₄), and concentrated to give a crude product which was purified by flash column chromatography to give the corresponding product.

5-Methyl-3,3-diphenyl-dihydro-furan-2-one 7a. Compound 7a was prepared according to the general procedure and isolated as a white solid (230 mg, 91% yield) after flash chromatography (EtOAc/petroleum 5%); mp 114–115 °C, lit.^{49 1}H NMR (400 MHz, CDCl₃) δ 7.26–7.08 (m, 10H), 4.36–4.30 (m, 1H), 2.93 (dd, J = 12.9, 4.7 Hz, 1H), 2.47–2.41 (m, 1H), 1.30 (d, J = 6.1 Hz, 3H). ¹³C NMR (100 MHz, CDCl₃) δ 177.3, 142.2, 140.0, 129.0, 128.4, 127.8, 127.7, 127.4, 127.2, 73.7, 58.7, 45.3, 20.3. Spectral data was consistent with the known 5-methyl-3, 3-diphenyl-dihydro-furan-2-one.⁴⁹

3,3,5-Trimethyl-dihydrofuran-2(3H)-one 7b. Compound 7b was prepared according to the general procedure and isolated as a white solid (98 mg, 75% yield) after flash chromatography (EtOAc/petroleum 5%); mp 48–50 °C. ¹H NMR (400 MHz, CDCl₃) δ 4.53–4.48 (m, 1H), 2.14 (dd, J = 12.7, 5.8 Hz, 1H), 1.65 (dd, J = 12.5, 10.1 Hz, 1H), 1.34 (d, J = 6.1 Hz, 3H), 1.20 (s, 3H), 1.18 (s, 3H). ¹³C NMR (100 MHz, CDCl₃) δ 182.1, 73.4, 45.1, 40.9, 25.0, 24.3, 21.0. Spectral data was consistent with the known 3,3,5-trimethyl-dihydrofuran-2(3H)-one.⁵⁰

3-Methyl-2-oxa-spiro[4.5]decan-1-one 7c. Compound 7c was prepared according to the general procedure and isolated as a colorless solid (2 mmol scale, 280 mg, 83% yield) after flash chromatography (EtOAc/petroleum 5%); mp 64–66 °C, lit.^{51 1}H NMR (400 MHz, CDCl₃) δ 4.52–4.45 (m, 1H), 2.34 (dd, J = 12.9, 6.1 Hz, 1H), 1.75–1.64 (m, 3H), 1.57–1.50 (m, 4H), 1.43 (d, J = 12.9 Hz, 1H), 1.34 (d, J = 6.1 Hz, 3H), 1.30–1.22 (m, 3H). ¹³C NMR (100 MHz, CDCl₃) δ 181.6, 73.7, 45.4, 41.2, 34.4, 31.5, 25.4, 22.2, 22.1, 21.4. Spectral data was consistent with the known 3-methyl-2-oxa-spiro[4.5]decan-1-one.⁵²

6-Methyl-3,3-diphenyl-tetrahydro-pyran-2-one 7d. Compound 7d was prepared according to the general procedure and isolated as a white solid (151 mg, 57% yield) after flash chromatography (EtOAc/petroleum 5%); mp 100–102 °C. ¹H NMR (400 MHz, CDCl₃) δ 7.25–7.06 (m, 10H), 4.38–4.29 (m, 1H), 2.62–2.58 (m, 1H), 2.52–2.47 (m, 1H), 1.83–1.78 (m, 1H), 1.60–1.55 (m, 1H), 1.21 (d, J = 6.3 Hz, 3H). ¹³C NMR (100 MHz, CDCl₃) δ 173.6, 143.0, 141.9, 128.5, 128.3, 128.3, 127.4, 127.1, 76.9, 56.8, 32.4, 27.6, 22.1. Spectral data was consistent with the known 6-methyl-3,3-diphenyl-tetrahydro-pyran-2-one.⁵³

3-Methyl-2-oxa-spiro[5.5]undecan-1-one 7e. Compound 7e was prepared according to the general procedure and isolated as a colorless oil (180 mg, 66% yield) after flash chromatography (EtOAc/petroleum 5%). ¹H NMR (400 MHz, CDCl₃) δ 4.37–4.32 (m, 1H), 2.00–1.92 (m, 2H), 1.78–1.72 (m, 2H), 1.60–1.52 (m, 7H), 1.46–1.33 (m, 3H), 1.28 (d, J = 6.2 Hz, 3H). ¹³C NMR (100 MHz, CDCl₃) δ 177.5, 76.9, 41.3, 35.7, 33.5, 28.7, 27.5, 25.4, 22.0, 20.9, 20.8. Spectral data was consistent with the known 3-methyl-2-oxa-spiro[5.5]undecan-1-one.⁵²

3-Ethyl-2-oxa-spiro[4.5]decan-1-one 7f. Compound 7f was prepared according to the general procedure and isolated as a yellow oil (130 mg, 72% yield) after flash chromatography (EtOAc/petroleum 5%). ¹H NMR (400 MHz, CDCl₃) δ 4.30–4.23 (m, 1H), 2.29 (dd, J = 12.9, 6.2 Hz, 1H), 1.73–1.18 (m, 13H), 0.93 (t, J = 7.4 Hz, 3H). ¹³C NMR (100 MHz, CDCl₃) δ 181.6, 78.6, 44.9, 39.0, 34.3, 31.6, 28.9, 25.3, 22.1, 22.1, 9.5. Spectral data was consistent with the known 3-ethyl-2-oxa-spiro[4.5]decan-1-one.⁵²

3-Isopropyl-2-oxa-spiro[4.5]decan-1-one 7g. Compound 7g was prepared according to the general procedure and isolated as a white solid (70 mg, 35% yield) after flash chromatography (EtOAc/petroleum 5%). ¹H NMR (400 MHz, CDCl₃) δ 4.04–3.98 (m, 1H), 2.22 (dd, J = 12.8, 6.2 Hz, 1H), 1.75–1.69 (m, 4H), 1.58–1.52 (m, 4H), 1.44–1.16 (m, 4H), 0.96 (d, J = 6.6 Hz, 3H), 0.86 (d, J = 6.8 Hz, 3H). ¹³C NMR (100 MHz, CDCl₃) δ 181.8, 82.7, 45.0, 37.2, 34.3, 33.3, 31.5, 25.3, 22.2, 22.1, 18.7, 17.3. IR: 2930, 2857, 1764, 1468, 1348, 1279, 1001 cm⁻¹. [M + H]⁺ calcd for C₁₂H₂₁O₂, 197.1542; found: 197.1540.

Acknowledgements

We acknowledge the financial support from National Natural Science Foundation of China (NSFC 20972072, NSFC 21272121).

Notes and references

1. (a) R. W. DeSimone, K. S. Currie, S. A. Mitchell, J. W. Darrow and D. A. Pippin, Comb. Chem. High Throughput Screening, 2004, 7, 473–494; (b) L. Costantino and D. Barlocco, Curr. Med. Chem., 2006, 13, 65–85; (c) C. D. Duarte, E. J. Barreiro and C. A. M. Fraga, Mini-Rev. Med. Chem., 2007, 7, 1108–1119.
2. (a) K. F. Karlsson, B. Walse, T. Drakenberg, S. Roy, K.-E. Bergquist, J. S. Pinkner, S. J. Hultgren and J. Kihlberg, Bioorg. Med. Chem., 1998, 6, 2085–2101; (b) L. A. Black, D. L. Nersesian, P. Sharma, Y.-Y. Ku, Y. L. Bennani, K. C. Marsh, T. R. Miller, T. A. Esbenshade, A. A. Hancock and M. Cowart, Bioorg. Med. Chem. Lett., 2007, 17, 1443–1446.
3. (a) N. de Kimpe and M. Boelens, J. Chem. Soc., Chem. Commun., 1993, 916–918; (b) N. de Kimpe, M. Boelens, J. Piqueur and J. Baele, Tetrahedron Lett., 1994, 35, 1925–1928.
4. (a) M. Beller and C. Breindl, Tetrahedron, 1998, 54, 6359–6368; (b) S. Hong and T. J. Marks, Acc. Chem. Res., 2004, 37, 673–686; (c) M. R. Crimmin, I. J. Casely and M. S. Hill, J. Am. Chem. Soc., 2005, 127, 2042–2043; (d) X. Zhang, T. J. Emge and K. C. Hultzsch, Organometallics, 2010, 29, 5871–5877; (e) J. Koller and R. G. Bergman, Organometallics, 2010, 29, 5946–5952.
5. (a) I. Bytschkov and S. Doye, Eur. J. Org. Chem., 2003, 935–946; (b) L. Ackermann, L. T. Kaspar and C. J. Gschrei, Org. Lett., 2004, 6, 2515–2518; (c) N. Hazari and P. Mountford, Acc. Chem. Res., 2005, 38, 839–849; (d) K. K. Hii, Pure Appl. Chem., 2006, 78, 341–349; (e) J. G. Taylor, N. Whittall and K. K. Hii, Org. Lett., 2006, 8, 3561–3564; (f) M. Dochnahl, J.-W. Pissarek, S. Blechert, K. Loehnwitz and P. W. Roesky, Chem. Commun., 2006, 3405–3407; (g) A. Fuerstner and P. W. Davies, Angew. Chem., Int. Ed., 2007, 46, 3410–3449; (h) A. Tsuhako, D. Oikawa, K. Sakai and S. Okamoto, Tetrahedron Lett., 2008, 49, 6529–6532; (i) H. Ohmiya, T. Moriya and M. Sawamura, Org. Lett., 2009, 11, 2145–2147; (j) X. Shen and S. L. Buchwald, Angew. Chem., Int. Ed., 2010, 49, 564–567; (k) L. A. Adrio and K. K. Hii, Curr. Org. Chem., 2011, 15, 3337–3361; (l) X. Giner, C. Najera, G. Kovacs, A. Lledos and G. Ujaque, Adv. Synth. Catal., 2011, 353, 3451–3466; (m) L.-P. Liu and G. B. Hammond, Chem. Soc. Rev., 2012, 41, 3129–3139; (n) F. Fischer, P. Jungk, N. Weding, A. Spannenberg, H. Ott and M. Hapke, Eur. J. Org. Chem., 2012, 5828–5838; (o) J. L. Arbour, H. S. Rzepa, J. Contreras-Garcia, L. A. Adrio, E. M. Barreiro and K. K. Hii, Chem.–Eur. J., 2012, 18, 11317–11324; (p) Y.-M. Wang, A. D. Lackner and F. D. Toste, Acc. Chem. Res., 2014, 47, 889–901.
6. B. Schlummer and J. F. Hartwig, Org. Lett., 2002, 4, 1471–1474.
7. (a) Z. Li, J. Zhang, C. Brouwer, C.-G. Yang, N. W. Reich and C. He, Org. Lett., 2006, 8, 4175–4178; (b) D. C. Rosenfeld, S. Shekhar, A. Takemiya, M. Utsunomiya and J. F. Hartwig, Org. Lett., 2006, 8, 4179–4182; (c) Y. Yin and G. Zhao, Chim. Oggi, 2007, 25, 42–45; (d) L. Ackermann, L. T. Kaspar and A. Althammer, Org. Biomol. Chem., 2007, 5, 1975–1978; (e) L. Ackermann and A. Altharnmer, Synlett, 2008, 995–998; (f) Y.-M. Wang, T.-T. Li, G.-Q. Liu, L. Zhang, L. Duan, L. Li and Y.-M. Li, RSC Adv., 2014, 4, 9517–9521.
8. (a) N. Seshu Babu, K. Mohan Reddy, P. S. Sai Prasad, I. Suryanarayana and N. Lingaiah, Tetrahedron Lett., 2007, 48, 7642–7645; (b) L. Yang, L. W. Xu and C. G. Xia, Tetrahedron Lett., 2008, 49, 2882–2885.
9. (a) H. Wei, G. M. Qian, Y. Z. Xia, K. Li, Y. H. Li and W. Li, Eur. J. Org. Chem., 2007, 4471–4474; (b) X. J. Cheng, Y. Z. Xia, H. Wei, B. Xu, C. G. Zhang, Y. H. Li, G. M. Qian, X. H. Zhang, K. Li and W. Li, Eur. J. Org. Chem., 2008, 1929–1936; (c) F. Mathia and P. Szolcsanyi, Org. Biomol. Chem., 2012, 10, 2830–2839.
10. (a) G.-Q. Liu and Y.-M. Li, Tetrahedron Lett., 2011, 52, 7168–7170; (b) G.-Q. Liu, W. Li, Y.-M. Wang, Z.-Y. Ding and Y.-M. Li, Tetrahedron Lett., 2012, 53, 4393–4396.
11. (a) M. Beller, O. R. Thiel and H. Trauthwein, Synlett, 1999, 243–245; (b) S. Kobayashi, I. Komoto and J.-i. Matsuo, Adv. Synth. Catal., 2001, 343, 71–74.
12. (a) M. Franck-Neumann, P. Geoffroy and D. Hanss, Tetrahedron Lett., 1999, 40, 8487–8490; (b) J. Cui, Q. Jia, R.-Z. Feng, S.-S. Liu, T. He and C. Zhang, Org. Lett., 2014, 16, 1442–1445; (c) G.-Q. Liu and Y.-M. Li, J. Org. Chem., 2014, 79, 10094–10109.
13. F. Ding, R. William, F. Wang, J. Ma, L. Ji and X.-W. Liu, Org. Lett., 2011, 13, 652–655.
14. (a) P. G. Sammes and D. J. Weller, Synthesis, 1995, 1205–1222; (b) J. Kaneti, A. J. Kirby, A. H. Koedjikov and I. G. Pojarlieff, Org. Biomol. Chem., 2004, 2, 1098–1103; (c) M. E. Jung and G. Piizzi, Chem. Rev., 2005, 105, 1735–1766; (d) M. R. Crimmin, M. Arrowsmith, A. G. M. Barrett, I. J. Casely, M. S. Hill and P. A. Procopiou, J. Am. Chem. Soc., 2009, 131, 9670–9685; (e) N. T. Patil, V. S. Raut, R. D. Kavthe, V. V. N. Reddy and P. V. K. Raju, Tetrahedron Lett., 2009, 50, 6576–6579; (f) J. Kostal and W. L. Jorgensen, J. Am. Chem. Soc., 2010, 132, 8766–8773; (g) C. Duncan, A. V. Biradar and T. Asefa, ACS Catal., 2011, 1, 736–750.
15. J. Zhang, C.-G. Yang and C. He, J. Am. Chem. Soc., 2006, 128, 1798–1799.
16. The crystal information files for compounds 2h and 2j have been deposited in The Cambridge Crystallographic Data Centre, CCDC Numbers: 2h: 1403973, 2j: 1403974.
17. (a) D. Karshtedt, A. T. Bell and T. D. Tilley, J. Am. Chem. Soc., 2005, 127, 12640–12646; (b) J. L. McBee, A. T. Bell and T. D. Tilley, J. Am. Chem. Soc., 2008, 130, 16562–16571.
18. L. L. Anderson, J. Arnold and R. G. Bergman, J. Am. Chem. Soc., 2005, 127, 14542–14543.
19. P. R. Leger, R. A. Murphy, E. Pushkarskaya and R. Sarpong, Chem.–Eur. J., 2015, 21, 4377–4383.
20. C. A. Wamser, J. Am. Chem. Soc., 1951, 73, 409–416.
21. A. V. Marenich, C. J. Cramer and D. G. Truhlar, J. Phys. Chem. B, 2009, 113, 6378–6396.
22. (a) A. M. Beauchemin, J. Moran, M.-E. Lebrun, C. Seguin, E. Dimitrijevic, L. Zhang and S. I. Gorelsky, Angew. Chem., Int. Ed., 2008, 47, 1410–1413; (b) J. Moran, S. I. Gorelsky, E. Dimitrijevic, M.-E. Lebrun, A.-C. Bedard, C. Seguin and A. M. Beauchemin, J. Am. Chem. Soc., 2008, 130, 17893–17906.
23. M. Yoshiki, R. Ishibashi, Y. Yamada and T. Hanamoto, Org. Lett., 2014, 16, 5509–5511.
24. G.-Q. Liu, W. Li and Y.-M. Li, Adv. Synth. Catal., 2013, 355, 395–402.
25. M. J. Frisch, G. W. Trucks, H. B. Schlegel, G. E. Scuseria, M. A. Robb, J. R. Cheeseman, G. Scalmani, V. Barone, B. Mennucci, G. A. Petersson, H. Nakatsuji, M. Caricato, X. Li, H. P. Hratchian, A. F. Izmaylov, J. Bloino, G. Zheng, J. L. Sonnenberg, M. Hada, M. Ehara, K. Toyota, R. Fukuda, J. Hasegawa, M. Ishida, T. Nakajima, Y. Honda, O. Kitao, H. Nakai, T. Vreven, J. A. Montgomery Jr, J. E. Peralta, F. Ogliaro, M. J. Bearpark, J. Heyd, E. N. Brothers, K. N. Kudin, V. N. Staroverov, T. Keith, R. Kobayashi, J. Normand, K. Raghavachari, A. P. Rendell, J. C. Burant, S. S. Iyengar, J. Tomasi, M. Cossi, N. Rega, N. J. Millam, M. Klene, J. E. Knox, J. B. Cross, V. Bakken, C. Adamo, J. Jaramillo, R. Gomperts, R. E. Stratmann, O. Yazyev, A. J. Austin, R. Cammi, C. Pomelli, J. W. Ochterski, R. L. Martin, K. Morokuma, V. G. Zakrzewski, G. A. Voth, P. Salvador, J. J. Dannenberg, S. Dapprich, A. D. Daniels, Ö. Farkas, J. B. Foresman, J. V. Ortiz, J. Cioslowski and D. J. Fox, Gaussian 09, Revision B.01, Gaussian, Inc., 2010.
26. K. Komeyama, T. Morimoto and K. Takaki, Angew. Chem., Int. Ed., 2006, 45, 2938–2941.
27. W. Zeng and S. R. Chemler, J. Am. Chem. Soc., 2007, 129, 12948–12949.
28. Y. Yin and G. Zhao, J. Fluorine Chem., 2007, 128, 40–45.
29. X. Wang, Z. Chen, X.-L. Sun, Y. Tang and Z. Xie, Org. Lett., 2011, 13, 4758–4761.
30. H. Yamamoto, G. Pandey, Y. Asai, M. Nakano, A. Kinoshita, K. Namba, H. Imagawa and M. Nishizawa, Org. Lett., 2007, 9, 4029–4032.
31. M. Harmata, P. Zheng, C. Huang, M. G. Gomes, W. Ying, K.-O. Ranyanil, G. Balan and N. L. Calkins, J. Org. Chem., 2006, 72, 683–685.
32. D. Jaspers, R. Kubiak and S. Doye, Synlett, 2010, 8, 1268–1272.
33. W. J. Hickinbottom, J. Chem. Soc., 1932, 2646–2654.
34. P. N. Liu, F. Xia, Z. L. Zhao, Q. W. Wang and Y. J. Ren, Tetrahedron Lett., 2011, 52, 6113–6117.
35. L. Yang, L.-W. Xu and C.-G. Xia, Synthesis, 2009, 12, 1969–1974.
36. A. J. Borah and P. Phukan, Chem. Commun., 2012, 48, 5491–5493.
37. K. D. Collins, A. Rühling, F. Lied and F. Glorius, Chem.–Eur. J., 2014, 20, 3800–3805.
38. D. A. Powell and H. Fan, J. Org. Chem., 2010, 75, 2726–2729.
39. X. Liu, Y. Zhang, L. Wang, H. Fu, Y. Jiang and Y. Zhao, J. Org. Chem., 2008, 73, 6207–6212.
40. M. Hatano, Y. Furuya, T. Shimmura, K. Moriyama, S. Kamiya, T. Maki and K. Ishihara, Org. Lett., 2011, 13, 426–429.
41. G. G. Smith and W. H. Wetzel, J. Am. Chem. Soc., 1957, 79, 875–879.
42. A. García Martínez, J. Osío Barcinaa, G. Hidalgo del Veccio, M. Hanack and L. R. Subramanian, Tetrahedron Lett., 1991, 32, 5931–5934.
43. T. Ohshima, T. Iwasaki, Y. Maegawa, A. Yoshiyama and K. Mashima, J. Am. Chem. Soc., 2008, 130, 2944–2945.
44. J. Zhou, C. Jin, X. Li and W. Su, RSC Adv., 2015, 5, 7232–7236.
45. L. Fu, C.-J. Yao, N.-J. Chang, J.-R. Chen, L.-Q. Lu and W.-J. Xiao, Org. Biomol. Chem., 2012, 10, 506–508.
46. I. Shiina, M. Kubota, H. Oshiumi and M. Hashizume, J. Org. Chem., 2004, 69, 1822–1830.
47. M. Minakawa, H. Baek, Y. M. A. Yamada, J. W. Han and Y. Uozumi, Org. Lett., 2013, 15, 5798–5801.
48. J.-C. Choi, K. Kohno, D. Masuda, H. Yasuda and T. Sakakura, Chem. Commun., 2008, 777–779.
49. P. N. Craig and I. H. Witt, J. Am. Chem. Soc., 1950, 72, 4925–4928.
50. Y. Ueki, H. Ito, I. Usui and B. Breit, Chem.–Eur. J., 2011, 17, 8555–8558.
51. V. Maslak, R. Matović and R. N. Saičić, Tetrahedron, 2004, 60, 8957–8966.
52. L. A. Adrio, L. S. Quek, J. G. Taylor and K. Kuok Hii, Tetrahedron, 2009, 65, 10334–10338.
53. K. Komeyama, Y. Mieno, S. Yukawa, T. Morimoto and K. Takaki, Chem. Lett., 2007, 36, 752–753.

---

Footnote

† Electronic supplementary information (ESI) available: Cartesian coordinates and energies for calculated intermediates, copies of NMR spectra, X-ray diffraction results for 2h and 2j. CCDC 1403973 and 1403974. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/c5ra10513g

---