Direct Catalytic Asymmetric Addition of Allylic Cyanides to Ketoimines

Abstract

Direct catalytic asymmetric addition of allylic cyanides to N-diphenylphosphinoyl ketoimines with a bimetallic catalytic system comprising Ph-BPE/[Cu(CH3CN)4]ClO4/LiOAr is described. Intermediary alpha-adducts readily isomerized to afford synthetically useful alpha,beta-unsaturated nitriles bearing an optically active tetrasubstituted carbon. Applicability to aromatic, heteroaromatic, and aliphatic ketoimines exemplifies wide substrate generality. Transformation of the product into densely functionalized material showcases the utility of the present protocol.

Roles of Bases in Transition-Metal Catalyzed Organic Reactions

“…作为对比 实验, 向这一反应体系中加入锂盐 LiPF 6 后进行反应, 则反应顺利进行, 以 80%的产率和 87% ee 值得到预期 产物. 这也证明了锂离子在这一反应过程中是十分重要 的 [37] . …”

Silylketenimine – vielseitige Nucleophile für die katalytische asymmetrische Synthese

“…[43a, 44] Zur Erweiterung der Bandbreite nucleophiler Allylnitrile in der asymmetrischen Synthese beschrieben wir vor Kurzem eine Methode für Lewis-Base-katalysierte vinyloge Aldoladditionen des von 2-Methyl-3-butennitril abstammenden NSilylvinylketenimins 70. [45] Die Hürde bei der Synthese dieser SKIs ist die Durchführung einer N-Silylierung anstelle der konkurrierenden C a -oder C g -Silylierung (siehe Abschnitt 3.5).…”

Development of Atom-Economical Catalytic Asymmetric Reactions under Proton Transfer Conditions: Construction of Tetrasubstituted Stereogenic Centers and Their Application to Therapeutics

“…In this context, we envisioned the direct catalytic asymmetric addition of allylic cyanides 20 to N-diphenylphosphinoyl (Dpp) ketoimines 21, 141) quent a-addition to ketoimines 21, affording the enantioenriched a,b-unsaturated nitriles 22 bearing a tetrasubstituted stereogenic center after spontaneous isomerization of the terminal olefin. 142 4 ](BF 4 ), resulted in poor catalytic efficiency, confirming that Cu was the best soft Lewis acid for the activation of 20. The substrate generality of the present protocol is summarized in Table 7.…”