Aldol-type reactions silyl enol ether

SCHEME 120. Lewis acid-catalyzed asymmetric aldol-type reaction of enol silyl ethers. 

Cationic Pd complexes can be applied to the asymmetric aldol reaction. Shibasaki and coworkers reported that (/ )-BINAP PdCP, generated from a 1 1 mixture of (i )-BINAP PdCl2 and AgOTf in wet DMF, is an effective chiral catalyst for asymmetric aldol addition of silyl enol ethers to aldehydes [63]. For instance, treatment of trimethylsi-lyl enol ether of acetophenone 49 with benzaldehyde under the influence of 5 mol % of this catalyst affords the trimethylsilyl ether of aldol adduct 113 (87 % yield, 71 % ee) and desilylated product 114 (9 % yield, 73 % ee) as shown in Sch. 31. They later prepared chiral palladium diaquo complexes 115 and 116 from (7 )-BINAP PdCl2 and (i )-p-Tol-BINAP PdCl2, respectively, by reaction with 2 equiv. AgBF4 in wet acetone [64]. These complexes are tolerant of air and moisture, and afford similar reactivity and enantioselec-tivity in the aldol condensation of 49 and benzaldehyde. Sodeoka and coworkers have recently developed enantioselective Mannich-type reactions of silyl enol ethers with imi-nes catalyzed by binuclear -hydroxo palladium(II) complexes 117 and 118 derived from the diaquo complexes 115 and 116 [65]. These reactions are believed to proceed via a chiral palladium(fl) enolate. 

In the first step of the reaction silyl enol ether 23 is formed. The use of bulky bases like NaHMDS at -78 °C ensures the formation of the so-called kinetic enolate 22, which is obtained by deprotonation of the ketone at the less-hindered a-position. Afterwards, 22 is protected by trimethylsilyl chloride (TMSCl), yielding TMS-enol ether 23. TMS ethers are often unstable under acidic and basic conditions and barely survive the simplest chemical transformation. TMS-enol ethers of this type are often used in Mukaiyama aldol reactions with catalytic amounts of Lewis acids. 

Stereoselective reactions with acetals. Noyori et al. (10,438) have used this Lewis acid to promote an aldol-type reaction between enol silyl ethers and acetals and have noted high. syn-selectivity in this process. Molander and Haar report that reaction of acetals with cyanotrimethylsilane promoted by TMSOTf results in a-alkoxy cyanides and that this reaction can be diastereoselective when the acetal is substituted at the 4-position by an alkoxy group. The diastereoselectivity depends on the nature of the acetal and the 4-alkoxy group. Dimethoxy acetals show slight diastereoselectivity, but diisopropoxy and dibenzyl acetals can show diastereoselectivity of 5-10 1. The diastereoselectivity also depends on the type of 4-substituent. Acetoxy and t-butyldimethylsilyloxy groups have no effect on the diastereoselectivity, but methoxy, benzyloxy, and allyloxy groups promote anri-selectivity. Since a metal template is not involved, the diastereoselectivity... 

For some condensations with silylated substrates as starting compounds, trimethylsilyl inflate can be used as a catalyst [103, 104, 105] Atypical example of such a reaction is the aldol type condensation of silyl enol ethers and acetals catalyzed by 1-5 mol% of trimethylsilyl inflate [103] (equation 53)... 

More recently, asymmetric Mannich-type reactions have been studied in aqueous conditions. Barbas and co-worker reported a direct amino acid catalyzed asymmetric aldol and Mannich-type reactions that can tolerate small amounts of water (<4 vol%).53 Kobayashi found that a diastereo- and enantioselective Mannich-type reaction of a hydrazono ester with silyl enol ethers in aqueous media has been successfully achieved with ZnF2, a chiral diamine ligand, and trifluoromethanesul-fonic acid (Eq. 11.31).54 The diastereoselective Mannich-type reaction... 

With these results in hand, we have next introduced new types of Lewis acids, e.g scandium tris(-dodecyl sulfate) (4a) and scandium trisdodecanesul-fonate (5a) (Chart 1).[1S1 These Lewis acid-surfactant-combined catalysts (LASCs) were found to form stable colloidal dispersions with organic substrates in water and to catalyze efficiently aldol reactions of aldehydes with very water-labile silyl enol ethers. 

Stereoselective aldol-type condensation.1 Enol silyl ethers do not undergo aldol condensation with aldehydes or ketones in the presence of this triflate,. but the reaction occurs at —78° (4-12 hours) with the corresponding acetals or ketals (and certain orthoesters). Moreover the erythro-aldol is formed with high stereoselectivity. 

Enantioselective condensation of aldehydes and enol silyl ethers is promoted by addition of chiral Lewis acids. Through coordination of aldehyde oxygen to the Lewis acids containing an Al, Eu, or Rh atom (286), the prochiral substrates are endowed with high electrophilicity and chiral environments. Although the optical yields in the early works remained poor to moderate, the use of a chiral (acyloxy)borane complex as catalyst allowed the erythro-selective condensation with high enan-tioselectivity (Scheme 119) (287). This aldol-type reaction may proceed via an extended acyclic transition state rather than a six-membered pericyclic structure (288). Not only ketone enolates but ester enolates... 

Figure 8C.7. Transition states of Mukaiyama-type aldol reaction of ketone silyl enol ethers.

BINOL-derived titanium complex was found to serve as an efficient catalyst for the Mukaiyama-type aldol reaction of ketone silyl enol ethers with good control of both absolute and relative stereochemistry (Scheme 8C.24) [57]. It is surprising, however, that the aldol products were obtained in the silyl enol ether (ene product) form, with high syn-diastereoselec-tivity from either geometrical isomer of the starting silyl enol ethers. 

The silatropic ene pathway, that is, direct silyl transfer from an silyl enol ether to an aldehyde, may be involved as a possible mechanism in the Mukaiyama aldol-type reaction. Indeed, ab initio calculations show that the silatropic ene pathway involving the cyclic (boat and chair) transition states for the BH3-promoted aldol reaction of the trihydrosilyl enol ether derived from acetaldehyde with formaldehyde is favored [60], Recently, we have reported the possible intervention of a silatropic ene pathway in the catalytic asymmetric aldol-type reaction of silyl enol ethers of thioesters [61 ]. Chlorine- and amine-containing products thus obtained are useful intermediates for the synthesis of carnitine and GABOB (Scheme 8C.26) [62],... 

Stereoselective synthesis of /1-amino esters via asymmetric aldol-type and aza-Diels-Alder reactions has been reviewed.81 Siliranes react cleanly with benzaldehyde to produce oxasilacyclopentanes—with inversion—under conditions of Bu OK catalysis enolizable aldehydes yield silyl enol ethers.82... 

Asymmetric aldol reactions.1 This diamine (1) when coordinated with tin(II) triflate and dibutyltin diacetate promotes highly stereoselective aldol-type reactions between silyl enol ethers and aldehydes. 

Aldol reaction,6 This triflate is an effective catalyst for an aldol-type reaction between silyl enol ethers and acetals at -78°. The reaction shows moderate to high svn-selectivity regardless of the geometry of the enol ether. 

Bis(pentafluorophenyl) tin dibromide effects the Mukaiyama aldol reaction of ketene silyl acetal with ketones, but promotes no reaction with acetals under the same conditions. On the other hand, reaction of silyl enol ether derived from acetophenone leads to the opposite outcome, giving acetal aldolate exclusively. This protocol can be applied to a bifunctional substrate (Equation (105)). Keto acetal is exposed to a mixture of different types of enol silyl ethers, in which each nucleophile reacts chemoselectively to give a sole product.271... 

Aldol-type reactions. Trityl perchlorate catalyzes an aldol-type reaction between silyl enol ethers and acetals or ketals to give p-alkoxy ketones. The yields are comparable to those obtained with TiCU (6, 594). The iyn-aldol is formed predominantly ( 4 1). 

Mukaiyama Aldol Condensation. The BINOL-derived titanium complex BINOL-T1CI2 is an efficient catalyst for the Mukaiyama-type aldol reaction. Not only ketone silyl enol ether (eq 25), but also ketene silyl acetals (eq 26) can be used to give the aldol-type products with control of absolute and relative stereochemistry. 

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