Oxazolidinone auxiliary carbonyl compounds

The chiral A/ -propionyl-2-oxazolidones (32 and 38) are also useful chiral auxiliaries in the enantioselective a-alkylation of carbonyl compounds, and it is interesting to observe that the sense of chirality transfer in the lithium enolate alkylation is opposite to that observed in the aldol condensation with boron enolates. Thus, whereas the lithium enolate of 37 (see Scheme 9.13) reacts with benzyl bromide to give predominantly the (2/ )-isomer 43a (ratio 43a 43b = 99.2 0.8), the dibutylboron enolate reacts with benzaldehyde to give the (3R, 25) aldol 44a (ratio 44a 44b = 99.7 0.3). The resultant (2R) and (25)-3-phenylpropionic acid derivatives obtained from the hydrolysis of the corresponding oxazolidinones indicated the compounds to be optically pure substances. 

The enolates of other carbonyl compounds can be used in mixed aldol condensations. Extensive use has been made of the enolates of esters, thioesters, and amides. Of particular importance are several modified amides, such as those derived from oxazolidinones, that can be used as chiral auxiliaries. The methods for formation of these enolates are similar to those for ketones. Lithium, boron, tin, and titanium derivatives have all been used. Because of their usefulness in aldol additions and other synthetic methods (see especially Section 6.4.2.3, Part B), there has been a good deal of interest in the factors that control the stereoselectivity of enolate formation from esters. For simple esters such as ethyl propanoate, the E-enolate is preferred under kinetic conditions using a strong base such as EDA in THE solution. Inclusion of a... 

The methods that we have just discussed can be used to control the ratio of syn and anti diastereomeric products. It is often desired to also control the reaction to provide a specific enantiomer. Nearby stereocenters in either the carbonyl compound or the enolate can impose facial selectivity. Chiral auxiliaries can achieve the same effect. Finally, use of chiral Lewis acids as catalysts can also achieve enantioselectivity. Much effort has also been devoted to the use of chiral auxiliaries and chiral catalysts to effect enantioselective aldol reactions." A very useful approach for enantioselective aldol additions is based on the oxazolidinones 4,5, and 6. 

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. ... 

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... 

A number of chiral auxiliaries has been designed for enantioselective 1,4-addition to a, -unsaturated carbonyl compounds. Chiral oxazolidinones are among the most efficient, affording the Michael-adducts with up to 99% ee. Asymmetric conjugate addition of an arylmagnesium reagent to cinnamoyloxazolidinone 151 is the key step in the synthesis of (+)-tolterodine 152, an important muscarinic receptor agonist (Scheme 2-58). 

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). ... 

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