Reduction, oxazole reactions

Isoxazotes are readily reduced, usually with concomitant ring fission (e.g. 262 — 263). They behave as masked 1,3-diketones 79AHC(25)147). 1,2-Benzisoxazoles are easily reduced to various products (Scheme 28) (67AHC(8)277). Chemical or catalytic reduction of oxazoles invariably cleaves the heterocyclic ring (Scheme 29) <74AHQ 17)99). For similar reactions of thiazoles, see Section 4.02.1.5.1. 

The synthesis of 3-H-oxazol-2-ones was described by Nam et al. [69]. The substituted benzoin 89 was formed from the coupling of 3,4,5-trimethoxy-benzaldehyde 18 with 3-nitro-4-methoxybenzaldehyde, Scheme 22. Reaction with PMB-isocyanate and subsequent cyclization gave the protected oxazolone derivative 90. The PMB group was removed by reflux in TFA and reduction of the nitro-group was performed using Zn to give the combretoxazolone-aniline 91. 

Oxazaborolidine, in reduction reactions, 9, 226-227 Oxazoles, in C-H bond alkylation, 10, 218 Oxazolidinone, via ring-closing diene metathesis, 11, 235 Oxazolines... 

The reactions of complex metal hydrides occur by an attack of the nucleophilic hydride ion on an electrophilic center.1 Aromatic nitrogen heterocycles in which the nitrogen has contributed only one electron to the -system (1) are electrophilic as compared with benzene, and have been shown to undergo reduction by the active reducing agent, lithium aluminum hydride. The nitrogen heterocycles in which the heteroatom has contributed two electrons to the 77-system (2) are electron-rich as compared with benzene and usually do not undergo reaction by reduction with complex metal hydrides.2 A combination of these two structural features, as in oxazoles (3), usually induces sufficient electrophilicity to allow attack by the hydride ion and reduction. 

Benzisoxazoles are easily reduced to various products (Scheme 75). Chemical or catalytic reduction of oxazoles invariably cleaves the heterocyclic ring (Scheme 76). For similar reactions of thiazoles, see Section 3.4.1.5.1. 

Such polycyclic aromatic hydrocarbons as anthracene or heteroaromatics as acridine, phenazine and 2,4,5-triphenyl oxazole act as Jt-donors for the Jt-acceptors AN and alkyl methacrylates [50-53]. Again, the interaction of the donor excited states with vinyl monomers leads to exciplex formation. But, the rate constants (k ) of these quenching processess are low compared to other quenching reactions (see Table 1). The assumed electron transfer character is supported by the influence of the donor reduction potential on the k value (see Table 1), and the detection of the monomer cation radicals with the anthracene-MMA system. Then, the ion radicals initiate the polymerization, the detailed mechanism of which is unsolved,... 

The particular reaction described in Scheme 2 using dimethyl diazomalonate produces oxazoles 5 that bear a methoxy group at C-5. If desired, this substituent may be removed in some cases by reductive cleavage using LiB(Et)3H to give the 5-unsubstituted oxazoles 6.3.15 Alternatively, the 5-unsubstituted derivatives 6 may be obtained directly through the use of diazo formylacetate (2) in place of dimethyl diazomalonate (1).3 15 Some additional, representative examples of the use of 1 and 2 are shown below in the Table. 

The oxazolium salt (160), formed from the oxazole (159) by reaction with methyl triflate in acetonitrile, may be reductively ring opened by treatment with phenylsilane in the presence of cesium fluoride to give the azomethine ylide (161) (presumably this species is in tautomeric equilibrium with the corresponding oxazoline). The azomethine ylide can be trapped as an adduct with a suitable dipolarophile, such as dimethyl acetylenedicarboxylate (DMAD). In the case of this reagent the adduct (162) can be ox-... 

Interestingly, alkyl-1,2-oxazoles (223) on reduction with LAH give aziri-dines 224 and 225. Preparative chromatography was used to separate one major (224, 40- 50%) and two minor (225, 226) components. Most likely, the reaction proceeds through a hydroxyazirine intermediate (227). 

The antiviral marine natural product, (-)-hennoxazole A, was synthesized in the laboratory of F. Yokokawa." The highly functionalized tetrahydropyranyl ring moiety was prepared by the sequence of a Mukaiyama aldol reaction, cheiation-controiied 1,3-syn reduction, Wacker oxidation, and an acid catalyzed intramolecular ketalization. The terminal olefin functionality was oxidized by the modified Wacker oxidation, which utilized Cu(OAc)2 as a co-oxidant. Interestingly, a similar terminal alkene substrate, which had an oxazole moiety, failed to undergo oxidation to the corresponding methyl ketone under a variety of conditions. 

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