Stereodivergent 1,3-difunctionalization of alkenes by charge relocation

• 成果类型: Article
• 署名作者: Brutiu, Bogdan R.; Iannelli, Giulia; Riomet, Margaux; Kaiser, Daniel; Maulide, Nuno
• 署名单位: University of Vienna
• 刊物名称: Nature
• ISSN/ISSBN: 0028-5957
• DOI: 10.1038/s41586-023-06938-0
• 发表日期: 2024-02-01
• 关键词: remote functionalization; c-o; 4-ipomeanol; acylation; difunctionalization; aluminum; fluoride; chloride; decalin

摘要

Alkenes are indispensable feedstocks in chemistry. Functionalization at both carbons of the alkene-1,2-difunctionalization-is part of chemistry curricula worldwide1. Although difunctionalization at distal positions has been reported2-4, it typically relies on designer substrates featuring directing groups and/or stabilizing features, all of which determine the ultimate site of bond formation5-7. Here we introduce a method for the direct 1,3-difunctionalization of alkenes, based on a concept termed 'charge relocation', which enables stereodivergent access to 1,3-difunctionalized products of either syn- or anti-configuration from unactivated alkenes, without the need for directing groups or stabilizing features. The usefulness of the approach is demonstrated in the synthesis of the pulmonary toxin 4-ipomeanol and its derivatives. We introduce a method for the direct 1,3-difunctionalization of alkenes, based on a concept termed 'charge relocation', which enables stereodivergent access to 1,3-difunctionalized products of either syn- or anti-configuration from unactivated alkenes.