Cancer Biology Institute, Yale School of Medicine, West Haven, Connecticut, 06516, USA.
Department of Chemistry, Michigan State University, East Lansing, MI 48824, USA.
Angew Chem Int Ed Engl. 2022 Feb 14;61(8):e202115173. doi: 10.1002/anie.202115173. Epub 2022 Jan 11.
Employing halenium affinity (HalA) as a guiding tool, the weak nucleophilic character of alkyl ketones was modulated by the templating effect of a tethered 2-tetrahydropyranyl(THP)-protected alcohol towards realizing a bromenium ion initiated spiroketalization cascade. Addition of ethanol aided an early termination of the cascade by scavenging the THP group after the halofunctionalization stage, furnishing monobromospiroketals. Alternatively, exclusion of ethanol from the reaction mixture biased the transient oxocarbenium towards α-deprotonation that precedes a second bromofunctionalization event thus, furnishing dibrominated spiroketals. The regio- and stereoselectivity exploited in the current methodology provides a novel and rapid access to the dibrominated spiroketal motifs exhibited by several natural products.
利用卤化铼亲和力(HalA)作为指导工具,通过连接的 2-四氢吡喃基(THP)保护醇的模板效应调节烷基酮的弱亲核性,实现溴化铼离子引发的螺缩酮化级联反应。添加乙醇后,通过在卤官能化阶段后清除 THP 基团,加速级联反应的早期终止,得到单溴螺缩酮。或者,从反应混合物中排除乙醇会使瞬态氧杂碳正离子偏向于α-去质子化,这发生在第二个溴官能化事件之前,从而得到二溴化螺缩酮。当前方法学中利用的区域和立体选择性为几种天然产物中展示的二溴化螺缩酮基序提供了一种新颖且快速的方法。