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

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

doi:10.1038/s41467-019-11245-2

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

Nat Commun. 2019 Jul 19;10(1):3234. doi: 10.1038/s41467-019-11245-2.

Authors

Bo Zhou¹, Ying-Qi Zhang¹, Kairui Zhang², Ming-Yang Yang¹, Yang-Bo Chen¹, You Li², Qian Peng³, Shou-Fei Zhu⁴, Qi-Lin Zhou², Long-Wu Ye^{5

6}

Affiliations

¹ State Key Laboratory of Physical Chemistry of Solid Surfaces, Key Laboratory of Chemical Biology of Fujian Province, and College of Chemistry and Chemical Engineering, Xiamen University, 361005, Xiamen, China.
² State Key Laboratory and Institute of Elemento-Organic Chemistry, College of Chemistry, Nankai University, 300071, Tianjin, China.
³ State Key Laboratory and Institute of Elemento-Organic Chemistry, College of Chemistry, Nankai University, 300071, Tianjin, China. qpeng@nankai.edu.cn.
⁴ State Key Laboratory and Institute of Elemento-Organic Chemistry, College of Chemistry, Nankai University, 300071, Tianjin, China. sfzhu@nankai.edu.cn.
⁵ State Key Laboratory of Physical Chemistry of Solid Surfaces, Key Laboratory of Chemical Biology of Fujian Province, and College of Chemistry and Chemical Engineering, Xiamen University, 361005, Xiamen, China. longwuye@xmu.edu.cn.
⁶ State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 200032, Shanghai, China. longwuye@xmu.edu.cn.

Abstract

Rearrangement reactions have attracted considerable interest over the past decades due to their high bond-forming efficiency and atom economy in the construction of complex 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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Alkenes / chemistry*
Alkynes / chemistry*
Catalysis
Cyclization*
Kinetics
Lactams / chemical synthesis
Lactams / chemistry*
Metals / chemistry*
Models, Chemical
Molecular Structure
Stereoisomerism

Substances

Alkenes
Alkynes
Lactams
Metals