N-Tosyl aziridines

While nitrogen sources such as chloramine-T and PhI=NTs have been used for aziridination reactions, TsNC12 has not been explored until now. The reaction of TsNCL, with Pd(OAc)2 and K2C03 provides the expected N-tosyl aziridines in good yields <06TL7225>. This reaction presumably proceeds through an initial amidohalogenation reaction catalyzed by palladium. The chloroamide is then converted to the aziridine via an intramolecular substitution reaction. 

Typically, the stereospecific formation of quaternary centers is as problematic as selective nucleophilic attack at the more substituted carbon of aziridines. Interestingly, a copper mediated methodology has been reported that does both <060L5105>. Although N-tosyl aziridines show favorable results, A-nosyl aziridines gave the best results. The reaction of 89 with a variety of phenols yielded 90 in moderate yields. 

Non-metal catalyzed aziridinations have also been reported. These methods are often more broadly applicable than the metal-catalyzed methods. The use of A -methylpyrrolidine-2-one hydrotribromide (MPHT) and chloramine-T is an effective route for the synthesis of N-tosyl aziridines <06MI16>. The aziridination of olefins using f-BuOI and sulfonamides appears to be a general method for aziridination <06CC3337>. The t-BuOI is prepared in situ from t-BuOCl and Nal. This is a broadly applicable method in that a wide variety of sulfonamides (tosyl, nosyl, SES) can be used with roughly equivalent yields. 

Intermolecular alkyl radical addition to imine derivatives proceeds in aqueous media when indium is used as an SET radical initiator. The one-pot reaction based on radical addition to glyoxylic hydrazone provides an a-amino acid (Scheme 8.94) [126]. A similar indium-mediated radical addition to an electron-deficient C-C bond gives the corresponding adduct. Chiral allylic amines are synthesized in high yields by treatment of 2-iodomethyl N-tosyl aziridines with indium in MeOH under reflux (Scheme 8.95) [127]. 

Indium trichloride induces rearrangement of aryl-substituted epoxides to the respective aryl-substituted acetaldehydes via an exclusive hydride shift As phenyl group migration occurs more readily than hydride migration, stilbene oxide is converted to diphenylacetaldehyde (Scheme 8.140) [184]. N-Tosyl aziridines react smoothly with carboxylic acids in the presence of a catalytic amount of indium triflate to afford the corresponding -aminoacetates and benzoates (Scheme 8.141) [185]. Indium trichloride and indium bromide catalyze regio- and diastereoselective azidolysis, bromolysis, and iodolysis of a, -epoxycarboxylates in water (Scheme 8.142) [186]. 

The reaction chemistiy of aziridines is underdeveloped. This is particularly surprising because aziridines are easily prepared in high enantiomeric purity. Arlette Solladie-Cavallo of the Universite L. Pasteur, Strasbourg, reports J. Org. Chem. 2004, 69, 1409) that addition of the pulegone-derived sulfonium ylide 6 to an aldehyde tosylimine. such as 7 proceeds to give the N-tosyl aziridine 8 in high ee and with good diastereocontrol. The sulfide precursor to 6 is recovered in almost quantitiative yield. N-Tosyl aziridines such as 8 are readily opened both by carbon and by heteroatom nucleophiles. 

Scheme 1.2S (a,b) Palladium-catalyzed carbonylation of N-tosyl aziridines. 

Like the carbonylation of epoxides, the carbonylation of aziridines occurs with increased rates and scope in the presence of catalysts containing a Lewis acidic cation and Co(CO) " anion. A particularly active version of fliis catalyst for the carbonylation of aziridines is the uncommon species [CpjTi(THF)2]""[Co(CO)J . As shown in Equation 17.56, this catalyst is substantially more active tiian COj(CO)g for the carbonylation of N-benzyl cyclohexene imine. The carbonylation of N-tosyl-2-methylaziridine has also been accomplished (Equation 17.57), and ttiis reaction is important because of the ability to prepare optically active N-tosyl aziridines. Although the reaction catalyzed by the titanium and cobalt system occurred to only 35% conversion, the carbonylation of the N-tosyl-2-methylaziridine catalyzed by the aluminum and cobalt system occurred to completion under the same reaction conditions. 

Ring opening of aziridines catalyzed by In(III) salts was studied by Yadav et al. and the results showed the same trend as above. InBrs was used for addition of amines to N-tosyl aziridines [86], In(OTf)3 for carboxylic acids [87], and InCh for trimethylsilyl azide [88] (Figure 8.45). 

Scheme 2.4 Aziridination of dienes with [(N-tosyl) iminojphenyliodinane 9.

Treatment of N-sulfmyl-as-aziridine-2-carboxylate 206 (Scheme 3.75) with LDA at -78 °C afforded 2H-azirine-2-carboxylate 207 in 47 % yield. The trans-aziridine 206 gave only a 9% yield of the desired product 207 [95]. Treatment of N-tosyl 2-substi-tuted aziridines 208 (Scheme 3.76) with LDA resulted in the formation of azirines 209 in 61-87% yield [95],... 

An alternative preparation of aziridines reacts an alkene with iodine and chloramine-T (see p. 1056) generating the corresponding A-tosyl aziridine. Bromamine-T (TsNBr Na ) has been used in a similar manner." Diazoalkanes react with imines to give aziridines." Another useful reagent is NsN=IPh, which reacts with alkenes in the presence of rhodium compounds or Cu(OTf)2 to give N—Ns aziridines. Manganese salen catalysts have also been used with this reagent. ... 

Fe(OTf)2-catalyzed aziridination of enol silyl ethers with PhlNTs followed by ring opening led to a-N-tosylamido ketones in good yields (Scheme 27) [81]. With silyl ketene ketal (R = OMe) as substrate, the N-tosyl-protected amino acid ester was obtained in 50% yield. In contrast, the copper (I) salt CuClOq was found not effective for this substrate [82]. 

Gold-based catalysis has attracted considerable attention in recent years. A gold-catalyzed aziridination reaction has recently been reported <06JOC5876>. A series of gold catalysts were examined for their ability to catalyze the aziridination of styrene with p-nitrophenylsulfonamide (NsNH2). Styrene and phenyl-substituted styrenes provided the N-nosyl aziridines in good to excellent yields. Cinnamate however provided the aziridine product in only 25% yield. The use of other sulfonamides (e.g. tosyl, trichloroethyl) gave much lower yields of the aziridine product. 

A complication in aziridination is that metal carbenoids can react directly with some imines to yield aziridines. Fortunately, imines bearing electron-withdrawing groups are less reactive to carbenoids and more reactive to ylides than electron-rich imines. Thus, N-tosyl, N-diphenylphosphinyl and N-[-(tri-methylsilyl)ethansulfonyl] imines (-(trimethylsilyl)ethansulfonyl = SES) were all suitable substrates using dimethylsulfide and Rh2(OAc)4, with no background reaction detected [77, 78]. Phenyldiazomethane, N,N-diethyl diazoacetamide and ethyl diazoacetate could be used as the diazo component, although the latter two required temperatures of 60 °C to decompose. 

In addition to epoxides, three-membered nitrogen heterocycles, aziridines, can be obtained by means of catalytic asymmetric aziridinations (Eq. 30). To this aim, chiral ruthenium(salen) complexes 67 [56] and 68 [57] were useful (Fig. 1). The former phosphine complexes 67 gave the aziridine from two cy-cloalkenes with 19-83% ee [56]. On the other hand, terminal alkenes selectively underwent aziridination in the presence of the latter carbonyl complex 68 with 87-95% ee [57]. In these examples, N-tosyliminophenyliodinane or N-tosyl azide were used as nitrene sources. Quite recently, catalytic intramolecular ami-dation of saturated C-H bonds was achieved by the use of a ruthenium(por-phyrin) complex (Eq. 31) [58]. In the presence of the ruthenium catalyst and 2 equiv iodosobenzene diacetate, sulfamate esters 69 were converted into cyclic sulfamidates 70 in moderate-to-good yields. 

A related reaction with epi-sulfides leads to 2-chlorothio-esters. Aziridines have been opened with MgBr2 to give 2-haloamides in a related reaction. N-Tosyl azir-idines react with KF 2 H2O to give the 2-fluorotosylamine product. ... 

The first breakthroughs in this chemistry appeared with the independent works of Breslow [5] and Mansuy [6] who reported the use of Fe(III) and Mn(ni) porphyrins complexes with tosylimidoiodobenzene (Phi = NTs) [7] as an N centered electro philic oxidant (Scheme 12.3). Treatment of an alkene with a high valent Mn nitrene favored the C H insertion product over the competing aziridination reaction. However, yields in these intermolecular reactions remained low. A mixture of N tosylated allylic products was obtained with the product distribution best ratio nalized by a radical C H abstraction/rebound process [6]. 

The synthesis of ( )-pancratistatin (211) has been achieved by application of a sequence of the reactions noted previously to a [Z-O-t-butyldimethylsilyl (TBS)-4,5-methylenedioxy]phenyl derivative. Namely, coupling of N-(p-tosyl)aziridine 232 with the cuprate derivative of [3-0-TBS-2-(A(,N-dimethylcarboxamido)-4,5-methylenedioxy]benzene, in a manner similar to that noted for 210, produced N-(6-arylcyclohex-4-enyl)-N-(p-tosyl)amide as a mixture of atropisomers, reductive N-... 

A number of catalysts have been used to promote ring opening of A-tosyl-aziridines, such as phospho-molybdic acid and silica gel, for azide, cyanide and alcohols " and tri-n-butylphosphine for thiols and amines. Opening with iodide occurs at room temperature with iodine and thiophenol in the presence of air. In the nucleophilic ring opening of A-tosyl-aziridines, silver ion catalysis facilitates reactions with electron-rich arenes or hetarenes. ... 

Desulfonylation. Aziridines are released from their N-tosyl derivatives with sodium naphthalenide in THE... 

Lewis Acid-catalyzed [3+2] Cycloaddition. The title compound efficiently catalyzed an efficient and highly regiose-lective 1,3-dipolar cycloaddition reaction of alkynes and N-tosylazomethine ylides (eq 36). Cleavage of the C-C bond of iV-tosyl aziridines under mild conditions was catalyzed by Sc(OTf)3, affording the Af-tosylazomethine ylides. The reaction proceeds smoothly with various internal alkynes to afford the desired cycloadducts in moderate to good yields. 

The direct transformation of 2-amino alcohols to V-tosyl aziridines can be achieved in moderate to good yields using potassium hydroxide and tosyl chloride in water/dichloromethane. This procedure works well for small amino alcohols. Ehgher substituted amino alcohols give better yields using a two-step procedure formation of the N, 0-ditosylate followed by cyclization with potassium carbonate in acetonitrile. 

Tetrahydropyrrolizines (210) and (211) can be formed via radical scission of either bond a or b in the intermediate vinyl-aziridine (208) but yields are moderate at best and the major product is the monocyclic pyrroline (209), formed by a 1,5-homo-dienyl rearrangement. The route therefore could provide a useful access to the pyrrolizidine framework if conditions could be identified which would allow more controlled and efficient breakdown of (208). The synthesis of substitute pyrrolines by ring expansion of vinyl aziridine derivatives has also been accomplished in a palladium-catalysed reaction. N -Tosyl-2-vinyl five- and six-membered nitrogen heterocycles (213) ace obtained in generally high yields under mild conditions from precursor dienyl nitrogen heterocycles (212) in the presence of a catalytic amount of [Pd(PPh ) ]. The complete diene unit is required for the... 

---