Addition to Azirines

Reactions between organolithium reagents and 3-(2-naphthyl)-2H-azirine in the presence of a range of chiral ligands have been studied. The product aziridines are obtained in at best moderate ees [61]. 

A similar but asymmetric variant of the reaction, involving the radical addition of alkyl iodides and trialkylboranes to chiral azirine esters derived from 8-phenyl-menthol and camphorsultam, in the presence of a Cu(i) catalyst, has subsequently been reported [64]. The diastereoselectivity of the addition is variable (0-92% de) 

Aziridines bearing heteroatom substituents are best prepared through treatment of the corresponding azirines with heteroatom nucleophiles. Thus, azirine carbox-ylates (in this case prepared by thermal decomposition of the corresponding vinyl 

---

Addition to azirines giving 2-trifluoromethylaziridines is also smooth. 

Important synthetic paths to azirines and aziridines involve bond reorganization, or internal addition, of vinylnitrenes. Indeed, the vinylnitrene-azirine equilibrium has been demonstrated in the case of trans-2-methyl-3-phenyl-l-azirine, which at 110 °C racemizes 2000 times faster than it rearranges to 2-methylindole (80CC1252). Created in the Neber rearrangement or by decomposition of vinyl azides, the nitrene can cyclize to the p -carbon to give azirines (Scheme 4 Section 5.04.4.1). 

The photochemical addition of azirines to the carbonyl group of aldehydes, ketones, and esters is also completely regiospecific (77H(6)143). Besides the formation of the isomeric oxazolines (50) from (39) and ethyl cyanoformate, there is also formed the imidazole (51) from addition to C=N in the expected regioselective manner. Thioesters lead to thiazolines (52), while isocyanates and ketenes produce heterocycles (53). 

The reactions of 1-azirines with ketenes and ketenimines represent non-concerted additions and are formally different from the additions to 47r-systems of dienes and 1,3-dipolar compounds (73JOC3466, 71CB2786). 

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. 

Addition of trichloromethide ion to azirine (210) generates aziridine (230). When this aziridine was treated with base, cyclization and rearrangement occurred and the azetidine (233) was isolated (73JA2982). 

Azirines react with alcohols in the presence of alkoxides to give alkoxyaziridines (67JA4456). Further treatment with alcohol and alkoxide results in the formation of amino ketone acetals. Alkoxyaziridines are not isolated in general from the acid-catalyzed addition of methanol to azirines. Azirines are also known to react with amines (66JOC1423). Frequently the initially produced adducts undergo subsequent transformations. 

In addition to the present method, 2H-azirines can be prepared by using a modified Neber reaction,or by heating 4,5-dihydro-l,2,5-oxazaphospholes. 1... 

H-Azirine-2-carboxylates such as 57 (Scheme 3.19) are a special class of imines that undergo additions to their C=N double bonds to give aziridine-2-carboxylates... 

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... 

Intramolecular addition of trialkylboranes to imines and related compounds have been reported and the main results are part of review articles [94, 95]. Addition of ethyl radicals generated from Et3B to aldimines affords the desired addition product in fair to good yield but low diaster control (Scheme 40, Eq. 40a) [96]. Similar reactions with aldoxime ethers [97], aldehyde hydrazones [97], and N-sulfonylaldimines [98] are reported. Radical addition to ketimines has been recently reported (Eq. 40b) [99]. Addition of triethylborane to 2H-azirine-3-carboxylate derivatives is reported [100]. Very recently, Somfai has extended this reaction to the addition of different alkyl radicals generated from trialkylboranes to a chiral ester of 2ff-azirine-3-carboxylate under Lewis acid activation with CuCl (Eq. 40c) [101]. 

The addition of methanol or hydrazoic acid to ethenylidenecydopentadiene 3 demonstrates that 3 behaves like an acceptor-substituted allene (Scheme 7.27) [226, 227]. More examples of nudeophilic additions to alkyl-substituted derivatives of 3 were reported by Hafner [228]. Photoelectron spectroscopy of the spirocyclic compound 165b, easily accessible from azide 164b, shows that the lone-pair orbital n(N) of the 2H-azirine nitrogen atom interacts strongly with the Jt1-orbital of the cyclo-pentadiene ring [227]. 

Addition of hydroxylamines to C=N double bonds produces stable compounds only for endocyclic C=N bonds. Addition of hydroxylamine to azirines of type 59 results in stable adducts 60 as seen in equation 40. Similar reactions have been observed in benzoxazoles and l,2,3-triazolo[4.5-rf]pyrimidones ° ... 

There are a few reports on the use of oximes as electrophilic amination reagents. Since 1984, ketone O-sulfonyloxknes have found applicability as amino transfer reagents to car-banions. In the reaction of organometaUic compounds with oximes, carbanions attack the carbonyl carbon of the oxime, giving Af-substituted hydroxylamines as addition products (Scheme 53, path a). However, a number of scattered reports have been also published on the formation of aziridines by a-deprotonation, followed by addition (path b) or formation of azirines by a-deprotonation before addition (path c). Addition of carbanions to azirines also yields aziridines, which are hydrolyzed to a-aminoalcohols. 

Aromatic cyclic 7r-electron delocalization does indeed stabilize the planar structure with bond equalization (84ZOR897)—the problem is that, in addition to that effect, there may exist some others that may eventually overshadow it. Thus, the foregoing warrants the conclusion that the preference of a planar or nonplanar geometry of heterocycle depends on a number of factors including aromaticity (antiaromaticity), which may not even be the most important. In any case, this factor should not be disregarded if one wishes to obtain a correct overall energy balance. For example, aromaticity is reflected in the values of inversion barriers. Thus, for antiaromatic 2-azirine the nitrogen inversion barrier is, as was mentioned earlier, 37.7 kcal/mol, whereas in the case of its saturated... 

Reports of pericyclic cyloadditions to other azepine systems are rare. Addition to the diene system of 6,7-dihydro-l//-azepines occurs readily with DMAD (72CPB1740) and with N-phenylmaleimide (73JA7320). The 5,5a-dihydro-3-benzazepin-2-one (157), a suspected but non-isolable intermediate in the formation of l,2,4,5-tetrahydro-3//-3-benzazepine-2,4-diones by photoaddition of diphenylketen to amino-2//-azirines, has been trapped in the photolysate by N-phenyl-1,3,4-triazoline-2,4-dione as the [4+2]tt adduct (158). Its structure was confirmed by X-ray analysis (80JOC2951). 

Irradiation of 2,3-diphenyl-2//-azirine in the presence of fullerene leads to the formation of mono- and oligo adducts (98,99). A monoadduct, l,9-(3,4-dihydro-2,5-diphenyl-2//-pyrrolo)fullerene-60 was isolated and characterized. Mechanistic studies showed that under conditions of direct irradiation it was formed by a classic nitrile ylide cycloaddition but in the presence of 1,4-napthalenedicarbonitrile (DCA) it resulted from reaction of the radical cation intermediate 108. Cycloaddition reactions have also been carried out with diaza-phospholes and diazaarsoles (100) to give adducts of the type 189 (A = As,P) and with cyanogen to give 190 and with aryldiazocyanides where addition to both the azo moiety and the cyano group were observed (101). 

Nucleophilic additions to 3-alkoxy (86RTC456) and 3-amino-2//-azirines (91AG(E>238) are especially well studied, e.g. Scheme 19. Many of these reactions involve assistance by protonation of the nitrogen. 

Azirines are also made by carbene addition to nitriles (89 — 90) and by thermal or photochemical (68JA2869) elimination of N2 from vinyl azides (e.g. 91 — 92). Vinyl azides are prepared by the Hassner reaction (68JOC2686, 71ACR9), where iodine azide is first added to an alkene and the resultant (3-iodoazide is dehydrohalogenated with base (Scheme 37) (86RTC456). 

---