A direct and asymmetric aldol reaction of N-acyl thiazinanethiones with aromatic aldehydes catalyzed by chiral nickel(II) complexes is reported. The reaction gives the corresponding O-TIPS-protected anti-aldol adducts in high yields and with remarkable stereocontrol and atom economy. Furthermore, the straightforward removal of the achiral scaffold provides enantiomerically pure intermediates of synthetic interest, which involve precursors for anti-a-aminob-hydroxy and a,b-dihydroxy carboxylic derivatives. Theoretical calculations explain the observed high stereocontrol.Scheme 1. Direct and enantioselective carbon-carbon bond-forming reactions from carbonylic compounds.

A direct and asymmetric triisopropylsilyltrifluoromethanesulfonate (TIPSOTf) mediated aldol reaction of N‐azidoacetyl‐1,3‐thiazolidine‐2‐thione with aromatic aldehydes catalyzed by a chiral nickel(II)‐Tol‐BINAP complex has been developed (BINAP=2,2’‐bis(diphenylphosphino)‐1,1’‐binaphthyl). The catalytic protocol gives the corresponding anti α‐azido‐β‐silyloxy adducts with outstanding stereocontrol and in high yields. Theoretical calculations account for the stereochemical outcome of the reaction and lay the foundations for a mechanistic model. In turn, the easy removal of the thiazolidinethione yields a wide array of enantiomerically pure derivatives in a straightforward and efficient manner. Such a noteworthy character of the heterocyclic scaffold together with the appropriate manipulation of the azido group open a new route to the synthesis of di‐ and tripeptide blocks containing a β‐aryl‐β‐hydroxy‐α‐amino acid.

A direct and asymmetric aldol reaction of N-acyl thiazinanethiones with aromatic aldehydes catalyzed by chiral nickel(II) complexes is reported. The reaction gives the corresponding O-TIPS-protected anti-aldol adducts in high yields and with remarkable stereocontrol and atom economy. Furthermore, the straightforward removal of the achiral scaffold provides enantiomerically pure intermediates of synthetic interest, which involve precursors for anti-a-aminob-hydroxy and a,b-dihydroxy carboxylic derivatives. Theoretical calculations explain the observed high stereocontrol.Scheme 1. Direct and enantioselective carbon-carbon bond-forming reactions from carbonylic compounds.

A direct and highly enantioselective reaction of N‐azidoacetyl‐1,3‐thiazolidine‐2‐thione with trimethyl orthoformate catalyzed by Tol‐BINAPNiCl2 in the presence of TESOTf and 2,6‐lutidine is reported. The heterocyclic scaffold can be easily removed by addition of a wide array of amines to give the corresponding enantiomerically pure 2‐azido‐3,3‐dimethoxypropanamides in high yields. Appropriate manipulation of the N‐benzyl amide derivative provides an efficient access to the antiepileptic agent lacosamide through a new enantioselective C−C bond‐forming process. DFT computational studies uncover clues for the understanding of the remarkable stereocontrol of the addition of a nickel(II) enolate to a putative oxocarbenium intermediate from trimethyl orthoformate.