Title: Stereoselective synthesis of medium lactams enabled by metal-free hydroalkoxylation/stereospecific [1,3]-rearrangement

Authors:

Bo Zhou, Ying-Qi Zhang, Kairui Zhang, Ming-Yang Yang, Yang-Bo Chen, You Li, Qian Peng, Shou-Fei Zhu, Qi-Lin Zhou & Long-Wu Ye

Abstract:

Rearrangement reactions have attracted considerable interest over the past decadesdue to their high bond-forming efficiency and atom economy in the construction ofcomplex organic architectures. In contrast to the well-established [3,3]-rearrangement, [1,3] O-to-C rearrangement has been far less vigorously investigated, and stereospecific [1,3]-rearrangement is extremely rare. Here, we report a metal-free intramolecular hydroalkoxylation/[1,3]-rearrangement, leading to the practical and atom-economical assembly of various valuable medium-sized lactams with wide substrate scope and excellent diastereoselectivity. Moreover, such an asymmetric cascade cyclization has also been realized by chiral Brønsted acid-catalyzed kinetic resolution. In addition, biological tests reveal that some of these medium-sized lactams displayed their bioactivity as antitumor agents against melanoma cells, esophageal cancer cells and breast cancer cells. A mechanistic rationale for the reaction is further supported by control experiments and theoretical calculations.

Published: 19 July 2019

Full Link: https://www.nature.com/articles/s41467-019-11245-2