Aziridines bicyclic

More recently, Cheeseman and coworkers have investigated cycloaddition reactions of 2,6-dioxypyrazines (80jCS(Pl)1603). 2,6-Dihydroxy-3,5-diphenylpyrazine (77) reacts with electron deficient dienophiles such as iV-phenylmaleimide, diethyl maleate and diethyl fumarate (Scheme 26) to yield adducts of the 3,8-diazabicyclo[3.2.1]octane class such as (78). This reaction is believed to proceed by way of the betaine (79) and has precedent (69AG(E)604) in that photolysis of the bicyclic aziridine (80) generates analogous betaines which have been trapped in cycloaddition reactions. 

Lewis acid-mediated asymmetric Diels-Alder reactions between 2H-azirines 59, bearing chiral auxiliaries, with enophiles such as 60 afforded mixtures of bicyclic aziridine-2-carboxylates 61 (Scheme 3.20) [68]. 8-Phenylmenthol appeared to be the auxiliary of choice in this reaction in terms of yield and diastereoselectivity. 

Scheme 3.33) afforded the bicyclic aziridine-2-phosphonate 103 in 89% yield [83]. 

The conversion of azidoformates to fused-ring aziridines via the thermal generation of a nitrene has previously been reported. More recently, the photolytic conversion of a sugar-derived azidoformate has been used to prepare fused-ring aziridines <06JOC8059>. Photolysis of azidoformate 66 at 254 nm provides aziridine 67 in excellent yield. The resulting bicyclic aziridine was reduced to provide oxazolidinone 68 in 95% yield. Oxazolidinone 68 was subsequently converted to L-daunosamine. 

The use of m-CPBA allows the formation of nitrones in the oxidation of tertiary amines. The resulting amines A-oxides are subject to either Cope or Meisenheimer rearrangements, providing formation of nitrones. Thus, the generated corresponding nitrones in the oxidation of bicyclic aziridines give nitrones as a result of a Meisenheimer rearrangement (Scheme 2.14) (93). 

Scheme 17.27 Bicyclic aziridine synthesis from homoallyl sulfamates.

Of course, the cleavage reactions of both 2-aryl- and 2-alkyl aziridines are stereoselective because only the trans-diastereomers of the corresponding regioisomers 1 and 2 are formed. In other words, 2-aryl substituted aziridines showed opposite regioselectivity to 2-alkyl aziridines. With bicyclic aziridines, exclusive formation of the trans diastereomer is observed in the case of symmetric bicyclic aziridines. Unsymmetrical aziridines such as styrene, octene, and undecene aziridines produce a minor amount of the other regioisomer. 

Thiazine 283 has been prepared through the nucleophilic ring opening of fused bicyclic aziridine isothiazoli-dine 1,1-dioxide 284 with MeOH in the presence of BF3-OEt2 (Equation 40) <20000L2327, 2004JOC6377>. 

Scheme 31 illustrates, as an example, the Co2(CO)8-catalyzed carbonylative ring expansion of bicyclic aziridine 220, forming the corresponding highly strained /ra r-bicyclic /3-lactam 221, and a proposed reaction pathway. In this reaction, it is believed that tetracarbonylcobaltate, Co(CO)4, generated from Co2(CO)8 is the active catalyst... 

Homo-l//-azepines (29), unlike their carbocyclic counterparts, show little tendency to isomerize to the thermodynamically less favoured bicyclic aziridine tautomers (30). Presumably, the homoazepine gains its stability from delocalization of the nitrogen lone pair through the dienamine system <71AG(E)ll). However, the aziridine tautomers (30 R1 = C02Me, R2 = Ac, C02Me or p-Ts) have been trapped as their all-cTs bis-l,3-dipolar cycloadducts with diazomethane (76CB3505). 

An alternative method of generating the betaines 482 in solution involves photolysis of the bicyclic aziridines 481.Irradiation in the presence... 

Besides o,/ -dibromopropan-l-ones, there are references related to using o,/ -dichloro [26], o-chloro [19] and a-iodo derivatives [27] in the Gabriel reaction. Bicyclic aziridines 16 were obtained by the treatment of ce-iodocyclohexene 14 with benzylamines 15 in the presence of cesium carbonate in xylene [27] (Scheme 1.4). 

One of the initial findings about bicyclic aziridines is reported in [88] the authors carried out the synthesis of 3,5a-dihydro-l//-azireno[l,2-c]imidazoles by reacting trwith carbonyl compounds in methanol saturated with ammonia in the presence of ammonium bromide. In particular, 2,2-dimethyl-6-(4-nitrophenyl)-4-phenyl-l,3-diazabicyclo[3.1.0]hex-3-ene 72 was obtained in the reaction of ketone 70 with ammonia and acetone 71 (Scheme 1.19). 

The possibility of bicyclic aziridine hydrochloride salt formation was first mentioned in [88]. The hydrochlorides of some azirenoimidazoles were obtained by passing dry hydrogen chloride through ether solutions. However, the protonation direction was not established in that work. 

Photolysis of 3-substituted pyridinium salt 234 in aqueous base provides the highly functionalized bicyclic aziridine 236, albeit in low yield (20%) <2005JOC5618>. Fortunately, the two regioisomers can be separated chromatographically. The reaction presumably proceeds through indiscriminant hydroxide addition onto an intermediate allylic cation 235. Compound 236 can be carried on to the desired acetamidocyclopentene derivative 237 in three steps and 80% yield (Scheme 42). 

Disrotatory photolysis of the bicyclic aziridine (300) occurred readily to give the azomethine imine (301) reaction in the presence of DMAD in dioxane gave (302). Photolysis of (301) in the presence of DMAD gave the isomeric photoproduct (303) along with 4% of (302) (69AG(E)604). 

Photolysis of 1-alkylpyridinium salts, e.g., 53, is considered to involve bicyclic aziridine allylic cations 54 as intermediates (Scheme 8) <2005JOC5618>, and similar behavior has been found in certain pyrylium cations (Schemes 9 and 10). Diazabenzvalenes are implicated in the rearrangement at 300 C of certain perfluoropyridazines to pyrimidines and pyrazines (Scheme 11). 

A strategy for the synthesis of trehazolamine has been developed from 1-methox-yethoxymethyl-3-pivaloyloxymethylpyridinium perchlorate via amino cyclopentane derivatives (Schemes 42 and 43).115 Pyridinium salt 351 was prepared by a two-step sequence from 3-(hydrooxymethyl)pyridine 349 via 350 (Scheme 42). Irradiation of 351 in aqueous NaHC03 led to production of the separable bicyclic aziridines 352 (20%) and 353 (16%). Ring opening of 352 by acetic acid, followed by removal of the... 

Allylphenyl sulfamate cyclizes under oxidizing conditions to furnish bicyclic aziridine. Subsequent nucleophilic addition of alcohols or H2O occurs selectively to afford 1,2,3-oxathiazocine stmctures 47a and 47b (Scheme 49 <2005OL4685>). Similarly, Rh-catalyzed oxidative transformation of hex-5-enyl sulfamate leads to 1,2,3-oxathio-azocane with annulated aziridine ring <2004AGE4349>. 

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