Diastereoselective synthesis of some novel benzopyranopyridine derivatives

Background: The formation of novel N-substituted-1,2,3,4-tetrahydro[1,3]-dioxolo-[6,7]-5H[1] benzopyrano [3,4-c]pyridines were observed unexpectedly during the acid- mediated ketal removal of ethylenedioxy ketal protected 4-piperidones. The literature revealed that benzopyranopyridine derivatives are of scientific interest and some exhibit interesting biological activities. Diastereomeric resolution was utilized to isolate optically pure chiral molecules. Results: The acid catalyzed deprotection of N-substituted- 4,4-ethylenedioxy-3-[(1,3-benzodioxol- 5-yloxy)methyl] piperidines, prepared by condensation of the corresponding phenols and mesylate derivatives, unexpectedly resulted in cyclodehydration leading to new benzopyrano derivatives, N-substituted- 1,2,3,4-tetrahydro[1,3]-dioxolo-[6,7]-5H-[1] benzopyrano [3,4c] pyridines. The process involves the deprotection of the carbonyl protecting group, and then the cyclization reaction occurs followed by dehydration to give the final product. T hese N-substituted- 1,2,3,4-tetrahydro[1,3]-dioxolo-[6,7]-5H-[1] benzopyrano [3,4-c] pyridines were dealkylated giving the corresponding N-unsubstituted derivatives. The cis-1,3,4,4a, 5,10b-hexahydro[6,7]- 2H-[1] benzopyrano [3,4-c] pyridine derivative was also obtained from the N-benzylated1,2,3,4- tetrahydro[1,3]-dioxolo-[6,7]-5H-[1] benzopyrano [3,4- c] pyridine via catalytic hydrogenation. The resolution of the enantiomers was carried out using D-(-)-mandelic acid as chiral reagent. The absolute configuration of the S, S-mandelate salt derivative was determined by X-ray crystallographic analysis. Conclusion: The approach led to the construction of N-substituted- 1,2,3,4- tetrahydro[1,3]dioxolo-[ 6,7]-5H-[1] benzopyrano [3,4- c] pyridines ring systems involving the one-pot deprotection, cyclization and dehydration of N-substituted- 4,4-ethylenedioxy-3- [(1,3-benzodioxol- 5-yloxy) methyl] piperidines. The hydrogenation of the N-benzylated benzopyrano [3,4- c] pyridine derivative followed by resolution led to the formation of a new compound.