Enantioconvergent Reactions

Since the foundational report from Noyori and co-workers describing the dynamic kinetic hydrogenation of β-keto esters, enantioconvergent reactions that proceed by addition to racemic, configurationally labile electrophiles have been recognized for their ability to furnish stereochemically complex alcohol building blocks. Because of their high acidity, which facilitates substrate enantiomerization, β-dicarbonyl derivatives have remained the factotum substrate in enantioconvergent alcohol syntheses and the majority of these reactions proceed via reduction to furnish secondary alcohols. In contrast, examples of enantioconvergent reactions employing less activated substrates are underexplored. Similarly, relatively few enantioconvergent additions proceed via carbon–carbon bond formation to furnish tertiary alcohol products.

In work published in Angewandte Chemie, International Edition, Blane Zavesky and Jeff Johnson from the Johnson Group, describe how the addition of terminal alkynes to racemic β-stereogenic α-keto esters was achieved in high levels of stereoselectivity, affording versatile tertiary propargylic alcohols containing two stereocenters. This environmentally benign enantioconvergent reaction proceeds with perfect atom economy, requires no solvent, and is catalyzed by a non-toxic zinc salt. The alkyne moiety can be leveraged in downstream transformations including hydrogenation to the corresponding saturated tertiary alcohol, which represents the product of a formal enantioconvergent aliphatic nucleophile addition. The substituted glycolate products can be converted into useful alkene and alkane products.

Studies aimed at the use of this reaction in the arena of total synthesis are ongoing.