A Rapid Aza-Bicycle Synthesis from Dendralenes and Imines

Abstract

The diene-transmissive 2-fold Diels–Alder sequence between carbon-based dienophiles and [3]­dendralenes is becoming an established method for polycarbocycle synthesis. Here, we demonstrate for the first time that imines are competent participants in intermolecular formal [4 + 2] cycloadditions with dendralenes. After a second Diels–Alder process with a carbadienophile, hexahydro- and octahydro-isoquinoline structures are formed. The formal aza-Diels–Alder reaction, which requires Lewis acid promotion, proceeds in high regio- and stereoselectivity under optimized conditions. ωB97XD/Def2-TZVP//M06-2X/6-31+G­(d,p) calculations reveal a stepwise ionic mechanism for the formal aza-dienophile cycloadditions and also explain an unexpected Z → E olefin isomerization of a non-reacting CC bond in the first formal cycloaddition.

Mild Stereoselective Synthesis of Densely Substituted [3]Dendralenes via Ru-Catalyzed Intermolecular Dimerization of 1,1-Disubstituted Allenes

“…Allenes often exhibit unusual chemo-, regio-, and diastereoselectivity due to their consecutive π-bonds in orthogonal configuration . To gain comprehensive insights into the reaction mechanism, density functional theory (DFT) calculations were performed with the Gaussian 16 package at the M06/6-31G(d)+SDD(Ru)/SMD(DCM) level of theory.…”

“…Moreover, [3]­dendralenes have found particularly elegant applications in the synthesis of complex polycyclic molecules . Owing to their unique structural feature, they can engage in the powerful diene-transmissive Diels–Alder reactions (DTDA, Scheme b), which have been demonstrated as key steps for the construction of the core skeletons of various natural products, including (+)-7,20-diisocyanoadociane and (−)-triptolide. As a result, considerable efforts have been devoted to the synthesis of [3]­dendralenes, mostly focusing on the use of cross-coupling of vinyl (di)­halides and/or vinyl metal species where stereochemistry and substitution patterns have been more or less predefined. In this context, additional mild and straightforward strategies remain in high demand for the efficient access to diversely substituted and functionalized [3]­dendralenes from simple substrates without prefunctionalization or predefined stereochemistry.…”