Oxazolium ylide

Rhodium-mediated decomposition (60) of diazoamide (158) led to formation of the mesoionic oxazolium ylide 159, which was efficiently trapped by the pendant alkene to produce the oxo-bridged tricyclic amide 160. 

The oxazoliumcarboxylic acid (147) is easily decarboxylated via the ylide (148) the neutral compound (149) is much more stable due to the low equilibrium concentration of the zwitterionic tautomer (150 Scheme 7). Oxazolium salts lacking substituents at the 2-position react with dialkyl acylphosphonates in the presence of triethylamine to give mixtures of l,4-oxazin-3-ones and 2-azetidinones the reaction (see Scheme 8) proceeds by electrophilic attack of the phosphonate on an oxazolium ylide, e.g. (151), followed by insertion of oxygen into the carbon-phosphorus bond, ring-opening, and formation of the enolate anion (152) which can cyclize in two alternative ways with expulsion of the phosphonate group. 

Prompted by our earlier work dealing with the internal dipolar cycloaddition reaction of mesoionic oxazolium ylides of type 74, we subsequently studied the rhodium(II) catalyzed reactions of the related a-diazo ketoamide system 154 <97JOC2001 04OL3241 05JOC2206>. Attack of the amido oxygen at the rhodium carbenoid produces a push-pull carbonyl ylide dipole (i.e., 155) that is isomeric with the isomiinchnone class of mesoionic betaines. 

Mesoionic oxazolium ylides (isomiinchnones) correspond to the cyclic equivalent of a carbonyl ylide embedded in a heteroaromatic ring, and these reactive intermediates readily undergo 1,3-dipolar cycloaddition with suitable chpolarophiles. Isomiinchnones are readily obtained through the transition metal—catalyzed cyclization of a suitable a-diazoimide precursor... 

Vedejs developed an enantiocontrolled synthesis of aziridinomitosenes involving internal alkylation of the oxazole 132 to produce an oxazolium salt 133 followed by nucleophilic addition of cyanide providing the adduct 134 <00JA5401>. Electrocyclic ring opening of 134 to the azomethine ylide 135 with internal [2+3] trapping produces the tetracyclic product 137 via the pyrroline 136. 

The photocycloaddition of aliphatic and aromatic aldehydes with 2,4,5-trimethyloxazole (131) gave bicyclic oxetanes 132 in almost quantitative yields hydrolitic cleavage led selectively to erytro a-amino-P-hydroxy methyl ketones 133 <00CC589>. The oxazolium salt 134 was converted to the azomethine ylide 136 via electrocyclic ring opening of the oxazoline 135. Intramolecular cycloaddition afforded 137 in 66% overall yield which was transformed into the aziridinomitosene derivative 138 . 

Azomethine ylides. Reduction of oxazolium salts (1) with phenylsilane and cesium fluoride provides an unstable 4-oxazoline (2), which can react as an azomethine ylide with a dipolarophile such as DM AD to give a dihydropyrrole (3). ... 

A series of publications by Vedejs et al. (17-19) outlined the use of oxazolines in the generation of azomethine ylides. Reduction of the oxazolium salts 71 (R = Ph or Me) with PhaSiH/CsF led to formation of the unstable 4-oxazolines (72) and their valence bond azomethine ylide tautomers (17), which could be trapped in situ with DM AD to afford the bicyclic adducts 73, where R and R = Ph or Me, in 75% yield via [2 + 2] cycloaddition (Scheme 3.18). 

Other important pyrrole syntheses of this type are cycloadditions involving mesoionic oxazolium 5-oxides, azomethine ylides or isonitriles, e.g. (145 +146 — 147) or (148 +149 — 150). 

Huisgen and coworkers have also described the cycloaddition behavior of the munchnones , unstable mesoionic A2-oxazolium 5-oxides with azomethine ylide character.166 Their reactions closely parallel those of the related sydnones. These mesoionic dipoles are readily prepared by cyclodehydration of N-acyl amino acids (216) with reagents such as acetic anhydride. The reaction of munchnones with alkynic dipolarophiles constitutes a pyrrole synthesis of broad scope.158-160 1,3-Dipolar cycloaddition of alkynes to the A2-oxazolium 5-oxide (217), followed by cycloreversion of carbon dioxide from the initially formed adduct (218), gives pyrrole derivative (219 Scheme 51) in good yield. Cycloaddition studies of munchnones with other dipolarophiles have resulted in practical, unique syntheses of numerous functionalized monocyclic and ring-annulated heterocycles.167-169... 

The proton at C(2) in oxazole is acidic, that at C(5) less so. Instantaneous deuteration at C(2) was observed when oxazole was dissolved in DMSO- 6 containing sodium methoxide a slower exchange occurred at C(5). The effect is enhanced by the presence of electron-attracting substituents at C(4) and even more in oxazolium ions, which owe their reactivity to the stability of ylides such as (145). Unlike thiamine and other thiazolirm... 

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-... 

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