Miinchnone intermediates

A similar example to obtain imidazoline carboxylic acids 1422 from a palladium-catalyzed multicomponent condensation reaction employs an imine 1420, an acid chloride 1421 and CO (Scheme 367). The reaction is also believed to proceed through a putative miinchnone intermediate <2001AGE3228>. 

Miinchnones are traditionally generated by the cyclodehydration of A -acylamino acids using acetic anhydride or a carbodiimide (e.g., A -(3-dimethylaminopropyl)-iV-ethylcarbodiimide hydrochloride (EDCI)). Newer methods of miinchnone syntheses include reacting a cyclohexenamide, which is a product of Ugi condensation, under acidic conditions to form a miinchnone intermediate 88. This intermediate was trapped by a dipolarophile such as DMAD to give a pyrrole product, for example, 89 (Scheme 17) <1996JA2574>. 

These studies have shown that the palladium catalyzed coupling imines, CO and acid chlorides is a viable and general route for the synthesis of a new class of peptide-based imidazolines. Mechanistic studies suggest this four-component coupling reaction proceeds via the in situ formation of Miinchnone intermediates, which undergo cyclization with imines in the presence of acid to yield the ob-... 

Kauhaluoma and Samanta used miinchnone as the key intermediate to obtain a triazole core (Scheme 9.41). Starting with Ameba resin 351, 3.84 equiv of amino acid ester 352 and 25 equiv of NaBHaCN were employed for the reductive alkylation in 1% acetic acid in DMF at room temperature for 12 h. Resin 353 was treated with 10 equiv of carboxylic acid chloride 354 in the presence of 12 equiv of A,A-diisopropylethylamine in DCM at room temperature for 12h to form amide 355, which was treated with 5% KOH in dioxane H20 (3 1) for 4h to give the corresponding carboxylic acid. Resin 356 was treated with 23.5 equiv of acetic acid anhydride, 3 equiv of DEAD (diethyl azodicarboxylate) 357, and 3 equiv of 4-phenyl-4/f-l,2,4-triazoline-3,5-dione 358 in DCM at room temperature for 5-10 h, giving the miinchnone intermediate 359, which reacted with compound 357 or 358 to form resin 360. Treatment of this with 30% TFA in DCM at room temperature for 1.5 h resulted in cleavage from the resin, producing 361. 

A related method with a resin-bound miinchnone intermediate was applied to the synthesis of 1,2,4-triazoles. Cycloaddition of resin-bound miinchnones with the N=N double bond of the dipolarophilic diethyl diazocarboxylate (DEAD) or 4-phenyl-4//-1,2,4-triazohne-3,5-dione gave resin-bound 1,2,4-triazoles. Traceless cleavage of the products from the 2-methoxy-substituted resin was achieved with 30% trifluoroacetic acid (Scheme 11.22). ... 

Armstrong proposed a mechanism for conversion of the cyclohexenamide into various products (Scheme 7.35) [54], In the presence of acid, protonation of the enamide 113 forms activated iminium intermediate 118, which undergoes an internal nucleophilic attack by the A-acyl group to form oxazolinium-5-one (miinchnone) intermediate 119 and eliminates cyclohexaimine. External nucleophilic attack (typically by the solvents used) onto the reactive miinchnone provides product 120. It must be noted that lack of an A-acyl group or its rapid loss prevents formation of miinchnone 119. 

In the presence of various metal ions, 2-(fluoroenone)benzothiazoline has been found to rearrange to A-2-mercaptophenylenimine, while a free radical mechanism involving the homolysis of C-S and C-N bonds has been invoked to explain the formation of 3-phenyl-1,2,4-triazole derivatives from the thermal fragmentation and rearrangement of 2-(arylidenehydrazino)-4-(5//)-thiazolone derivatives. The cycloadducts (36) formed from the reaction of 3-diethylamino-4-(4-methoxyphenyl)-5-vinyl-isothiazole 1,1-dioxide (34) with nitric oxides or miinchnones (35) have been found to undergo pyrolytic transformation into a, jS-unsaturated nitriles (38) by way of pyrrole-isothiazoline 1,1-dioxide intermediates (37). 

A mechanism has been proposed involving a meso-ionic 1,3-oxazol-5-imine (miinchnone imine) intermediate for the acid-catalyzed forma-... 

The reaction mechanism involved the formation of highly reactive miinchnones 7 (Scheme 2.3) as intermediates. Evidence for the assigned mechanism was provided by trapping the miinchnones with dimethyl acetylenedicarboxylate. The initial 1,3-dipolar cycloaddition product eliminated CO2 to give pyrroles 8 (Scheme 2.3) [6b],... 

In a similar context Amdtsen developed a new pyrrole synthesis from alkynes, acid chlorides either imines or isoquinolines, based on the reactivity of isocyanides (Scheme 35a) [197]. Although all atoms from the isocyanide are excluded from the final structure, its role in the reaction mechanism is crucial. The process takes place through the activation of the imine (isoquinoline) by the acid chloride to generate the reactive M-acyliminium salt, which is then attacked by the isocyanide to furnish a nitrilium ion. This cationic intermediate coordinates with the neighboring carbonyl group to form a miinchnone derivative, which undergoes a [3+2] cycloaddition followed by subsequent cycloelimination of the isocyanate unit, to afford the pentasubstituted pyrrole adducts 243 and 244 (Scheme 35a, b). 

Dhawan et al. reported that the reaction of the imine 476 with benzoyl chloride and carbon monoxide in the presence of the palladium catalyst 478 gave miinchnone 477 (Scheme 147).209 This reaction proceeds through formation of the acyliminium salt 479, the insertion of CO into the C—Pd bond of the intermediate 480, dehydrochlorination from the resulting acylpalladium complex 481, and cyclization by attack of the oxygen to the electron-deficient carbonyl coordinated to palladium (see 482). 

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