Stereoselective Synthesis of Cyclohexane Derivatives: Tandem Lithium Iodide Mediated Intramolecular Conjugate Addition of Thiols to α,β-Bisenones

Abstract

A tandem intramolecular conjugate addition reaction was conducted with α,β-bisenones as selected Michael acceptors which were converted into 1,2,3-trisubstituted six-membered rings in the presence of activated sulfur nucleophiles. The products were obtained in good to excellent yields (maximum yield: 99%). Various substituted α,β-bisenones and sulfur nucleophiles were examined to understand the substrate scope of the reaction. Only one diastereomer was isolated, as lithium iodide mediated enolate trapping reactions improve the stereoselectivity of reactions involving 1,2,3-trisubstituted cyclohexanes.

Key words

stereoselectivity - tandem conjugate addition - lithium iodide - α,β-bisenones - thiols

Publication History

Received: 22 December 2021

Accepted after revision: 28 January 2022

Accepted Manuscript online:
28 January 2022

Article published online:
23 March 2022

• References


For reviews, see:
• 1a Tietze LF. Chem. Rev. 1996; 96: 115
• 1b Denmark SE, Thorarensen A. Chem. Rev. 1996; 96: 137
• 1c Parsons PJ, Penkett CS, Shell AJ. Chem. Rev. 1996; 96: 195
• 1d Sibi MP, Manyem S. Tetrahedron 2000; 56: 8033
• 1e Krause N, Hoffmann-Roder A. Synthesis 2001; 171
• 1f Fagnou K, Lautens M. Chem. Rev. 2003; 103: 169
• 1g Guo H.-C, Ma J.-A. Angew. Chem. Int. Ed. 2006; 45: 354
• 1h Enders D, Grondal C, Hüttl MR. M. Angew. Chem. Int. Ed. 2007; 46: 1570
• 1i Chanda T, Zhao JC.-G. Adv. Synth. Catal. 2018; 360: 2

For reviews, see:
• 2a Jerphagnon T, Pizzuti MG, Minnaard AJ, Feringa BL. Chem. Soc. Rev. 2009; 38: 1039
• 2b Csákÿa AG, Herrán G, Murcia MC. Chem. Soc. Rev. 2010; 39: 4080
• 2c Dong N, Zhang Z, Xue X, Li X, Cheng J. Angew. Chem. Int. Ed. 2016; 55: 1460
• 2d Sekino E, Kumamoto T, Tanaka T, Ikeda T, Ishikawa T. J. Org. Chem. 2004; 69: 2760
• 2e Fu N, Zhang L, Luo S, Cheng J. Org. Lett. 2014; 16: 4626
• 3a Liu Y, Zhu J, Qian J, Jiang B, Xu Z. J. Org. Chem. 2011; 76: 9096
• 3b Hagare AK, Datrange LS, Vyas D, Bhuniya D, Reddy DS. Tetrahedron Lett. 2010; 51: 5291
• 3c Davies SG, Mujtaba N, Roberts PM, Smith AD, Thomson JE. Org. Lett. 2009; 11: 1959
• 4a Meng D, Chen W, Zhao W. J. Nat. Prod. 2007; 70: 824
• 4b Sabarre A, Love J. Org. Lett. 2008; 10: 3941
• 4c Yus M, Gutiérrez A, Foubelo F. Tetrahedron 2001; 57: 4411
• 4d Metzner P, Thuillier A. Sulfur Reagents in Organic Synthesis . Academic Press; San Diego: 1994
• 4e Belen’kii LI. Chemistry of Organosulfur Compounds . Ellis Horwood; New York: 1990
• 4f Konkolewicz D, Gray-Weale A, Perrier S. J. Am. Chem. Soc. 2009; 131: 18075
• 4g Roncali J. Chem. Rev. 1992; 92: 711
• 4h Feng Z.-N, Luo J.-Y, Zhang Y, Du G.-F, He L. Org. Biomol. Chem. 2019; 17: 4700
• 4i Chavan SP, Subbarao YT, Chittiboyina AG, Sivappa R, Suresh CG. Tetrahedron: Asymmetry 2001; 12: 1101
• 4j Gigant N, Drège E, Retailleau P, Joseph D. Chem. Eur. J. 2015; 21: 15544
• 5 Gulino V, Brighi M, Dematteis EM, Murgia F, Nervi C, Černy R, Baricco M. Chem. Mater. 2019; 31: 5133
• 6a Loupy A, Tchoubar B. Salt Effects in Organic and Organometallic Chemistry. VCH; Weinheim: 1992
• 6b Manna S, Falck JR, Mioskowski C. Synth. Commun. 1985; 15: 663
• 7 Zewge D, King A, Weissman S, Tschaen D. Tetrahedron Lett. 2004; 45: 3729
• 8a Kawai D, Kawasumi K, Miyahara T, Hirashita T, Araki S. Synlett 2008; 2977
• 8b Kawai D, Kawasumi K, Miyahara T, Hirashita T, Araki S. Tetrahedron 2009; 65: 10390
• 8c Yoshimura A, Koski SR, Kastern BJ, Fuchs JM, Jones TN, Yusubova RY, Nemykin VN, Zhdankin VV. Chem. Eur. J. 2014; 20: 5895
• 9a Miyabe H, Yamaoka Y, Naito T, Takemoto Y. J. Org. Chem. 2004; 69: 1415
• 9b Park SH, Yoon HK, Lee HW. Bull. Korean Chem. Soc. 2006; 27: 1519
• 10 Hirner S, Somfai P. Synlett 2005; 3099
• 11a Yatagai H, Yamamoto Y, Maruyama K. Chem. Lett. 1980; 669
• 11b Yanada R, Obika S, Kobayashi Y, Inokuma T, Oyama M, Yanada K, Takemoto Y. Adv. Synth. Catal. 2005; 347: 1632
• 12a Bonini C, Giuliano C, Righi G, Rossi L. Synth. Commun. 1992; 22: 1863
• 12b Federici C, Righi G, Rossi L. Tetrahedron Lett. 1994; 35: 797
• 12c Bonini C, Federici C, Rossi L, Righi G. J. Org. Chem. 1995; 60: 4803
• 12d Infante I, Bonini C, Lelj F, Righi G. J. Org. Chem. 2003; 68: 3773
• 13a Too PC, Chan GH, Tnay YL, Hirao H, Chiba S. Angew. Chem. Int. Ed. 2016; 55: 3719
• 13b Hong Z, Ong DY, Muduli SK, Too PC, Chan GH, Tnay YL, Chiba S, Nishiyama Y, Hirao H, Soo HS. Chem. Eur. J. 2016; 22: 7108
• 14 Ong DY, Tejo C, Xu K, Hirao H, Chiba S. Angew. Chem. Int. Ed. 2017; 56: 1840
• 15 Kaga A, Hayashi H, Hakamata H, Oi M, Uchiyama M, Takita R, Chiba S. Angew. Chem. Int. Ed. 2017; 56: 11807
• 16 Huang Y, Chan GH, Chiba S. Angew. Chem. Int. Ed. 2017; 56: 6544
• 17a Marques MV, Sá MM. J. Org. Chem. 2014; 79: 4650
• 17b Tokuda O, Aikawa T, Ikemoto T, Kuriomoto I. Tetrahedron Lett. 2010; 51: 2832
• 18 Thirupathaiah B, Seo S. Chem. Commun. 2015; 51: 4216
• 19a Wang L.-C, Luis AL, Agapiou K, Jang H.-Y, Krische MJ. J. Am. Chem. Soc. 2002; 124: 2402
• 19b Reynolds TE, Binkley MS, Scheidt KA. Org. Lett. 2008; 10: 2449
• 19c Wang CE, Dermenci A, Miller SJ. Tetrahedron 2009; 65: 4069
• 19d Aroyan CE, Dermenci A, Miller SJ. J. Org. Chem. 2010; 75: 5784
• 19e Osuna S, Dermenci A, Miller SJ, Houk KN. Chem. Eur. J. 2013; 19: 14245
• 19f Brown PM, Käppel N, Murphy PJ, Coles SJ, Hursthouse MB. Tetrahedron 2007; 63: 1100