Oxazoles 5-methoxy-4-substituted-2-

Substituted binaphthyl compounds can be synthesized in high optical yields using nucleophilic aromatic substitution reactions in which the chiral leaving groups are alkoxy moieties derived from naturally occurring alcohols28-29. For example, the condensation of 2-(l-alkoxynaphth-2-yl)-4.5-dihydro-4,4-dimethyl-l,3-oxazole with 1-naphthyllithium or 2-methoxy-l-naphthyl 2-magnesium bromide leads to (ft)- or (.S)-(l,T-binaphthyl-2-yl)-4,5-dihydro-4,4-dimethyl-l,3-oxazole derivatives. 

Jacobi s group cyclodehydrated iV-carbobenzyloxy-D-prolyl-L-alanine methyl ester 438 using POCVpyridine to prepare large quantities (50 g) of the 5-methoxy-4-methyl-2-substituted oxazole 439 (Scheme 1.121). Both 439 and ent-439 were key starting points for their enantiospecific syntheses of (+)-norsecurinine and (—)-norsecurinine. 

Irradiation of a methanolic solution of an oxazole at —78°C in the presence of O2 and rose bengal produced a 2,5-disubstituted 5-hydroperoxy-4-methoxy-4,5-dihydrooxazole 709 (Scheme 1.197). Here again, the oxazole substitution pattern determined the product distribution. For example, 4,5-diphenyl-2-methyloxazole 231a produced only N, iV-dibenzoyl acetamide 706 (Ri = CH3, R2 = R3 = CeHs). On the other hand, 4-methyl-2-phenyloxazole 701a gave 709 (Ri = CgHs, R2 = CH3, R3 = H), which decomposed on warming to room temperature to yield... 

Bristol-Myers Squibb chemists converted substituted 4-nitrobenzaldehydes to 5-(substituted 4-nitrophenyl)oxazoles 1625 using TosMIC (Scheme 1.416). As an example, 5-(2-methoxy 4-nitrophenyl)oxazole 1625 (R = CH3O), evaluated as an IMPDH antagonist, was prepared from 2-methoxy-4-nitrobenzaldehyde in 84% yield. 

Substituted 5-alkoxyoxazoles reacted with dimethyl acetylenedicarboxyl-ate to give a nitrile [145] by 1,4-addition for example, 5-butoxy-4-methoxy-oxazole gave acetonitrile and dimethyl 2-butoxyfuran-3,4-dicarboxylate. When 5-acyl-3-aryl-2-isoxazolines react with a strong base such as sodium hydride or triethylamine, nitriles are produced in moderately good yields [146]. 

The 1,3-dipolar cycloaddition of araldehyde hydrazones and araldoximes with 1-aroyl-2-arylsulfonylethenes in the presence of chloramine-T produces a mixture of 2-pyrazolines and 2-isoxazolines7 The thermally induced intramolecular 1,3-dipolar cycloaddition of 3-(alk-3-enylamino)-2,2-dimethylpropionaldehyde oximes (61) yields isoxazolo[4.3-c]pyridine derivatives (62) under mild conditions (Scheme 22)7 (/f)-Methylaluminium jS-binaphthoxide catalyses the formal 3 -I- 2-cycloaddition of 5-methoxy-2-(o-methoxyphenyl)oxazole with benzaldehyde or para- and meta-substituted benzaldehyde to produce cw-2-oxazoline-4-carboxylates with high enan-tioselectivity (90% ee)P... 

Synthesis of Oxazoles and Fnrans. Dimethyl diazomalonate reacts with a variety of nitriles in the presence of rhodium(II) acetate to afford 2-substituted 5-methoxy-4-methoxycarbonyl-1,3-... 

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