State Key Laboratory of Organometallic Chemistry, Center for Excellence in Molecular Synthesis, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.
Department of Chemistry, Zhejiang University, Hangzhou, China.
Nat Commun. 2021 Feb 10;12(1):930. doi: 10.1038/s41467-021-21190-8.
α-Pyridones and α-pyrones are ubiquitous structural motifs found in natural products and biologically active small molecules. Here, we report an Rh-catalyzed electrochemical vinylic C-H annulation of acrylamides with alkynes, affording cyclic products in good to excellent yield. Divergent syntheses of α-pyridones and cyclic imidates are accomplished by employing N-phenyl acrylamides and N-tosyl acrylamides as substrates, respectively. Additionally, excellent regioselectivities are achieved when using unsymmetrical alkynes. This electrochemical process is environmentally benign compared to traditional transition metal-catalyzed C-H annulations because it avoids the use of stoichiometric metal oxidants. DFT calculations elucidated the reaction mechanism and origins of substituent-controlled chemoselectivity. The sequential C-H activation and alkyne insertion under rhodium catalysis leads to the seven-membered ring vinyl-rhodium intermediate. This intermediate undergoes either the classic neutral concerted reductive elimination to produce α-pyridones, or the ionic stepwise pathway to produce cyclic imidates.
α-吡喃酮和α-吡喃是天然产物和生物活性小分子中普遍存在的结构基序。在这里，我们报告了 Rh 催化的丙烯酰胺与炔烃的电化学烯丙基 C-H 环化反应，以良好到优异的收率得到环状产物。通过分别使用 N-苯基丙烯酰胺和 N-对甲苯磺酰基丙烯酰胺作为底物，实现了 α-吡喃酮和环状异氰酸酯的发散合成。此外，当使用不对称炔烃时，可获得优异的区域选择性。与传统的过渡金属催化的 C-H 环化反应相比，这种电化学过程具有环境友好性，因为它避免了使用化学计量的金属氧化剂。DFT 计算阐明了反应机理和取代基控制的化学选择性的起源。在铑催化下，通过顺序 C-H 活化和炔烃插入，生成七元环乙烯基-铑中间体。该中间体通过经典的中性协同还原消除生成 α-吡喃酮，或者通过离子分步途径生成环状异氰酸酯。
