Synthesis of Tricyclic Benzazocines by Aza-Prins Reaction

Abstract

The aza-Prins reaction of 3-vinyltetrahydroquinolines with aldehydes proceeded smoothly in the presence of hydrogen halides, and the tricyclic benzazocine derivatives were isolated in good to high yields. The reaction would proceed through the formation and cyclization of the iminium ion intermediate.

The Aza-Prins Reaction of 1,2-Dicarbonyl Compounds with 3-Vinyltetrahydroquinolines: Application to the Synthesis of Polycyclic Spirooxindole Derivatives

“…A mixture of 1 ( 7 ) (1.0 equiv), butane-2,3-dione ( 2a , 2.5 equiv), and 2 M HCl (5.0 equiv) in diethyl ether was heated in acetonitrile at 80 °C for 18 h, and the tricyclic benzazocine 3a was isolated in 61% yield (entry 1). In contrast to the aza-Prins reaction of 1 with aldehydes, where a mixture of diastereomers was isolated, this reaction proceeded in a selective manner.…”

“…The results are in sharp contrast to the results of the reaction of 1 with aldehydes, where the formation of a mixture of diastereomers ( cis and trans isomers) with varying ratios was observed. 7 …”

“…The attack of the chloride ion will proceed as shown in Scheme 3 because the presence of the bridging methylene group and the acyl group would prevent the formation of the 2,4- cis isomer. 7 …”

“…Recently we reported the aza-Prins reaction of 2-vinyltetrahydroquinolines with aldehydes ( Scheme 2 a). 7 The reaction proceeded in the presence of hydrogen halides, and tricyclic benzazocines were isolated as a mixture of 2,4- cis- and 2,4- trans- isomers in good to high yields under mild conditions. We envisioned that we could significantly expand the scope of the aza-Prins reaction by introducing 1,2-dicarbonyl compounds as the substrates for this reaction.…”

The Aza‐Prins Reaction in the Synthesis of Natural Products and Analogues

“…However, the asymmetric catalysis route remains to be developed, although the first successful examples of catalytic asymmetric Prins reactions have appeared recently , . The other fascinating aspect of the most recent research is this area is the evolution towards more and more complex compounds . This was made possible by combination of aza‐Prins cyclization with other reactions.…”