Silyl mukaiyama aldol reaction

As an extension of this work, these authors have applied this catalyst system to vinylogous asymmetric Mukaiyama-type aldol reactions, involving silyl vinyl ketene acetals and pyruvate esters. These reactions afforded the corresponding y,5-unsaturated a-hydroxy diesters with quaternary centres in high yields and enantioselectivities of up to 99% ee (Scheme 10.25). It was shown that the presence of CF3CH2OH as an additive facilitated the turnover of the catalyst. 

In the Mukaiyama cross-aldol reaction, an aldehyde and a ketene silyl acetal [e.g. (43)] react via Lewis acid catalysis to give a jS-silyloxy ester (44). The reaction... 

A Mukaiyama-type aldol reaction of silyl ketene thioacetal (48) with an aldehyde with large and small a-substituents (e.g. Ph and Me), catalysed by boron trifluoride etherate, gives mainly the iyn-isomer (49), i.e. Cram selectivity. For the example given, changing R from SiBu Me2 to Si(Pr )3 raises the syn preference considerably, which the authors refer to as the triisopropylsilyl effect. Even when the and R groups are as similar as ethyl and methyl, a syn. anti ratio of 5.4 was achieved using the triisopropylsilyl ketene thioacetal. 

Owing to the high Lewis acidity the group 14 organometallic cations are polymerization catalysts par excellence. so Silanorbonyl cations and triethylsilyl arenium have been shown to be efficient catalysts for metal-free hydrosilylation reactions. Chiral silyl cation complexes with acetonitrile have been applied as cata -lysts in Diels Alder-type cyclization reactions °792 intramolecularly stabilized tetracoordinated silyl cations have been successfully used as efficient catalysts in Mukaiyama-type aldol reactions. 

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. 

A stereoselective Mukaiyama-type aldol reaction of bis(trimethylsilyl)ketene acetals produces silyl aldols with syn stereoselectivity, predominantly due to steric effects.23... 

Recently, Corey and coworkers prepared the cinchonidine-derived bifluoride 20 from the corresponding bromide by passage of a methanolic solution through a column of Amberlyst A-26 OH- form, and subsequent neutralization with 2 equiv. of 1 N HF solution and evaporation (the modified method C in Scheme 9.5). The catalytic activity and chiral efficiency of 20 (dried over P205 under vacuum) have been demonstrated by the development of a Mukaiyama-type aldol reaction of ketene silyl acetal 21 with aldehydes under mild conditions, giving mostly syw-P-hydroxy-a-amino esters 22 as the major diastereomer with good to excellent enantiomeric excesses (Table 9.4) [23],... 

Table 4.1 The chiral ammonium bifluoride 12-catalyzed asymmetric Mukaiyama-type aldol reaction of ketene silyl acetal 13 with aldehydes. (For experimental details see Chapter 14.1.5)...

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. 

I n 1993, the first cinchona-catalyzed enantioselective Mukaiyama-type aldol reaction of benzaldehyde with the silyl enol ether 2 of 2-methyl-l -tetralone derivatives was achieved by Shioiri and coworkers by using N-benzylcinchomnium fluoride (1, 12 mol%) [2]. However, the observed ee values and diastereoselectivities were low to moderate (66-72% for erythro-3 and 13-30% ee for threo-3) (Scheme 8.1). The observed chiral inductioncan be explained by the dual activation mode ofthe catalyst, that is, the fluoride anion acts as a nucleophilic activator of the silyl enol ethers and the chiral ammonium cation activates the carbonyl group of benzaldehyde. Further investigations on the Mukaiyama-type aldol reaction with the same catalyst were tried later by the same [ 3 ] and another research group [4], but in all cases the enantioselectivities were too low for synthetic applications. 

As shown in Scheme 8.2, chiral P-hydroxy-a-amino adds can be obtained by the Mukaiyama-type aldol reaction of aldehydes with glycine-derived enol silyl ethers using cinchona-based quaternary ammonium salts. In 2004, Castle and coworkers [9] found that dnchona-based quaternary ammonium salts such as 13 are also able to catalyze the dired aldol readion of aldehydes with the glydne donor 14 in the presence of a phosphazene base such as BTTP (t-butyliminotri(pyrrolidino)phos-... 

Other important aldol condensations are the Mukaiyama-type aldol reactions of silyl enol ethers with aldehydes that usually require catalyst activation. Yamamoto reported that such reactions under high pressure proceed (i) without catalyst even at room temperature, (ii) without isomerization of the formed adducts and (iii) with a reversed synlanti stereoselectivity compared with that of the TiCU-catalysed reactions. ... 

Metal Free Transition metal catalysts are highly effective for C—H bond activation. However, transition metal complexes are not only expensive, but also difficult to remove from the reaction products, resulting in toxicity concerns. DDQ is a well-known oxidant in organic chemistry [33]. For many years, it has been used for the oxidation of alcohols to ketones and aromatization. The first intermolecular C—C bond formation was realized by DDQ-mediated Mukaiyama-type aldol reactions [34], The reactions of electron-rich benzyl ethers and silyl enol ethers afforded 3-alkoxy-3-phenylpropionyl derivatives at ambient temperature with moderate to excellent yields (Equation 11.12). 

The latter process can form part of a novel tandem addition reaction.[19c] The lack of accompanying silyl transfer is in contrast to other asymmetric Mukaiyama-type aldol reactions. [20]... 

Catalyzed Mukaiyama-type aldol reactions of silyl enol ethers or silyl ketene acetals with aldehydes lead to the same products. For recent advances see a) G. E. Keck, D. Krishnamurthy, J. Am. Chem. Soc. 1995, 117, 2363 b) M. Sato, S. Sunami, Y. Sugita, C. Kaneko, Heterocycles 1995, 41, 1435, and references therein. 

Indeed, the first example of other Lewis add, except for TiCU and BX3, catalyzed chalcogenide-MBH reactions dates back to the 1980s, when Noyori et al. first demonstrated that the conjugated addition of a silyl selenide to an enone catalyzed by TMSOTf provided a silyl enol ether, which can be successfully engaged in subsequent Mukaiyama retro-aldol reactions with various... 

Recently, Kobayashi noticed that the presence of a small amount of a surfactant such as sodium dodecyl sulfate (SDS) showed a remarkable enhancement of the reactivity in the Mukaiyama-catalyzed aldol reaction in pure water using Yb(OTf)3 or better Sc(OTf )3 as the catalyst without addition of the surfactant, the reaction was very sluggish (Scheme 8.4). Other surfactants such as calix[6]arene derivatives bearing sulfonate and alkyl groups or aromatic and aliphatic anionic surfactants have also been found to be highly effective in the aqueous Mukaiyama aldol reactions in pure water, affording the aldol products in high yields. This was probably due to the formation of micelles which stabilized the labile silyl enol ethers and thus promoted the aldol reaction. 

Kitazume and coworkers used microreactors with microchaimels 100 pm wide and 40 pm deep for the synthesis of a series of organofluorine compounds [19,20]. The silylation of4,4,4-trifluorobutan-2-one and the Mukaiyama-type aldol reaction of the resulting enol silyl ether with acetals gave good yields of the desired products [20]. They also described nitro-aldol reactions of 2,2-difluoro-l-ethoxyethanol and Michael additions of nitroalkanes to ethyl 4,4,4-trifluorocrotonate and ethyl 4,4-difluorocrotonate [19,20]. Reactions were carried out at room temperature, and... 

Aldol Reactions. The title reagent and its various congeners continue to find application in Mukaiyama-t3fpe aldol reactions as versatile nucleophilic propionate synthons with predictable behavior.For example, the ( )-isomer of the reagent produced the expected major isomer in a boron trifiuoride etherate mediated addition to a complex aldehyde en route to a C19-C35 subunit of swinholide A (eq 14). Remote stereoinduction in Mukaiyama aldol reactions of the reagent with (2-sulfinylphenyl)acetaldehydes was recently observed anti aldol adducts were obtained preferentially regardless of the geometry of the silyl ketene thioacetal employed. ... 

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). 

The asymmetric Mukaiyama-type aldol reaction is a representative example of ammonium fluoride-catalyzed reactions (Scheme 14.7) (25). In the first step, silyl enol ether 10 reacts with ammonium fluoride to produce ammonium enolate 11 with generation of trialkylsilyl fluoride. The ammonium enolate 11 then reacts with aldehyde to produce ammonium alkoxide 12. Attack of this alkoxide anion on silyl enol ether 10 leads to the regeneration of ammonium enolate 11 and the formation of silylated aldol product 13. 

Cinchona alkaloid-derived ammonium phenoxides as Lewis base catalysts have been appUed to asymmetric vinylogous Mukaiyama-type aldol reactions (Scheme 14.8) [30]. In the first step of this reaction, silyl compound 14 reacts with ammonium phenoxide to produce ammonium dienolate 15 with generation of trimethyl(phenoxy) silane. The latter part of this reachon mechanism is basically simQar to the reaction mechanism of ammonium fluoride-catalyzed reactions with silyl nucleophiles as shown in Scheme 14.7. This reaction system was also appUed to other asymmetric transformations [6a, 31]. 

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