1-Methoxy-2-[2-[(2-methoxyphenyl)-phenylphosphoryl]ethyl-phenylphosphoryl]benzene → 3-(4-Cyano-4-(3,4-dimethoxyphenyl)-5-methylhex-1-yl)-1,2,3,4-tetrahydro-6,7-dimethoxy-2-methylisoquinoline

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Reaction Conditions

Reaction Steps

is added to a solution of RhCl(Pφ3)3 in isopropanol at 3 atm, and the mixture heated at 50° C. for 4 hours. The product is purified to produce 3-[4-(3,4-dimethoxyphenyl)-4-isopropyl-4-cyanobutyl]-6,7-dimethoxy-N-methyl-1,2,3,4-tetrahydroisoquinoline (1). Alternatively, one may hydrogenate the double bond stereoselectively using a hydrogenation catalyst with an appropriate chiral ligand, for example, 1,2-bis[P-(2-methoxyphenyl)-P-phenylphosphinyl]ethane, usually abbreviated "DiPAMP." See Knowles, Acc. Chem. Res., 6, 106-112 (1983) and the references cited therein, incorporated herein by reference in full. Thus, for example, 3-[4-(3,4-dimethoxyphenyl)-4-isopropyl-4-cyanobutyl]-6,7-dimethoxy-N-methyl-1,2-dihydroisoquinoline (39) is added to a solution of Rh(DiPAMP)2 in isopropanol under 3 atm of H2, and the mixture heated at 50° C. for 4 hours. The product is purified to produce optically active 3-[4-(3,4-dimethoxyphenyl)-4-isopropyl-4-cyanobutyl]-6,7-dimethoxy-N-methyl-1,2,3,4-tetrahydroisoquinoline (1).

Provenance & Evidence