Multiplicative enhancement of stereoenrichment by a single catalyst for deracemization of alcohols

• 成果类型: Article
• 署名作者: Wen, Lu; Ding, Jia; Duan, Lingfei; Wang, Shun; An, Qing; Wang, Hexiang; Zuo, Zhiwei
• 署名单位: Chinese Academy of Sciences; Shanghai Institute of Organic Chemistry, CAS; University of Chinese Academy of Sciences, CAS
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-11868
• DOI: 10.1126/science.adj0040
• 发表日期: 2023-10-27
• 页码: 458-464
• 关键词: cyclization; molecules; cleavage; route

摘要

Stereochemical enrichment of a racemic mixture by deracemization must overcome unfavorable entropic effects as well as the principle of microscopic reversibility; recently, photochemical reaction pathways unveiled by the energetic input of light have led to innovations toward this end, most often by ablation of a stereogenic C(sp(3))-H bond. We report a photochemically driven deracemization protocol in which a single chiral catalyst effects two mechanistically different steps, C-C bond cleavage and C-C bond formation, to achieve multiplicative enhancement of stereoinduction, which leads to high levels of stereoselectivity. Ligand-to-metal charge transfer excitation of a titanium catalyst coordinated by a chiral phosphoric acid or bisoxazoline efficiently enriches racemic alcohols that feature adjacent and fully substituted stereogenic centers to enantiomeric ratios up to 99:1. Mechanistic investigations support a pathway of sequential radical-mediated bond scission and bond formation through a common prochiral intermediate and reveal that, although the overall stereoenrichment is high, the selectivity in each individual step is moderate.