Building Up Quaternary Stereocenters Through Biocatalyzed Direct Insertion of Carbon Nucleophiles on Ketones

Quaternary stereocenters are privileged structural motifs, widely distributed in natural products and in pharmaceutically active compounds. Asymmetric methods for the efficient construction of these prominent frameworks are rapidly increasing. Biocatalysis represents an alternative to the existing methods of using hazardous metals and chemicals. Enzymes discussed in this mini‐review involve thiamine‐bisphosphate (ThDP)‐dependent lyases, aldolases and hydroxynitrile lyases. The chiral products, (α‐alkyl‐α‐hydroxy ketones, α‐alkyl‐α‐hydroxy‐β‐diketones, β‐hydroxy ketones, ketone cyanohydrins) obtained by these enzymes, are valuable intermediates suitable for further transformations affording a variety of multi‐functionalized useful building blocks bearing a tetrasubstituted stereocenter, such as amino alcohols, diols, α‐hydroxy carboxylic acids, β‐hydroxy‐α‐amino acids to cite only a few.