Oxazolium olates

5-Trifluoromethyl-3-hydroxypyrazoles 786 were obtained selectively through the regioselective attack of phenylhy-drazine on mesoionic 4-trifluoroacetyl-l,3-oxazolium-5-olates 785 in refluxing benzene the same reaction in DMF and 1,2-dichloroethane at room temperature, respectively, gave 6-trifluoromethyl-l,2,4-triazines and 3-trifluoro-methyl-5-pyrazolones (Equation 171) 1998TL663 . 

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There are two common forms of mesoionic compound that belong to the oxazole ring system mlinchnones (1,3-oxazolium-5-olates) 86, named by Huisgen for the city Miinchen, and isomilnchnones (l,3-oxazolium-4-olates) 87 (Figure 4). These are highly versatile compounds which are often used as 1,3-dipoles in cycloaddition chemistry <2002HC(59)681>. 

Mechanistically, the authors proposed that this reaction most probably proceeds by cyclodehydration of 499 with TFAA to afford a mesoionic 1,3-oxazolium-5-olate 505. Trilluoroacetylation of 505 yields 506, which is ring opened with trifluoroacetate to produce 507 from which the enol trifluoroacetate 508 is produced by decarboxylation (Scheme 1.137). Cyclization of508 gives the IV-alkyloxazolium salt 509 that is dealkylated by trifluoroactate to furnish 500. This dealkylation is consistent with the observation that 499 (Rj = Bn) are better substrates than 499... 

Although several resonance structures can be imagined for munchnones (1,3-oxazolium 5-oxides or 1,3-oxazolium 5-olates) and isomunchnones (1,3-oxazolium 4-oxides or 1,3-oxazolium 4-olates), I will draw those forms depicted in 1 and 2, respectively, which capture the flavor of the 1,3-dipolar reactivity of these heterocycles. In addition, this chapter covers the relatively few new developments involving munchnone imines and isomunchnone rmines. The format follows that used by Gingrich and Baum. 

Kawase M, Miyamae H, Saito S (1999) Synthesis of functionalized pyrrolidines from mesoionic 4-trifluoroacetyl-1,3-oxazolium-5-olates and aminomalonate. Heterocycles 50 71-74... 

In two instances, 3-(poly-0-acetylalditol-l-yl)pyrroles were prepared by 1,3-dipolar cycloaddition of 2-(penta-0-acetylpentitol-l-yl)-l-nitroethene (228) as dipolarophiles to 3-(alkylamino)crotonic esters [80JCS(P1)1199] or to the mesoionic oxazolium olate 231 (89MI6) to give 230 and 233, respectively (Scheme 50). 

Dipolar cycloaddition reactions of thioisoraunchnones (l,3-thiazolium-4-olates) have not been as extensively studied as those of munchnones (l,3-oxazolium-5-olates) despite offering rapid access to novel heterocyclic compounds. The cycloaddition of the thioisomunchnone (52) with trans-P-nitrostyrene results in the formation of two diastereoisomeric 4,5-dihydrothiophenes (53) and (54) via transient cycloadducts. These cycloadducts then undergo rearrangement under the reaction conditions <96JOC3738>. 

Under Dakin-West reaction conditions (trifluoroacetic anhydride-MeCN/80 °C/5 h), At-methoxycarbonylproline (128 R = Me) yielded Af-methoxycarbonyl-4-trifluoro-acetyl-2,3-dihydropyrrole (129 R = Me) and none of the expected Dakin-West product, the trifluoromethyl ketone (127). A possible mechanism proposed by the authors involves initial formation of a mesoionic l,3-oxazolium-5-olate (130 R = Me), but the pathway to the iV-methoxycarbonyl-2,3-dihydropyrrole (131 R = Me) and thence the final product (129 R = Me) was unexplained. ... 

A novel transformation of iV-alkoxycarbonylprolines to trifluoroacetyl-2,3-dihydropyrroles has been achieved by utilizing trifluoroacetic anhydride. A mesoinic l,3-oxazolium-5-olate is thought to be the probable intermediate in this transformation. 

Although the mesoionic l,3-oxazolium-4-olates, isomiinchnones , occupied only a few pages in the reviews by Potts (1) and Gingrich and Baum (10), in the intervening years this ring system has exploded in popularity, largely due to the efforts of Padwa and co-workers. Padwa has summarized his isomtinchnone work in several reviews (22-27). While isomiinchnones are rarely isolable, these carbonyl... 

In this chapter, oxazole and its derivatives are named and numbered as in Chemical Abstracts. Thus compound (6) is called 4,5-dihydrooxazole rather than 2-oxazoline or A2-oxazoline, (7) is 2,5-dihydrooxazole, the betaines (3) are named anhydro-5-hydroxy-oxazolium hydroxides and not oxazolium 5-oxides or oxazolium 5-olates, and the oxo derivatives (4) and (5) are 5(4//)-oxazolone and 5(2//)-oxazolone, respectively, the position of the extra hydrogen atom being indicated in parentheses. The fully saturated compound (8) is oxazolidine its oxo derivatives are named oxazolidinones and oxazolidinediones, e.g. compound (9) is 2-oxazolidinone and (10) is 4,5-oxazolidinedione. A formula such as (11) is not meant to imply that all the substituents are methyl groups it represents a general oxazolidine derivative and is used in place of the cumbersome expression (12 R-R = H, alkyl or aryl). 

The phosphaalkyne 403 adds to 3-phenylsydnone regioselectively to give the heterocycle 404 in high yield. Mnchnones (l,3-oxazolium-5-olates), traditionally generated by the cyclodehydration of A-acylamino acids using acetic anhydride or a carbodiimide, also take part in cycloadditions, as exemplified in Scheme 89 <1996JA2574>. The... 

Unsubstituted isoxazolium salts 96 react with hydrazines to yield 3-aminopyrazoles 97 (Scheme 53) <1988S203>. Likewise, 5-trifluoromethyl-3-hydroxypyrazoles 99 were obtained selectively through the regioselective attack of phenylhydrazine on mesoionic 4-trifluoroacetyl-l,3-oxazolium-5-olates 98 in refluxing benzene (Scheme 54) C1998TL663, CHEC-III(4.01.9.1.2)103>. 

Oxazoles 1, benzoxazoles 2, oxazolium salts 3, and oxazole A -oxides 4 are fully conjugated compounds (Figure 1). In addition, the two mesoionic structures l,3-oxazolium-5-olates 5 and (l,3-oxazolium-4-olates) 6, commonly known as miinchnones and isomiinchnones, respectively, are also considered to be conjugated rings. There are five systems of hydroxyl-substituted oxazoles and they exist in their oxo forms the 2(3H)-, 2(5H)-, 4(5//)-, 5(2//)-, 5(4//)-oxazolones 7-11. Three forms of dihydrooxazoles are known 2,3-, 2,5-, and 4,5-dihydrooxazoles respectively 12-14. The fully saturated ring is called oxazoline 15. The monooxo derivatives are 2-oxazolidinone 16,4-oxazolidinone 17, and 5-oxazolidinone 18. The three variants of oxazolidinediones are 19-21 and the fully oxidized oxazolidi-netrione is 22. 

Isomiinchnones (l,3-oxazolium-4-olates) used to be an obscure and esoteric ring system prior to the efforts of Padwa and co-workers in the 1990s, who demonstrated new methods of synthesis and application of these powerful dipoles in the area of complex molecule syntheses <1996CRV223>. 

Alkylmercaptomethyleneiminium salts as well as alkoxymethyleneiminium salts are transformed to amide thioacetals (443 equation 206) by alkali metal thiolates and thiols. - The action of alcoholic alkoxides on 2-alkoxy-2-dialkylaminocarbonitriles (444 equation 207) produces amide acetalsJ Spi-locyclic amide acetals (446 Scheme 82) were prepared from oxazolium salts (445) and substituted sal-icyl aldehydes. The addition of alcohols to the l,3-oxazolium-4-olate (447) affords heterocyclic amide acetals (448). ... 

Knorr, R. Mechanism of the Dakin-West reaction. III. Course of ring opening during the Dakin-West reaction of an oxazolium 5-olate. Chem. Ber. 1971,104, 3633-3643. 

Y-Acylprolines, in a reaction with trifluoroacetic anhydride and catalytic base, rearrange to oxazoles via mesoionic oxazolium-5-olates (168) <93TL859>. The yields are good for N-benzoyl, N-cinnamoyl, and 7V-pivaloylprolines, but no oxazole is formed with N-acyl groups bearing a hydrogens on an sp carbon. A possible mechanism is shown in Scheme 78. 

The cycloaddition of 223 with diazoethane in 1,4-dioxane gave the nitro-pyrazoline 227, whose aromatization was effected with HCl to give pyrazole 228 (91MI7). 3-Methyl-2-(4-nitrophenyl)-4-phenyl-l,3-oxazolium-5-olate (226) reacted regioselectively with 223 to give the respective pyrrole derivatives 225, which could be deacetylated with sodium methoxide (89MI4). 

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