Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA, 92037, USA.
Department of Chemistry, University of Pittsburgh, 219 Parkman Avenue, Pittsburgh, PA, 15260, USA.
Nat Commun. 2020 Dec 22;11(1):6432. doi: 10.1038/s41467-020-20182-4.
2,3-Dihydrobenzofurans and indolines are common substructures in medicines and natural products. Herein, we describe a method that enables direct access to these core structures from non-conjugated alkenyl amides and ortho-iodoanilines/phenols. Under palladium(II) catalysis this [3 + 2] heteroannulation proceeds in an anti-selective fashion and tolerates a wide variety of functional groups. N-Acetyl, -tosyl, and -alkyl substituted ortho-iodoanilines, as well as free -NH variants, are all effective. Preliminary results with carbon-based coupling partners also demonstrate the viability of forming indane core structures using this approach. Experimental and computational studies on reactions with phenols support a mechanism involving turnover-limiting, endergonic directed oxypalladation, followed by intramolecular oxidative addition and reductive elimination.
2,3-二氢苯并呋喃和吲哚啉是药物和天然产物中常见的结构单元。在此，我们描述了一种方法，可从非共轭烯基酰胺和邻碘代苯胺/酚直接构建这些核心结构。在钯（II）催化下，该[3+2]杂环加成反应以反选择性方式进行，并能容忍多种官能团。N-乙酰基、-甲苯磺酰基和-烷基取代的邻碘代苯胺，以及游离的-NH 变体，都很有效。与碳基偶联试剂的初步结果也证明了使用这种方法形成吲哚烷核心结构的可行性。与酚类的反应的实验和计算研究支持一种涉及周转限制、吸热导向氧钯化，然后进行分子内氧化加成和还原消除的反应机制。
