Efficient access to aliphatic esters by photocatalyzed alkoxycarbonylation of alkenes with alkyloxalyl chlorides

Siyu Wang,Qi Tang,Jian-Qiang Chen,Jie Wu,Liang Xu,Mingjuan Ji,Xiaodong Tu,Zhiming Li,Ke Li

doi:10.1038/s41467-021-25628-x

Abstract

Aliphatic esters are essential constituents of biologically active compounds and versatile chemical intermediates for the synthesis of drugs. However, their preparation from readily available olefins remains challenging. Here, we report a strategy to access aliphatic esters from olefins through a photocatalyzed alkoxycarbonylation reaction. Alkyloxalyl chlorides, generated in situ from the corresponding alcohols and oxalyl chloride, are engaged as alkoxycarbonyl radical fragments under photoredox catalysis. This transformation tolerates a broad scope of electron-rich and electron-deficient olefins and provides the corresponding β-chloro esters in good yields. Additionally, a formal β-selective alkene alkoxycarbonylation is developed. Moreover, a variety of oxindole-3-acetates and furoindolines are prepared in good to excellent yields. A more concise formal synthesis of (±)-physovenine is accomplished as well. With these strategies, a wide range of natural-product-derived olefins and alkyloxalyl chlorides are also successfully employed.

Highlights

Aliphatic esters are essential constituents of biologically active compounds and versatile chemical intermediates for the synthesis of drugs
Direct catalytic and regioselective synthesis of aliphatic ester derivatives from unactivated olefins under mild conditions remains an unsolved challenge in modern synthetic chemistry
Having demonstrated the capacity of activated alkenes in this alkoxycarbonylchlorination reaction, we investigated the conversion of various alkyloxalyl chlorides

Summary

Introduction

Aliphatic esters are essential constituents of biologically active compounds and versatile chemical intermediates for the synthesis of drugs Their preparation from readily available olefins remains challenging. Transition-metal-catalyzed alkoxycarbonylation reactions are powerful tools to synthesize esters, these processes rely on the use of high pressure of CO, which often require specific equipment and safety precautions[7]. Application of these transformations is limited by the challenges associated with the regioselective alkoxycarbonylation of olefins as well as the harsh reaction conditions. The alkoxycarbonylation of olefins will provide the desirable linear esters

Methods

Results

Conclusion