Synthesis of alpha-keto-imides via oxidation of ynamides.

A de novo preparation of alpha-keto-imides via ynamide oxidation is described. With a number of alkyne oxidation conditions screened, a highly efficient RuO2-NaIO4 mediated oxidation and a DMDO oxidation have been identified to tolerate a wide range of ynamide types. In addition to accessing a wide variety of alpha-keto-imides, the RuO2-NaIO4 protocol provides a novel entry to the vicinal tricarbonyl motif via oxidation of push-pull ynamides, and imido acylsilanes from silyl-substituted ynamides. Chemoselective oxidation of ynamides containing olefins can be achieved by using DMDO, while the RuO2-NaIO4 protocol is not effective. These studies provide further support for the synthetic utility of ynamides.

A sequential metal-catalyzed C-N bond formation in the synthesis of 2-amido-indoles.

A sequential metal-catalyzed C-N bond formation employing ortho-haloaryl acetylenic bromides is described. The initial amidation is highly selective for C (sp)-N bond formation, leading to o-haloaryl-substituted ynamides that can be useful building blocks, while the overall sequence provides a facile construction of 2-amido-indoles.

A rhodium(I)-catalyzed demethylation-cyclization of o-anisole-substituted ynamides in the synthesis of chiral 2-amido benzofurans.

A Rh(I)-catalyzed demethylation-cyclization sequence for a direct transformation of o-anisole-substituted ynamides to benzofurans is described here. The Ag salt functions synergistically with Rh(I) for the key demethylation step.