5-Formyl-oxazoles

The construction of 2-substituted 5-formyl-oxazoles was performed starting from aryl, heteroaryl, and alkyl propargylamides through treatment with Pd(ll) salts with tolerance of various functional groups [103] (Scheme 53). 

Beccalli EM, Borsini E, Broggini G, Pahnisano G, Sottocomola S (2008) Intramolecular Pd (Il)-catalyzed cyclization of propargylantides straightforward synthesis of 5-formyl-oxazoles. J Org Chem 73 4746-4749... 

L abbe and coworkers studied the synthesis and thermolysis of 5-azido-4-formyl-oxazoles. They found, for example, that azides 17a-b rearrange at room temperature to yield isolable, isomeric oxazoles 18a-b. 

N-Carboxy-a -amino-carbonsaure-anhydride (Leuchs-Anhydride, 2,4-Dioxo-tetrahy-dro-l,3-oxazole) werden durch Lithiumalanat reduktivzu 2-Amino-alkoholen (neben wenig N-Formyl-aminosaure) aufgespalten z.B.2 ... 

The preparation of 3-vinylpyrroles was investigated utilizing the Horner-Wads worth-Emmons reaction with 3-formyl-lV-tosylpyrrole <06S1494>. The intramolecular acylation of pyrrole-2-Weinreb amides provided access to novel indolizinone derivatives <06T6182>. The amidation of pyrrole-2-carbonyl chloride was utilized as a key step in the preparation of pyrrole-oxazole analogue 90 of the insecticide Pirate <06S1975>. 

Conceptually interesting is the synthesis of the oxazole system 94 through a Beckmann rearrangement of a-formyl ketoxime dimethyl acetals 93 which demonstrated the possibility of a non-amino acid pathway in the biosynthesis of marine derived oxazoles <06CC1742>. 

When the pyrrolo[l,2-c]oxazole 269 was treated with trimethyl orthoformate in the presence of BF3 Et20, in dichloromethane at — 78 °C, a mixture of compounds was obtained from which the expected 5-dimethoxymethyl derivative, 270, was isolated in poor yield (12%) with another dimethoxylated compound 271 (23%). The formation of 271 could be explained by the addition of the formyl cation equivalent at C-7, followed by the protonation at C-6 of the resulting enamide 272 leading to the electrophilic iV-acyliminium ion 273 (Scheme 40). The regioselectivity of this electrophilic addition of trimethylorthoformate to the silyloxypyrrole 269 at C-7, in a non-vinylogous manner, is unusual <1999TL2525>. 

Chiral hydroxy benzimidazole 267 was dialkylated with dibromomethane or benzaldehyde dimethyl acetal to form benzo[4,5]imidazo[l,2-f]oxazoles 268 and 269 (Equation 118) C1997TA1491, 1998TA2245>. After removal of the BOC group and formylation of the liberated amine, formylaminomethylthiazole cyclized in phosphoryl chloride to... 

Sie sind Vorstufen auch Fur stereoselektive3 Synthesen von a-Amino-/l-hydroxy-car-bonsauren2 (s. Bd. E5, S. 581). 4-Alkoxycarbonyl-5-aryl-4,5-dihydro-l,3-oxazole IV (R3 oder R4 = Aryl) ergeben bei der katalytischen Hydrierung N-Formyl-phenylalanin-ester z.B.3 ... 

Alkyl-substituted oxazoles have been found to react with maleic acid or its anhydride in a diene synthesis to yield substituted pyridine readily converted to pyridoxine (39). In this route, ethyl d, 1-alaninate hydrochloride is treated with formic-acetic anhydride to yield ethyl N-formyl d,1-alaninate (78%). This compound is refluxed in chloroform with phosphorous pentoxide (40), quenched with aqueous potassium hydroxide, and the organic layer distilled to give 4-methyl-5-ethoxyoxazole (I) (60%). The resulting oxazole (I) is condensed readily with a number of appropriate dienophiles to form 2-methyl-3-hydroxy-4,5-disubstituted-pyridines containing substituents (III, a, b, c) which could be converted to pyridoxine as follows ... 

A less general synthesis of oxazoles is the condensation of bromoketones with amides. What is the mechanism for the formation of oxazole 3.44 How does 3.44 relate to the oxazole which might be prepared from the same bromoketone by conversion to the corresponding aminoketone, N-formylation, and cyclocondensation ... 

Note Added in Proof We find111 that while the benzoyl derivative (228) R = Ph gave the corresponding oxazole (229), the acetyl derivative gave the oxazole (229) R = Me together with the imidazole (230a) and no imidazole (230). The formyl derivative... 

As an alternative to the alkylation of 113 for the preparation of compounds of type 103-105, 110, and 111, Meyers et al. developed a variant of the Com-forth oxazole synthesis. This had been used previously to prepare 113-115 (67, 70). In this scheme, the imino ether 128, the adduct of methanol, HC1, and acetonitrile, is condensed with methyl glycinate (129) to yield 130, which is for-mylated to 131. Deprotonation of the formyl anion 131 at the incipient 2-methyl position of the oxazole followed by alkylation with the electrophile of choice [in this case the acetonide 132 derived from (S)-malic acid] and Lewis acid-... 

A systematic study of substitution reactions of oxazole itself has not been reported. Bromination of 2-methyl-4-phenyloxazole or 4-methyl-2-phenyloxazole with either bromine or NBS gave in each case the 5-bromo derivative, while 2-methyl-5-phenyloxazole was brominated at C(4). Mercuration of oxazoles with mercury(II) acetate in acetic acid likewise occurs at C(4) or C(5), depending on which position is unsubstituted 4,5-di-phenyloxazole yields the 2-acetoxymercurio derivative. These mercury compounds react with bromine or iodine to afford the corresponding halogenooxazoles in an electrophilic replacement reaction (81JHC885). Vilsmeier-Haack formylation of 5-methyl-2-phenyloxazole with the DMF-phosphoryl chloride complex yields the 4-aldehyde. 

The addition of carbonylated electrophiles to the 2-lithio derivative of 4-oxazolinyloxazole 132 allowed the efficient preparation of 5-phenyloxazoles 134 bearing a variety of hydroxyalkyl groups at C-2 position and a carboxyl (or formyl) function at C-4. This protocol suppresses the troublesome electrocyclic ring-opening reaction and allows access to the target compounds by simple chemical transformation of the oxazoline moiety of 133 <02JOC3601>. A direct chemoselective C-2 silylation of oxazoles was performed by treatment of the lithiated parent compounds with silyl triflates <02TL935>. 

Benzoxazol 2-(Cyan-formyl-methylen)-2,3-dihydro- E15/2, 1812 [aus 2-(l,2-Oxazol-4-yl)-1,3-benzoxazol]... 

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