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 wide array of new N-acyl thiazinanethiones are employed in a number of direct and enantioselective carbon-carbon bond forming reactions catalyzed by nickel(II) complexes. The electrophilic species are mostly prepared in situ from ortho esters, methyl ethers, acetals, and ketals, which makes the overall process highly efficient and experimentally straightforward. Theoretical calculations indicate that the reactions proceed through an open transition state in a S N 1-like mechanism. The utility of this novel procedure has been demonstrated by the asymmetric preparation of synthetically useful intermediates and the total synthesis of peperomin D.

A concise synthesis of the C9-C19 fragment of peloruside A that is both highly stereoselective and efficient is described. Achieving an overall yield of 23% over 14 steps, this synthesis not only is high yielding but also involves four chromatography steps. This approach is based on the addition of metal enolates of chiral auxiliary scaffolds generated by either catalytic or stoichiometric amounts of nickel(II) or titanium(IV) Lewis acids.

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.

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