L-Isoleucine derived bifunctional phosphine catalyses asymmetric [3 + 2]-annulation of allenyl-esters and -ketones with ketimines

Abstract

The zwitterionic 1,3-dipoles generated by the addition of a bifunctional L-isoleucine derived N-acylaminophosphine to allenic esters as well as ketones were successfully trapped with isatin derived ketimines in a [3 + 2]-annulation reaction to deliver 3,2′-dihydropyrrolyl spirooxindoles in high yields (up to 88%) and with excellent enantioselectivities (up to >99%). The asymmetric annulation reaction provides a facile access to biologically relevant small molecules embodying the natural product spirocyclic core.

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Introduction

The biological relevance of the core-structures representing small molecule collections is an important criterion that influences their potential to deliver disease or biology modulating chemical entities.¹ The privileged spirooxindole framework often occurs in complex and diversely bioactive natural products as well as in therapeutically useful synthetic small molecules (Scheme 1a).^2,3 Asymmetric dipolar annulation reactions that introduce different spiro-ring-systems to an oxindole scaffold are therefore highly desired.⁴ Asymmetric phosphine catalyzed dipolar annulation of electron-poor allenes, in particular allene esters with various electron deficient substrates is one of the important transformations that afford a range of carbo- and heterocycles and thereby contribute valuable building blocks finding applications in synthesis of a wide range of bioactive natural products and medicinally important substances.^5,6 Although several phosphine-catalyzed reactions have been developed for the syntheses of various acyclic and cyclic motifs, only a limited number of asymmetric variants have evolved.^5c In particular, the asymmetric annulation reactions between allene derived zwitterions and imines remain limited to aldimines^{6b–e,g,l–q} and the potential of ketimines in asymmetric phosphine catalysis to build diverse ring-systems with quaternary centres remain underexplored. Compared to the aldimines, ketimines are typically less reactive and are challenging substrates for enantioselective transformations.⁷ We envisioned that the annulation reactions employing isatin derived ketimine (1, Scheme 1b), which are readily accessible and stable compounds,⁸ can provide rapid and concise access to biologically relevant class of spirooxindole small molecules.

Scheme 1 (a) Bioactive natural and synthetic small molecules containing a pyrrolidinyl-spirooxindole core. (b) Phosphine catalyzed [3 + 2] annulation reaction to build 3,2′-dihydropyrrolyl-spirooxindoles.

Only recently, chemists have begun to explore the potential of isatin derived ketimines in organic synthesis. In 2012, Chi et al. reported an N-heterocyclic carbene (NHC)-catalyzed enantioselective annulation reaction of isatin N-Boc ketimines with enals to build spirocyclic oxindole-γ-lactams.⁹ In 2013, Kumar and coworkers have utilized isatinimine for phosphine mediated dipolar annulation reaction of Huisgen zwitterions to generate dihydro-1H-1,2,4-triazoles.^8b In 2014, Ye et al. reported the synthesis of spirocyclic oxindolo-β-lactams from isatinimines via NHC-catalyzed reaction of ketenes.¹⁰ Recently, Ye et al. reported NHC-catalyzed [4 + 2]-annulation of α,β-unsaturated carboxylic acid with isatinimine to generate spirocylic oxindolodihydropyridinones.¹¹ Enders et al. had described the synthesis of a new class of pyrrolidinyl-dispirooxindoles via an organocatalytic Mannich/Boc-deprotection/aza-Michael sequence from isatinimine.¹² Concurrently, Li and coworkers introduced a formal asymmetric [3 + 2]-annulation of 1,4-dithiane-2,5-diol with isatinimines to produce 4-thiazolidinone.¹³ Marinetti and co-workers had recently reported a binepine catalysed asymmetric [3 + 2]-annulation reaction of allene esters with 3-arylidene indolin-2-ones to generate cyclopentene fused spirooxindoles.^6k Herein, we report an efficient phosphine catalyzed asymmetric [3 + 2]-annulation reaction of allenyl carbonyl compounds with electron-deficient isatin derived ketimines affording a facile entry to 3,2′-dihydropyrrolyl spirooxindoles (Scheme 1b).¹⁴

Results and discussion

We began our investigation using N-Boc isatinimine 1a and ethyl 2,3-butadienoate 2a as model substrates for asymmetric dipolar annulation reaction (Table 1 and Fig. 1). The binepine monophosphine catalyst (I) that had been successfully used by Fu et al. in an enantioselective [4 + 2] annulation reaction of allene esters 1 with aldimines,^6q provided only moderate yield of 3a with very low enantiomeric excess (ee) (entry 1). Spiro-phosphine (R)-SITCP (II) that Shi et al. had successfully employed in a [3 + 2] annulation reaction of allene esters with olefins,¹⁵ though provided adduct 3a in good yield, but failed to provide good asymmetric induction (entry 2). While (S,S)-Et-DUPHOS (III) failed to catalyse the reaction (entry 3), the DiPAMP (IV) gave a moderate yield for 3a and with only low ee (entry 4). With these disappointing results, we resorted to bifunctional N-acylaminophosphines with the hope that H-bond donating ability of these phosphines might positively influence the desired enantioselective annulation.^6g,16L-tert-Leucine derived aminophosphines (V–VII) afforded spirooxindole 3a in moderate yield but with slightly improved enantiomeric excess (entry 5–7). We were pleased to observe that L-phenyl alanine derived aminophosphine catalyst (VIII) enhanced the yield as well as enantiomeric excess of product (ee, entry 8). However, other similar catalysts IX and X showed very poor results (entry 9 & 10). L-Threonine based catalyst XI also failed to steer the reaction efficiently and enantioselectively (entry 11). Some encouraging results were finally obtained with L-isoleucine based aminophosphines when catalysts XII & XIII provided adduct 3a in good yields and with moderate ee's (entry 12 & 13). Catalyst XIV supporting bis(3,5-trifluoro-methyl)benzamide displayed highly encouraging results (64% yield, 70% ee) (entry 14). Catalyst XV with a stronger H-bond donating thiourea functionality however failed to improve the results (entry 15). Further reaction condition optimization (entries 16–20) with catalyst XIV revealed that the reaction at −40 °C and in toluene using 0.035 M solution of isatinimine delivered the best result for the formation of 3a (84% yield and 97% ee, entry 19). Further lowering the temperature to −78 °C did not produce any reaction (entry 20).

Table 1 Screening of phosphine catalysts for asymmetric [3 + 2]-annulation of alleneoate 2a with isatinimine 1a^a

Entry^b	Catalyst	Solvent	Temp. (°C)	Yield (%)	ee (%)
a Reaction conditions: 1a (1.0 equiv., 0.06 M), 2a (1.2 equiv.), cat. (20 mol%), 12 h, rt. b Reaction was monitored by TLC analysis as well as HPLC-MS. c 0.035 M solution of 1a in toluene was used. d Reaction is very sluggish.
1	I	Toluene	25	49	−16
2	II	Toluene	25	70	+16
3	III	Toluene	25	—	N/A
4	IV	Toluene	25	56	−12
5	V	Toluene	25	43	−25
6	VI	Toluene	25	61	−30
7	VII	Toluene	25	68	−38
8	VIII	Toluene	25	55	−58
9	IX	Toluene	25	48	+4
10	X	Toluene	25	36	N/A
11	XI	Toluene	25	65	−14
12	XII	Toluene	25	71	−40
13	XIII	Toluene	25	49	−33
14	XIV	Toluene	25	64	−70
15	XV	Toluene	25	41	+57
16	XIV	DCM	25	62	−59
17	XIV	Dioxane	25	0	—
18	XIV	Toluene	−20	68	−91
19	XIV	Toluene ^c	−40	84	−97
20	XIV	Toluene	−78^d	—	^—

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Fig. 1 List of phosphines used for the screening.

Under the optimized reaction conditions for asymmetric [3 + 2] annulation reaction, the scope of the reaction was investigated by using a variety of substituted isatinimines 1 and different allene esters 2 (Scheme 2). Pleasingly, all the reactions proceeded smoothly to furnish the corresponding products 3 in high yields and with excellent enantioselectivities (Scheme 2). Isatinimines with electron-withdrawing functionalities afforded spirooxindoles (3b–3d) in high yields and better ee's as compared to 3a. Meanwhile adducts obtained from ketimines with electron rich aryl rings maintained higher ee's albeit with slightly decreased yields (3e and 3f). The annulation reaction of 1 with zwitterion derived from benzyl allenoate 2b also ran smoothly to offer [3 + 2] adducts 3g–3l in high yields and with excellent enantiomeric excess (Scheme 2). The absolute stereochemistry of all the spirooxindole products 3 was unambiguously assigned on the basis of a single crystal X-ray analysis of 3j (Fig. 2).¹⁷

Scheme 2 Asymmetric [3 + 2]-annulation of allene esters with isatinimines 1.

Fig. 2 Single crystal X-ray structure of compound 3j.

Phosphine catalysis has more often engaged the allene esters as substrates of the zwitterions and the corresponding allenic ketones have only rarely been explored in the zwitterionic annulation reactions.¹⁸ We employed allenyl ketones 2c and 2d in the [3 + 2]-annulation reaction with isatinimines 1 (Scheme 3). With allenyl phenyl ketone 2c, the annulation reaction of isatinimines 1 performed well to afford adducts 3m and 3n in high yields and with very good enantioselectivities (Scheme 3). The acetyl allene, which has a very low boiling point, also sustained well with the asymmetric annulation reaction conditions and afforded the corresponding spiro-adduct in very good yields and with excellent ee's (3o–3t).

Scheme 3 Asymmetric [3 + 2]-annulation of allenic ketones with isatinimines.

The role of Brønsted acid function in the aminophosphine catalysts XIV to steer the stereoselectivity of the reaction is obvious and plausibly helps in stabilizing the enolate zwitterion 4 with the help of H-bonding as well as O–P interaction (Scheme 4).¹³ The amino acid backbone as well as the bulky benzamide function are the key steric blocks that steer a highly facially discriminative approach of isatinimine as depicted in Scheme 4. We assume that the lactam function of oxindole might also interact by hydrogen bonding and thereby exposing the re-face of ketimine for an attack of zwitterion and leading to intermediate 5. Addition of amide function in 5 to the vinyl phosphonium moiety closes the ring (6). A proton transfer leading to enolate 7 is followed by the phosphine elimination to provide the spirooxindole adduct 3.

Scheme 4 Plausible mechanism for [3 + 2]-annulation.

The synthetic utility of the enantio-enriched spirooxindoles 3 in delivering more enantiopure small molecules based on a natural product core-structure was further investigated as depicted in Scheme 5. Debenzylation of the spirooxindole 3g with Pd/C and under hydrogen atmosphere delivered the spirooxindole 8 in good yield and with a carboxylic acid as synthetic handle for parallel synthesis in the construction of a focused compound library (Scheme 5a). For instance, a coupling reaction of 8 with n-propylamine using HBTU as coupling reagent provided the amide 9. Suzuki coupling of the bromoaryl function in 3j under standard conditions afforded the aryl substituted spirooxindole 10 (Scheme 5b). Acid mediated removal of N-Boc group afforded the free amine 11 which reacted well with 2-fluoro-benzaldehyde under reductive amination condition to furnish compound 12 and thus demonstrating the amenability of the substituted spirooxindoles 3 in compound collection synthesis.

Scheme 5 Elaboration of the 3,2′-dihydropyrrolyl-spirooxindoles.

Conclusions

In conclusion, we have developed a highly enantioselective [3 + 2]-annulation reaction of isatin-derived ketimines as the electrophiles with zwitterions generated from allenyl esters as well as allenyl ketones. The key to success in this asymmetric transformation was the catalysis performed by L-isoleucine derived bifunctional N-acylaminophosphine. This catalytic protocol allows a rapid and efficient access to construct enantiopure small molecules with a dihydropyrrolyl-spirooxindole framework.

Experimental section

General information

All the chemicals were purchased from Aldrich, Acros, or Alfa and were used without further purification. Reactions were carried out in standard glassware or a Radleys Carousel 12 parallel reactor. Thin layer chromatography (TLC) was performed on Merck silica gel ⁶⁰F₂₅₄ aluminum sheet. Column chromatography (CC) purifications were carried out using silica gel (Acros Organics, particle size 35–70 μm) was used. Solvents used for CC are commercially available. Fourier transform infrared spectroscopy (FT-IR) data were obtained from Bruker Tensor 27 spectrometer (ATR, neat) and are reported in terms of frequency of absorption. ¹H and ¹³C-NMR spectroscopic data were recorded on a Varian Mercury VX 400 or Varian 500-inova500 spectrometer at RT. ¹H and ¹³C-NMR spectra were calibrated to the solvent signals of CDCl₃ (=7.26 and 77.00 ppm); multiplicities are indicated brs (broadened singlet), s (singlet), d (doublet), t (triplet), q (quartet), m (multiplet), dd (doublets of a doublet); coupling constants (J) are given in Hertz (Hz). LC/MS analysis were done using an Agilent 6150 single quadrupole (SQ) mass spectrometer coupled to an Agilent 1290 Infinity LC System. High resolution mass spectra were recorded on a LTQ Orbitrap mass spectrometer coupled to an Acceka HPLC-System (HPLC column: Hypersyl GOLD, 50 mm × 1 mm, particle size 1.9 μm, ionization method: electron spray ionization). Optical rotations were measured in a Schmidt + Haensch Polartronic HH8 polarimeter. The enantiomeric excesses were determined by Agilent-1100 series HPLC system using a chiral stationary phase column (column: CHIRALPAK IC, CHIRALPAK IA, eluent: (DCM/EtOH = 100/2), iso-hexane). Chemical yields refer to pure isolated substances.

General procedure for the [3 + 2]-dipolar annulation reaction

To a stirred solution of isatinimine 1 (1.0 equiv.) and allene 2 (1.2 equiv.) in degassed toluene (0.035 M of 1) was added the isoleucine derived bifunctional aminophosphine XIV (20 mol%) at −40 °C and the reaction mixture was continued to stir at −40 °C overnight (12 h). The reaction was monitored by TLC using Pet.ether/ethyl acetate (1 : 1) as eluent. After completion, the reaction mixture was concentrated to give the crude compound that was purified by flash column chromatography on silicagel using 35–60% ethyl acetate in petroleum ether as gradient eluent and afforded the spirooxindole 3.

3′-Ethyl-1′-(tert-butyl)-(R)-1-methyl-2-oxo-1,2,5′-trihydrospiro-[indole-3,2′-pyrrole]-1′,3′-dicarboxylate (3a). To a stirred solution of N-methyl isatinimine 1a (20 mg, 0.0768 mmol, 1.0 equiv.) and allene 2a (10.3 mg, 0.0922 mmol, 1.2 equiv.) in degassed toluene (2.2 mL, 0.035 M) was added the bifunctional aminophosphine catalyst XIV (20 mol%) at −40 °C and the reaction mixture was continued to stir at −40 °C overnight (12 h). The reaction was monitored by TLC using Pet.ether/ethyl acetate (1 : 1) as eluent. After completion, the reaction mixture was concentrated to give the crude compound that was purified by flash column chromatography on silicagel using 35–60% ethyl acetate in petroleum ether as gradient eluent to give the spirooxindole 3a; yield: 84%; ee = 97.1%; [α]²⁰_D = −19.8° (c 1.17, CH₂Cl₂); IR ν_max/cm⁻¹ 3058, 2978, 2934, 1788, 1721, 1703; ¹H NMR (5 : 1 rotamer ratio, asterisks denote minor rotamer peaks, 400 MHz, CDCl₃) δ 7.30 (td, J = 7.6, 1.5 Hz, 1H), 7.13 (t, J = 2.2 Hz, 1H), 7.08* (t, J = 2.2 Hz, 0.2H), 7.06–7.03 (m, 1H), 7.00 (td, J = 7.4, 0.9 Hz, 1H), 6.97* (td, J = 7.4, 0.9 Hz, 0.2H), 6.83* (d, J = 7.7 Hz, 0.3H), 6.79 (d, J = 7.7 Hz, 1H), 4.62 (dd, J = 18.3, 2.2 Hz, 1H), 4.56 (dd, J = 18.3, 2.2 Hz, 1H), 4.48* (dd, J = 18.1, 2.1 Hz, 0.2H), 4.05–3.86 (m, 2H), 3.28* (s, 0.5H), 3.23 (s, 3H), 1.36 (s, 1.5H), 1.07 (s, 9H), 1.09–0.99 (m, 3H); ¹³C NMR (asterisks denote minor rotamer peaks, 101 MHz, CDCl₃) δ 174.24, 161.02, 152.56, 144.88*, 144.81, 140.20*, 140.06, 134.87*, 134.78, 134.68*, 130.28*, 129.67, 129.44, 129.09*, 128.67*, 122.87, 122.76, 122.74*, 122.59*, 108.29*, 108.02*, 107.86, 98.42, 83.41*, 80.95, 80.88*, 72.61, 60.99, 60.93*, 54.31*, 54.02, 53.62*, 28.54, 28.29*, 28.01, 27.89, 26.87*, 26.61, 14.01, 13.96*; HRMS [ESI]: calculated for C₂₀H₂₅N₂O₅ [M + H⁺]: 373.17580, found: 373.17624; RT = 21.1 min (chiral HPLC, column: chiralpak IC, eluent: 50% of mixture of EtOH–DCM (1 : 50) in isohexane, flow rate: 0.5 mL min⁻¹).

3′-Ethyl-1′-(tert-butyl)-(R)-5-bromo-1-methyl-2-oxo-1,2,5′-trihydrospiro[indole-3,2′-pyrrole]-1′,3′-dicarboxylate (3b). Yield: 86%; ee = 98.1%; [α]²⁰_D = −66.4° (c 0.95, CH₂Cl₂); IR ν_max/cm⁻¹ 3060, 2977, 2929, 2869, 1789, 1725, 1704; ¹H NMR (4 : 1 rotamer ratio, asterisks denote minor rotamer peaks, 400 MHz, CDCl₃) δ 7.43 (dd, J = 8.2, 2.0 Hz, 1H), 7.40* (dd, J = 8.2, 2.0 Hz, 0.3H), 7.18 (d, J = 2.0 Hz, 1H), 7.15* (d, J = 1.9 Hz, 0.3H), 7.15 (t, J = 2.1 Hz, 1H), 7.10* (t, J = 2.1 Hz, 0.3H), 6.71* (d, J = 8.3 Hz, 0.3H), 6.68 (d, J = 8.2 Hz, 1H), 4.63 (dd, J = 18.4, 2.2 Hz, 1H), 4.61* (dd, J = 18.2, 2.1 Hz, 0.3H), 4.56 (dd, J = 18.4, 2.1 Hz, 1H), 4.47* (dd, J = 18.2, 2.1 Hz, 0.3H), 4.06–3.93 (m, 2H), 3.26* (s, 0.8H), 3.22 (s, 3H), 1.38 (s, 2H), 1.11 (s, 9H), 1.12–1.06 (m, 3H); ¹³C NMR (asterisks denote minor rotamer peaks, 101 MHz, CDCl₃) δ 173.72, 173.68*, 160.88*, 160.83, 152.31, 151.91*, 144.06*, 143.92, 140.66*, 140.50, 134.41*, 134.36, 132.46*, 132.42, 131.48, 126.20, 126.05*, 115.21, 115.12*, 109.77*, 109.30, 81.35, 81.28*, 72.40, 61.20, 61.13*, 54.35*, 54.12, 28.54, 28.07, 26.96*, 26.72, 14.07, 14.02*; HRMS [ESI]: calculated for C₂₀H₂₄BrN₂O₅ [M + H⁺]: 451.08631, found: 451.08619; calculated for C₂₀H₂₄⁸¹BrN₂O₅ [M + H⁺]: 453.08426, found: 453.08414; RT = 51.9 min (chiral HPLC, chiralpak IC-column and using 30% of mixture of EtOH–DCM (1 : 50) in isohexane as eluent, Flow rate: 0.5 mL min⁻¹) (chiral HPLC, column: chiralpak IC, eluent: 30% of mixture of EtOH–DCM (1 : 50) in isohexane, flow rate: 0.5 mL min⁻¹).

3′-Benzyl-1′-(tert-butyl)-(R)-5-bromo-1-methyl-2-oxo-1,2,5′-trihydrospiro[indole-3,2′-pyrrole]-1′,3′-dicarboxylate (3j). Yield: 80%; ee = 97.6%; [α]²⁰_D = −62.8° (c 1.1, CH₂Cl₂); IR ν_max/cm⁻¹ 3064, 2976, 2934, 1727, 1703; ¹H NMR (3.5 : 1 rotamer ratio, asterisks denote minor rotamer peaks, 400 MHz, CDCl₃) δ 7.41 (dd, J = 8.2, 2.0 Hz, 1H), 7.37* (dd, J = 8.2, 2.0 Hz, 0.28H), 7.34–7.29 (m, 3H), 7.23 (t, J = 2.2 Hz, 1H), 7.18 (d, J = 2.0 Hz, 1H), 7.17* (t, J = 2.2 Hz, 0.28H), 7.16* (d, J = 2.0 Hz, 0.28H), 7.08–7.05 (m, 2H), 7.03* (dd, J = 6.3, 3.2 Hz, 0.56H), 6.51* (d, J = 7.8 Hz, 0.28H), 6.49 (d, J = 8.2 Hz, 1H), 4.96 (d, J = 12.1 Hz, 1H), 4.89 (d, J = 12.1 Hz, 1H), 4.86* (d, J = 12.1 Hz, 0.28H), 4.63 (dd, J = 18.5, 2.2 Hz, 1H), 4.61* (dd, J = 18.5, 2.2 Hz, 0.28H), 4.56 (dd, J = 18.5, 2.2 Hz, 1H), 4.47* (dd, J = 18.3, 2.1 Hz, 0.3H), 2.95* (s, 0.8H), 2.91 (s, 3H), 1.37* (s, 2.6H), 1.09 (s, 9H); ¹³C NMR (asterisks denote minor rotamer peaks, 101 MHz, CDCl₃) δ 173.56, 173.51*, 160.78*, 160.69, 152.26, 151.86*, 143.90*, 143.78, 141.65*, 141.49, 134.83, 134.06*, 134.00, 132.34, 131.33, 129.00, 128.79, 128.76*, 128.73*, 126.20, 126.03*, 115.17, 115.07*, 110.02*, 109.51, 81.36, 81.31*, 72.30, 67.26, 54.33*, 54.10, 28.53, 28.04, 26.61*, 26.36; HRMS [ESI]: calculated for C₂₅H₂₆BrN₂O₅ [M + H⁺]: 513.10196, found: 513.10250; calculated for C₂₅H₂₆⁸¹BrN₂O₅ [M + H⁺]: 515.09991, found: 515.10048; RT = 17.7 min (chiral HPLC, column: chiralpak IC, eluent: 50% of mixture of EtOH–DCM (1 : 50) in isohexane, flow rate: 0.5 mL min⁻¹).

tert-Butyl-(R)-3′-benzoyl-1-methyl-2-oxo-1,2,5′-trihydrospiro-[indole-3,2′-pyrrole]-1′-carboxylate (3m). Yield: 71%; ee = 97.7%; [α]²⁰_D = −3.1° (c 0.7, CH₂Cl₂); ¹H NMR (7 : 1 rotamer ratio, asterisks denote minor rotamer peaks, 400 MHz, CDCl₃) δ 7.64 (d, J = 7.1 Hz, 1H), 7.52 (t, J = 7.4 Hz, 1H), 7.40 (t, J = 7.6 Hz, 1H), 7.30–7.26 (m, 1H), 7.12 (d, J = 7.2 Hz, 1H), 6.98 (t, J = 7.4 Hz, 1H), 6.95* (t, J = 7.4 Hz, 0.15H), 6.85* (d, J = 7.9 Hz, 0.16H), 6.83 (t, J = 2.2 Hz, 1H), 6.81 (d, J = 7.8 Hz, 1H), 6.75* (t, J = 2.0 Hz, 1H), 4.74 (d, J = 2.1 Hz, 1H), 4.68* (dd, J = 20.5, 2.1 Hz, 1H), 3.35* (s, 0.4H), 3.30 (s, 1H), 1.39* (s, 1.4H), 1.09 (s, 9H); ¹³C NMR (asterisks denote minor rotamer peaks, 101 MHz, CDCl₃) δ 189.69, 174.38, 152.70, 145.05, 145.01*, 141.60, 140.97, 140.81*, 137.66*, 137.58, 132.97, 132.90*, 129.77*, 129.73, 129.15, 128.66*, 128.63, 122.70, 122.55*, 122.46, 122.33*, 108.68*, 108.20, 81.05, 80.96*, 73.50, 54.95*, 54.71, 28.58, 28.04, 27.05*, 26.76; HRMS [ESI]: calculated for C₂₄H₂₅N₂O₄ [M + H⁺]: 405.18088, found: 405.18136; RT = 29.3 min (chiral HPLC, column: chiralpak IC, eluent: 50% of mixture of EtOH–DCM (1 : 50) in isohexane, flow rate: 0.5 mL min⁻¹).

Acknowledgements

This research was supported by funds from Max-Planck-Gesellschaft. We thank Nils Schloemp for his help in some experiments.

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Footnote

† Electronic supplementary information (ESI) available. CCDC 1472155. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/c6ra12387b

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