Consecutive Aminolithiation–Carbolithiation of a Linear Aminoalkene Bearing Terminal Vinyl Sulfide Moiety to Give Hydro­indolizine

This paper is dedicated to Professor Victor Snieckus on the occasion of his 80th birthday

Abstract

Aminolithiation–carbolithiation tandem cyclization of an aminoalkene bearing vinyl sulfide moiety proceeded smoothly using stoichiometric amounts of BuLi. Both aminolithiation and carbo­lithiation were in equilibrium at room temperature, and the stereochemistry of the cyclization was thermodynamically controlled. At –78 °C the reaction was kinetically controlled and the cyclized product, 1,2-disubstituted octahydroindolizine, was obtained with good dia­stereoselectivity.

Key words

aminolithiation - carbolithiation - vinyl sulfide - N-hetero­cycles - domino reaction

• References and Notes

• 1a Huang L. Arndt M. Gooßen K. Heydt H. Gooßen LJ. Chem. Rev. 2015; 115: 2596
• 1b Hannedouche J. Schulz E. Chem. Eur. J. 2013; 19: 4972
• 1c Müller TE. Hultzsch KC. Yus M. Foubelo F. Tada M. Chem. Rev. 2008; 108: 3795 ; and references therein
• 2a Doi H. Sakai T. Iguchi M. Yamada k. Tomioka K. J. Am. Chem. Soc. 2003; 125: 2886
• 2b Sakai T. Doi H. Tomioka K. Tetrahedron 2006; 62: 8351
• 2c Harada S. Sakai T. Takasu K. Yamada K. Yamamoto Y. Tomioka K. J. Org. Chem. 2012; 77: 7212 ; and references therein
• 3a Ogata T. Ujihara A. Tsuchida S. Shimizu T. Kaneshige A. Tomioka K. Tetrahedron Lett. 2007; 48: 6648
• 3b Ogata T. Kimachi T. Yamada K. Yamamoto Y. Tomioka K. Heterocycles 2012; 86: 469
• 4 Tsuchida S. Kaneshige A. Ogata T. Baba H. Yamamoto Y. Tomioka K. Org. Lett. 2008; 16: 3635

Recent reviews for the synthesis of indolizines, see:
• 5a Sadowski B. Klajn J. Gryko DT. Org. Biomol. Chem. 2016; 14: 7804
• 5b Cordero FM. Giomi D. Brandi A. Curr. Top. Med. Chem. 2014; 14: 1294
• 5c Kim IS. Jung YH. Heterocycles 2011; 83: 2489
• 5d Michael JP. Nat. Prod. Rep. 2008; 25: 139
• 5e Cardona F. Goti A. Brandi A. Eur. J. Org. Chem. 2007; 1551 ; and references therein
• 6a Corey EJ. Seebach D. Angew. Chem. Int. Ed. Engl. 1965; 4: 1075
• 6b Seebach D. Synthesis 1969; 19
• 6c Corey EJ. Erickson BW. J. Org. Chem. 1971; 36: 3553
• 6d Bernasconi CF. Kittredge KW. J. Org. Chem. 1998; 63: 1944
• 7a For aminolithiation of vinyl sulfide, see: Quinet C. Sampoux L. Markó IE. Eur. J. Org. Chem. 2009; 1806
• 7b For an intramolecular hydroamination of dithioketene acetals, see: Xu H.-C. Moeller KD. Org. Lett. 2010; 12: 5174

For carbolithiation of vinyl sulfide, see:
• 8a Kim S. Kim BS. Jon SY. Bull. Korean Chem. Soc. 1994; 15: 701
• 8b Krief A. Kenda B. Remacle B. Tetrahedron Lett. 1995; 36: 7917
• 8c Krief A. Kenda B. Remacle B. Tetrahedron 1996; 52: 7435
• 8d Chen F. Mudryk B. Cohen T. Tetrahedron 1999; 55: 3291
• 8e Hoffmann RW. Koberstein R. Harms K. J. Chem. Soc., Perkin Trans. 2 1999; 183
• 8f Ashweek NJ. Coldham I. Snowden DJ. Vennall GP. Chem. Eur. J. 2002; 8: 195
• 9 Miyake H. Yamamura K. Bull. Chem. Soc. Jpn. 1988; 61: 3752
• 10 Beckwith AL. J. Meijs GF. J. Org. Chem. 1987; 52: 1922
• 11 Typical procedure (Table [1], entry 1): Under Ar atmosphere, to a solution of n-BuLi (1.62 M in hexane, 0.19 mL, 0.3 mmol) in THF (1.5 mL) was added a solution of 1a (71 mg, 0.2 mmol) in THF (0.5 mL) dropwise at –20 °C. The mixture was stirred for 2 h at room temperature, then the reaction was quenched with water (5 mL). The mixture was extracted with Et₂O (20 + 10 + 10 mL), and the combined organic layers were washed with brine (20 mL), dried over K₂CO₃ and concentrated. Column chromatography (hexane/EtOAc, 5:1 to 0:1, then EtOAc/Et₃N 1:1) gave 3a (42 mg, 60%). The diastereomers of 3a were partially separated by column chromatography to give tc-3a, tt-3a and ct-3a. tt-3a: ¹H NMR (CDCl₃): δ = 1.09–1.21 (m, 2 H), 1.50 (m, 1 H), 1.59 (m, 1 H), 1.76 (m, 1 H), 1.81 (m, 1 H), 1.88 (m, 1 H), 1.93 (ddd, J = 3.0, 11.5, 11.5 Hz, 1 H), 2.21 (m, 1 H), 2.32 (dd, J = 9.0, 9.0 Hz, 1 H), 2.84 (dd, J = 6.0, 9.4 Hz, 1 H), 2.87 (dd, J = 10.3, 12.6 Hz, 1 H), 2.97 (br d, J = 10.5 Hz, 1 H), 3.01 (dd, J = 2.0, 9.4 Hz, 1 H), 3.15 (dd, J = 4.3, 12.6 Hz, 1 H), 7.17 (m, 1 H), 7.23–7.28 (m, 7 H), 7.38–7.42 (m, 2 H). ¹³C NMR (CDCl₃): δ = 24.0 (CH₂), 25.1 (CH₂), 29.7 (CH₂), 38.7 (CH₂), 43.2 (CH), 53.0 (CH₂), 57.2 (CH), 57.8 (CH₂), 70.8 (CH), 125.9 (CH), 127.4 (CH), 128.9 (CH x 2), 129.3 (CH), 133.0 (CH), 134.4 (C), 136.0 (C). IR, MS and elemental analysis data were taken as a mixture of diastereomers. IR (neat): 2932, 1582, 1481 cm^–1. EIMS: m/z = 355 [M]⁺. Anal. Calcd for C₂₁H₂₅NS₂: C, 70.94; H, 7.09; N, 3.94. Found: C, 71.12; H, 7.23; N, 3.70. tc-3a: ¹H NMR (CDCl₃): δ = 1.20–1.27 (m, 2 H), 1.53 (m, 1 H), 1.66 (m, 1 H), 1.78–1.84 (m, 2 H), 1.98–2.04 (m, 2 H), 2.07 (dd, J = 9.0, 9.0 Hz, 1 H), 2.71 (m, 1 H), 2.83 (dd, J = 12.0, 12.0 Hz, 1 H), 3.08 (br d, J = 10.9 Hz, 1 H), 3.31 (dd, J = 4.0, 12.0 Hz, 1 H), 3.45 (dd, J = 10.0, 10.0 Hz, 1 H), 3.47 (dd, J = 7.2, 9.4 Hz, 1 H), 7.14–7.18 (m, 2 H), 7.21–7.28 (m, 8 H). ¹³C NMR (CDCl₃): δ = 24.1 (CH₂), 25.3 (CH₂), 30.1 (CH₂), 36.6 (CH₂), 37.4 (CH), 53.2 (CH₂), 53.5 (CH), 61.3 (CH₂), 68.2 (CH), 125.5 (CH), 126.1 (CH), 127.8 (CH), 128.8 (CH), 129.0 (CH), 129.5 (CH), 135.9 (C), 137.4 (C). ct-3a: ¹H NMR (CDCl₃): δ = 1.14–1.24 (m, 2 H), 1.49–1.69 (m, 3 H), 1.78 (m, 1 H), 1.90–1.97 (m, 2 H), 2.24 (m, 1 H), 2.49 (m, 1 H), 2.79 (dd, J = 9.2, 12.9 Hz, 1 H), 3.07 (dd, J = 5.5, 12.9 Hz, 1 H), 3.14 (br d, J = 11.2 Hz, 1 H), 3.34 (dd, J = 7.7, 9.2 Hz, 1 H), 3.55 (dd, J = 4.0, 6.3 Hz, 1 H), 7.14–7.29 (m, 8 H), 7.38–7.41 (m, 2 H). ¹³C NMR (CDCl₃): δ = 24.1 (CH₂), 24.8 (CH₂), 27.8 (CH₂), 38.3 (CH₂), 44.5 (CH), 53.7 (CH₂), 55.2 (CH), 60.4 (CH₂), 67.4 (CH), 126.1 (CH), 126.5 (CH), 128.8 (CH), 128.9 (CH), 129.5 (CH), 131.1 (CH), 135.6 (C), 136.3 (C).
• 12 Kabanyane ST. Magee DI. Can. J. Chem. 1992; 70: 2758
• 13 Ashweek NJ. Coldham I. Snowden DJ. Vennall GP. Chem. Eur. J. 2002; 8: 195
• 14a Nigam SC. Mann A. Taddei M. Wermuth C.-G. Synth. Commun. 1989; 19: 3139
• 14b Murray AJ. Parsons PJ. Hitchcock P. Tetrahedron 2007; 63: 6485
• 15a Bailey WF. Khanolkar AD. Gavaskar K. Ovaska TV. Rossi K. Thiel Y. Wiberg KB. J. Am. Chem. Soc. 1991; 113: 5720
• 15b Liu H. Deng K. Cohen T. Jordan KD. Org. Lett. 2007; 9: 1911