Conversion of 10-bromo-10,11-dihydrocinchonidine into 8-oxa-1-azabicyclo[4.3.0]nonane derivatives and related compounds: a structural study

The structure of dehydrobromination products of 10-bromo-10,11-dihydrocinchonidine 2c has been investigated in order to explore the scope of the conversions so far observed for quinine and cinchonine. The 2c rearranges into a mixture of 4(S)-(E-propenyl)- 6(S),7(R)-(quinol-4-yl)-8-oxa-1(R)-azabicyclo[4.3.0]nonane 6 and its Z-propenyl diastereomer 8 in the ratio 3: 1 and also provides Z-3,10-didehydro-10,11-dihydrocinchonidine 18. The mixture of 6 and 8 undergoes catalytic hydrogenation giving 4(S)-propylo-6(S),7(R)- (quinol-4-yl)-8-oxa-1(R)-azabicyclo[4.3.0]nonane 10. On treatment with an acid the alkaloid 6 yields [4(S)-E-propenyl-2(S)-piperidinyl]-4- quinoline a(R)-methanol 14. Its side chain undergoes hydrogenation affording 4(S)-propylo-derivative 12 which also forms on treatment of 10 by acid. The alkaloids 6, 8, 10, 12 and 14 appear as dominating conformers in their equilibrium mixtures. q 2004 Elsevier B.V. All rights reserved