Activation of Chiral (Salen)AlCl Complex by Phosphorane for Highly Enantioselective Cyanosilylation of Ketones and Enones

Abstract

Phosphoranes 2 are identified as a class of effective Lewis bases to activate chiral (salen)AlCl complex 1 to enhance its electrophilicity. Accordingly, a three-component catalyst system consisting of complex 1, phosphorane 2e, and Ph3PO is developed as a powerful tool for asymmetric ketone cyanosilylation. In particular, an unprecedented highly enantioselective cyanosilylation of linear aliphatic ketones is achieved. A tandem Wittig-cyanosilylation sequence starting from phosphorane 2a and enals 10 is further achieved, which internally utilizes the Ph3PO byproduct and remaining phosphorane 2a as cocatalysts for cyanosilylation of α,β,γ,δ-unsaturated enones, providing atom-efficient access to valuable chiral conjugated dienes and enynes. The high efficiency of the cyanosilylation originates from orthogonal activation of both (salen)AlCl complex 1 and cyanotrimethylsilane by the phosphorane and Ph3PO, respectively. This mechanistic insight is supported by NMR, MS, and ReactIR analyses and DFT calculations. Furthermore, the formation of charged complexes through the activation of chiral complex 1 by phosphorane 2a is confirmed by electrical conductivity experiments.

Metal‐Organic Frameworks as Platform for Lewis‐Acid‐Catalyzed Organic Transformations

“…Cyanosilylation reaction which is nucleophillic addition of trimethylsilylcyanide (TMSCN) to carbonyl compounds producing cyanohydrins is a very important organic transformation. Cyanohydrins are considered as versatile building blocks for fine chemicals, agrochemicals and pharmaceuticals, that is, α‐hydroxyacids, β‐hydroxyamines, α‐aminonitriles, α‐hydroxyketones and β‐aminoalcohols . In contrast to other toxic substances such as KCN, HCN and NaCN, TMSCN is a preferred reagent for cyanosilylation reaction as it is easy to handle, the Si−C bond has low dissociation energy and most importantly it has high atom economy without giving side reactions .…”

A Comparison of Me2(CH2Cl)SiCN and Me3SiCN in Catalytic Enantioselective Cyanation of Aldehydes

“…然而, Kim 等 [18] [19] , [20] . [14] , 显示这一氰化试剂有望在一些活性较低的底 物参与的氰化反应中有更广阔的应用前景, 实现一些传 统 TMSCN 所不能实现的反应活性或选择性. 研究还表 明, 利用手性(salen)AlCl/叶立德络合物来发展醛的加成 反应时, 虽有部分叶立德被消耗, 但通过使用稍过量的 具有大位阻取代基的叶立德, 可以很好的保持催化体系 的活性.…”

“…我们小组 [11～15] 一直致力于不对称氰化反应的研究 工作, 先后发展了手性金鸡纳碱衍生的双功能(硫)脲催 化剂催化的高选择性的氟代烷基酮亚胺 [11a] 和靛红亚 胺 [11b] 的高选择性 Strecker 反应, 以及氧化吲哚衍生的烯 酮的硅氰化反应 [12] . 在对串联 Wittig-烯酮的不对称硅氰 化反应进行机理研究时 [13] , 我们发现叶立德能够高效 活化手性(salen)AlCl (R,R)-1 形成 Lewis 酸性更强的 (salen)AlCl/叶立德络合物, 结合 Ph 3 PO 活化 TMSCN, 实现了一系列酮的不对称硅氰化反应(图 2A), 包括非常 具有挑战性的直链状脂肪酮的高对映选择性硅氰化反 应 [14] . 最近, 我们还开发了一种新型双功能硅氰化试剂 Me 2 (CH 2 Cl)SiCN 4; 使用手性(salen)AlCl/叶立德络合物 作为催化剂时, 该试剂在醚类溶剂中展示了比 TMSCN 更高的反应活性; 进而实现了芳香酮、开链脂肪酮以及 具有末端烯基或炔基的 α,β-不饱和酮的高对映选择性氰 化反应(图 2B) [15] .…”

Mechanism of Enolate Transfer between Si and Cu

“…Silylated enolates are used as latent nucleophiles in many reactions, and their activation is induced through Lewis acids or bases . In the case of base activation, Si−O bond breaking leading to transfer of the enolate to a copper (or more generally metal) complex is proposed . This can be formally described as a chain transfer between Si and Cu in which enolate exchanges with an X group whose nature depends on the exact reaction at stake.…”

“…[1] In the case of base activation,S i ÀOb ond breaking leadingt ot ransfer of the enolatet oacopper( or more generally metal) complex is proposed. [2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] This can be formally described as ac hain transferb etween Si and Cu in which enolate exchanges with an Xg roup whose nature depends on the exact reaction at stake. For instance, in the case of the coppercatalyzed asymmetric vinylogousM ukaiyamaa ldol (Cu-CAVM) reaction, [21] which has been at the origin of our studies, ad ienolate transfer from at rimethylsilyl (TMS)m oiety to aC u I complex is proposed to form aC u-bonded nucleophile (Scheme 1).…”