Van Brabandt Willem, De Kimpe Norbert
Department of Organic Chemistry, Faculty of Bioscience Engineering, Ghent University, Coupure links 653, B-9000 Ghent, Belgium.
J Org Chem. 2005 Apr 29;70(9):3369-74. doi: 10.1021/jo048158f.
[reaction: see text] The diastereoselective synthesis of highly functionalized gamma-lactams starting from 4-(1-bromoalkyl)-2-azetidinones via N-acyliminium intermediates is described. The carbenium ions, formed by dissociation of bromide from 4-(1-bromoalkyl)-2-azetidinones in polar medium, are converted via a ring expansion toward N-acyliminium ions, which are susceptible to attack of oxygen, nitrogen, and carbon nucleophiles. In this way, a variety of 5-hydroxy-, 5-alkoxy, 5-cyano-, 5-allylamino- and 5-azido-4,4-dimethyl-2-pyrrolidinones were synthesized. It was found that dehydrobromination of 4-(1-bromoalkyl)-2-azetidinones constituted an important side reaction when the title reactions were carried out in DMSO. When THF was used as a solvent, generally no dehydrobromination was observed, implying that higher yields of gamma-lactams were obtained in THF compared to reactions performed in DMSO. Also substituents of the 4-(1-bromoalkyl)-2-azetidinones play an important role concerning the obtained diastereoselectivity and the degree of dehydrobromination.
[反应：见正文] 描述了从4-(1-溴烷基)-2-氮杂环丁酮开始，通过N-酰基亚胺离子中间体进行高官能化γ-内酰胺的非对映选择性合成。在极性介质中，4-(1-溴烷基)-2-氮杂环丁酮中的溴解离形成的碳正离子通过环扩张转化为N-酰基亚胺离子，该离子易于受到氧、氮和碳亲核试剂的进攻。通过这种方式，合成了多种5-羟基-、5-烷氧基-、5-氰基-、5-烯丙基氨基-和5-叠氮基-4,4-二甲基-2-吡咯烷酮。发现在二甲基亚砜中进行标题反应时，4-(1-溴烷基)-2-氮杂环丁酮的脱溴化氢反应是一个重要的副反应。当使用四氢呋喃作为溶剂时，通常未观察到脱溴化氢反应，这意味着与在二甲基亚砜中进行的反应相比，在四氢呋喃中获得的γ-内酰胺产率更高。4-(1-溴烷基)-2-氮杂环丁酮的取代基对于所获得的非对映选择性和脱溴化氢程度也起着重要作用。
