Chen Ming, Hartwig John F
Department of Chemistry, University of California , Berkeley, California 94720, United States.
J Am Chem Soc. 2015 Nov 4;137(43):13972-9. doi: 10.1021/jacs.5b09980. Epub 2015 Oct 23.
The enol silanes of vinylogous esters and amides are classic dienes for Diels-Alder reactions. Here, we report their reactivity as nucleophiles in Ir-catalyzed, enantioselective allylic substitution reactions. A variety of allylic carbonates react with these nucleophiles to give allylated products in good yields with high enantioselectivities and excellent branched-to-linear ratios. These reactions occur with KF or alkoxide as the additive, but mechanistic studies suggest that these additives do not activate the enol silanes. Instead, they serve as bases to promote the cyclometalation to generate the active Ir catalyst. The carbonate anion, which was generated from the oxidative addition of the allylic carbonate, likely activates the enol silanes to trigger their activity as nucleophiles for reactions with the allyliridium electrophile. The synthetic utility of this method was illustrated by the synthesis of the anti-muscarinic drug, fesoterodine.
烯醇式乙烯基酯和酰胺的硅烷是狄尔斯-阿尔德反应的经典二烯。在此，我们报道了它们作为亲核试剂在铱催化的对映选择性烯丙基取代反应中的反应活性。多种烯丙基碳酸酯与这些亲核试剂反应，以高对映选择性和优异的支链与线性比例，高产率地得到烯丙基化产物。这些反应在氟化钾或醇盐作为添加剂的情况下发生，但机理研究表明这些添加剂不会活化烯醇硅烷。相反，它们作为碱促进环金属化以生成活性铱催化剂。烯丙基碳酸酯氧化加成产生的碳酸根阴离子可能活化烯醇硅烷，从而引发它们作为亲核试剂与烯丙基铱亲电试剂反应的活性。抗毒蕈碱药物非索罗定的合成说明了该方法的合成实用性。
