Tandem aza-Heck Suzuki and carbonylation reactions of O-phenyl hydroxamic ethers: complex lactams via carboamination.

The palladium-catalysed tandem aza-Heck-Suzuki and aza-Heck-carbonylation reactions of O-phenyl hydroxamic ethers are reported. These formal alkene carboamination reactions provide highly versatile access to wide range complex, stereogenic secondary lactams and exhibit outstanding functional group tolerance and high diastereoselectivity.

Synthesis of N-H Bearing Imidazolidinones and Dihydroimidazolones Using Aza-Heck Cyclizations.

The synthesis of unsaturated, unprotected imidazolidinones via an aza-Heck reaction is described. This palladium-catalyzed process allows for the cyclization of N-phenoxy ureas onto pendant alkenes. The reaction has broad functional group tolerance, can be applied to complex ring topologies, and can be used to directly prepare mono- and bis-unprotected imidazolidinones. By addition of Bu4 NI, dihydroimidazolones can be accessed from the same starting materials. Improved conditions for preparing unsaturated, unprotected lactams are also reported.

Synthesis of Secondary Unsaturated Lactams via an Aza-Heck Reaction.

The preparation of unsaturated secondary lactams via the palladium-catalyzed cyclization of O-phenyl hydroxamates onto a pendent alkene is reported. This method provides rapid access to a broad range of lactams that are widely useful building blocks in alkaloid synthesis. Mechanistic studies support an aza-Heck-type pathway.

The discovery and structure-activity relationships of indole-based inhibitors of glutamate carboxypeptidase II.

A series of N-substituted 3-(2-mercaptoethyl)-1H-indole-2-carboxylic acids were synthesized as inhibitors of glutamate carboxypeptidase II (GCPII). Those containing carboxybenzyl or carboxyphenyl groups at the N-position exhibited potent inhibitory activity against GCPII. These indole-based compounds represent the first example of achiral GCPII inhibitors and demonstrate greater tolerance of the GCPII active site for ligands with significant structural difference from the endogenous substrate, N-acetyl-aspartylglutamate.