Stereoselective anti-S_N2′-Substitutions of Secondary Alkylcopper-Zinc Reagents with Allylic Epoxides: Total Synthesis of (3S,6R,7S)-Zingiberenol

Abstract

Chiral secondary mixed alkylcopper-zinc reagents were prepared from the corresponding alkyl iodides and reacted with allylic epoxides via an anti-S_N2′-substitution and retention of configuration of the chiral alkylorganometallic, leading to chiral allylic alcohols. This method was used in a total synthesis of the natural product (3S,6R,7S)-zingiberenol in 8 steps and 9.7% overall yield [dr (3S,6R) = 99:1; dr (6R,7S) = 81:19] starting from commercially available 3-methyl-2-cyclohexenone.

Key words

lithium - stereoselective - copper - allylic epoxides - natural products

• References

• 1a Bertozzi F, Crotti P, Feringa BL, Macchia F, Pineschi M. Synthesis 2001; 483
• 1b Cullis CA, Mizutani H, Murphy KE, Hoveyda AH. Angew. Chem. Int. Ed. 2001; 40: 1456
• 1c Trost BM, Crawley ML. Chem. Rev. 2003; 103: 2921
• 1d Campbell JE, Hoveyda AH. J. Am. Chem. Soc. 2004; 126: 11130
• 1e van Zijl AW, Szymanski W, Lopez F, Minnaard AJ, Feringa BL. J. Org. Chem. 2008; 73: 6994
• 1f Alexakis A, Bäckvall JE, Krause N, Pàmies O, Diéguez M. Chem. Rev. 2008; 108: 2796
• 1g Goth SS, Guduguntla S, Kikuchi T, Lutz M, Otten E, Fujita M, Feringa BL. J. Am. Chem. Soc. 2018; 140: 7052
• 1h Cheng Q, Tu C, Zheng H.-F, Qu J.-P, Helmchen G, You S.-L. Chem. Rev. 2019; 119: 1855
• 2a Harrington-Frost N, Leuser H, Calaza MI, Kneisel FF, Knochel P. Org. Lett. 2003; 5: 211
• 2b Calaza MI, Hupe E, Knochel P. Org. Lett. 2003; 5: 1059
• 2c Breit B, Demel P, Studte C. Angew. Chem. Int. Ed. 2004; 43: 3786
• 2d Leuser H, Perrone S, Liron F, Kneisel FF, Knochel P. Angew. Chem. Int. Ed. 2005; 44: 4627
• 2e Soorukram D, Knochel P. Angew. Chem. Int. Ed. 2006; 45: 3686
• 2f Perrone S, Knochel P. Org. Lett. 2007; 9: 1041
• 2g Welker M, Woodward S, Alexakis A. Org. Lett. 2010; 12: 576
• 3a Gini F, Del Moro F, Macchia F, Pineschi M. Tetrahedron Lett. 2003; 44: 8559
• 3b Pineschi M, Del Moro F, Crotti P, Di Bussolo V, Macchia F. J. Org. Chem. 2004; 69: 2099
• 3c Falciola C, Tissot-Croset K, Alexakis A. Angew. Chem. Int. Ed. 2006; 45: 5995
• 3d Perez M, Fananas-Mastral M, Bos PH, Rudolph AS, Harutyunyan R, Feringa BL. Nat. Chem. 2011; 3: 377
• 4 Skotnitzki J, Spessert L, Knochel P. Angew. Chem. Int. Ed. 2019; 58: 1509
• 5a Moriya K, Schwärzer K, Karaghiosoff K, Knochel P. Synthesis 2016; 48: 3141
• 5b Morozova V, Skotnitzki J, Moriya K, Karaghiosoff K, Knochel P. Angew. Chem. Int. Ed. 2018; 57: 5516
• 5c Skotnitzki J, Morozova V, Knochel P. Org. Lett. 2018; 20: 2365
• 6a Morais de Oliveria MW, Borges M, Andrade CK. Z, Laumann RA, Barrigossi JA. F, Blassioli-Moraes MC. J. Agric. Food Chem. 2013; 61: 7777
• 6b Khrimian A, Shirali S, Guzman F. J. Nat. Prod. 2015; 78: 3071
• 6c Shirali S, Guzman F, Weber DC, Khrimian A. Tetrahedron Lett. 2017; 58: 2066
• 7a Khrimian A, Zhang A, Weber DC, Ho H.-Y, Aldrich JA, Vermillion KE, Siegler MA, Shirali S, Guzman F, Leskey TC. J. Nat. Prod. 2014; 77: 1708
• 7b Khrimian A, Shirali S, Vermillion KE, Siegler MA, Guzman F, Chauhau K, Aldrich JA, Weber DC. J. Chem. Ecol. 2014; 40: 1260
• 8 Sureshkumar D, Maity S, Chandrasekaran S. J. Org. Chem. 2006; 71: 1653
• 9 Demay S, Harms K, Knochel P. Tetrahedron Lett. 1999; 40: 4981
• 10 Mori K, Ogoche JI. J. Liebigs Ann. Chem. 1988; 903
• 11 Burgess EM, Penton HR. J, Taylor EA. J. Am. Chem. Soc. 1970; 92: 5224
• 12 Blay G, Cardona L, Collado AM, Garcia B, Pedro JR. J. Org. Chem. 2006; 71: 4929
• 13 Mori K, Hazra BG, Pfeiffer RJ, Gupta AK, Lindgren BS. Tetrahedron 1987; 43: 2249
• 14 The enantiomeric excess was determined via chiral GC analysis. For details, see the Supporting Information.
• 15a The stereochemistry was assigned according to literature: Khrimian A, Shirali S, Vermillion KE, Siegler MA, Guzman F, Chauhau K, Aldrich JA, Weber DC. J. Chem. Ecol. 2014; 40: 1260
• 15b For details, see the Supporting Information.
• 16 For details, see Supporting Information.