Control of Remote Stereochemistry in the Synthesis of Spirocyclic Oxindoles: Vinylogous Organocascade Catalysis

摘要

Cascade reactions are powerful tools for rapidly achieving molecular complexity since multiple chemical bonds are formed in a single synthetic operation. Their recent marriage to asymmetric organocatalysis has led to highly innovative techniques, which are now recognized as reliable strategies for the one-step enantioselective synthesis of stereochemically dense molecules.To fully harness the synthetic power of organocascade catalysis, it was crucial to identify the iminium ion/enamine activation sequence as an enabling approach to highly efficient domino reactions (Scheme 1 a).The strategy is based on the conjugated addition of a nucleophile to α,β-unsaturated aldehydes or ketones and subsequent a functionalization of the resulting saturated carbonyls. In this well-defined sequence, the chiral amine catalyst has an active role in both steps, initially forming the activated iminium ion species (not shown in Scheme 1 a) and later the electron-rich enamine intermediate. The strategy has been extensively applied by the synthetic community to access α- and β-functionalized carbonyl chiral building blocks.