Scholarlink

<p>The enantiodiscrimination of minimally distinct alkyl groups, such as methyl versus ethyl groups, remains a formidable challenge due to the subtle steric and electronic differences involved. Concurrently, the stereoselective construction of all-carbon quaternary stereocentres is inherently hindered by steric congestion. The convergence of these two challenges, enantioselectively constructing all-carbon quaternary centres bearing minimally distinct alkyl substituents, represents a notable challenge. Here we report the development of a photobiocatalytic strategy that merges thiamine diphosphate-dependent enzymes with visible-light-driven photoredox catalysis. Using aromatic aldehydes as acyl donors and azonitriles as prochiral radical precursors, this dual catalytic system achieves excellent discrimination between alkyl groups with minimal steric disparity, enabling the enantioselective construction of all-carbon quaternary stereocentres. The utility of this method is showcased across a range of examples, forming products in yields up to 99% and enantioselectivities up to 98% enantiomeric excess. Mechanistic studies reveal the origins of radical generation and the determinants of enantiocontrol within the enzyme active site.</p><p></p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Thiamine-based photobiocatalysis for the enantioselective construction of all-carbon quaternary stereocentres with two minimally different alkyl groups

  • 期刊论文

  • 发表日期：

    2026年5月15日

查看全文
  • Jintong Bai,
  • Yuanyuan Xu,
  • Ruobin Sun,
  • Fuhua Che,
  • Guohui Shang,
  • Guangtao Zhang,
  • Xiaoqiang Huang,
  • Chunshuai Huang

摘要

The enantiodiscrimination of minimally distinct alkyl groups, such as methyl versus ethyl groups, remains a formidable challenge due to the subtle steric and electronic differences involved. Concurrently, the stereoselective construction of all-carbon quaternary stereocentres is inherently hindered by steric congestion. The convergence of these two challenges, enantioselectively constructing all-carbon quaternary centres bearing minimally distinct alkyl substituents, represents a notable challenge. Here we report the development of a photobiocatalytic strategy that merges thiamine diphosphate-dependent enzymes with visible-light-driven photoredox catalysis. Using aromatic aldehydes as acyl donors and azonitriles as prochiral radical precursors, this dual catalytic system achieves excellent discrimination between alkyl groups with minimal steric disparity, enabling the enantioselective construction of all-carbon quaternary stereocentres. The utility of this method is showcased across a range of examples, forming products in yields up to 99% and enantioselectivities up to 98% enantiomeric excess. Mechanistic studies reveal the origins of radical generation and the determinants of enantiocontrol within the enzyme active site.