Silyl ketene acetals Lewis acid mediated

The controlled polymerization of (meth)acrylates was achieved by anionic polymerization. However, special bulky initiators and very low temperatures (- 78 °C) must be employed in order to avoid side reactions. An alternative procedure for achieving the same results by conducting the polymerization at room temperature was proposed by Webster and Sogah [84], The technique, called group transfer polymerization, involves a catalyzed silicon-mediated sequential Michael addition of a, /f-unsaluralcd esters using silyl ketene acetals as initiators. Nucleophilic (anionic) or Lewis acid catalysts are necessary for the polymerization. Nucleophilic catalysts activate the initiator and are usually employed for the polymerization of methacrylates, whereas Lewis acids activate the monomer and are more suitable for the polymerization of acrylates [85,86]. 

Preparation of (R)-(+)-3-hydroxy-4-methylpentanoic acid has been reported previously by the submitters.5 Alternative syntheses of (R)-(+)- or (S)-(-)-3-hydroxy-4-methylpentanoic acid rely on aidoi reactions of chiral ketone, ester, or amide enolates,2 8 10 and Lewis-acid mediated additions of chiral silyl ketene acetals to Isobutyraldehyde.3 11 Since both enantiomers of HYTRA are readily available this method enables one to prepare (S)-3-hydroxy-4-methylpentanoic acid as well. 

Minehan, T G, Kishi, Y, p-selective C-glycosidations Lewis-acid mediated reactions of carbohydrates with silyl ketene acetals. Tetrahedron Lett., 38, 6815-6818, 1997. 

As part of a series of studies on the use of BINOL-Ti(IV) complex 53 as a catalyst in a number of C-C bond-forming reactions, Mikami has reported the aldol addition reactions of thioacetate-derived silyl ketene acetals 55, 56 to a collection of highly functionalized aldehydes (Eq. (8.13)) [28]. As little as 5 mol% of the catalyst mediates the addition reaction and furnishes adducts 57 in excellent yields and up to 96% ee. One of the noteworthy features of the Mikami process is the fact that aldehyde substrates containing polar substituents can be successfully employed, a feature exhibited by few other Lewis-acid-catalyzed aldehyde addition reactions. 

In a landmark study of Mukaiyama aldol addition reactions, Heathcock proposed that the observed stereochemical outcome of the products in the Lewis acid-mediated addition of silyl ketene acetals to aldehydes was consistent with extended, open transition-state structures [38a, 38b]. This analysis has gained wide acceptance as a consequence of its predictive power. Alternative models involving cyclic, closed structures have also been postulated, in particular, the latter have been invoked with increasing regularity in the analyses of catalytic, enantioselective aldol addition reactions [7,30b,39a,39b. ... 

The TiCU-mediated reaction of enol silanes with imines was first introduced by Ojima and coworkers in 1977. The reaction was then extended to several similar substrates, i.e. nitrones, ot-methoxycarba-mates, aminals, 4-acetoxyazetidin-2-one, 40 anj to different Lewis acids, i.e. SnCU, TiCU-(0PH)2, catalytic ZnX2, catalytic TMSOTf, ° to give good yields of the addition products with low levels ( 80 20) or a complete lack of simple stereoselection. Moderate to good anti selectivities were reported in the addition of silyl ketene acetals to imines under particular reaction conditions (equation 9) significant results are summarized in Table 4. 

Table 4 Ratio of Diastereoisomers in the Lewis Acid Mediated Reactions of Silyl Ketene Acetals with Imines...

Chiral silyl ketene acetals (Il)-(20) were recently introduced for diastereoselective aldol-type additions. Camphor derivatives (11)-(16) are conformationally rigid with one diastereotopic face of the enol silane sterically shielded. - A -Methylephedrine derivatives (17)-(20) are likely to bind to TiCU through the NMe2 group with consequent dramatic conformational constraint.As a result the Lewis acid mediated additions to C=X occur in a highly stereoselective way. The chiral auxiliaries can then be removed (and recycled) by reduction, saponification or displacement with various nucleophiles to give useful synthetic intermediates. 

This reaction was first reported by Mukaiyama et al. in 1974. It is a Lewis acid-catalyzed Michael conjugate addition of silyl enol ether to o ,/3-unsaturated compounds. Therefore, it is generally referred to as the Mukaiyama-Michael reaction. Because this reaction is essentially a conjugate addition, it is also known as the Mukaiyama-Michael addition or Mukaiyama-Michael conjugate addition. This reaction is a mechanistic complement for the base-catalyzed Michael addition, j and often occurs at much milder conditions and affords superior regioselectivity. s Besides silyl enol ether, silyl ketene acetals are also suitable nucleophiles in this reaction.For the hindered ketene silyl acetals, the Lewis acid actually mediates the electron transfer from the nucleophiles to o ,/3-unsaturated carbonyl molecules.On the other hand, the Q ,j8-unsaturated compounds, such as 3-crotonoyl-2-oxazolidinone, alkylidene malonates, and a-acyl-a,/3-unsaturated phosphonates are often applied as the Michael acceptors. It has been found that the enantioselectivity is very sensitive to the reactant structures —for example, Q -acyl-Q ,j8-unsaturated phosphonates especially prefers the unique syn- vs anft-diastereoselectivity in this reaction. In addition,... 

Thiolesters, which are electronically more similar to ketones than esters because of the weak overlapping of the C(2p) and S(3p) orbitals, can undergo a wide variety of further synthetic transformations and are therefore very attractive reagents. The staggered transition structures for the Lewis acid mediat reaction of E and Z thiolester silyl ketene acetals with an aldehyde are summarized in Figure 1. It is assumed that the Lewis... 

Lewis acid-mediated addition of silyl ketene acetals to a chiral sulfimine gives precursors of /1-amino acids in fair to excellent deP Mixed diesters of both symmetrical and unsymmetrical diols have been prepared by reaction of carboxylic acids with cyclic ketene acetals of the diols, with the less substituted carbon of the cyclic dioxonium ion intermediate being attacked in most cases. Hydration of trifluoroacetylketene is discussed later under Enolization. 

Reactions Forming Carbon-Carbon Bonds. The reagent described herein has the structural features of an 0-silyl ketene acetal, and it therefore undergoes the typical reactions known for this class of compounds, especially Lewis acid-mediated C-C bond-forming processes. Since the reagent is extremely electron rich and therefore very reactive, catalytic amounts of mild Lewis acids such as ZnX2 suffice. The nucleophile which reacts with... 

Michael addition of the reagent to enoates and enones occurs at low temperature (—50 to —78 °C) in the presence of catalytic amounts of various Lewis acids. A catalytic amount of triph-enylmethyl perchlorate (5 mol %) effectively catalyzes the tandem Michael reaction of ethyl acetate-derived silyl ketene acetal to a, -unsaturated ketones and the sequential aldol addition to aldehydes with high stereoselectivity.HgL mediates the Michael addition to chiral enones, followed by Lewis acid-mediated addition to aldehydes. The Michael-aldol protocol has been used for the stereoselective synthesis of key intermediates on the way to prostaglandins, compactin, and ML-236A (eq 19). ... 

In the Mukaiyama addition of the aldol reaction [16], silyl ketene acetals or silyl enol ethers are added to aldehydes in a reaction mediated by Lewis acids or fluoride. Here again the Z-syn correlation is sometimes not observed [69, 70]. Thus, the Z-syn, E-anti correlation seems to be a rule with several exceptions [71]. 

Reductive aldol reaction of a,(5-unsaturated esters and enones with aldehyde mediated by a transition metal hydride complex and a hydride source, such as hydrosilane, is a versatile process to produce p-hydroxy carbonyl compounds (Scheme 15a) [21]. This reaction is thought to be an alternative transformation of Lewis acid-catalyzed Mukaiyama-type aldol reaction with silyl enol ethers or silyl ketene acetals (Scheme 15b). 

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