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

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 (1S)-(+)-ketopinic acid and (1S)-(+)-10-camphorsulfonic acid. The structures of the diamines are all based on thed-(+)-camphor scaffold and feature isomeric diversity in terms of regioisomeric attachment of the primary and the tertiary amine function and theexo/endo-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) totrans-beta-nitrostyrene. The highest enantioselectivity was achieved in the reaction with acetylacetone as nucleophile usingendo-1,3-diamine derived catalyst52(91.5:8.5 er). All new organocatalysts48-63have been fully characterized. The structures and the absolute configurations of eight intermediates and thiourea derivative52were also determined by X-ray diffraction.