Enantioselective Protonation

Significance

Chiral bicyclic guanidine derivative 1 catalyzes a tandem process involving a conjugate addition followed by enantioselective protonation or deuteration. By using thiols as nucleophiles, this Brønsted base catalyzed methodology allows the preparation of enantioenriched d-cysteine analogues by subsequent deprotection of the products. High yields (82-99%) are reported alongside excellent enantioselectivities (er = 92:8 up to 97:3). The cleavage/formation of a bond containing H (or D) is involved in the rate-determining step as a small but significant kinetic isotope effect was found. Furthermore, a tandem conjugate addition-enantioselective protonation reaction of N-substituted itaconimides and secondary phosphine oxides as nucleophiles is reported.