Intramolecular Carbolithiation of 3-Lithioxy-5-alkenyllithiums as a Platform for Cyclopentanols and Cyclopentanones

Abstract

Intramolecular carbolithiation of 3-lithioxy-5-hexenyllithiums was studied. Unlike the case of 5-hexenyllithium, the cyclization of 3-lithioxy-5-hexenyllithium was very sluggish. Acceleration was observed when lithium chloride was added, suggesting that intramolecular lithioxy coordination would hinder the cyclization. Introduction of a silyl or thiophenyl group at the olefin terminus caused smooth cyclization. The resulting dianions having a cyclopentane framework are subjected to C–C bond-forming reaction with electrophiles to give 3-substituted cyclopentanols. Coupled with the Swern oxidation, the overall protocol served as a platform for 3-substituted cyclopentanones.

Key words

intramolecular carbolithiation - dianion - cyclopentanols - cyclopentanones

• References and Notes


For reviews, see:
• 1a Mehta G, Srikrishna A. Chem. Rev. 1997; 97: 671
• 1b Biellmann J.-F. Chem. Rev. 2003; 103: 2019
• 1c Das S, Chandrasekhar S, Yadav JS, Grée R. Chem. Rev. 2007; 107: 3286
• 1d Manna MS, Mukherjee S. Org. Biomol. Chem. 2015; 13: 18
• 2 Bailey WF, Patricia JJ, DelGobbo VC, Jarret RM, Okarma PJ. J. Org. Chem. 1985; 50: 1999

For selected reviews and recent references on the intramolecular carbolithiation leading to five-membered rings, see:
• 3a Mealy MJ, Bailey WF. J. Organomet. Chem. 2002; 646: 59
• 3b Fañanás FJ, Sanz R In The Chemistry of Organolithium Compounds . Vol. 2. Rappoport Z, Marek I. Wiley; Chichester: 2006: 295
• 3c Hogan A.-ML, O’Shea DF. Chem. Commun. 2008; 3839
• 3d Girard A.-L, Lhermet R, Fressigné C, Durandetti M, Maddaluno J. Eur. J. Org. Chem. 2012; 2895
• 3e Bailey WF, Bakonyi JM. J. Org. Chem. 2013; 78: 3493
• 3f Bailey WF, Fair JD. Beilstein J. Org. Chem. 2013; 9: 537
• 3g Fressigné C, Lhermet R, Girard A.-L, Durandetti M, Maddaluno J. J. Org. Chem. 2013; 78: 9659
• 3h Rodríguez C, Nudelman NS. Synth. Commun. 2014; 44: 772
• 3i Rodríguez C, Nudelman NS. J. Phys. Org. Chem. 2014; 27: 322

For reviews on the asymmetric intramolecular carbolithiation in the presence of (–)-sparteine, see:
• 4a Marek I. J. Chem. Soc., Perkin Trans. 1 1999; 535
• 4b Clayden J. Organolithiums: Selectivity for Synthesis . Pergamon Press; New York: 2002: 273
• 4c Normant JF In Organolithiums in Enantioselective Synthesis . Vol. 5. Hodgson DM. Springer; Berlin: 2003: 287
• 4d Gómez-SanJuan A, Sotomayor N, Lete E. Beilstein J. Org. Chem. 2013; 9: 313
• 4e Tian L, Du W, Zhang Y, Tang S. Chin. J. Org. Chem. 2014; 34: 507

For our work on ketone α,β-dianions, see:
• 5a Nakahira H, Ryu I, Ikebe M, Kambe N, Sonoda N. Angew. Chem., Int. Ed. Engl. 1991; 30: 177
• 5b Ryu I, Nakahira H, Ikebe M, Sonoda N, Yamato S, Komatsu M. J. Am. Chem. Soc. 2000; 122: 1219
• 5c Ryu I, Ikebe M, Sonoda N, Yamato S, Yamamura G, Komatsu M. Tetrahedron Lett. 2000; 41: 5689
• 5d Ryu I, Ikebe M, Sonoda N, Yamato S, Yamamura G, Komatsu M. Tetrahedron Lett. 2002; 43: 1257
• 5e Nakahira H, Ikebe M, Oku Y, Sonoda N, Fukuyama T, Ryu I. Tetrahedron 2005; 61: 3383
• 5f Yamato S, Yamamura G, Komatsu M, Arai M, Fukuyama T, Ryu I. Org. Lett. 2005; 7: 2489
• 5g Ryu I, Yamamura G, Omura S, Minakata S, Komatsu M. Tetrahedron Lett. 2006; 47: 2283
• 6a Komine N, Tomooka K, Nakai T. Heterocycles 2000; 52: 1071
• 6b Bailey WF, Jiang X. Tetrahedron 2005; 61: 3183
• 6c Bailey WF, Jiang X. ARKIVOC 2005; (vi): 25
• 7 Bailey WF, Gavaskar KV. Tetrahedron 1994; 50: 5957
• 8 3-Trimethylsilylmethylcyclopentanol (5b); Typical Procedure To a solution of γ-stannylalcohol 1b (221 mg, 0.48 mmol) in THF (3 mL) was added n-BuLi (0.63 mL, 1.57 M solution in hexane, 1.01 mmol) dropwise over a period of 5 min at –78 °C. This solution was allowed to warm to 0 °C and stirred for 1 h. The resulting solution was quenched with H₂O and extracted with Et₂O twice. The combined organic solution was washed with sat. aq NH₄Cl and dried over MgSO₄ and then concentrated under reduced pressure. Purification by flash chromatography (elution with hexane–Et₂O, 2:1) provided the desired 3-tri-methylsilylmethylcyclopentanol (5b, 70 mg, 85%) with 94:6 (cis/trans) ratio as a colorless oil. R_f = 0.2 (hexane–Et₂O, 3:1). ¹H NMR (270 MHz, CDCl₃ for cis isomer): δ = –0.01 (s, 9 H), 0.71 (d, 2 H, J = 7.3 Hz), 1.06–1.16 (m, 1 H), 1.33–1.43 (m, 1 H), 1.60–1.90 (m, 5 H), 2.16–2.26 (m, 1 H), 4.25–4.29 (m, 1 H). ¹³C NMR (68 MHz, CDCl₃ for cis isomer): δ = –0.74, 24.53, 33.99, 35.06, 35.70, 45.90, 73.78. MS (EI): m/z (%) = 157 (13) [M⁺ – CH₃], 139 (29), 91 (32), 73 (Me₃Si, 100). IR (KBr): 837, 1248, 3348 cm^–1. HRMS: m/z calcd for C₈H₁₇OSi [M⁺ – CH₃]: 157.1049; found: 157.1037. Anal. Calcd for C₉H₂₀OSi₃: C, 62.72; H, 11.70. Found: C, 62.48; H, 11.69.

For conversion of acyllithium into lithium enolates, see:
• 9a Murai S, Ryu I, Iriguchi J, Sonoda N. J. Am. Chem. Soc. 1984; 106: 2440
• 9b Ryu I, Hayama Y, Hirai A, Sonoda N, Orita A, Ohe K, Murai S. J. Am. Chem. Soc. 1990; 112: 7061
• 9c Ryu I, Yamamoto H, Sonoda N, Murai S. Organometallics 1996; 15: 5459
• 9d Fukuyama T, Totoki T, Ryu I. Org. Lett. 2014; 16: 5632
• 10 Ross GA, Koppang MD, Bartak DE, Woolsey NF. J. Am. Chem. Soc. 1985; 107: 6742