Aldol condensations Mukaiyama-like

It seems likely that the reaction proceeds through a prototropic ene reaction pathway, a pathway that has not been previously recognized as a possible mechanism in the Mukaiyama aldol condensation. Usually an acyclic antiperiplanar transition-state model has been used to explain the formation of the syn diastereomer from either ( )- or (Z)-silyl enol ethers [91]. The cyclic ene mechanism, however, now provides another rationale for the syn diastereoselectivity irrespective of enol silyl ether geometry (Sch. 32). 

It appears likely that the reaction proceeds through an ene reaction pathway. Such an ene reaction pathway has not been previously recognized as a possible mechanism in the Mukaiyama aldol condensation. Usually, an acyclic antiperi-... 

For these reasons, this variation is not as widely used as the anionic reaction (the aldol condensation). The base catalyzed reaction often leads to dimers, polymers, self-condensation products or a, 5-unsaturated carbonyl derivatives, as described in Section 9.4.A. Mukaiyama and co-workers modified the acid-catalyzed reaction to include silyl enol ethers. He found that they react with carbonyl compounds to produce aldol-like... 

A likely cyclic transition state makes the Mukaiyama aldol condensation diastereoselective, that is, strongly favoring one diastereomer of the product. Addition of a chiral ligand or chelator (such as a chiral diamine) can make the process enantioselective as well, that is, favoring one enantiomer. 

Although no examples are presented in this chapter where amino acids are prepared via an Aldol condensation, "Aldol-like" reactions have been used. The Mukaiyama Aldol reaction (or just the Mukaiyama reaction) involves the condensation of a silyl enol ether with an aldehyde, catalyzed by metal salts such as TiCLt. This approach has been reported several times for the synthesis of amino acids. This section will show the basic approach, along with some variations that have proved to be useful. 

Mukaiyama found that Lewis acids can induce silyl enol ethers to attack carbonyl compounds, producing aldol-like products.22 The reaction proceeds usually at -78 °C without selfcondensation and other Lewis acids such as TiCl4 or SnCI4 are commonly used. The requisite silyl enol ether 27 was prepared by treatment of ketone 13 with lithium hexamethyl disilazide (LiHMDS) and trapping the kinetic enolate with chlorotrimethylsilane. When the silyl enol ether 27 was mixed with aldehyde 14 in the presence of BF3-OEt2 a condensation occurred via transition state 28 to produce the product 29 with loss of chlorotrimethylsilane. The induced stereochemistry in Mukaiyama reactions using methylketones and a, -chiral aldehydes as substrates... 

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