Trisubstituted 4-oxazolines

In a stereoselective one-pot synthesis, (ii)-olefins of the styrene type are reacted with stoichiometric amounts of nitriles, NBS, H2O, and NuHCOb in the presence of Cu or Zn triflate as Ltwis-acidic catalysts to give 2,4,5-trisubstituted oxazolines 2, in which the 4,5-substituents attain trans-configuration [294] ... 

Hojo and co-workers " described a novel synthesis of 4-aryl-5-(trifluoro-methyl)oxazoles 331, starting from aldehyde tert-butyl(methyl)hydrazones (Scheme 1.89). Triiluoroacetylation of a tert-butyl(methyl)hydrazone 327 yields 328 that cyclizes to a 4,5,5-trisubstituted oxazoline 329 upon refluxing in toluene in the presence of silica gel. Dehydration of 329 was then accomplished in two steps using POCI3 and a base to generate the 4-aryl-5-(trifluoromethyl)oxazoles 331. 

The most selective catalyst in this series, complex 32 c, with very bulky substituents at the oxazoline and the imidazolylidene moiety, was used to hydrogenate a range of trisubstituted alkenes with enantiomeric excesses of greater than... 

Lowenthal and Masamune (44) investigated the cyclopropanation of trisubsti-tuted alkenes leading to a chrysanthemic acid synthesis. They found that ligand 50c provided poor selectivities in this case (24% de for the trans isomer). Substitution in the 5 position of the oxazolines leads to increased selectivities, with excellent results provided by the BHT ester (94 6, 94% ee), Eq. 32. This ligand proved to be applicable to other trisubstituted and several cis-disubstituted alkenes, providing the corresponding cyclopropanes in ee values of 82-95%. These authors note that catalysts generated from CuOTf, CuOf-Bu, and Cu(II) precursors (with activation) provided similar yields and enantioselectivities. 

Although many different bisoxazolines and other semicorrin-type ligands have been prepared [53,54], the bis(ferf-butyl)oxazoline 11 is still the most versatile ligand for cyclopropanation. However, there are certain applications which give better results with other ligands. For the cyclopropanation of trisubstituted and 1,2-disubstituted (Z)-olefins, Lowenthal and Masamune found the bisoxa-zoline 12 to be superior to the bis(ferf-butyloxazoline) 11 [56]. This is illustrated by the reaction of 2,5-dimethyl-2,4-hexadiene leading to chrysanthemates (Scheme 9). Again, the best diastereo- and enantioselectivities were obtained with bulky diazoacetates. Both the trans/cis ratios and ees were similar to those reported for Aratani s catalyst (Scheme 5). 

Hoefle and Steglich164 have recently found that thermolysis of 2,4-disubstituted 4-acyl-2-oxazoline-5-ones and 2,4-disubstituted 2-acyl-3-oxazolin-5-ones gives 2,4,5-trisubstituted oxazoles (93 and 94, respectively), with elimination of carbon dioxide. In the latter case, the substituents at C-2 and C-4 were interchanged. 

Equilibration of the Z-E isomers also occurs in acetonitrile.25 With 2-acetoxyphenylmethylene oxazolones, isomerization to the E isomer was observed.63 Isomerizations to benzamidocoumarin derivatives under photochemical conditions have also been reported 64,65 While the 2-oxazolin-5-ones are thermally stable, the introduction of a 4-acyl or aroyl group, a potential site for further reaction, markedly decreases the stability. Thus, when 2,4-dialkyl-4-aroyl-2-oxazolin-5-ones are heated to 180°, decarboxylation occurs readily with the formation of trisubstituted oxazoles in yields of 71-95%66 [Eq. (13)). 

Vedejs and Grissom" described the synthesis and reactions of azomethine ylides generated from 4-oxazolines. They found that alkylation of a 2,5-disubsti-tuted or a 2,4,5-trisubstituted oxazole 15 gave an A -alkyloxazolium salt, which was... 

Trisubstituted 4-oxazolines 155 were efficiently prepared from 1-sulfonyl-l,2,3-triazoles 154 and aldehydes in the presence ofRh(II) catalysts, likely through Rh(II)-azavinyl carbenes I and ylides II as reaction intermediates (13AGE1507). 

The obvious first test of methylene-bis(oxazolines) 6 was the copper-catalyzed cyclopropanation. Among the various derivatives that we had prepared (6 R = benzyl, c-alkyl, phenyl, tert-hutyl the bulky t rt-butyl-substituted derivative proved to be the most effective ligand, giving similarly high enantiomeric excesses as the semicorrin Ic (R = CMe20H) (Scheme 14) [25]. The same results were obtained by Masamune and coworkers in an independent parallel study [28]. More recently, Lowenthal and Masamune showed that the method works also well for certain trisubstituted and unsymmetrically disubstituted cis-olefins if the di-t rt-butyl-substituted ligand is replaced by structurally modified bis(oxazolines) [32]. 

The original method for the synthesis of triflnoromethyl-snbstitnted oxazoles is based on the transformation of acyloxazolin-5-ones. Thus, 2-acyl-2-trifluoromethyl-A -oxazolin-5-ones 38 undergo cycloelimination of CO2 on heating at 200-230 °C to yield trisubstituted oxazoles 39. In this case snbstituents at positions 2 and 4 of the oxazole ring are formally interchanged [37]. Flash vacnnm pyrolysis (540-600 °C/0.01 mm Hg) of N-trifluoroacetylisoxazole-5-one also leads to 2-trifiuoro-methyloxazole [38]. 

---