Abstract

This article highlights our recent efforts toward developing the cascade reactions constructing the carbon-carbon and carbonheteroatom bond based on radical chemistry. The diethylzinc-promoted reaction of dehydroamino acid derivatives with acid anhydride or π-allyl palladium complex gave α,α-disubstituted amino acids via the radical and anionic carbon-carbon bond-forming process. This reaction was successfully expanded into the reductive transformation of N-phthaloyl dehydroalanine using Bu₃SnH and Pd(PPh₃)₄. The chiral Lewis acid-mediated cascade radical addition-cyclization-trapping reaction proceeded smoothly with good enantioselectivities by using hydroxamate ester functionality as a chiral Lewis acid-coordinating tether between two radical acceptors. This method was applied into cascade reaction involving the unfavorable polarity-mismatched addition of electrophilic perfluoroalkyl radicals to electron-deficient acceptors. Additionally, cascade sequence terminated by radical-radical coupling was also reported.

Keywords: Cascade reaction, radical reaction, palladium, chiral Lewis acid, cyclization, perfluoroalkyl radical