Enantioselective Functionalization of Allylic C鈥揌 Bonds Following a Strategy of Functionalization and Diversification

详细信息    查看全文

• 作者：Ankit Sharma ; John F. Hartwig
• 刊名：Journal of the American Chemical Society
• 出版年：2013
• 出版时间：November 27, 2013
• 年：2013
• 卷：135
• 期：47
• 页码：17983-17989
• 全文大小：445K
• 年卷期：v.135,no.47(November 27, 2013)
• ISSN：1520-5126

文摘

We report the enantioselective functionalization of allylic C鈥揌 bonds in terminal alkenes by a strategy involving the installation of a temporary functional group at the terminal carbon atom by C鈥揌 bond functionalization, followed by the catalytic diversification of this intermediate with a broad scope of reagents. The method consists of a one-pot sequence of palladium-catalyzed allylic C鈥揌 bond oxidation under neutral conditions to form linear allyl benzoates, followed by iridium-catalyzed allylic substitution. This overall transformation forms a variety of chiral products containing a new C鈥揘, C鈥揙, C鈥揝, or C鈥揅 bond at the allylic position in good yield with a high branched-to-linear selectivity and excellent enantioselectivity (ee 鈮?7%). The broad scope of the overall process results from separating the oxidation and functionalization steps; by doing so, the scope of nucleophile encompasses those sensitive to direct oxidative functionalization. The high enantioselectivity of the overall process is achieved by developing an allylic oxidation that occurs without acid to form the linear isomer with high selectivity. These allylic functionalization processes are amenable to an iterative sequence leading to (1,n)-functionalized products with catalyst-controlled diastereo- and enantioselectivity. The utility of the method in the synthesis of biologically active molecules has been demonstrated.