Functionalizations oxazole

The difficulty of a consistent application of the Li6ge rules is connected with the termination -e, which in German indicates the plural. Therefore, it is not possible to use the endings -an and -ane, -in and -ine, -ol and -ole as designations of different functions. Oxazole in German is simply the plural form of OxazoL Similar difficulties, however, are encountered in Scandinavian and other languages, where it has been found advantageous to introduce the system as far as possible. 

New achievements in the chemistry of functional oxazole derivatives 03MI68. Novel oxazoline-mediated syntheses of heterocycles 03MI73. 

Smith 111 et al. reported an effective synthesis of a variety of 2,4-orthogonally functionalized oxazoles with shorter reaction times and modest to excellent overall yields (48-90%). 2-Chloromethyl-4-vinyloxazole (36) was obtained in 78% yield via the Stille coupling of 2-chloromethyl-4-triflate with vinyltributyltin [40]. 

Wipf and Miller explored a number of reaction conditions for preparing highly functionalized oxazoles required for natural product synthesis. They introduced a mild two-step process (Scheme 1.142) wherein a p-hydroxy amide 520 is oxidized... 

The range of oxidative heterocyclizations was successfully extended to the construction of intramolecular C-O bonds. Zheng et al. [26] showed that enamides 29 can be oxidatively cyclized to functionalized oxazoles 30 using PIDA as an oxidant and BF3-OEt2 as a Lewis acid (Scheme 7 (1)). A similar strategy was adopted by Yu and coworkers portraying the synthesis of benzoxazoles in high... 

Formation of ring-fused systems by this procedure is not as common. If the vicinally substituted hydroxyamino derivative is available, then Pb(OAc)4 treatment will lead to a ring-fused oxazole as in the conversion of (272) into (273) (71JCS(C)1482). In a different approach the CH=N— functional group is generated in situ. The 2-(l-pyrrolidinyl)ethanol... 

The aldehyde functionality present in 3-phenyl-2H-azirine-2-carbox-aldehyde reacts selectively with amines and with Qrignard and Wittig reagents to give a variety of substituted azirines. These azirines have been used, in turn, to prepare a wide assortment of heterocyclic rings such as oxazoles, imidazoles, pyrazoles, pyrroles, and benzazepins. ... 

A constant interest in the development of new rapid methodologies for the preparation of oxazole hbraries is motivated by their presence in numerous biologically active natural products. Janda and coworkers were hrst to show that oxazoles can be obtained by microwave-assisted treatment of polymer-bound a-acylamino-/f-ketoesters with Burgess reagent [68]. Hydroxybutyl-functionalized /anda/el resin was used for this investigation, with key steps being monitored by on-bead FT-IR. First, a resin-bound acetoacetate was pre-... 

To date most of the nitriles studied have been simple alkyl or aromatic derivatives with little other functionality. We recently attempted to extend the reaction to iV-protected a-aminonitriles, derived by dehydration of a-aminoacid amides (Path A, Scheme 25), but this proved unsatisfactory, and therefore we investigated an alternative diazocarbonyl based route in which the order of steps was reversed, i.e. a rhodium catalysed N-H insertion reaction on the amide followed by cyclodehydration to the oxazole (Path B, Scheme 25). 

Furthermore, oxazoles of type 9-82 bearing a secondary amino functionality can be converted into pyrrolo[3,4-b]pyridines 9-86 by reaction with appropriate acid chlorides 9-83 in a triple domino process consisting of amide formation/hetero Diels-Alder reaction and retro-Michael cycloreversion via 9-84 and 9-85 (Scheme 9.17). The pyrrolo[3,4-fc]pyridines can be obtained in even higher yields when the whole sequence is carried out as a four-component synthesis in toluene. Here, 1.5 equiv. NH4C1 must be added for the formation of the now intermediate oxazoles [56b]. 

The ceric ammonium nitrate (CAN) promoted oxidation of oxazoles with various substitution patterns was investigated and yielded the corresponding imides 108 in good yields, tolerating a wide variety of functional groups and substituents on the oxazole moiety <06OL5669>. 

The group of Janda has presented a microwave-mediated oxazole synthesis utilizing /3-ketoestcrs bound to a novel polymeric resin [57]. The desired polymer support was prepared by transesterification reactions of tert-butyl /f-ketoesters and hydroxy-butyl-functionalized JandaJel resin and subsequent standard diazo transfer. The resulting a-diazo /f-ketoesters were employed for the synthesis of an array of oxa-zoles (Scheme 7.41). 

The carbonylation of imidazole derivatives with several olefins takes place in high yields with the aid of an Ru3(CO)i2 catalyst.112,112a The carbonylation occurs exclusively at the a-position to the sp2 nitrogen (Equation (85)). A wide range of olefins can be utilized in this reaction, and a variety of functional groups are compatible under the reaction conditions. The (/i-H)triruthenium clusters such as 12 are proposed as a key species in this carbonylation reaction. Other five-membered A-heteroaromatic compounds, such as pyrazoles, oxazoles, and thiazoles, can be used for the carbonylation reactions, where the carbonylation takes place at the a-C-H bond to the sp2 nitrogen. 

Finally, the phosphinite-oxazole catalyst 29 (Fig. 29.16) was recently reported and used to hydrogenate a series of functionalized and unfunctionalized alkenes [31]. It was anticipated that the planar oxazole unit and the fused ring system would improve the enantioselectivity compared to the PHOX catalyst by increasing rigidity in the six-membered chelating ring [32]. Indeed, these catalysts... 

Condensation of aryl halides with various active methylene compounds is readily promoted by catalytic action of palladium to give the corresponding arene derivatives containing a functionalized ethyl group [7]. Yamanaka et al. extended this chemistry to haloazoles including oxazoles, thiazoles and imidazoles [8]. Thus, in the presence of Pd(Ph3P)4,2-chlorooxazole was refluxed with phenylsulfonylacetonitrile and NaH to form 4,5-diphenyl-a-phenylsulfonyl-2-oxazoloacetonitrile, which existed predominantly as its enamine tautomer. In a similar fashion, 4-bromooxazole and 5-bromooxazole also were condensed with phenylsulfonylacetonitrile under the same conditions. 

Silicon protection is also commonly used to direct lithiation chemistry in five-membered heterocycles. For example, oxazoles , thiazoles and Ai-alkylimidazoles ° ° lithiate preferentially at C-2, where the inductive effect of the heteroatoms is greatest. If C-2 is blocked, lithiation occurs at C-5, where there is no adjacent lone pair to destabilize the organolithium. Functionalization of these heterocycles at C-5 can therefore be achieved by first silylating C-2, reacting at C-5 and then removing the silyl group. The synthesis of 666 illustrates this sort of sequence (Scheme 258) °. ... 

In 2007, Tron and Zhu reported the multicomponent synthesis of 5-iminoox-azolines (42) starting from a,a-disubstituted secondary isocyano amides (41), amines, and carbonyl components (see Fig. 15) [155]. The reaction presumably follows a similar mechanism as in the 2,4,5-trisubstituted oxazole MCR (described in Fig. 11) however, because of the absence of a-protons at the isocyano amide 41, the nonaromatized product is obtained. As in the 2,4,5-trisubstituted oxazole MCR, toluene was found to be the optimal solvent in combination with a weak Brpnsted acid. The reaction was studied for a range of aldehydes and secondary amines. In addition, a variety of functionalities such as acetate, free hydroxyl group, carbamate, and esters are tolerated. Clean conversions were observed for this MCR as indicated by NMR analysis of the crude products (isolated yield 50-68%). The... 

Because of the retained isocyano functionality, the dihydropyridone MCR product 85 can be used in various follow-up (multicomponent) reactions. For example, the Passerini reaction between 85, a carboxylic acid, and an aldehyde or ketone produces a series of dihydropyridone-based conformationally constrained depsipeptides 86 [171]. The subsequent Passerini reaction could also be performed in the same pot, resulting in a novel 6CR toward these complex products containing up to seven points of variation. Reaction of 85 with an aldehyde or ketone and amine component resulted in the isolation of dihydrooxazolopyridines (DHOPs, 87) [172] via a similar approach as the 2,4,5-trisubstituted oxazole variant toward 42 reported by Tron and Zhu (Fig. 15) [155]. The corresponding DHOPs (87), which... 

Methoxycarbonyl-2-methyl-1,3-oxazole (3) is metalated exclusively at C5 with n-butyllithium. Selective functionalization at the methyl group of 3 can be achieved with N-bromosuccinimide to yield the 2-bromomethyl derivative 8. The latter affords a route to... 

Of the many substituted and functionalized alkenes that have been combined with diazo dipoles to give A -pyrazolines or products derived from them (i.e., A -pyrazolines, pyrazoles, cyclopropanes), only a selection will be mentioned. These include ot-alkylidene-cycloalkanones (62), -flavanones, -thioflavanones, -chroma-nones, and thiochromanones (63,64) a-arylidene-indanones and -indolones (65) diarylideneacetones (66) l-benzopyran-2(77)-ones (coumarins) (67,68) 4-nitro-1,2-oxazoles (69) 2-alkylidene-2-cyanoacetates (70) dimethyl 2,3-dicyanofuma-rate (71) tetracyanoethylene (72) tetraethyl ethylenetetracarboxylate (72) 1,4-quinones (35,73-75) 2-X-l,l,l-trifluoro-2-propene [X = Br, (76), SPh, SOPh, S02Ph (77)] nitroalkenes (78) including sugar nitroalkenes (79) 1-diethoxyphos-phoryl-1-alkenyl-sulfoxides (80) methyl 2-(acetylamino)cinnamate and -acrylate... 

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