A multi-component catalytic assembly reaction for the synthesis of nitrogen-containing heterocycles and Umpolung transformations of aldehydes and acylsilanes

A catalytic, multi-component coupling reaction for the synthesis of nitrogen-containing heterocycles has been developed. The reaction of an imine, alpha-diazoester and unsaturated coupling partner in the presence of a copper(I) or rhodium(II) transition metal catalyst with excellent diastereoselectivities and high yields. The transition metal-catalyzed decomposition of a diazo compound in the presence of an imine generates a transient azomethine ylide that undergoes addition with various dipolarophiles in a convergent manner to substituted pyrrolidine and 3-pyrroline heterocycles.; In addition to examining the general scope of the multi-component reaction, modification of the dipolarophile allowed access to more structurally complex 3,3'-pyrroldinyl spirooxindoles. Substitution of the alpha-diazoester with diazoacetonitrile allowed access to 1,2-diarylpyrroles.; Umpolung reactions involving acylsilanes and aldehydes have also been developed. Acylsilanes treated sequentially with alpha-lithio diazoacetates followed by alkyl halides lead to substituted beta-ketoesters in a single-flask, multi-component operation. The treatment of aryl acylsilanes with tosylmethyl isocyanide (TosMIC) leads to the formation of 5-aryl-substituted oxazoles in excellent yield.; Two catalytic Umpolung reactions of aldehydes were also developed. Using an azolium salt as a precursor to a N-heterocylic carbene (NHC) catalyst, a mechanistic investigation into the nucleophilic acylation of 2-chlorooxazoles was conducted. Finally, investigations into a reaction using a 2,3-epoxyalcohol as a starting material, a tandem oxidation mediated bis-acetoxyiodosobenzene (BAIB) with catalytic TEMPO followed by NHC-catalyzed esterification leading to acetate aldol-products is reported.