Studies on Intramolecular Diels−Alder Reactions of Furo[3,4-c]pyridines in the Synthesis of Conformationally Restricted Analogues of Nicotine and Anabasine
journal contributionposted on 26.04.2003, 00:00 by Tarun K. Sarkar, Sankar Basak, Zdenek Slanina, Tahsin J. Chow
En route to conformationally restricted analogues of nicotine and anabasine, a novel synthetic route to bridged anabasines is described that hinges on a domino intramolecular [4 + 2]-cycloaddition/ring opening−elimination sequence of 3-amino-substituted furo[3,4-c]pyridines. Extension of this route to bridged nicotines, however, proved abortive, even when the dienophile tether is activated by a p-tolylsulfonyl group or when the diene moiety is activated by an electron-releasing methoxy substituent. A detailed density functional theoretical study (B3LYP/6-31+G**) was undertaken to provide insight into the factors that facilitate an intramolecular Diels−Alder reaction in the former case.