Trichlorosilyl enol ether

In the following a few examples of the asymmetric aldol reaction are given. Silyl enol ethers (0-Si) resemble very much allylsilanes (C-Si) in terms of structure and mode of action. That is why Lewis base catalyzed aldol reactions of silyl enol ethers have been extensively studied. The first example of Lewis base catalyzed asymmetric aldol reaction of trichlorosilyl enol ether with chiral phosphoramide [80-91] was reported by Denmark et al. (Scheme 24). 

The coordination state of the silyl enol ether in the transition state strongly influences the diastereoselectivity (synlanti). If a ligand is sterically demanding, like phosphoramide 33, a boat-like transition state with a pentacoordinated silicate is formed and affords the syn product in the reaction of trichlorosilyl enol ether with benzaldehyde. In contrast, the less hindered ligand 34 gave the anti product through a chair-like transition state with a hexacoordinated silicate (Scheme 25). 

Next to phosphoramides, Denmark reported an axially chiral A -oxide to catalyze the asymmetric aldol reaction of trichlorosilyl enol ethers with ketones [99]. Hashimoto reported an aldol reaction with 3 mol% of another axially chiral A -oxide [100] which gave good yields and enantioselectivities. 

Scheme 7.10 Asymmetric aldol addition of trichlorosilyl enol ethers to aldehydes.

In stark contrast to trichlorosilyl enol ethers (55 and 65, etc.), their more readily obtainable trimethylsilyl counterparts, such as 67, are insensitive to the presence... 

Chiral phosphorarnides, as developed by Denmark during the late 1990s [25], are efficient catalysts for the allylation of aldehydes with allyl trichlorosilane [26a] or the aldol condensation of trichlorosilyl-enol ethers with aldehydes [26b]. However, the first example of supported chiral phosphorarnides on a polymeric matrix was reported only in 2005 [27]. 

This supported triamide was utilized in the model reaction between the trichlorosilyl enol ether of cyclohexanone and benzaldehyde (Scheme 3.2), carried out at — 78 °C after 3 h the aldol product was obtained in 80% yield and 1 1 synjanti diastereoselectivity when the temperature was increased to — 23 °C,... 

Michael additions [202]. Phosporamide 66 was prepared as an insoluble equivalent for HMPA and was studied for the aldol condensation between trichlorosilyl enol ethers and aldehydes to give keto alcohols 70 (Scheme 10.13). Moderate to good yields and selectivities were obtained. In the presence of 10% of the catalyst at -23 °C the rate was significantly accelerated, albeit the syn/anti stereoselectivity was decreased by a factor of 5 [203]. 

Enolsilylation. a-Bromo ketones and esters are transformed into trichlorosilyl enol ethers by HSiCls and EtsN (catalytic Ph3PO), which condense with ArCHO. The overall process is superior to the Wittig reaction. 

Trichlorosilyl enol ethers. The reaction of tributylstannyl enol ethers with SiCl results in trichlorosilyl analogs that are highly reactive as donors in aldol reactions without catalysts. Asymmetric synthesis in the presence of chiral phosphoramides is realized. 

Following from the examples of allyltrichlorosilanes 21.5, Denmark introduced the related eno)g4 richlorosilanes 21.97 (Scheme 21.13) to cany out Mukaiyama-lype nucleophilic additions to carbonyl compounds. " According to Mayr s nucleophilicity scale, silyl enol ethers derived from aldehydes and ketones and, in particular, silyl ketene acetals are even more powerful nucleophilic reagents than the respective allyl silanes. Indeed, the aldol-type addition of trichlorosilyl enol ethers 21.97a-d to aldehydes 21.4 proceeds readily at room temperature without a catalyst exhibiting simple first-order kinetics in each component (Scheme 21.13), which contrasts with the lack of reactivity of allyl silanes in the absence of a catalyst. 

In the aldol addition of chiral trichlorosilyl enol ethers 21.97 containing a remote stereogenic centre the latter has been found to exercise only a weak to modest influence on the stereochemical course of this reaction. In most cases, diastereoselectivity was controlled mainly by the chiral catalyst [e.g., 21.102). ... 

Nakajima has further shown that enantio- and diastereoselective aldol reactions can be effectively catalysed by BINAPO (21.14) in dichloromethane at —78 °C (Scheme 21.13). Thus, at 10 mol% catalyst loading and in the presence of z-PrNEta (1.2 equivalents), the reaction of the cyclohexanone-derived trichlorosilyl enol ether (21.97e) with various aromatic, a,p-unsaturated, and aliphatic aldehydes 21.4 can reach up to 48 1 diastereomeric ratio in favour of the antz-21.100 with up to 96% enantiomeric excess. ... 

A similar pattern is observed in the reactions of silyl enol ethers derived from aldehydes. Aldehyde-aldehyde aldol reactions had already been reduced to practice in the context of the Lewis base-catalyzed aldol reaction of trichlorosilyl enol ethers, thanks to the stabilizing effect of the trichlorosilyl chlorohydrin (Scheme 9) [25-27]. Because the product of the aldehyde-aldehyde aldol reaction is an aliphatic aldehyde, it can be quickly transformed into an umeactive chlorohydrin such... 

Nakajima M, Yokota T, Saito M, Hashimoto S (2004) Enantioselective aldol reactions of trichlorosilyl enol ethers catalyzed by chiral iVA/-dioxides and monodentate V-oxides. Tetrahedron Lett 45 61-64... 

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]. 

In 1996, Denmark introduced chiral phosphoramide 1, which could be readily synthesized from the parent commercially available (R)-2,2 -diamino-l,l-binaphthalene, as an effective catalyst for the aldol reaction of the preformed trichlorosilyl enol ether of methyl acetate with aldehydes under mild conditions (Scheme 7.1) (2). 

This system could be successfully extended to the catalytic enantioselective crossed-aldol reaction of aldehydes [3], The geometrically defined ( )- and (Z)-trichlorosilyl enol ethers of aldehydes underwent efficient, highly diastereoselec-tive addition to different aldehydes under the influence of chiral bis-phosphoramide 2, which possess a tether of five methylene units, to give the corresponding anti-and syn-P-hydroxy aldehydes as a form of dimethyl acetal, respectively, with good yet variable enantioselectivity (Scheme 7.2). 

This class of chiral Lewis base catalysts was also applicable to the enantioselective aldol reactions of trichlorosilyl enol ethers (Scheme 7.14) [24, 25). As included in Scheme 7.14, Denmark devised chiral bipyridine N.N -dioxide 8 and demonstrated that it smoothly catalyzed the aldol addition of methyl acetate-derived trichlorosilyl ketene acetal to a series of ketones with good to high enantioselectivi-ties [25],... 

Scheme 7.14 Aldol additions of trichlorosilyl enol ethers.

The potential of 9 as a chiral Lewis base catalyst was further demonstrated by application to the aldol reaction of trichlorosilyl enol ethers of ketones with aldehydes, which proceeded with high diastereo- and enantioselectivity [32], The observed stereospecificity suggested the intervention of a six-membered cyclic transition state (Scheme 7.17). Notably, enoHzation of cyclohexanone derivatives and aliphatic aldehydes appeared feasible by SiCLt with the assistance of amine base and 9, leading to the estabhshment of a new protocol for direct aldol-type reactions between ketones and aldehydes or two aldehydes (Scheme 7.18) [33]. 

In stark contrast to trichlorosilyl enol ethers (76 and 88, etc), their more readily obtainable trimethylsilyl counterparts, such as 90, are insensitive to the presence of Lewis bases, owing to the lower Lewis acidity of the silicon atom. Therefore, a different approach was required if these nucleophiles were to be used in aldol chemistry. Here, Denmark turned to the well-estabUshed electrophilic activation of the aldehyde but in an interestingly innovative way. He employed SiCU, which... 

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