Enantioselective Polyene Cyclization Catalyzed by a Chiral Brønsted Acid

Abstract

The first enantioselective polyene cyclization initiated by a BINOL‐derived chiral N‐phosphoramide (NPA) catalyzed protonation of an imine is described. The ion‐pair formed between the iminium ion and chiral counter anion of the NPA plays an important role for controlling the stereochemistry of the overall transformation. This strategy offers a highly efficient approach to fused tricyclic frameworks containing three contiguous stereocenters, which are widely found in natural products. In addition, the first catalytic asymmetric total synthesis of (−)‐ferruginol was accomplished with an NPA catalyzed enantioselective polyene cyclization, as the key step for the construction of the tricyclic core, with excellent yield and enantioselectivity.

Review of the Total Synthesis of the Aromatic Abietane Diterpenoid Ferruginol

“…Zhao and his co-workers developed the first enantioselective polyene cyclization in 2018. 42 This cyclization was initiated by BINOL-derived chiral NPA-catalyzed protonation of imine. The NPA acted as an artificial protonase, which initiated and controlled the overall transformation stereochemistry.…”

Ynamide Protonation-Initiated Cis -Selective Polyene Cyclization and Reaction Mechanism

“…[54][55][56][57][58][59] Recently, our group has been interested in both ynamide chemistry [60][61][62][63][64][65] and developing new reactions and strategies for efficient construction of polycyclic compounds. [66][67] Based on these advances, we hypothesized that an ynamide functional group would be a promising initiator for polyene cyclization. More importantly, the final polycyclic products bearing an extra amino functionality will be highly useful for the synthesis of terpene alkaloids and further manipulation.…”