Use of (NHC)Pd(eta(3)-allyl)Cl (NHC = N-heterocyclic carbene) in a palladium-mediated approach to Cryptocarya alkaloids

The palladium-mediated intramolecular aryl amination of 7-benzyloxy-1-(2-bromo-4,5-dimethoxy-benzyl)-1,2,3,4-tetrahydro-6-methoxy-isoquinoline catalyzed by a recently discovered, air and moisture stable (NHC)Pd(eta(3)-allyl)Cl (NHC = N-heterocyclic carbene) complex provides 2-benzyloxy-5,6,12,12a-tetrahydro-3,9,10-trime-thoxydibenz-[b,g]-indolizine in high yield. Effects of the solvent, the catalyst loading and the nature of the NHC-ancilliary ligand on the efficacy of the reaction were examined. Using identical conditions 7-benzyloxy-1-(2-chloro-4,5-methylendioxybenzyl)-1,2,3,4-tetrahydro-6-methoxyisoquinoline leads to 2-benzyloxy-5,6-12,12a-tetrahydro-3-methoxy-9,10-methylendioxydibenz-[b,g]-indolizine, also in high yield. Use of the catalytic intramolecular aryl amination step allows for the straightforward synthesis of the alkaloids rac-cryptaustoline and rac-cryptowoline.