Enantioselective radical addition reactions

Abstract

During the past decade, enantioselective radical reactions have been investigated with great interest. Among the various reaction types, conjugate radical addition to $\alpha - \beta$ unsaturated carbonyl compounds has attracted a great deal of attention because of its synthetic utility. A majority of these reactions utilizes carboxylic acid derivatives. To carry out these reactions one needs the use of an achiral template such as alkylidene malonates, Evans’ oxazolidinones, and the imide group. To extend the scope of achiral template in radical conjugate addition reactions, we have introduced $\alpha$’-hydroxy enone and $\alpha$’-phosphoric enone for the construction of new stereogenic carbon centers. Both templates were successively applied to make new chiral compounds in good yields and enantioselectivities. In case of $\alpha$’-phosphoric enone, two adjacent carbon centers were created at once using allyltributyltin reagent with high diastereo- and enantioseletivities. Despite of stunning progresses in organocatayst, only a few radical reactions were reported using organocatalyst in asymmetric radical chemistry. Among the widely used organocatalysts, a chiral phosphoric acid and phosphoramide were tolerable during radical reactions. 2,4,6-$iPr_3Ph$ substituted binol derived phosphoramide catalyst gave the best result as high as 84% ee in enantioselective radical addition reactions to 4-biphenyl substitued imine. Both electro-withdrawing and donating substituents and the usage of $2^o$ and $3^o$ radical sources didn`t influence the selectivities.