Stereodivergent Synthesis of Camphor-Derived Diamines and Their Application as Thiourea Organocatalysts

摘要

A series of 18 regio- and stereo-chemically diverse chiral non-racemic 1,2-, 1,3-, and 1,4-diamines have been synthesized from commercial (1 )-(+)-ketopinic acid and (1 )-(+)-10-camphorsulfonic acid. The structures of the diamines are all based on the -(+)-camphor scaffold and feature isomeric diversity in terms of regioisomeric attachment of the primary and the tertiary amine function and the -isomerism. Diamines were transformed into the corresponding noncovalent bifunctional thiourea organocatalysts, which have been evaluated for catalytic activity in the conjugative addition of 1,3-dicarbonyl nucleophiles (dimethyl malonate, acetylacetone, and dibenzoylmethane) to -β-nitrostyrene. The highest enantioselectivity was achieved in the reaction with acetylacetone as nucleophile using -1,3-diamine derived catalyst (91.5:8.5 er). All new organocatalysts – have been fully characterized. The structures and the absolute configurations of eight intermediates and thiourea derivative were also determined by X-ray diffraction.