Mukaiyama-type aldol

Stereoselectivities of 99% are also obtained by Mukaiyama type aldol reactions (cf. p. 58) of the titanium enolate of Masamune s chired a-silyloxy ketone with aldehydes. An excess of titanium reagent (s 2 mol) must be used to prevent interference by the lithium salt formed, when the titanium enolate is generated via the lithium enolate (C. Siegel, 1989). The mechanism and the stereochemistry are the same as with the boron enolate. 

A few a/j/r -selective amide and imide enolates which arc able to provide high induced diastereo-selectivity have been uncovered very recently. The /V-propionylsultam 1 w hich opens a way to sryn-aldols as described in Section D.1.4.3.2.3.1. also allows the synthesis of r/nh-adducls. For this purpose. 1 is converted into the silyl-iV.O-ketene acetal 2 and subsequently added to aldehydes in a Mukaiyama-type aldol reaction106 to give awi-adducts 310<>f. 

Thus, the inherent selectivity of a chiral aldehyde is much stronger in Mukaiyama-type aldol reactions than in the additions of lithium or magnesium enolates17. 

Chiral sulfur-containing ligands have also been involved in other reactions such as metal-catalysed enantioselective Mukaiyama-type aldol reactions." ... 

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. 

Scheme 10.24 Cu-catalysed Mukaiyama-type aldol reactions with Ci-symmetric benzene-bridged aminosulfoximine ligands.

Polar polyoxyethylene-polyoxypropylene (POEPOP) resin, deriva-tized with a 4-hydroxymethyl phenoxy linker, was used as a solid support for lanthanide triflate-catalyzed Mukaiyama-type solid-phase aldol reactions.282 The use of an aqueous solvent was found to be crucial. The reactions on an N-terminal peptide aldehyde substrate proceeded in very high yields. 

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. 

Analysis of the Mukaiyama-type aldol coupling (Eq. 2) and the well-known hydrosilyla-tion of a,/l-unsaturated carbonyl compounds 11 in the presence of a rhodium catalyst, indicate that both can be explained by the intervention of the rhodium enolate 13. This line of reasoning provided the impetus to develop a new crossed aldol coupling using a hydrosilane, an a,yS-unsaturated ketone 11, and an aldehyde to form 15 (Scheme 6.4). 

Mukaiyama-type aldol reactions and vinylogous aldol reactions... 

It has been reported that the chiral NMR shift reagent Eu(DPPM), represented by structure 19, catalyzes the Mukaiyama-type aldol condensation of a ketene silyl acetal with enantiose-lectivity of up to 48% ee (Scheme 8B1.13) [29-32]. The chiral alkoxyaluminum complex 20 [33] and the rhodium-phosphine complex 21 [34] under hydrogen atmosphere are also used in the asymmetric aldol reaction of ketene silyl acetals (Scheme 8BI. 14), although the catalyst TON is quite low for the former complex. 

Recently, highly enantioselective Mukaiyama-type aldol reactions using a substoichiometric amount of chiral Lewis acid have been reported from three research groups. Mukaiyama et al. 

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... 

Table 9.1 Asymmetric Mukaiyama-type aldol reactions of a glycine derivative catalyzed by in situ-generated chiral quaternary ammonium fluoride.

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],... 

Chiral sulfoximines liganded to copper(II) give highly enantioselective vinylogous Mukaiyama-type aldol reactions under mild conditions.137 A chiral sulfinyl group has been used to achieve 1,5- and 1,6-asymmetric induction in Mukaiyama aldols, using Yb(OTf)3 catalysis.138... 

Aldol reactions using a carbocation as an organocatalyst An organocatalytic aldol reaction based on a different concept was developed by the Chen group. The chiral triarylcarbenium ion 34 was used as a novel non-metallic Lewis acid catalyst in a Mukaiyama-type aldol reaction which led to enantiomerically enriched aldol products (Scheme 6.17) [67]. Although non-chiral trityl salt-mediated catalytic aldol reactions had previously been reported by Mukaiyama and co-workers [68], the construction of a suitable chiral carbenium ion remained a challenge. Optically active salts of type 34 were synthesized as Lewis acids based on a reactive carbe-... 

Intermolecular Michael addition [4.1] Intermolecular aldol reaction [6.2.1] Intramolecular aldol reaction [6.2.2] Aldol-related reactions (e.g. vinylogous Mukaiyama-type aldol) [6.2.3]... 

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