Azirines cyclization reactions

The protonated azirine system has also been utilized for the synthesis of heterocyclic compounds (67JA44S6). Thus, treatment of (199) with anhydrous perchloric acid and acetone or acetonitrile gave the oxazolinium perchlorate (207) and the imidazolinium perchlorate (209), respectively. The mechanism of these reactions involves 1,3-bond cleavage of the protonated azirine and reaction with the carbonyl group (or nitrile) to produce a resonance-stabilized carbonium-oxonium ion (or carbonium-nitrilium ion), followed by attack of the nitrogen unshared pair jf electrons to complete the cyclization. 

Acyl sulfenes, like all sulfenes, prefer to participate as 2it components of [2 + 2] or [4 + 2] cycloadditions (Chapter 5). Nonetheless, a range of [4 + 2] cycloaddition reactions of acyl sulfenes have been described46,47 (Scheme 8-XII), including their 4n- participation in dimerization reactions46-48 and reactions with imines,49 carbodiimides,50 ketenimines,51 1-azirines,52 vinyl ethers,53 and ketenes.47 The reactions often provide mixtures of [4 + 2] and [2 + 2] cycloadducts, and the observed course of the reaction usually depends on the reaction conditions. Consequently, many of the observed [4 + 2] cycloadditions of acyl sulfenes proceed by a stepwise, polar addition-cyclization reaction. 

Azirines (three-membered cyclic imines) are related to aziridines by a single redox step, and these reagents can therefore function as precursors to aziridines by way of addition reactions. The addition of carbon nucleophiles has been known for some time [52], but has recently undergone a renaissance, attracting the interest of several research groups. The cyclization of 2-(0-tosyl)oximino carbonyl compounds - the Neber reaction [53] - is the oldest known azirine synthesis, and asymmetric variants have been reported. Zwanenburg et ah, for example, prepared nonracemic chiral azirines from oximes of 3-ketoesters, using cinchona alkaloids as catalysts (Scheme 4.37) [54]. 

The presence of a 2-substitutent in 3-phenylazirines (17, R —H in Scheme 21) modifies the mode of reaction with molybdenum carbonyl.47 In contrast to pyrazine formation for (17, R =H see Section V,C,2), the alkenyl azirine (18, Scheme 22) is transformed in excellent yield into 2-phenyl-5-carboxy-methylpyrrole. This product probably arises by intramolecular cyclization within an intermediate dienylnitrene intermediate, and related reactions have been devised to synthesize isoxazoles (see Section IV,E,2) and pyrazoles (see Section IV,D,1).47 The molybdenum carbonyl-promoted formation of 2,5-disubstituted pyrroles47 has analogy in uncatalyzed thermal, but not photochemical decomposition of 3-phenyl-2//-azirine 2-acrylate.49... 

There have been a number of reports where alicyclic-bridged precursors underwent an IAAC reaction. Thus, the dioxolane (203b), formed from triflate (203a), cyclized in situ to a tricyclic triazoline (Scheme 63).113 Treatment of this triazoline with sodium ethoxide converted it to a diazopyrrolidine in 86% yield, which underwent smooth catalytic hydrogenation in 89% yield. The (Z)-azidoalkene (204), bridged by a (3-lactam, cyclized at 20 °C to triazoline (205).114 The triazoline (205) extruded nitrogen at 80 C providing a tricyclic aziridine. The ( )-isomer of (204) did not cyclize to a triazoline but instead produced an azirine, presumably via a nitrene intermediate. 

The treatment of azirine (92) with hydrazine perchlorate to give aminopyrazole (118)46 probably follows a mechanism similar to that for the reaction of anilinium perchlorate with azirine (26). However, now the intermediate 117 can cyclize to the pyrazole. 

Second, intramolecular cyclization involving the azido group and the double bond could yield 1,2,3-triazoline derivatives these may be thermally unstable and may undergo nitrogen elimination to afford azirine derivatives. The reaction of perfluoro-2-methylpent-2-ene with NaN3 in a 1 2 acetonitrile-ethanol mixture at — 10°C (2 h) yielded stable 5-ethoxy-5-pentafhioroethyl-4,4-bis(trifluoromethyl)-4,5-dihydro-1H-1,2,3-triazole 9, whose structure was confirmed by X-ray analysis, Fig. 1 (01 JFC(110)21, 97ZOR772). 

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