We report the first highly diastereo-and enantioselective C-C bond-forming reaction of racemic α-branched ketones to construct tertiary alcohols with adjacent stereocenters.Accordingly,a highly stereoselective cyanos...We report the first highly diastereo-and enantioselective C-C bond-forming reaction of racemic α-branched ketones to construct tertiary alcohols with adjacent stereocenters.Accordingly,a highly stereoselective cyanosilylation of racemic ketones is developed using our bifunctional cyanating reagent,Me_(2)(CH_(2)Cl)SiCN,giving C^(α)-tetrasubstituted silyl cyanohydrins withtwovicinal stereocenters inupto>20:1 diastereomeric ratio(dr)and 90-98% enantiomeric excess(ee)values,which can undergo various diversification reactions bymanipulating the chloromethyl group.A highly selective kinetic resolution of acyclicα-branched ketones is also developed that allows facile access to acyclic α-alkyl,allyl,and propargyl ketones with good recovery and excellent ee values.The synthetic value of this protocol is further demonstrated by the formal synthesis of the anti-obesity agent,taranabant(MK-0364).The activation of Jacobsen’s privileged catalyst(salen)AlCl by a suitable phosphorane plays a crucial role in the reaction.X-ray crystallographic analysis of single crystals of phosphorane-(salen)AlCl complexes and theoretical calculations help provide a working model.The present transformation opens a new path for the catalytic stereoselective synthesis of stereochemically complex tertiary alcohols featuring two stereocenters(adjacent or not)from racemic ketones.展开更多
基金supported by the National Natural Science Foundation of China(grant no.21725203)the Ministry of Education(PCSIRT)The Fundamental Research Funds for the Central Universities is highly appreciated.
文摘We report the first highly diastereo-and enantioselective C-C bond-forming reaction of racemic α-branched ketones to construct tertiary alcohols with adjacent stereocenters.Accordingly,a highly stereoselective cyanosilylation of racemic ketones is developed using our bifunctional cyanating reagent,Me_(2)(CH_(2)Cl)SiCN,giving C^(α)-tetrasubstituted silyl cyanohydrins withtwovicinal stereocenters inupto>20:1 diastereomeric ratio(dr)and 90-98% enantiomeric excess(ee)values,which can undergo various diversification reactions bymanipulating the chloromethyl group.A highly selective kinetic resolution of acyclicα-branched ketones is also developed that allows facile access to acyclic α-alkyl,allyl,and propargyl ketones with good recovery and excellent ee values.The synthetic value of this protocol is further demonstrated by the formal synthesis of the anti-obesity agent,taranabant(MK-0364).The activation of Jacobsen’s privileged catalyst(salen)AlCl by a suitable phosphorane plays a crucial role in the reaction.X-ray crystallographic analysis of single crystals of phosphorane-(salen)AlCl complexes and theoretical calculations help provide a working model.The present transformation opens a new path for the catalytic stereoselective synthesis of stereochemically complex tertiary alcohols featuring two stereocenters(adjacent or not)from racemic ketones.
