Ring expansion aziridines

A soln. of l-cyclohexyl-2-phenyl-3-p-toluoylaziridine and p-nitrophenyl isothiocyanate refluxed 17 hrs. in dry benzene -> 3-cyclohexyl-5-p-nitrophenylamino-2-phenyl-4-p-toluoyl 4-thiazoline. Y 54%. J. W. Lown,G. Dallas, and T. W. Maloney, Can. J. Chem. 47, 3557 (1969) aziridine ring expansion, review, s. F. N. Gladysheva, A. P. Sineokov, and V. S. Etlis, Russ. Chem. Rev. 39, 118 (1970) (Eng. transL) heterocyclics by aziridine ring expansion, review, s. J. W. Lown, Record Chem. Progr. 32, 51 (1971). 

With respect to ring-expansion reactions of aziridines, 4-aryltetrahy-droisoquinolines were synthesized by a scandium(III) triflate-mediated intramolecular aziridine ring expansion (14TL6787). Additionally, a regi-oselective aziridine-to-pyrrolidinone ring expansion was reported as part of an asymmetric synthesis of (-i-)-lentiginosine (14TA497), while NBS was... 

The most useful reactions combine carbanion nucleophiles with activated aziridines. For example, the ring expansion which occurs on treatment of aziridines (219) with malonate salts typifies the heterocyclic synthesis possible. The conversion is quite general since many analogous transformations have been observed in which different carbanion stabilizing substituents were employed (73S546). 

Ring expansion of activated aziridines (43) with sulfur ylides also provides a synthesis of azetidines (75JOC2990, 58BSF345, 81CC417). The highly reactive sulfonium methylide (44 R = R = H) undergoes further reaction with the azetidines (46), but the reaction is satisfactory for substituted methylides. The less reactive sulfoxonium methylide (45 R = R = H)... 

A number of 2-acylazetidines have been prepared by reaction of 1,3-dihaloacyl compounds with amino derivatives (Section 5.09.2.3.l(m)). This is illustrated for azetidine 2-carboxylic acid (56), the only known naturally occurring azetidine. Ring expansion of activated aziridines (43) and contraction of 4-oxazolines (55) has also found limited use (Section 5.09.2.3.2(f) and Hi)). 

Aziridine, cis-7V-t-butyl-3-ethynyl-2-vinyl-rearrangement, 7, 540 Aziridine, 2-chlorocarbonyl-ring expansion, 7, 42 Aziridine, 2-chloromethyl-synthesis, 7, 42 Aziridine, Mcyanodiphenyl-irradiation, 7, 61 Aziridine, dihalo-reduction, 7, 74 thermolysis, 7, 73... 

Aziridine, 2,3-diphenyl-l-(2,4,6-trinitrophenyl)-irradiation, 7, 61 Aziridine, 1,2-divinyl-rearrangement, 7, 539 Aziridine, 2,3-divinyl-rearrangement, 7, 42, 65, 539 Aziridine, N-ethyl-inversion, 7, 6 Aziridine, 2-halo-reactions, 7, 74 Aziridine, A/-halo-invertomers, 7, 6 Aziridine, 2-methyl- N NMR, 7, 11 Aziridine, methylene-ring-ring valence isomerizations, 7, 22 synthesis, 7, 92 Aziridine, iV-nitroso-reactions, 7, 74 Aziridine, iV-phosphino-inversion, 7, 7 Aziridine, 1-phthalimido-UV irradiation, 7, 62-63 Aziridine, l-(3-thienyl)-2-vinyl-rearrangement, 4, 746 Aziridine, 7V-trimethylsilyl-inversion, 7, 7 Aziridine, 1,2,3-triphenyl-irradiation, 7, 61 Aziridine, vinyl-isomerization, S, 287 Aziridinecarboxylic acid ring expansion, 7, 262 Aziridine-2,2-dicarboxylic acid, 1-methoxy-diethyl ester... 

Likewise, the isomeric fused aziridines 22 and 24, obtained from 1,4,5,6,7,8-hexahydronaph-thalene, undergo bromination. dehydrobromination and ring expansion to the 6,7,8,9-tetra-hydro-3//-3-benzazepine 23 and the 2,7-bridged azepine 25, respectively.61... 

N-Acylaziridine-2-carboxylates readily rearrange to oxazolines under thennal, acidic, or nucleophilic conditions [91, 123-127]. Treatment of trans-aziridine-2-car-boxylate 176 (Scheme 3.63) with Nal in acetonitrile, for example, resulted in ring-expansion product 177 through the so-called Heine reaction. The reaction involves initial opening of the aziridine ring by iodide and subsequent oxazoline ring-closure by Sn2 displacement of the resultant iodide intermediate [127]. 

Treatment of aziridine 137 (Scheme 3.64) with benzoyl chloride in the presence of pyridine and DMAP afforded ring-expansion product 179 in 90% yield [45], The reaction was believed to proceed through the intermediate N-acylaziridine 178. 

When aziridine 194 (Scheme 3.71) was treated with a catalytic amount of NaOEt in ethanol it underwent an intramolecular ring-expansion to pyrrolidinone 195 in 88% yield [130]. The ring-opening took place via an internal SN2 reaction, which was confirmed by an X-ray analysis of the product 195. It is interesting to note that under similar reaction conditions 196 (Scheme 3.72) afforded P-lactam product 197 [130]. 

Keywords Aziridine-2-carboxylic esters. Ring expansion reactions, Azirine carboxylic esters, Aziridine carbinols. Anomalous amino acids... 

It should be noted that this sequence shown in Scheme 31 is complementary to that depicted in Scheme 30 in which a-hydroxy-j9-amino acids are prepared. This chemistry of aziridine- and oxiranecarboxylic esters and the corresponding ring expansion reactions has been elaborated to a general protocol for the synthesis of j9-hydroxy-a-amino and a-hydroxy-j9-amino acids, respectively [1,411. 

Thermal ring expansion of M-acylaziridines by simple heating in chloroform also gives oxazolines in excellent yields, despite the fact that the aziridine ring has a rather sophisticated substituent (Scheme 32) [42]. 

An intramolecular ring expansion of aziridine esters can be accomplished by installing an appropriate nucleophilic entity in these substrates. Conversion of the ester moiety into carboxamides derived from aminomalonate ester gives compounds 44 containing the requisite nucleophilic site in the malonate moiety (Scheme 35). 

The aza-[2,3]-Wittig rearrangement [47] and the related aza-[3,3]-Claisen rearrangement [48] of vinylaziridines are elegant examples of expansion of the aziridine ring in a stereocontrolled fashion (Scheme 38). 

The highly strained and reactive 2iT-azirines have been extensively studied for various synthetic purposes, such as ring expansion reactions, cycloaddition reactions, preparation of functionalized amines and substituted aziridines. The older literature on azirines in synthesis has extensively been reviewed [69]. Concerning azirines with defined chirality only scarce information is available. Practically all reactions of azirines take place at the activated imine bond. Reduction with sodium borohydride leads to cz5-substituted aziridines as is shown in Scheme 48 [26,28]. 

In 2003, Bonini et al. reported a new synthesis of ferrocenyloxazolines based on an iodide-mediated ring expansion of A-ferrocenoyl-aziridine-2-carboxylic esters. The thus-formed ligands were successfully employed as palladium chelates for the test reaction, since they allowed the product to be formed in quantitative yields and good to high enantioselectivities (Scheme 1.69). According to the results, it seemed that the additional chiral centre present in the oxazoline backbone of these ligands did not play a major role for the asymmetric induction and the activity of the corresponding catalysts. 

These findings can be interpreted in terms of a normal ring-opening mechanism of intermediate 325 with proton transfer favored by protic solvent, whilst in aprotic solvent cycloreversion of the unstable aziridinium grouping in 325 followed by ring expansion prevails. Likewise, 2,3-disubstituted aziridines follow this reaction pattern, while N-substituted aziridines do not225. ... 

Ring Expansion Via Carbonyiation Reactions 11.15.5.1 Ring Expansion of Aziridines... 

Since Alper and co-workers reported the first Rh-catalyzed carbonylative ring expansion of aziridines, yielding /3-lactams in 1989, this ring-expansion reaction catalyzed by Rh or Co complexes and its mechanism have been extensively studied. ... 

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... 

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