Enolate compounds Evans oxazolidinones

Guided by the success of the Evans and related auxiliaries, several attempts were made to use enantiomerically pure a-bromoacyl oxazolidinones for stereoselective Reformatsky reactions. Fukuzawa and coworkers developed the reaction of various bromoacetyl oxazolidinones 323 as an alternative to an asymmetric acetate aldol addition. The conversion was mediated by samarium iodide and yielded P-hydroxy carbonyl compounds 325 with high diastereoselectivity in optimal combinations of auxiliary group and aldehyde. Among the different auxiliaries, the geminal dimethyl- and diphenyl-substituted ones performed better than the original Evans oxazolidinones. The stereochemical outcome was rationalized by assuming that an O-bound samarium(III) enolate reacts via a chair-like... 

Chiral Auxiliary Chemistry The introduction of a sulfur atom to alkanes through a C—H activation is currently limited to enolizable C—H bonds such as a-sulfeny-lation of carbonyl compounds. Although there are other synthetic routes to a-sulfenylated carbonyl compounds, the preparation of chiral compounds has relied on the chiral auxiliary-assisted diastereoselective thioalkylation. In 1985, Paterson et al. reported that the chiral (9-silylated imide enolates 385 of Evans oxazolidinone could be sulfenylated with high diastereoselectivities by phenylsulfenyl chloride (Scheme 46.44). ... 

The approach for the enantioselective aldol reaction based on oxazolidinones like 22 and 23 is called Evans asymmetric aldol reaction.14 Conversion of an oxazolidinone amide into the corresponding lithium or boron enolates yields the Z-stereoisomers exclusively. Reaction of the Z-enolate 24 and the carbonyl compound 6 proceeds via the cyclic transition state 25, in which the oxazolidinone carbonyl oxygen and both ring oxygens have an anti conformation because of dipole interactions. The back of the enolate is shielded by the benzyl group thus the aldehyde forms the six-membered transition state 25 by approaching from the front with the larger carbonyl substituent in pseudoequatorial position. The... 

The alkylations of the oxazolidinone-containing amide enolate of Figure 13.43 occur with diastereoselectivities of 93 7 and > 99 1, respectively. The hydrogen peroxide-accelerated alkaline hydrolysis of these compounds occurs with complete retention of the previously established configuration at the a-stereocenter. To date, the Evans synthesis offers the most versatile access to enantiomerically pure a-alkylated carboxylic acids. 

The oxazoline 184 provides an attractive approach to lactacystin as it is a protected form of 3-hydroxyleucine. The other half of the molecule was made in the LeukoSite synthesis by a very different method the alkylation of an Evans chiral auxiliary. This was chosen partly because they wished to vary the alkyl group on the pyrrolidone ring and we use the propyl compound as example. The phenylalanine derived oxazolidinone 193 (chapter 27) was acylated and then the titanium enolate of 194 was alkylated to give 195 with very high selectivity and the chiral auxiliary removed to give the simple acid 196. 

The aldol reaction is an important carbon-carbon bond formation reaction. The general concept of the reaction involves the nucleophilic addition of a ketone enolate to an aldehyde to form a P-hydroxy ketone, or aldol , a structural unit found in many naturally occurring molecules and pharmaceuticals. Since the aldol addition reaction creates two new stereocenters, up to four stereoisomers may result. The Evans aldol reaction performs a diasteroselective aldol transformation using an Evans s acyl oxazolidinone (also known as Evans chiral auxiliary), a chiral carbonyl compound that creates a temporary chiral enolate for the aldol addition. Upon subsequent removal of the auxiliary, the desired aldol stereoisomer is revealed. ... 

After the intermolecular palladium-catalyzed arylation of enolates had been discovered by the research groups of Buchwald, Hartwig, and Miura [63], it was an obvious idea to explore a stereoselective variant that was based on the reliable Evans auxiliaries, while catalytic, enantioselective protocols (cf. Section 5.2) were developed at the same time. However, only relatively moderate diastereoselectivity in the formation of arylation products 133 was achieved when the silyl ketenimine (S)-132 derived from Af-propionyl oxazolidinone was coupled with aryl bromides under palladium catalysis, as disclosed by Hartwig and Liu [64]. The additive zinc(ll) f-butoxide permitted to lower the temperature to 25 °C so that the diastereoselectivity could be enhanced (Scheme 4.26). The authors noticed that Ley s chiral dioxanone 134 proves itself as an auxiliary that induced excellent diastereoselectivity and led to the formation of arylated compounds 135 in very high diastereomeric ratios. The chiral auxiliary group was readily removed by treatment with chlorotrimethylsUane and methanol, so... 

The utility of the Al-acyl oxazolidinone alkylation has been demonstrated in the context of numerous total syntheses. For instance, in 2003, Evans and Connell used this method in the asymmetric total synthesis of the antifungal macrolide (-l-)-roxaticin 221. (+)-Roxaticin 221 is a pen-taene macrolide isolated from an unidentihed streptomycete similar to Strepfomyces ruber. Like similar compounds, it shows antifungal but not antibacterial activity. In the alkylation step (Scheme 7.32), 202 was treated with TiCLj and EtsN to provide the required Z-(0)-enolate, which was then treated with BOMCl to afford 209 in 99% yield and >200 1 diastereoselectivity. Removal of the auxiliary was... 

---