Timmerman Jacob C, Filiberti Sara
Department of Synthetic Molecule Process Chemistry, Genentech, Inc., South San Francisco, California 94080, United States.
J Org Chem. 2024 Aug 16;89(16):11796-11801. doi: 10.1021/acs.joc.4c01215. Epub 2024 Aug 1.
A catalytic, two-step protocol for the expedient synthesis of -2,4-disubstituted tetrahydrofurans is described. In the first step, an enantioselective and regioselective Pd-catalyzed Hayashi-Heck arylation was developed using ()-hexaMeOBiphep to generate 5-aryl-2,3-dihydrofurans. A subsequent Rh-catalyzed hydroformylation step proceeds at low Rh loading with high regio- and diastereoselectivity for the -2,4-disubstituted tetrahydrofuran isomer. Key to the development of the hydroformylation reaction was the utilization of either ()-Me--Pr-INDOLphos or (,)-Ph-BPE to control the regioselectivity and provide the kinetic product isomer.
描述了一种用于便捷合成-2,4-二取代四氢呋喃的催化两步法。第一步，使用()-六甲基联苯膦开发了对映选择性和区域选择性钯催化的林原-赫克芳基化反应，以生成5-芳基-2,3-二氢呋喃。随后的铑催化氢甲酰化步骤在低铑负载量下进行，对-2,4-二取代四氢呋喃异构体具有高区域选择性和非对映选择性。氢甲酰化反应开发的关键是使用()-甲基-异丙基-吲哚膦或(,)-苯基-双酚醚来控制区域选择性并提供动力学产物异构体。
