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A novel biocatalytic system to access a wide variety of β-hydroxydioxinones from β-ketodioxinones employing commercial engineered ketoreductases has been developed. This practical system provides a remarkably straightforward solution to limitations in accessing certain chemical scaffolds common in β-hydroxydioxinones that are of great interest due to their diversification capabilities. A few highlights of this system are that it is high yielding, highly enantioselective, and chromatography-free. We have demonstrated both a wide substrate scope and a high degree of scalability.

We report a concise, enantioselective synthesis of the yohimbine alkaloids (−)-rauwolscine and (−)-alloyohimbane. The key transformation involves a highly enantio-and diastereoselective NHC-catalyzed dimerization and an amidation/N-acyliminium ion cyclization sequence to furnish four of the five requisite rings and three of the five stereocenters in two operations. This route also provides efficient access to all four diastereomeric arrangements of the core stereotriad of the yohimbine alkaloids from a common intermediate. This platform approach in combination with the ability to access both enantiomers from the carbene-catalyzed reaction is a powerful strategy that can produce a wide range of complex alkaloids and related structures for future biomedical investigations.

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