2-Azabicyclo[4.2.0]octane derivatives: Stereoselective photochemical Synthesis and Chemical Reactivity

Photochemical addition of acrylonitrile to 1,4-dihydropyridines 1 and 2 followed by catalytic hydrogenation of the products gave trans-8- and trans-7-cyano-cis-2-azabicyclo[4.2.0]octane-6-carboxylates 6a, b and 8a, b; the corresponding cis 7b, 9 and trans 6b, 8b stereoisomers were both obtained from 1,4,5,6-tetrahydropyridine 4. Using the chiral 1,4-dihydropyridine 3, azabicyclo[4.2.0]-octanes 6c, 7c and 8c were obtained with an enantiomeric excess in the range 45-15%. Thermal cycloaddition of p-chlorobenzonitrile oxide on the same substrates yielded compounds 10 and 11, with site- and regio-selectivity but without stereoselectivity. Cyclobutane ring opening under basic or acid conditions was observed only for 8-cyano-2-azabicyclo[4.2.0]octane 6b which gave the 1,4,5,6-tetrahydropyridylpropionitrile 15 or the piperidine-2-ol 17.