Lee Sarah Yunmi, Fujiwara Yuji, Nishiguchi Atsuko, Kalek Marcin, Fu Gregory C
†Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, California 91125, United States.
‡Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States.
J Am Chem Soc. 2015 Apr 8;137(13):4587-91. doi: 10.1021/jacs.5b01985. Epub 2015 Mar 27.
Substantial progress has been described in the development of asymmetric variants of the phosphine-catalyzed intermolecular [3+2] annulation of allenes with alkenes; however, there have not been corresponding advances for the intramolecular process, which can generate a higher level of complexity (an additional ring and stereocenter(s)). In this study, we describe the application of chiral phosphepine catalysts to address this challenge, thereby providing access to useful scaffolds that are found in bioactive compounds, including diquinane and quinolin-2-one derivatives, with very good stereoselectivity. The products of the [3+2] annulation can be readily transformed into structures that are even more stereochemically rich. Mechanistic studies are consistent with β addition of the phosphepine to the allene being the turnover-limiting step of the catalytic cycle, followed by a concerted [3+2] cycloaddition to the pendant olefin.
在膦催化的丙二烯与烯烃的分子间[3+2]环化反应的不对称变体开发方面已有大量进展描述；然而，分子内反应过程却没有相应进展，分子内反应过程能够产生更高水平的复杂性（额外的环和立体中心）。在本研究中，我们描述了手性膦嗪催化剂的应用以应对这一挑战，从而能够以非常好的立体选择性获得生物活性化合物中存在的有用骨架，包括二喹烷和喹啉-2-酮衍生物。[3+2]环化反应的产物能够很容易地转化为立体化学更丰富的结构。机理研究表明，膦嗪对丙二烯的β加成是催化循环的限速步骤，随后是与侧链烯烃的协同[3+2]环加成反应。
