Synthetic approaches to the alkaloids of the ancistrocladaceae. Part 3. The total synthesis of (-)-ancistrocladinine: Control of the diastereoisomer excess in the synthesis of axially chiral biaryls

Abstract

The total synthesis of the naphthylisoquinoline alkaloid (-)-ancistrocladinine[(-)-(S,3S)-6-hydroxy-5-(4,5-dimethoxy-2-methyl-1-naphthyl) -8-methoxy-3,4-dihydro-1,3-dimethylisoquinoline] is described. The key step was the construction of the disymmetric biaryl linkage by a coupling between the Grignard reagent derived from 2-(3-benzyloxy-2-bromo-5-methoxyphenyl)-1,3- dioxane and (+)-(4S,5S)-4-methoxymethyl-5-phenyl-2-(1,4,5-trimethoxy-2-naphthyl) -4,5-dihydroxazole. The reactions between the last-mentioned compound and a variety of 2,6-disubstituted phenyl Grignard reagents have been investigated and an attempt has been made to delineate the factors which control the diastereoisomeric excess..