Catalyst-Free Synthesis of Novel Dimeric Tetrahydroisoquinoline Derivatives through [2+2+2] Annulation

A simple, straightforward, and atom economic catalyst-free [2+2+2] annulation of dihydroisoquinolines and allenoates has been developed. A diverse range of novel dimeric tetrahydroisoquinoline derivatives can be prepared in moderate to good yields (37-87 %) from readily available material. Dihydro-beta-carboline can also be used in this reaction system delivering corresponding dimeric dihydro-beta-carboline derivatives. Notably, the reaction could be easily scaled up to gram scale. The easy scale-up of this process may provide structurally diversified natural product-like molecules possessing privileged scaffold for potential application in biomedical research and other research fields. Interestingly, in contrast to the alpha,beta-selectivity observed in our previous study, beta,gamma-selective [2+2+2] annulation was preferred in this work.