ENANTIOSELECTIVE SYNTHESIS OF ALLYL-AMINES, PROPARGYL-AMINES, AND 4-EN-2-YNYL-AMINES VIA 1,2-ADDITION OF ORGANOCERIUM REAGENTS TO CHIRAL ALDEHYDE IMINES

(E)- and (Z)-Allyl-, propargyl-, and 4-en-2-ynyl-amines 5 and 14, useful bifunctional building blocks and of pharmaceutical interest, are synthesized in high enantiomeric purity(e.e. greater than or equal to 97%). Key step is the diastereoselective 1,2-addition (d.e. 86 to greater than or equal to 98%) of organocerium reagents to chiral alpha,beta-unsaturated aldehyde imines 3 or 8 to produce adduct amines 4 and 9 (Schemes 1 and 4, resp.). The propargylamine 9 is a substrate for Pd-catalyzed coupling with alkenyl halides to produce the enynylamine 11a and the thienyl-substituted alkynylamine 11b. The chiral auxiliary (S,S)-2 is removed from 4 and 11 in 3 steps affording the title compounds 5 and 14. Diastereoisomer enrichment of the hydrochloride of 6 by crystallization is possible.