Chemo-, regio-, and diastereoselectivity preferences in the reaction of a sulfur ylide with a dienal and an enone?

Organic & Biomolecular Chemistry Pub Date: 2011-01-21 DOI: 10.1039/C0OB00675K

Abstract

Mechanistic insights into an interesting class of reaction between sulfur ylides with (i) a dienal, and (ii) an enone, obtained by using density functional theory, is reported. The kinetic and thermodynamic factors responsible for chemo-, regio-, and diastereoselectivities are established by identifying all key transition states and intermediates along the reaction pathway for 1,2-, 1,4-, and 1,6- modes of attack of dimethylsulfonium benzylide to 5-phenylpenta-2,4-dienal. The reaction profiles for 1,2- and 1,4- modes of addition are also evaluated for the reaction between dimethylsulfonium benzylide and pent-3-en-2-one. Our results show that the final outcome of the reaction with both these substrates would be decided by the interplay between kinetic and thermodynamic factors. It is found that the addition of a semi-stabilized ylide to conjugated carbonyl compounds prefers to proceed through a 1,4- (conjugate) pathway under thermodynamic conditions, which is in accordance with the available experimental reports. However, the formation of epoxidesvia a 1,2- (direct) addition pathway is computed to be equally competitive, which could be the favored pathway under kinetic conditions. Even though the lower barrier for the initial addition step is kinetically advantageous for the direct (or 1,2-) addition pathway, the higher energy of the betaine intermediates—as well as the reversibility of the accompanying elementary step—may disfavor product formation in this route. Thus, high diastereoselectivity in favor of 2,3-trans cyclopropanecarbaldehyde is predicted in the case of the dienal, using the most favored conjugate addition (1,4-addition) pathway. Along similar lines, ylide addition to the enone is identified to exhibit a preference toward conjugate addition over direct (1,2-) addition. The importance of transition state analysis in delineating the controlling factors towards product distribution and diastereoselectivity is established.

Graphical abstract: Chemo-, regio-, and diastereoselectivity preferences in the reaction of a sulfur ylide with a dienal and an enone
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