1,1-Diborylalkanes as Versatile Precursors for Copper-Catalyzed Diastereo- and Enantioselective Allylic Substitution

Abstract

While copper-catalyzed asymmetric allylic alkylation has undergone substantial advances, achieving high levels of stereocontrol with hard nucleophiles remains a formidable challenge. We have recently reported an efficient copper-catalyzed regio-, diastereo-, and enantioselective allylic alkylation of allyl bromides using 1,1-diborylalkanes as prochiral hard nucleophiles. This methodology employs CuBr as a catalyst, an (R)-BINOL-derived phosphoramidite as a chiral ligand, and lithium benzoate as a crucial additive, providing enantioenriched homoallylic boronic esters in good yields with excellent stereoselectivity. Our mechanistic investigations revealed that lithium benzoate is the key to facilitating highly selective anti-S_N2′-type oxidative addition, offering valuable insights for further development of asymmetric copper catalysis.

1 Introduction

2 Copper-Catalyzed Regio-, Diastereo-, and Enantioselective Allylic Alkylation with 1,1-Diborylalkanes

3 Conclusions and Perspectives

Key words

copper - allylic substitution - chiral organocopper - diastereoselectivity - enantioselectivity

Publikationsverlauf

Eingereicht: 12. März 2025

Angenommen nach Revision: 16. April 2025

Accepted Manuscript online:
16. April 2025

Artikel online veröffentlicht:
13. Juni 2025

• References

• 1a Hartwig JF, Pouy MJ. Iridium-Catalyzed Allylic Substitution . In Iridium Catalysis . Andersson PG. Springer; Berlin/Heidelberg: 2011: 169
• 1b Hartwig JF, Stanley LM. Acc. Chem. Res. 2010; 43: 1461
• 1c Hoveyda AH, Zhou Y, Shi Y, Brown MK, Wu H, Torker S. Angew. Chem. Int. Ed. 2020; 59: 21304
• 1d Tosatti P, Nelson A, Marsden SP. Org. Biomol. Chem. 2012; 10: 3147
• 2a Trost BM, Crawley ML. Chem. Rev. 2003; 103: 2921
• 2b Trost BM, Van Vranken DL. Chem. Rev. 1996; 96: 395
• 3 Cheng Q, Tu H.-F, Zheng C, Qu J.-P, Helmchen G, You S.-L. Chem. Rev. 2019; 119: 1855
• 4a Karlström AS. E, Huerta FF, Meuzelaar GJ, Bäckvall J.-E. Synlett 2001; 923
• 4b van Klaveren M, Persson ES. M, del Villar A, Grove DM, Bäckvall J.-E, van Koten G. Tetrahedron Lett. 1995; 36: 3059
• 5 Dübner F, Knochel P. Angew. Chem. Int. Ed. 1999; 38: 379
• 6a Alexakis A, Malan C, Lea L, Benhaim C, Fournioux X. Synlett 2001; 927
• 6b Malda H, van Zijl AW, Arnold LA, Feringa BL. Org. Lett. 2001; 3: 1169
• 7a Brown MK, Hoveyda AH. J. Am. Chem. Soc. 2008; 130: 12904
• 7b Luchaco-Cullis CA, Mizutani H, Murphy KE, Hoveyda AH. Angew. Chem. Int. Ed. 2001; 40: 1456
• 8 Pérez M, Fañanás-Mastral M, Bos PH, Rudolph A, Harutyunyan SR, Feringa BL. Nat. Chem. 2011; 3: 377
• 9a Gao F, Carr JL, Hoveyda AH. Angew. Chem. Int. Ed. 2012; 51: 6613
• 9b Jung B, Hoveyda AH. J. Am. Chem. Soc. 2012; 134: 1490
• 9c Shi Y, Jung B, Torker S, Hoveyda AH. J. Am. Chem. Soc. 2015; 137: 8948
• 9d Takeda M, Takatsu K, Shintani R, Hayashi T. J. Org. Chem. 2014; 79: 2354
• 10a Hojoh K, Shido Y, Ohmiya H, Sawamura M. Angew. Chem. Int. Ed. 2014; 53: 4954
• 10b Nagao K, Yokobori U, Makida Y, Ohmiya H, Sawamura M. J. Am. Chem. Soc. 2012; 134: 8982
• 10c Ohmiya H, Yokobori U, Makida Y, Sawamura M. J. Am. Chem. Soc. 2010; 132: 2895
• 10d Shido Y, Yoshida M, Tanabe M, Ohmiya H, Sawamura M. J. Am. Chem. Soc. 2012; 134: 18573
• 11a Skotnitzki J, Morozova V, Knochel P. Org. Lett. 2018; 20: 2365
• 11b Kim M, Kim G, Kim D, Lee JH, Cho SH. Beilstein J. Org. Chem. 2025; 21: 639
• 12 Skotnitzki J, Spessert L, Knochel P. Angew. Chem. Int. Ed. 2019; 58: 1509
• 13 Lee J, Torker S, Hoveyda AH. Angew. Chem. Int. Ed. 2017; 56: 821
• 14a Kim M, Park B, Shin M, Kim S, Kim J, Baik M.-H, Cho SH. J. Am. Chem. Soc. 2021; 143: 1069
• 14b Lee Y, Han S, Cho SH. Acc. Chem. Res. 2021; 54: 3917
• 14c Kim M, Kim G, Kim D, Cho SH. J. Am. Chem. Soc. 2024; 146: 34861
• 15a Harrington-Frost N, Leuser H, Calaza MI, Kneisel FF, Knochel P. Org. Lett. 2003; 5: 2111
• 15b Soorukram D, Knochel P. Org. Lett. 2004; 6: 2409
• 16 Hong K, Liu X, Morken JP. J. Am. Chem. Soc. 2014; 136: 10581
• 17a Osato H, Jones IL, Chen A, Chai CL. L. Org. Lett. 2010; 12: 60
• 17b Usami Y, Takaoka I, Ichikawa H, Horibe Y, Tomiyama S, Ohtsuka M, Imanishi Y, Arimoto M. J. Org. Chem. 2007; 72: 6127
• 18a Ito H, Kunii S, Sawamura M. Nat. Chem. 2010; 2: 972
• 18b Shintani R. Synthesis 2016; 48: 1087
• 19 Guzman-Martinez A, Hoveyda AH. J. Am. Chem. Soc. 2010; 132: 10634
• 20a Hornillos V, Pérez M, Fañanás-Mastral M, Feringa BL. J. Am. Chem. Soc. 2013; 135: 2140
• 20b Li J, Huang J, Wang Y, Liu Y, Zhu Y, You H, Chen F.-E. Chem. Sci. 2024; 15: 8280
• 21a Miralles N, Maza RJ, Fernández E. Adv. Synth. Catal. 2018; 360: 1306
• 21b Yamanaka M, Kato S, Nakamura E. J. Am. Chem. Soc. 2004; 126: 6287
• 21c Yoshikai N, Zhang S.-L, Nakamura E. J. Am. Chem. Soc. 2008; 130: 12862