Proton magnetic resonance studies of compounds with bridgehead nitrogen. Part 33. Effect of a fused aromatic ring on the conformational preferences of perhydropyrido[1,2-c][1,3]oxazines 2 and related compounds

Abstract

In contrast to 4,4a,5,10-tetrahydro-1H,3H-[1,3]oxazino[3,4-b]isoquinoline which adopts the trans-fused ring conformation in solution, 1,6,7,11b-tetrahydro-2H,4H-[1,3]oxazino[4,3-a]isoquinoline predominantly adopts the cis-B/C-O-inside conformation. The analogous cis-fused conformation for 1,6,7,11b-tetrahydro-2H,4H-[1,3]-thiazino[4,3-a]isoquinoline is also preferred. 3-Methyl-1,2,3,4,7,11b-hexahydro-6H-pyrimido[6,1-a]isoquinoline exists in solution as a conformational equilibrium containing less (ca. 54%) of the equatorial NMe-trans-fused ring conformation than does 2-methylperhydropyrido[1,2-c]pyrimidine (ca. 75%). These results have been discussed largely in terms of ring fusion strain.