Puumi Jukka, Sahari Aleksi, Žáková Andrea, Mannisto Jere K, Maier Norbert M, Repo Timo
Department of Chemistry, University of Helsinki, A. I. Virtasen aukio 1, Helsinki 00014, Finland.
ACS Omega. 2025 Jul 24;10(30):33843-33849. doi: 10.1021/acsomega.5c05230. eCollection 2025 Aug 5.
Conventional CO-based carboxylation of amino alcohols to cyclic carbamates is often hindered by poor chemo- and stereoselectivity, the need for high pressure or subzero temperatures, reliance on expensive or toxic reagents and catalysts, and the formation of hazardous waste. To address these limitations, we evaluated mild dehydrating reagents for their ability to promote the cyclization. Among the reagents tested, -butyl chloride emerged as the optimal choice, offering a desirable combination of low cost, low toxicity, and high selectivity. In contrast to conventional highly reactive dehydrating reagents, -BuCl provides high selectivity toward carbamate anion alkylation. Upon heating, the resulting linear carbamate intermediate cyclizes, liberating benign butanol and yielding almost exclusively stereoretentive five- and six-membered cyclic carbamates in 17-98% yields.
传统的基于一氧化碳的氨基醇羧化反应制备环状氨基甲酸酯常常受到化学和立体选择性差、需要高压或零下温度、依赖昂贵或有毒的试剂和催化剂以及产生有害废物的阻碍。为了解决这些限制，我们评估了温和的脱水试剂促进环化反应的能力。在所测试的试剂中，叔丁基氯成为最佳选择，它具有低成本、低毒性和高选择性的理想组合。与传统的高活性脱水试剂不同，叔丁基氯对氨基甲酸酯阴离子烷基化具有高选择性。加热时，生成的线性氨基甲酸酯中间体环化，释放出无害的丁醇，几乎只生成立体保持的五元及六元环状氨基甲酸酯，产率为17% - 98%。
