SYNTHESIS OF A TRANS-BENZO-[F]-HETERODECALIN BY CATALYTIC-HYDROGENATION - THE IMPORTANT PARAMETERS FOR HIGH STEREOSELECTIVITY AND CHEMOSELECTIVITY

Racemic trans-1A (trans-10-methoxy-1,3,4,4a,5, 10b-hexahydro-2H- [1]benzopyrano[ 3,4-b] pyridine, see Scheme 1) was obtained in high chemical yield (up to 89%) and with excellent stereoselectivity (95% trans) by catalytic hydrogenation-dehydrogenation of 7-chloro-10-methoxy-3,4,4a,5-tetrahydro-2H-[1]benzypyrano[3,4]pyridine 2A. The best results were obtained using Pd/C catalysts in dimethyl formamide (DMF) in presence of N,N-diisopropylethylamine (DIPEA) with high amounts of catalyst at low hydrogen pressure and low initial temperature. At higher initial temperatures, partial aromatization of the N-heterocycle occurred, leading on further hydrogenation to increased levels of cis-1A. Under these conditions, partial demethoxylation at the 10-position was observed as a side reaction as well. In presence of organic bases, the C = C bond was hydrogenated faster than the C-Cl bond. Inorganic bases in protic solvents favored dehalogenation over double bond reduction. Interestingly, the rate of dehalogenation decreased when the hydrogen pressure was increased. Reaction schemes are presented to rationalize these results and a comparison of our catalytic system with other methods described in the literature is made.