Organocatalyzed Asymmetric Vinylogous Addition of Oxazole-2(3H)-thiones to α,β-Unsaturated Ketones: An Additive-Free Approach for Diversification of Heterocyclic Scaffold

Abstract

A straightforward organocatalyzed asymmetric addition of oxazole-2(3H)-thiones to α,β-unsaturated ketones is described. This additive-free Michael reaction in the presence of chiral cinchonine-derived primary amines as catalysts has proven to be highly effective for a wide range of cyclic and acyclic enones, leading to the Michael adducts in very good yields and excellent enantioselectivities. The absolute configuration (R) of compound 5j was unambiguously assigned by X-ray diffraction analysis. Furthermore, experimental and theoretical studies were performed and a mechanism is presented and discussed for this novel reaction.

The Vinylogous Michael Addition of 3‐Alkylidene‐2‐oxindoles to β,γ‐Unsaturated α‐Keto Esters by Bifunctional Cinchona Alkaloids

“…Over the last few years, research involving catalytic asymmetric direct vinylogous reactions have been growing rapidly A variety of vinylogous pronucleophiles such as butenolides, butyrolactams, coumarins, allyl alkyl/aryl ketones, 5‐alkyl‐4‐nitroisoxazoles, 3‐alkylidene oxindoles, α‐alkyl/arylidene pyrazolinones, 2‐allylazaarenes, β,γ‐unsaturated amides and esters, oxazole‐2‐thiones, N ‐2,2,2‐trifluoroethyl isatin ketimines, enals and enones, nitrones, and α,α‐dicyanoalkenes (Scheme ). have been explored for direct vinylogous Michael reaction.…”