Catalyzed Mukaiyama reaction

In general, BF3 -catalyzed Mukaiyama reactions lack a cyclic organization because of the maximum coordination of four for boron. In these circumstances, the reactions show a preference for the Felkin type of approach and exhibit a preference for syn stereoselectivity that is independent of silyl enol ether structure.119... 

The copper-catalyzed conjugate addition of methyhnagnesium iodide to cyclohexenone and trapping of the resulting enolate as its trimethylsilyl enolate, followed by TrSbCle-catalyzed Mukaiyama reaction, are the first steps of an elegant synthesis of enantiomeri-caUy pure clerodanes (equation 45). 

The copper-catalyzed conjugate addition of methyl magnesium iodide to cyclohexenone and trapping the enolate as its trimethylsilyl enol ether, followed by a trityl hexachloro-antinomate-catalyzed Mukaiyama reaction, is apphed to / -(—jcarvone. C-2, C-3 functionalized chiral cyclohexanones are converted into their a-cyano ketones, which are submitted to Robinson annulation with methyl vinyl ketone. Highly functionalized chiral decalones are obtained that can be used as starting compounds in the total synthesis of enantiomerically pure clerodanes (equation 70). 

Scheme 2.8 gives some examples of chiral Lewis acids that have been used to catalyze aldol and Mukaiyama reactions. 

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. 

In 1989, Isayama and Mukaiyama reported a related Co-catalyzed coupling reaction that employs a,b-unsaturated nitriles, amides, and esters with PhSiLb as a hydrogen source [9]. Cobalt-bis(diketonato) complex, Co(II)(dpm)2 [dpm = bis(dipivaloylmethanato)] (5mol%), exhibited high catalytic activity at 20 °C in the coupling of excess acrylonitrile and ben-zaldehyde to provide b-hydroxy nitrile 4 in 93% yield (syn anti = 50 50) (Scheme 5). N,N-Dimethylacrylamide and methyl cinnamate both reacted... 

Mukaiyama reaction (Lewis acid-catalyzed Michael reaction) with electron-poor olefins, ketals and acetals, and enones 32... 

The aldol reactions introduced thus far have been performed under basic conditions where enolate species are involved as the reactive intermediate. In contrast to the commonly accepted carbon-anion chemistry, Mukaiyama developed another practical method in which enol species can be used as the key intermediates. He is the first chemist to successfully demonstrate that acid-catalyzed aldol reactions using Lewis acid (such as TiCU) and silyl enol ether as a stable enol equivalent can work as well.17 Furthermore, he developed the boron tri-fluoromethane sulfonate (triflate)-mediated aldol reactions via the formation of formyl enol ethers. 

The isomerization of an O-silyl ketene acetal to a C-silyl ester is catalyzed by a cationic zirconocene—alkoxide complex [92], This catalysis was observed as a side reaction in the zirconocene-catalyzed Mukaiyama aldol reactions and has not yet found synthetic use. The solvent-free bis(triflate) [Cp2Zr(OTf)2] also catalyzes the reaction in nitromethane (no reaction in dichloromethane), but in this case there may be competitive catalysis by TMSOTf (cf. the above discussion of the catalysis of the Mukaiyama aldol reaction) [91] (Scheme 8.51). 

Scheme 54 Salt 52 catalyzed Mukaiyama aldol reaction...

The Mukaiyama Reaction. The Mukaiyama reaction refers to Lewis acid-catalyzed aldol addition reactions of enol derivatives. The initial examples involved silyl enol ethers.40 Silyl enol ethers do not react with aldehydes because the silyl enol ether is not a strong enough nucleophile. However, Lewis acids do cause reaction to occur by activating the ketone. The simplest mechanistic formulation of the Lewis acid catalysis is that complexation occurs at the carbonyl oxygen, activating the carbonyl group to nucleophilic attack. 

Quite a number of Lewis acids besides TiCLt and BF3 can catalyze the Mukaiyama reaction, including Bu2Sn(03SCF3)2 45 Bu3SnC10446 Sn(03SCF3)2 47 Zn(03SCF3)248 and LiClC>4.49 Triaryl perchlorate salts are also very active catalysts.50 Examples of these reactions are included in Scheme 2.5. 

Effective catalysts include TiCL,57 SnCl4,58 (CH3)3Si03SCF3,59 and Bu2Sn03SCF3.60 61 Indium trichloride catalyzes Mukaiyama additions in aqueous solution. The reaction is best conducted by preforming the aldehyde-InCl3 complex and then adding the silyl enol ether and water. 

Bismuth-Catalyzed Mukaiyama Aldol Reaction of Silyloxyfurans. 102... 

Table 16 Vinylogous Bi(OTf)3-catalyzed Mukaiyama aldol reactions involving benzaldehyde and 2-(trimethylsilyloxy)furan...

The 9-catalyzed Mukaiyama-aldol reaction [74] of benzaldehyde and 1,2-dimethoxy benzaldehyde with a ketene silyl acetal in the presence of 10mol% thiourea 9 furnished the target product in low yield (36%), while the same reaction... 

The asymmetric aldol reaction is one of the most important topics in modern catalytic synthesis [54]. The products, namely />-hydroxy carbonyl compounds, have a broad range of applications and play a key role in the production of pharmaceuticals [55], Since the discovery of the catalytic asymmetric aldol reaction with enolsi-lanes by Mukaiyama et al. [56], steady improvements of the metal-catalyzed asymmetric aldol reaction have been made by many groups [57]. For this type of aldol reaction a series of chiral metal catalysts which act as Lewis acids activating the aldol acceptor have been shown to be quite efficient. It was recently shown by the Shibasaki group that the asymmetric metal-catalyzed aldol reaction can be also performed with unmodified ketones [57a], During the last few years, several new concepts have been developed which are based on use of organocatalysts [58], Enolates and unmodified ketones can be used as aldol donors. 

Harada, T. Mukaiyama, T. Trityl antimonate-catalyzed sequential reactions of epoxides with silylated nucleophiles. Rearrangement of epoxides and C-C or C-O bond forming nucleophilic reaction onto the intermediate carbonyl compounds. Bull. Chem. Soc. Jpn. 1993, 66, 882-891. 

The indium trichloride-catalyzed Mukaiyama aldol reaction of 3-aminoketoesters with various silylenolethers gave under solvent-free conditions 1,3-amino alcohols with high stereoselectivity [36], Several Robinson annelation reactions have been carried out enantio-selectively using (S)-proline as a chiral catalyst [37]. Remarkably, the enantioselectivity was distinctly higher in the absence of solvent than in DMSO. 

Table 6.18 Thiourea-catalyzed Mukaiyama-Mannich reactions of aldimines.

Table 6.44 Bis-triflamide-catalyzed Mukaiyama aldol reactions.

Table 6.45 Taddol-catalyzed Mukaiyama aldol reactions of N,Q-acetals.

Taddol-Catalyzed Mukaiyama Aldol Reactions of Aldehydes [7] (p. 245)... 

Thiourea-Catalyzed Mukaiyama-Mannich Reactions of Aldimines [12] (p. 215)... 

Song JJ, Tan Z, Reeves JT, Yee NK, Senanayake CH (2007) A-Heterocyclic carbene-catalyzed Mukaiyama aldol reactions. Org Lett 9 1013-1016... 

Scheme 6. Palladium-catalyzed Mukaiyama aldol reactions according to Shibasaki.

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