2/7-Azirine 3- -2,2-dimethyl

Nitrile ylides derived from the photolysis of 1-azirines have also been found to undergo a novel intramolecular 1,1-cycloaddition reaction (75JA3862). Irradiation of (65) gave a 1 1 mixture of azabicyclohexenes (67) and (68). On further irradiation (67) was quantitatively isomerized to (68). Photolysis of (65) in the presence of excess dimethyl acetylenedicar-boxylate resulted in the 1,3-dipolar trapping of the normal nitrile ylide. Under these conditions, the formation of azabicyclohexenes (67) and (68) was entirely suppressed. The photoreaction of the closely related methyl-substituted azirine (65b) gave azabicyclohexene (68b) as the primary photoproduct. The formation of the thermodynamically less favored endo isomer, i.e. (68b), corresponds to a complete inversion of stereochemistry about the TT-system in the cycloaddition process. 

Carbanions in the form of ylides also add to azirines. For example, treatment of 1-azirine (227) with dimethylsulfonium methylide gives 1-azabicyclobutane (229) in good yield (72JA2758). The addition of the methylene group occurs by initial nucleophilic attack by the ylide to give intermediate (228) which cyclizes with expulsion of dimethyl sulfide. 

The dimethyl 4//-azepine-2,3-dicarboxylate 17 is obtained in high yield by the action of dimethyl acetylenedicarboxylate on jV,Ar,2-trimethyl-2-vinyl-2//-azirin-3-arninc (16).42 The structure of this surprising product has been confirmed by X-ray analysis. 

Subsequently, it was shown that cyclopentadienones are very efficient in trapping 2//-azirines formed transiently during the thermolysis of vinyl azides,109 and that 3//-azepines may be formed by heating the vinyl azide directly in the presence of the cyclopentadienone rather than with the often foul-smelling 2//-azirine.31,109 An example of this procedure is the preparation of the dihydro-3/f-naphth[2,l-fe]azepine 29 by thermolysis of 4-azido-l,2-dihydronaph-thalene (28) with 2,5-dimethyl-3,4-diphenylcyclopentadienone in refluxing toluene. 

Recent examples of this synthesis are of two types. The first involves condensation of the activated phenol, 2-amino-4,6-dinitrophenol (346a) with 2-dimethyl-amino-3,3-dimethyl-3//-azirine (346b) (in MeCN, 0°C- 20°C, A, 24 h) to afford a separable mixture of four products, one of which was 2-dimethylamino-3,3-dimethyl-5,7-dinitro-3,4-dihydroquinoxaline (346c) ( 20% yield) and another its hydrolysis product, 3,3-dimethyl-5,7-dinitro-3,4-dihydro-2(l//)-quinoxalinone (346d) ( 8%) the mechanism of such condensations has been discussed. ... 

The second type is examplified in the condensation of 1,2-benzenediamine with dimethyl 3-bromo-3//-azirine-2,3-dicarboxylate to give dimethyl 2,3-quinoxaline-dicarboxylate (347) (Me2NCHO, 20°C, ultrasound, 2 h 69%) analogs were made likewise. 

This simple procedure resulted in 2H-azirines exclusively in high yields and with retention of chirality at C-2 [24]. Mechanistically, this oxidative synthesis of azirines can be rationalized by invoking the intermediacy of chloro-dimethyl-sulfonium chloride (Me2SCl+- Cl ), which then reacts with the aziridine as indicated in Scheme 12. 

Independent work by Schmid93 and by Padwa94 on the photochemistry of 2H-azirines has shown that irradiation of such systems leads in the first instance to the formation of nitrile ylids (nitrilium betaines). Subsequent 1,3-addition to a variety of dipolarophiles affords five-membered heterocycles. These additions take place in a stereospecific and regioselective manner thus, irradiation of the diphenyl-2f/-azirine 117 in the presence of dimethyl maleate leads to the formation of the two isomeric 1-pyrrolines... 

The first example of a [ 6 + 4] cycloaddition of a nitrile ylid has recently been reported104 irradiation of 3-phenyl-2,2-dimethyl-2i/-azirine (129) in the presence of 6,6-dimethylfulvene (130) in cyclohexane gave the [n6 + 4] adduct 131 together with the [ 4 + 2] adduct 132. 

The reaction of 4-methyl-2,3,4,6-tetrahydro[l,2,4]triazino[3,4-a]-isoindole-3,6-dione 671 with 3-dimethylamino-2,2-dimethyl-2//-azirine... 

Heimgartner and co-workers conducted a detailed mechanistic investigation of the reaction of [ NJlabeled 2,2-dimethyl-3-(dimethylamino)-27/-azirine 332 with NH-acidic heterocycles (Scheme 6.71). Based on these studies the authors proved that ring opening of 188a with 332 afforded the imidazolone 336 in which... 

TABLE 6.12. IMIDAZOLONES FROM 5,5-DIMETHYL-2,4-OXAZOLIDINEDIONE AND 2//-AZIRINES ... 

It was also reported " that the reaction of 4,4-disubstituted-2-(trifluoromethyl)-5(4f/)-oxazolones 251 with 2,2-dimethyl-3-(dimethylamino)-2//-azirine afforded 5-(dimethylamino)-3,6-dihydropyrazin-2(l//)-ones 252 (Scheme 7.81). In this case, the reaction only occurs when electron-withdrawing substituents are present at C-2 of the oxazolone. 

Methyl-N-(phenyl-acet)l>-alanin-dimethylamidEine Ldsung von 500 mg (3,67 mmol) Phenyl-essigsaure in 15 m) Acetonitril wird unter Riihren mit 415 mg (3,71 mmol) 2,2-Dimethyl-3-dimelhylamino-2H-azirin in 3 ml Acetonitril versetzt. Nach 12 h filtriert man das Produkt ab und kristallisiert aus Toluol um Aus-beute 790 mg (86,3%) Schmp. 135,5-136,5". 

The reaction of a-amino ketones (508d) with thiosemicarbazides (761) affords 3-amino-4,5-dihydro-l,2,4-triazines (762) and the dihydrotriazine-3-thiones (763) (57MI21900). 2,2-Dimethyl-3-dimethylamino-2i/-azirine (764) reacts with benzohydrazides (765 R = Ar) via the open-chain intermediates (766) to give 3-aryl-6-dimethyIamino-2,5-dihydro-l,2,4-triazines (767 R = Ar). With ethyl carbazidate (765 R = OEt) the corresponding triazin-3-one (768) is formed (78HCA2419,78C332). 

Smith and Most13 developed a modified Neber reaction for the synthesis of aminoketones which was used successfully by Parcell for the synthesis of 3,3-dimethyl-2-phenyl-l-azirine (26).14... 

An attempt by Sato17 to prepare 2-phenyl-1 -azirine from the dimethyl-hydrazone methiodide (30) resulted in the formation of 2,4-diphenyl-pyrrole (31). Although the 1-azirine may be an intermediate (see Section IV, B, 2) in this reaction, its presence could not be detected. 

Nair has recently observed a similar reaction with 2-phenyl-3-methyl- and 2-phenyl-3,3-dimethyl-l-azirine.69... 

It can be prepared by treatment of 3-amino-2//-azirines (e.g. 3-(dimethyl-amino)-2,2-dimethyl-2//-azirine) with an amino acid or peptide and, finally, with a (u-hydroxyacid. The formation of the oxazolone, VI/121, is observed when VI/120 is treated with acid. The ring enlargement step, the conversion of VI/121 to VI/122, is observed under the same conditions. The transformation of (-)-(R,R)2- 2-[2-(2-hydroxy-2-phenylacetamido)-2-methylpropionato]-2-phenylacetamido -N,N,2-trimethylpropionamide (VI/123) to (-)-(R,R)-3,3,9,9-tetramethyl-6,12-diphenyl-l,7-dioxa-4,10-diazacyclododecane-2,5,8,ll-tetrone (VI/126) in dry toluene/hydrochloric acid at 100° was observed in a 88 % yield. Compounds VI/124 and VI/125 are discussed to be intermediates. In an analogous reaction sequence cyclopeptides can be synthesized [93]. 

Dimethylamino-2,2-dimethyl-2//-azirine (23) and methyl 2-amino-3-phenyl-propionate gave 3-benzyl-5-dimethylamino-6,6-dimethyl-3,6-dihydro-2(17/)-... 

Dimethylamino-2,2-dimethyl-2//-azirine (27) and 4-isopropyl-2-trifluo-romethyl-5-oxazolinone (28) gave 5-dimethylamino-3-isopropyl-6,6-di-methyl-3,6-dihydro-2(l//)-pyrazinone (29) (MeCN, reflux, N2, 1 h 60% a rational mechanism was suggested) 944 analogues, like 3-allyl-5-dimethy-lamino-6,6-dimethyl-3-phcnyl-3,6-dihydro-2(l//)-pyrazinone (44%),958 were made similarly.944 958... 

An interesting application of PET mediated bond cleavage reaction from azirine 63 has been reported by Mattay et al. [67] for synthesizing N-substituted imidazoles (65) via the (3 + 2) cycloaddition reaction of resultant 2-azaallenyl radical cations with imines 64. Synthesis of pyrrolophane 3,4-dimethyl ester (68) has been reported recently [68] by the ring opening of 66 followed by inter-molecular cycloaddition with dimethyl acetylene dicarboxylate (67) as shown in Scheme 13. 

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