Acids to acids: A practical method for the preparation of highly valuable enantiomerically pure α-amino acids has been developed. The described transformation rapidly converts feedstock alkyl carboxylic acids to α-amino acids, and is enabled by innate radical cross-coupling with a chiral imine radical acceptor. The scope of this transformation is broad and has been field-tested in three different industrial medicinal chemistry laboratories.

Abstract

The direct union of primary, secondary, and tertiary carboxylic acids with a chiral glyoxylate-derived sulfinimine provides rapid access into a variety of enantiomerically pure α-amino acids (>85 examples). Characterized by operational simplicity, this radical-based reaction enables the modular assembly of exotic α-amino acids, including both unprecedented structures and those of established industrial value. The described method performs well in high-throughput library synthesis, and has already been implemented in three distinct medicinal chemistry campaigns.

Supporting Information

References

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Volume57, Issue44

Special Issue:150th Anniversary of the Technical University of Munich

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A General Amino Acid Synthesis Enabled by Innate Radical Cross-Coupling

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