Organocatalytic Conjugate Addition in Stereoselective Synthesis

Abstract

Conjugate addition is a privileged method in organic synthesis allowing for the formation of new CC bonds, molecules that can serve as valuable synthons for total synthesis. It is highly attractive thanks to the presence of at least one functional group on the Michael partners, a group that can be easily derivatized. In this field, organocatalyzed reactions have recently changed the way of thinking about synthetic approaches, notably, as soon as carbonyl groups are involved. As a result, numerous applications of organocatalytic Michael additions in natural product synthesis have emerged in the last few years.

Inter- and Intramolecular Annulation Strategies to a Cyclopentanone Building Block Containing an All-Carbon Quaternary Stereogenic Center

“…In order to optimize atom efficiency, we reverted to 1 equiv of 5 and added a catalytic quantity of 18-crown-6 to activate the enolate, which led to an increased yield without loss of diastereoselectivity (entry 7). In the literature it has been observed that adding crown ethers in catalytic quantities enhances the reactivity of enolates to alkylation by complexing the sodium ion . Optimum conditions were obtained by portionwise addition of sodium hydride to provide a low concentration of free base and afforded cyclopentane 7 in both excellent yield and selectivity (85%, 9:1 dr , entry 8).…”