On- and Off-Cycle Catalyst Cooperativity in Anion-Binding Catalysis

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• 作者：David D. Ford ; Dan Lehnherr ; C. Rose Kennedy ; Eric N. Jacobsen
• 刊名：Journal of the American Chemical Society
• 出版年：2016
• 出版时间：June 29, 2016
• 年：2016
• 卷：138
• 期：25
• 页码：7860-7863
• 全文大小：404K
• 年卷期：0
• ISSN：1520-5126

文摘

Chiral, neutral H-bond donors have found widespread use as catalysts in enantioselective reactions involving ion-pair intermediates. Herein, a systematic mechanistic study of a prototypical anion-binding reaction, the thiourea-catalyzed enantioselective alkylation of α-chloroethers, is detailed. This study reveals that the catalyst resting state is an inactive dimeric aggregate that must dissociate and then reassemble to form a 2:1 catalyst–substrate complex in the rate-determining transition structure. Insight into this mode of catalyst cooperativity sheds light on the practical limitations that have plagued many of the H-bond donor-catalyzed reactions developed to date and suggests design strategies for new, highly efficient catalyst structures.