Copper enolates enantioselective aldol reaction

After the first reports of the above-mentioned highly eflident catalytic enantioselective aldol reaction, some groups independently reported catalytic symmetric aldol reactions of silicon enolates vith aldehydes using chiral boron [72], titanium [73], zirconium [74], and copper Le vis acids [75], or by transmetalation to chiral Pd(II) enolates [44]. Chiral phosphoramide-promoted aldol reactions of trichlorosilyl enol ethers have been reported as Le vis base-catalyzed asymmetric aldol reactions [76]. 

Shibasaki et al. also developed catalytic reactions of copper, some of which can be applied to catalytic asymmetric reactions. Catalytic aldol reactions of silicon enolates to ketones proceed using catalytic amounts of CuF (2.5 mol%) and a stoichiometric amount of (EtO)3SiF (120 mol%) (Scheme 104).500 Enantioselective alkenylation catalyzed by a complex derived from CuF and a chiral diphosphine ligand 237 is shown in Scheme 105.501 Catalytic cyanomethyla-tion by using TMSCH2CN was also reported, as shown in Scheme 106.502... 

Kobayashi and coworkers reported addition of enol silanes (72) to aldehydes (71) catalyzed by Cu(OTf)2/(52) (Scheme 17.14) [19]. Moderate to good enantioselectivities could be obtained with low syn/antiselectivity. The reduced enantioselectivity relative to bidentate acceptors employed may be attributed to single-point coordination to the Lewis acid. This point is noteworthy, as acceptors restricted to single-point coordination continue to be challenging substrates in copper-catalyzed aldol reactions. 

Shibasaki and Kanai developed a catalytic enantioselective nitrile aldol reaction using CuOf-Bu-DTBM-SEGPHOS complex as a catalyst (Fig. 3) [27] (for other reports of direct catalytic nitrile aldol reactions, see [31, 32]). Despite moderate enantioselectivity, it is noteworthy that chemoselective generatimi of an enolate equivalent (copper ketene imide 6 in Fig. 4) is possible from acetonitrile in the presence of aldehydes containing more acidic a-protons. The pATa values of a-protons of acetonitrile and aliphatic aldehydes are 31.3 and ca. 23 (in DMSO), respectively. Key for the selective deprotonation from acetonitrile is the chemoselective interaction between soft Cu(I) and soft nitrile, which selectively acidifies a-protons of acetonitrile (Fig. 4, 5). 

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