Chiral Tert-Butanesulfinamide Chelated With Metals To Construct Novel Chiral Centers And Its Applications

The great demand in life science,especially in the field of medicinal drugs,has helped boost the preparation of chiral compounds.Among these compounds,it is universally recognized that chiral,enantiomerically pure sulfoxide derivatives,including sulfoxides,sulfinamides and sulfoximines are used as powerful chiral auxiliaries and chiral ligands in asymmetric synthesis.In recent years,significant progress has been made on the generation of new chiral centers with the strategy of chiral tert-butanesulfinamide derivatives chelated with different metals,the main group metals and the transition metals.As a result,the past decades have seen a number of researches.However,some aspects haven't been fully explored,such as:(a)chiral tert-butanesulfinamide as inner ligand to chelate with alkali metals for the construction of quaternary chiral carbons;(b)chiral tert-butanesulfinamide as inner ligand to chelate with transition metals(e.g.Rh,Pd)to achieve intra-and inter-molecular decarboxylative allylation,the construction of quaternary chiral carbons in particular;(c)Chiral tert-butanesulfinamide chiral used for the chirality control in radical reactions(e.g.,radical aminotrifluoromethylation of alkenes).The dissertation is made up of seven parts.The first chapter is review,which highlights the most relevant contributions of the generation of new chiral centers in virtue of chiral tert-butanesulfinamide derivatives chelated with different metals,including the main group metals and the transition metals.The second chapter interprets NaHMDS-promoted diastereoselective alkylation for the construction of quaternary chiral centers of chiral sulfinimines.Besides,various oxycarbonyls and acyls were employed as electron-withdrawing directing groups.Against the standard condition,the products,which bear various substitutions,were obtained with high yields as well as high regionselectivities and diastereoselectivities.Furthermore,either the directing group(Allyl group)or chiral auxiliary could be cleaved under the optimized conditions.This synthetic strategy also exerts a profitable role in producing imine and ketone scaffolds with?-quaternary chiral carbons in diastereomeric or enantiomeric pure form.The third chapter offers the investigation on the synthesis of a series of novel cyclic?-amino acids,which bear?-quaternary stereocenters.A range of cyclic?-amino acid hydrochlorides have been successfully achieved with high yields.This method could be easily scaled up for achieving chiral?-amino acids,which makes them potentially beneficial for chemical or pharmaceutical manufacture.The fourth chapter explains diastereoselective Rh-catalyzed intramolecular decarboxylative allylation for the construction of quaternary chiral centers at the?-position of chiral sulfinimines,which has been achieved firstly.The process was efficiently catalyzed by the commercially available and achiral Rh catalyst(Wilkinson's catalyst)in a mild condition.Meanwhile,diastereoselective Pd-catalyzed intramolecular allylation has also been achieved.The plausible mechanism gives explanation to the sulfinimine group which plays a significant role via the formation of intramolecular Rh or Pd complexs.The fifth chapter,Rh-and Pd-catalyzed intermolecular allylic alkylation to form?-quaternary stereocenters of cyclic-sulfinimines has been achieved as complements to Rh-and Pd-catalyzed intramolecular allylic alkylation reactions.Rh-catalyzed intermolecular allylic alkylation harbors a crucial feature that only unusual linear-type products are obtained with great efficacy under the effective chiral tert-butanesulfinamide group.The sixth chapter demonstrates CuI/L-proline catalytic highly diastereoselective radical aminotrifluoromethylation of alkenyl sulfinamides.This synthetic strategy provides a straightforward access to CF₃-containing aziridines which bear a?-tertiary and?-quarternary stereocenters with good chemical yield and high diastereoselectivity.This method also featured by excellent functional group tolerance.In addition,the mechanism was extensively studied by DFT calculations,which not merely introduces Cu(I)/L-proline as catalytic system to construct an intramolecular intermediate Cu^IIIspecies,but also employs sulfinamide as both directing group and nucleophile.Finally,the last chapter summarizes the whole dissertation.