865692-67-7Relevant academic research and scientific papers
Regioselectivity of Michael additions to 3-(pyridin-3-yl or pyrimidin-2-yl)-propenoates and their N-oxides - Experimental and theoretical studies
Lewandowska, Elzbieta,Chatfield, David C.
, p. 3297 - 3303 (2005)
We demonstrate that nucleophilic addition to α,β-unsaturated carbonyl compounds can be redirected from the usual β-carbon (Michael) to an α-carbon regioselectivity by attaching a π-deficient aromatic substituent to the β-carbon atom. In particular, propanethiol addition to 3-(pyridin-3-yl or pyrimidin-2-yl)propenoate gives a β-carbon adduct, while addition to the corresponding more π-deficient N-oxides gives the α-adduct or a mixture of α- and β-adducts. This adds to the number of carbon-carbon bond-forming reactions at the α-position of Michael receptors documented recently. Density functional calculations reveal that the regioselectivity is due to a combination of reduction of the barrier for α-addition and increase of the barriers for β-addition and carbonyl addition as the π-deficient character of the aromatic substituent is increased. The calculations predict a significant solvent effect on the regioselectivity in some cases. The regioselectivity is also consistent with Hammett constants σ-. Wiley-VCH Verlag GmbH & Co. KGaA, 2005.
