4-iodo-5- oxazole

In their cross-coupling survey, Hodgetts showed C2-chlorides, C4-bromides or C5-bromides are competent partners in the Suzuki reaction. Stambuli surveyed bromo- and iodo-oxazoles and found iodooxazoles more reactive in the Suzuki coupling at both the 4- and the 5-position7 ... 

The Suzuki-Miyaura cross-coupling reaction between oxazole-4-yl boronate and 2-iodo-oxazole derivatives was carried out under microwave irradiation at 150 W maximum power for 20 min to afford bis-oxazoles in good to excellent yields. A two fold increase in the yield and a six fold decrease in the reaction time were observed as compared to conventional heating (Flegeau et al., 2008). 

For the recifeiolide synthesis, the oxazole carbanion was alkylated with iodo THP ether (340) (an 85 15 mixture of (E)- and (Z)-isomers). Acid hydrolysis of the THP group, photooxygenation and cyclization gave a mixture of (E)- and (Z)- ( )-recifeiolide (341) from which the pure (E)-form could be isolated by chromatography on silver nitrate-impregnated silica gel (Scheme 74). 

Methyl-4-[3-iodo-5-nitro-(4-methoxy-phenoxy)-benzylidene]-4-H-oxazol-5-one... 

Attempts to carry out substitution reactions on oxazoles in acid media, such as nitration with nitric and sulfuric acids or chlorosulfonation, fail because the highly electron-deficient oxazolium cation is involved. Phenyloxazoles are nitrated at the para positions of the phenyl groups 2,5-diphenyloxazole affords 5-(4-nitrophenyl)-2-phenyloxazole, as expected. Nitrooxazoles are now available by the action of dinitrogen tetroxide on the corresponding iodo compounds (81JHC885). Benzoxazoles are nitrated at the benzene ring thus 2-methyl-benzoxazole gives a mixture of 5- and 6-nitro derivatives. 

The Negishi reaction of oxazol-l-ylzinc chloride with 6-iodo partial ergoline alkaloid was also documented to synthesize potent S-HT. agonists [76]. 

Reactions of Isoxazoles. The kinetics of the isoxazole azirine rearrangement (336) -> (337) and those of the isoxazole oxazole transformation (338) (339) have been determinedPalladium(II) chloride-triphenyl-phosphine catalyses the cross-coupling of 4-iodo-3,5-dimethylisoxazole with styrene to yield the trans- compound (340). 3,5-Dimethylisoxazole can be lithiated in two stages, first at the 5-methyl group and then at the 3-methyl group. Isoxazoles add hypochlorous acid to form 4-chloro-2,3-dihydro-... 

Reactions of Oxazoles. 2-, 4-, and 5-Nitro-oxazoles can be prepared by the action of dinitrogen tetroxide on the corresponding iodo-compounds. Whereas oxazoles are metallated at C-5, the acid (371) undergoes lithiation at the methyl substituent.The reaction of 2,4-dimethyloxazole with ethyl propiolate yields a mixture of the furans (373) and (374) these are formed by extrusion of acetonitrile from intermediate Diels—Alder adducts such as (372). s3... 

In two modern versions of ring closures in this category of ring synthesis, oxazoles are produced by base-catalysed closure of iniino-chloride derivatives of glycine, obtained by acylation of ethyl isocyanoacetate and in the second, by base-catalysed closure of 3-acylamino-2-iodo-l-phenylsulfonylalkenes. In yet another use of an isonitrile, 2-tosylaminoimidazoles can be prepared. ... 

Rather good yields of polysubstituted oxazoles are obtained starting from a variety of carbonyl compounds using sequential treatment with HDNIB [hydroxy-(2,4-dinitrobenzenesulfonyloxy)iodo] benzene and amides under the action of irradiation according to Scheme 10.88 [172]. 

Short and Ziegler employed propargylamides as precursors to (E)-p-iodo (vinyl)sulfones, which were key intermediates in their synthesis of 5-[(phenylsul-fonyl)methyl]-2-substituted oxazoles (Scheme 1.73). Here, a propargylamide 274 was iodosulfonated photolytically to afford the key ( )-p-iodo(vinyl)sulfones 275. 

TABLE 1.21. 5-[(PHENYLSULFONYL)METHYL]-2-SUBSTITUTED OXAZOLES FROM PROPARGYL AMIDES VIA ( )-P-IODO(VINYL)SULFONES ... 

Vedejs and Luchetta exploited the ambident reactivity of 2-lithiooxazoles to prepare a series of 4-iodo-5-substituted-oxazoles 917 (Scheme 1.246). Initially, they found that 896 (R = H, Ri 7 H) reacted with LiHMDS and I2 to produce a mixture containing the desired 4-iodo-5-substituted oxazole 917 together with the 2-iodo-5-substituted oxazole 918 and the 2,4-diiodo-5-substituted oxazole 919. The ratio of 917 918 depended on the nature of the electrophile, the solvent, and the base. 

TABLE 1.64. 4-IODO-5-SUBSTITUTED AND 2-IODO-5-SUBSTITUTED OXAZOLES FROM 2-LITHIOOXAZOLES AND IODINE"... 

Vedejs and Luchetta coupled 5-(4-methylphenyl)oxazol-2-ylzinc chloride 968 with 4-iodo-5-(2-phenylethyl)oxazole 969 and isolated 5-(4-methylphenyl)-... 

Lilly chemists prepared 998b as part of a series of 4-amino-6-heteroaryl-l,3,4,5-tetrahydrobenz[c,d]indoles evaluated as anti-emetic agents via coupling of 2-(tributylstannyl)oxazole 996 with (+)- 2aR, 45)-l-benzoyl-6-iodo-4-(di-n-pro-pylamino)-l,2,2a,3,4,5-hexahydrobenz[c,d]indole 997. They isolated 998b after deprotection as shown in Scheme 1.266. 

Imembrine, a tropolone natural product related to colchicine was also synthesized via an oxazole-acetylene Diels-Alder reaction followed by a [4 -H 3]-oxyallyl cycloaddition.Here, 8-iodo-5,6,7-trimethoxyisoquinoline 269 was converted to 5-substituted oxazole 270 in four steps and 42% overall yield (Fig. 3.81). Thermolysis of 270 in refluxing o-dichlorobenzene effected the desired intramolecular Diels-Alder cycloaddition with concomitant loss of the Boc-protecting group to afford the tetracyclic furan 271 in 90% yield. At this point, 271 was subjected to the [4 + 3] cycloaddition in the presence of l,3,3-trichloro-2-propanone and 2,2,2-trifluoroethanol. Subsequent dechlorination of the intermediate (not shown) with zinc provided the oxabicyclic 272 as a single regioisomer in 73% yield. The synthesis of imembrine was completed in three steps from 272. 

Syntheses of potent 5-HT agonists were accompUshed in several steps from a 6-iodo partial ergoline alkaloid. A new and general methodology critical for the construction of oxazole-containing alkaloids was developed for the synthesis of the 5-HT agonists using a novel palladium(O)- and copper(I)-cocatalyzed cyanation reaction [56]. 

The sUylation of aromatic or heteroaromatic compounds can be performed via magnesiated or lithiated intermediates, which can be accessed by hydrogen-metal or halogen-metal atom exchange. Thus, C-4 silylation of imidazoles is achieved from4-iodo imidazoles (eq 45), while C-2 silylated oxazoles are prepared by addition of TMSOTf to the lithiated oxazole (eq 46) interestingly, for this reaction, the employment of TMSCl as electrophile... 

To functionalize the C5 position, Williams and Fu developed a 2-phenylsulfonyl substituted oxazole. The C5 position of this oxazole can be cleanly deprotonated with LDA and trapped with either NIS or NBS to form the 5-iodo- or 5-bromo-2-phenylsulfonyloxazole in good yield. The same report details that the 2-phenylsulfonyl group can subsequently be displaced with alkyl, alkenyl, or aryl lithium reagents to form 2,5-disubstituted oxazoles efficiently. A triflate at the C5 position can be prepared from the corresponding oxazolone however, the oxazolone decomposes at room temperature, and Kelly reported that attempted Stille coupling with C5 triflates failed due to decomposition of the triflate. ... 

The fused oxazole derivative 100 was synthesized from 3-azido-3-deoxy-l,2 5,6-di-O-isopropylidene-a-D-allofuranose, the key final step being the reaction of methyl 3-amino-3-deoxy-5,6-0-isopropylidene-p-D-alloside with DMF dimethyl acetal. The annelated pyranoside 101 was obtained by cyclization of a branched chain hexosulose derivative, and the fused triazole-piperidinoses such as 102 were made by a radical cyclization of a 3-pyrazolo-6-iodo-sugar derivative. The spiro-isoxazohne 103 and related isomers have been synthesized by dipolar cycloadditions of mesitonitrile oxide to 2-deoxy-2-C-methyl-ene-pentonic acids, themselves available in five steps from D-mannitol. Intra-... 

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