Enantioselective synthesis of gabapentin analogues via organocatalytic asymmetric Michael addition of α-branched aldehydes to β-nitroacrylates??

Organic & Biomolecular Chemistry Pub Date: 2012-05-16 DOI: 10.1039/C2OB25413A

Abstract

Michael addition reaction of α-branched aldehydes to β-nitroacrylates was successfully carried out by using a mixed catalyst consisting of a primary amino acid, L-phenylalanine, and its lithium salt to give β-formyl-β′-nitroesters having a quaternary carbon centre in good yields (up to 85%) with high enantioselectivity (up to 98% ee). By using benzyl β-nitroacrylates as Michael acceptors, the obtained β-formyl-β′-nitroesters were converted into various 4,4-disubstituted pyrrolidine-3-carboxylic acids including analogues of gabapentin (Neurotin?) in one step from the Michael adducts in high yields.

Graphical abstract: Enantioselective synthesis of gabapentin analogues via organocatalytic asymmetric Michael addition of α-branched aldehydes to β-nitroacrylates
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