Acetate enolates diastereofacial selectivity

Further support for this explanation is the fact that the chiral acetate enolates derived from A -acetyl-2-oxazolidone (46). in which the developing Rj <-> CH3 interaction leading to diastereomer A is absent, exhibit only poor diastereofacial selection. 

Chiral acetate (204) shows excellent diastereofacial selectivity and has obvious utility as a reagent for asymmetric aldol reactions. As shown in equation (122), reaction of (204) with benzaldehyde provides diastereomers (205) and (206). As shown in Table 23, entry 1, the diastereoselectivity is 83% if the lithium enolate is formed in the conventional manner and the aldol reaction is carried out in THF at -78 C. A significant improvement is obtained by using the magnesium enolate (Table 23, entry 5), and diastereoselectivity of up to 98% is obtained by the use of very low reaction temperatures (Table 23, entries 10-13). 

Largely stimulated by the synthesis of 3-lactam antibiotics, there have been widespread investigations into the stereochemical aspects of imine condensations, mainly involving reactions of enolates of carboxylic acid derivatives or silyl ketene acetals. In analogy to the aldol condensation, stereoselectivity of imine condensations will be discussed in terms of two types in this chapter (i) simple dia-stereoselectivity or syn-anti selectivity, when the two reactants are each prochiral (equation 12) and (ii) diastereofacial selectivity, when a new chiral center is formed in the presence of a pre-existing chiral center in one of the reactants (e.g. equation 13). The term asymmetric induction may be used synonymously with diastereofacial selectivity when one of the chiral reactants is optically active. For a more explicit explanation of these terms, see Heathcock s review on the aldol condensation. ... 

Tylonolide hemiacetal (33), the aglycone of the antibiotic tylosin, possesses an anti 14-hydroxymethyl-15-acyloxy stereochemistry conveniently contained in 26, which may be viewed as the western half of 33. In order to prepare the eastern half of 33, an aldol reaction leading to the desired syn stereochemistry at C-3 and C-4 is exploited. The reaction of achiral aldehyde 27 with the S-boron enolate 28 proceeds with the expected diastereofacial selectivity to provide, in a combined yield of 80% after O-silylation, a separable mixture of 29 (derived from the / -enantiomer of 27) and 30 (from the S-enantiomer of 27). Subsequent functional group transformation of 30 ultimately leads to the a-(TMS)methylketone 31. The anion of 31, generated with lithium hexamethylsilazide in THF at — 78 °C, undergoes a Peterson condensation with 26 to afford in 60% yield the seco-diC d 32. Treatment of 32 with 70% acetic acid at 85 °C for one hour affords 33 in 60% yield. The attractive feature of this... 

Optically active syn and anti diol units can be easily prepared by the asymmetric aldol reaction of aldehydes with silyl enolates (4) and (5), respectively, under the influence of chiral tin(II) Lewis acid (6). Diastereofacial selectivities are controlled simply by choosing the protective group of the ct-alkoxy part of ketene silyl acetals (eqs 2 and 3). 

Seebach has devised a clever method that utilizes the inherent stereochemical information of chiral a- and /3-heteroatom-substituted carboxylic acids in stereoselective alkylations (Scheme 3.10) [57, 61-64]. In this approach, the resident stereogenic center of the starting hydroxy acid dictates the configuration at C2 of the derived acetal 67. The new stereogenic center in turn controls the diastereofacial selectivity in the subsequent alkylation of the intermediate enolate 68. Alkylation reactions of these systems are observed to proceed with high levels of induction to give products such as 69 dr =93 7) [61]. In the final step of the sequence, hydrolysis of the acetal furnishes the optically active a-hydroxy acid 70. 

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