Tandem furo[3,4-b]pyridine formation—Diels-Alder reaction: an approach to the synthesis of nitrogen containing heterocyclic analogues of 1-arylnaphthalene lignans

The coupling of Fischer carbene complexes with 2-alkynyl-3-pyridine carbonyl derivatives has been examined. The reaction affords furo[3,4-b]pyridine as transient intermediates; the latter undergo [4+2] cycloaddition with an electron-deficient dienophile. Acid/base-induced ring opening of the exo-cycloadducts followed by aromatization give substituted quinolines related to heterocyclic analogues of 1-arylnaphthalene lignans. An intramolecular variant of this protocol is also feasible with use of unactivated alkenyl tethers; however, the bridged cycloadducts are unisolable as they undergo spontaneous ring opening to yield alcohol. This method is also useful for the in situ generation of the furo[3,4-b]quinoline intermediate for the first time, which can be trapped with dienophiles.