Mukaiyama aldol methodology

The pioneering discovery by Mukaiyama in 1974 of the Lewis acid mediated aldol addition reaction of enol silanes and aldehydes paved the way for subsequent explosive development of this innovative method for C-C bond formation. One of the central features of the Mukaiyama aldol process is that the typical enol silane is un-reactive at ambient temperatures with typical aldehydes. This reactivity profile allows exquisite control of the reaction stereoselectivity by various Lewis acids additionally, it has led to the advances in catalytic, enantioselective aldol methodology. Recent observations involving novel enol silanes, such as enoxy silacyclobutanes and O-si-lyl M(9-ketene acetals have expanded the scope of this process and provided additional insight into the mechanistic manifolds available to this versatile reaction. 

Mukaiyama aldol reactions. Catalyst 69 has been used in the synthesis of bryosta-tin and epothilone segments and, for example, using silyl enol ether 70 high levels of stereocontrol are possible (Scheme 9-23) [48]. This methodology has recently been used in an approach to acutiphycin [49]. 

Cyclohepta-3,5-dienone)iron complexes can be stereoselectively methylated and hydroxylated. The electrophile adds exclusively anti to the tricarbonyliron fragment. Double methylation or hydroxylation of the a and a positions is accomplished in high overall yield (Scheme 4-146). Silyl enol ethers adjacent to tricarbonyl(Ti -diene)iron units can be subjected to Mukaiyama aldol reaction with aldehydes to provide aldol adducts with varying diastereoselectivity. This methodology has, for example, been applied to the enantioselective synthesis of the dienetriols streptenol C and D (Scheme 4-147). ... 

Because the products of 1,7- and 1,6,7-asymmetric induction reactions have structures frequently found in polyketide compounds and multifunctional groups to be manipulated, these reactions have been applied to synthesize polyketide in short steps. For example, the saii-Helicobacter pylori agent actinopyrone A 313 was synthesized in nine steps from ent -305 (Scheme 8.52). The total synthesis started from the vinylogous Mukaiyama aldol reaction to give the C11-C18 moiety 311 as a single isomer. Protection of the secondary alcohol was followed by DIBAL reduction to give aldehyde 312. As mentioned, the methodology makes it possible to synthesize polyketide compounds in short steps. 

Recently, Yamamoto et al. have shown that the chiral acyloxyborane complex 31 is an excellent catalyst for the asymmetric Mukaiyama condensation of simple silyl enol ethers (Scheme 8B1.19 Table 8B1.11 entries 1-7) [43], The syn-aldol adducts are formed preferentially with high enantiomeric excess regardless of the stereochemistry (EI7) of the silyl enol ethers, suggesting an extended transition state (entries 4, 7). This methodology has been... 

Lewis acid, by enolsilane addition to chiral oxonium ions (cf. equation 40). Oxonium ions are also probably involved in the diastereoselective AlCb-mediated additions of enolsilanes to chiral 2-benzenesulfo-nyl cyclic ethers. In the diastereoselective additions to chiral acetals - (see Section 2.4.4.4), an extension of the methodology shown in Scheme 9 to the enantio differentiation of meso 1,2- and 1,4-diols was reported. An intramolecular Mukaiyama acetal-aldol reaction (see Section 2.4.4.S) was reported as the key step to construct the 11-memboed ring of hydroxyjatrophone A and B. "... 

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