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 the d-(+)-camphor scaffold and feature isomeric diversity in terms of regioisomeric attachment of the primary and the tertiary amine function and the exo/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) to trans-β-nitrostyrene. The highest enantioselectivity was achieved in the reaction with acetylacetone as nucleophile using endo-1,3-diamine derived catalyst 52 (91.5:8.5 er). All new organocatalysts 48–63 have been fully characterized. The structures and the absolute configurations of eight intermediates and thiourea derivative 52 were also determined by X-ray diffraction.

Monoalkylation of aniline with trichloroacetimidate catalyzed by (±)-camphorsulfonic acid through an SN1 reaction based on dual hydrogen-bonding activation modes

Herein, the monoalkylation of anilines with trichloroacetimidates catalyzed by CSA was investigated theoretically, and it was found that the reaction occurred through an SN1 reaction involving the dual hydrogen-bonding activation modes.