Evans’ acyloxazolidinone

Evans and co-workers investigated the effect of a number of -symmetric bis(oxazoline) ligands on the copper(II)-catalysed Diels-Alder reaction of an N-acyloxazolidinone with cyclopentadiene. Enantiomeric excesses of up to 99% have been reported (Scheme 3.4). Evans et al." suggested transition state assembly 3.7, with a square planar coordination environment around the central copper ion. In this scheme the dienophile should be coordinated predominantly in an cisoid fashion in... 

Chiral a,/ -unsaturated A-acyloxazolidinones have been regarded as a complement for type I dienophile reagents. Evans et al.4 reported a Diels-Alder reaction promoted by dialkyl aluminum chloride. In this reaction, chiral a,/ -unsaturated A-acyloxazolidinones were used as highly reactive and diaster-eoselective dienophiles. The stereogenic outcome of the Diels-Alder adducts... 

The MgX2/R3N systems offer another useful synthetic interest. Recently, Evans and coworkers have demonstrated that substoichiometric amounts of magnesium halides in the presence of an amine and chlorotrimethylsilane catalyze the direct aldol reaction of A-acyloxazolidinones and A-acylthiazolidininethiones with high diastereoselectivity (equation 59). 

Recently, Evans has reported diastereoselective magnesium hahde-catalyzed anti-aldol reactions of chiral Af-acyloxazolidinones 88 (equation 115) and A-acylthiazolidine-thiones 90 (equation 116) . ... 

Chiral glycine enolate synthons have been employed in diastereoselective alkylation reactions [15]. A complementary approach to the synthesis of a-amino acids is the electrophilic amination of chiral enolates developed by Evans [16]. Lithium enolates derived from A-acyloxazolidinones 38, reacted readily with DTBAD to produce the hydrazide adducts 39 in excellent yields and diastereoselectivities (Scheme 18). Carboximides 38 were obtained by A-acylation of (S)-4-(phenylmethyl)-2-oxazoli-dinone and the lithium-Z-enolates of 38 were generated at -78 °C in THF under inert atmosphere using a freshly prepared solution of lithium diisopropylamide (LDA, 1.05 equiv.) [17]. 

The Evans-aldol method using a boron enolate derived from chiral iV-acyloxazolidinone reacted with aldehydes to give syn-aldols via attack exclusively on the re face of the double bond of the enolate (Equation (177)). Unexpected and unusual si face attack was resulted in the reaction with fluorine-containing carbonyl compounds such as trifluoro acetaldehyde (Equation (178)).680 681... 

Evans DA, Chapman KT, Bisaha J (1988) Asymmetric Diels-Alder cycloaddition reactions with chiral a,fS-iinsatiirated N-acyloxazolidinones. J Am Chem Soc 110 1238-1256... 

Evans and co-workers have reported successful diazo transfer from p-nitrobenzenesulfonyl azide (PNBSA) to the enolate derivatives of an N-acyloxazolidinone and a benzyl ester (a) Evans, D. A. Britton, T. C. Ellman, J. A. Dorow, R. L. J. Am. Chem. Soc. 1990, 112, 4011. However, we have not been able to achieve efficient diazo transfer to ketone enolates employing these conditions. For example, exposure of the lithium enolate of acetophenone to 1.2 equiv of PNBSA in THF at -TS C for 15 min gave a-diazoacetophenone in only 21% yield. 

In order to maximize the diastereoselectivity observed for an auxiliary, it would appear reasonable that the stereo controlling functional group is in a position in space as close as possible to the newly forming stereogenic centre. Chiral imide auxiliaries such as Evans N-acyloxazolidinones (1.43) are used for asymmetric alkylation and asymmetric aldol condensation (Scheme 1.10). 

Aminomethylation. This reagent serves as an electrophile for Evans Al-acyloxazolidinones. The Cbz group can withstand conditions for removal of the chiral auxiliary (e.g., LiOH, HjO ) but is cleavable by hydrogenolysis. 

The reductive cleavage of the amide residue of many chiral auxiliaries is recommended for recovery of chiral compounds and auxiliary regeneration [S.3]. Evans s acyloxazolidinones 3.184 have been transformed into aldehydes by DIBAH or Red-Al at low temperature [CW2, EB5, MSS], but in the case of R =SPh, some epimetization occurs (Figure 3.70). DIBAH has also been proposed to transform N-acylthiazolidintliiones 3.185 [NKl] into the coiresponding aldehydes (Figure... 

In 2002, Evans and co-workers (139) reported a highly diastereoselec-tive direct anti-aldol reaction with chiral acyloxazolidinones 84 promoted by catal3d ic amounts of MgCl2 in the presence of triethylamine (EtaN) and... 

The catalytic enantioselective direct alkylation reaction of enolates is a less developed field. Early research from Evans group demonstrated that preformed titanium enolates derived from chiral Af-acyloxazolidinones reacted with orthoesters to provide the alkylated adducts with high levels of diastereo-control. In2005, the same group reported the enantioselective nickel-catalysed... 

---