A catalytic, multi-component coupling reaction for the synthesis of nitrogen-containing heterocycles has been developed, via the reaction of an imine, α-diazoester and unsaturated coupling partner in the presence of a copper(I) or rhodium(II) transition metal catalyst with excellent diastereo-selectivities 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 α-diazoester with diazoacetonitrile allowed access to 1,2-diarylpyrroles. Umpolung reactions involving acylsilanes and aldehydes have also been developed. Acylsilanes treated sequentially with α-lithio diazoacetates followed by alkyl halides lead to substituted β-ketoesters in a single-flask, to substituted β-ketoesters in a single-flask, multi-component operation. The treatment of aryl acylsilanes with tosylmethyl isocyanide (TosMIC) leads to the formation of 5-arylsubstituted 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.

Last modified

• 06/01/2018

Creator

• Chris Galliford

DOI

• https://doi.org/10.21985/N2CX1M

Subject

• Chemistry

Keyword

• Chemistry
• Organic

Date created

• 2007-05-11

Resource type

• Dissertation

Rights statement

• In Copyright