Use of (NHC)Pd(η³-allyl)Cl (NHC =N-Heterocyclic Carbene) in a Palladium-mediated Approach toCryptocaryaAlkaloids

Abstract

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(h 3 -allyl)Cl (NHC = Nheterocyclic 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.

FeCl2/TBAC efficiently catalyzes domino coupling reactions for constructing indoline-fused tetrahydroisoquinolines

“…Tetracyclic indoline-fused tetrahydroisoquinoline is an important module structure for the synthesis of some natural products and related alkaloids. 1–10 Some synthesis protocols have been reported for intramolecular coupling of aryl halides with amines, 11–15 cascade electrocyclic reactions, 16 or N -aziridinyl imines, 17 which have been summarized in our previous report. 18 However, these methods seriously suffered from quite complex catalysts and expensive precursors.…”