Lewis Base-Catalyzed Enantioselective Conjugate Reduction of β,β-Disubstituted α,β-Unsaturated Ketones with Trichlorosilane: E/Z‑Isomerization, Regioselectivity, and Synthetic Applications

• Published in: Journal of organic chemistry 2019-09, Vol.84 (18), p.11458-11473
• Main Authors: Sugiura, Masaharu, Ashikari, Yasuhiko, Takahashi, Yuka, Yamaguchi, Koki, Kotani, Shunsuke, Nakajima, Makoto
• Format: Article
• Language: English
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/acs.joc.9b01298

The chiral bisphosphine dioxide-catalyzed asymmetric conjugate reduction of acyclic β,β-disubstituted α,β-unsaturated ketones with trichlorosilane affords saturated ketones having a stereogenic carbon center at the carbonyl β-position with high enantioselectivities. Because the E/Z-isomerizations of enone substrates occur concomitantly, reduction products with the same absolute configurations are obtained from either (E)- or (Z)-enones. Conjugate reduction is accelerated in the presence of an electron-rich aryl group at the β-position of the enone owing to its carbocation-stabilizing ability. Computational studies were also conducted in order to elucidate the origin of the observed enantioselectivity. The regio- and enantioselective reductions of dienones were realized and applied to the syntheses of ar-turmerone, turmeronol A, mutisianthol, and jungianol, which are optically active sesquiterpenes.