Diastereoselective synthesis of trans-3,5-disubstituted dihydrofuran-2(3H)-ones via SmI sub(2)-mediated reductive coupling of 2-alkylacrylates of N,N-diisopropyl-2-hydroxybenzamide with aldehydes

• Published in: Tetrahedron 2016-02, Vol.72 (5), p.664-673
• Main Authors: Lai, Yecai, Sun, Lijie, Sit, Man Ki, Wang, Yan, Dai, Wei-Min
• Format: Article
• Language: English
• Subjects: Acrylates; Aldehydes; Aliphatic compounds; Carbonyls; Conjugates; Joining; Reduction; Synthesis
• ISSN: 0040-4020
• DOI: 10.1016/j.tet.2015.12.009

Samarium(II) diiodide has been used to mediate reductive coupling reactions of aldehydes with a variety of substituted acrylates, in both achiral and chiral forms, for accessing substituted dihydrofuran-2(3H)-ones ( gamma -butyrolactones). Two major issues, concerning with self-dimerization of alpha -non-branched aliphatic aldehydes and low diastereoselectivity of the products, render limited application of the reductive coupling protocol in total synthesis of natural products. We report here on a novel type of substituted acrylates derived from the 2-amido arenols (HO-Ar super(am)) such as N,N-diisopropyl-2-hydroxybenzamide. The acrylates of HO-Ar super(am) enable: (a) preferential conjugate reduction of the acrylates than carbonyl reduction of aliphatic aldehydes, leading to diminished aldehyde self-dimerization; and (b) organization of an eight-membered ring among the amide carbonyl oxygen atom and samarium(III) to form a 7/8-bicyclic transition state, resulting in highly diastereoselective protonation of the samarium(III) enolate intermediate. Examples of synthesis of trans-3,5-disubstituted dihydrofuran-2(3H)-ones from 2-alkylacrylates of HO-Ar super(am) and aliphatic aldehydes are provided.