Styrene aziridination

The first reports on iron-catalyzed aziridinations date back to 1984, when Mansuy et al. reported that iron and manganese porphyrin catalysts were able to transfer a nitrene moiety on to alkenes [90]. They used iminoiodinanes PhIN=R (R = tosyl) as the nitrene source. However, yields remained low (up to 55% for styrene aziridination). It was suggested that the active intermediate formed during the reaction was an Fev=NTs complex and that this complex would transfer the NTs moiety to the alkene [91-93]. However, the catalytic performance was hampered by the rapid iron-catalyzed decomposition of PhI=NTs into iodobenzene and sulfonamide. Other reports on aziridination reactions with iron porphyrins or corroles and nitrene sources such as bromamine-T or chloramine-T have been published [94], An asymmetric variant was presented by Marchon and coworkers [95]. Biomimetic systems such as those mentioned above will be dealt with elsewhere. 

Several alkenes are converted to aziridines by treating with oxaziridine (52) at elevated temperatures. Styrene, a-methylstyrene and their derivatives substituted in the benzene ring react smoothly, and so do 1,1-diphenylethylene, indene and acrylonitrile (74KGS1629). 

The reaction used to test these solid catalysts was the aziridination of styrene with AT-tosyliminophenyliodinane (Phi = NTos) (Scheme 10). In most cases, enantioselectivities were low or moderate (up to 60% ee). The loss of enantioselectivity on changing from ligand 11a to ligand 12 was attributed to the fact that ligand 12 is too big for the copper complex to be accommodated into the zeolite supercages. Further studies carried out with hgands 11a and 11b [62] demonstrated that the reaction is more enantioselective with the supported catalyst (82% ee with 11a and 77% ee with 11b) than in solution (54% ee with 11a and 31% ee with 11b). This trend supports the confinement effect of the zeolite structure on the stereoselectivity of the reaction. 

Table 11 Effect of bis(oxazoline) on the aziridination of styrene with zeolite-supported ...

The mild iron-based Lewis acid, [(q -CsH5)Fe(CO)2(THF)]BF4 reported by Hossain, catalyzed the aziridination of styrene derivatives with PhlNTs with product... 

A more practical, atom-economic and environmentally benign aziridination protocol is the use of chloramine-T or bromamine-T as nitrene source, which leads to NaCl or NaBr as the sole reaction by-product. In 2001, Gross reported an iron corrole catalyzed aziridination of styrenes with chloramine-T [83]. With iron corrole as catalyst, the aziridination can be performed rmder air atmosphere conditions, affording aziridines in moderate product yields (48-60%). In 2004, Zhang described an aziridination with bromamine-T as nitrene source and [Fe(TTP)Cl] as catalyst [84]. This catalytic system is effective for a variety of alkenes, including aromatic, aliphatic, cyclic, and acyclic alkenes, as well as cx,p-unsaturated esters (Scheme 28). Moderate to low stereoselectivities for 1,2-disubstituted alkenes were observed indicating the involvement of radical intermediate. 

On the other hand, other chiral dirhodium(II) tetracarboxylate catalysts based on azetidine- and aziridine-2-carboxylic acids have been prepared by Zwanenburg et al. and submitted to the cyclopropanation of styrene with... 

Scheme 6.18 Rh-catalysed cyclopropanation of styrene with sulfonamide ligands derived from aziridine- and azetidine-2-carboxylic acids.

Jacobsen et al. reported that a different type of dintrogen ligand (48), fe[(2,6-dichlorophenyl)-methylideneaminojcyclohexane, was an efficient chiral ligand for copper-mediated asymmetric aziridination (Scheme 35).154 The reactions of conjugated c/.v-olefins show high enantioselectivity with this catalyst, but enantioselectivity of the reactions of simple olefins such as styrene and indene is moderate. 

Burrow et al. examined aziridination with chiral Mn(salen) in the presence of PhI=NTs, but no enantioselectivity was observed.160 However, Katsuki et al. reported that the aziridination of styrene with complex (52) showed moderate enantioselectivity, though the chemical yield was poor (Scheme 38).161 Remarkable improvements of both enantioselectivity (up to 94% ee) and chemical yield have been achieved by using a new type of Mn(salen) (53) as the catalyst.162... 

Chiral Mn111porphyrin (55) catalyzes the aziridination of styrene derivatives in the presence of PhI=NTs. Though enantioselectivity is moderate, the turnover number of the catalyst is high (Scheme 40).164 A MnIV—PhINTs adduct (56) has been proposed as the active intermediate for this reaction, on the basis of UV-vis and EPR analyses. 

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. 

Diphenylphosphorylazide (DPPA) has also been shown to be an excellent nitrene source in aziridination reactions <06JOC6655>. The reaction of styrene and substituted styrenes with DPPA and tetraphenylporphyrin cobalt (CoTPP) provided the A-diphenylphosphinyl aziridines in moderate yields. 

Tanner et al. (58) investigated the use of chelating diaziridines (85) as ligands for transition metals. The cyclopropanation of styrene using CuOTf complexes of phenyl-substituted aziridine (85a) proceeds in modest enantioselectivity and dias-tereoselectivity, but improved enantioselectivity is observed with complexes derived from benzyl-substituted bis(aziridine) (85b), Eq. 42 (59). Complexes derived... 

Evans et al. (34) reported preliminary results showing that 55c CuOTf is moderately selective in mediating the aziridination of styrene, producing the heterocycle in 61% ee. Lowenthal and Masamune (44) mention in a footnote to their cyclopropanation paper that the copper complex of camphor-derived bis(oxa-zoline) (103) provides the aziridine of styrene in 91% yield and 88% ee. However, this reaction has been found to be irreproducible (76,77) and further reports of aziridination from the Masamune laboratories have not appeared. 

Optimal selectivities of cinnamate aziridines are provided by the phenyl-substituted bis(oxazoline) (55d). In contrast, /ra .v-p-mcthyl styrene proved to be most selective with ferf-butyl substituted 55c and acetonitrile as solvent, Eq. 56, conditions that afford the cinnamate ester-derived aziridine in only 19% ee. Styrene is a poor substrate for this catalyst and provides the opposite antipode as the major enantiomer from the same ligand, Eq. 57. 

Treatment of a solution of 55cCu(OTf)2 complex with a stoichiometric amount of PhI=NTs in CH2C12 resulted in rapid uptake of the insoluble iodinane. This complex, when treated with styrene, provided aziridine in quantitative yield in the same selectivity (37% ee) as the catalytic reaction (in CH2C12 at 25°C, 36% ee), Eq. 59. Addition of toluene at -78°C resulted in deposition of the complex as an oil. Analysis of the supernatant liquid revealed that <5% Phi was present, suggesting that the iodobenzene was still part of the complex. Unfortunately, this material resisted repeated attempts at crystallization. Whatever its true nature, it seems that this complex is not a classical copper nitrenoid (77). 

A number of other bis(oxazolines) have been applied as ligands in the copper-catalyzed aziridination reaction. Knight and co-workers (80) examined tartrate-derived ligands. Diastereomeric bis(oxazolines) 110 and 111 were each found to be poorly effective in mediating the asymmetric aziridination of styrene, Eq. 63. 

Tanner et al. (58) investigated the asymmetric aziridination of styrene using bis(aziridines) such as 85. Low induction is observed with these ligands, Eq. 64. A significant electronic effect was noted with the p-fluoro-phenyl substituted bis(az-iridine) 85c (59). A binaphthyl-derived diamine was used as a ligand for the copper-catalyzed aziridination of dihydronaphthalene (81). The product was formed in 21% ee and 40% yield, Eq. 65. Other structurally related ligands proved to be less selective in this reaction. 

The cis alkenes are more reactive and more selective than their trans counterparts. As with the Evans system, this reaction is not stereospecific. Acyclic cis alkenes provide mixtures of cis and trans aziridines. cis-p-Methylstyrene affords a 3 1 ratio of aziridines favoring the cis isomer, Eq. 67, although selectivity is higher in the trans isomer. A fascinating discussion of this phenomenon, observed in this system as well as the Mn-catalyzed asymmetric oxo-transfer reaction, has been advanced by Jacobsen and co-workers (83). Styrene provides the aziridine in moderate selectivity, Eq. 68, not altogether surprising since bond rotation in this case would lead to enantiomeric products. 

Investigations into the mechanism of this reaction revealed several interesting facts (61). Compelling evidence was presented that a discreet Cu nitrenoid was involved in the catalytic cycle. Photolysis of a solution of tosyl azide and styrene in the presence of the catalyst afforded aziridine with the same enantioselectivity as obtained from the PhI=NTs reaction, Eq. 69. Since photolysis of tosyl azide is known to extrude dinitrogen and form the free nitrene, the authors argue that this is indicative of a common Cu-nitrenoid intermediate in this reaction. 

The mesityl diimine 88d was as effective a ligand in the aziridination as the 2,6-dichlorophenyl diimine 88a ( 65% ee vs 66% ee) (61). The bound face of the styrene undergoes aziridination (in contrast with Fu s selective crystallization of the wrong face of styrene in his copper-catalyzed cyclopropanation reaction, cf. Section II.A.8). Unfortunately, the potential racemization of 118 (by the mechanism... 

The first catalytic, asymmetric aziridination of an alkene in good yield and high enantioselectivity was recently reported56. Thus styrene (63) was treated with [N-(p-toluenesulphonyl)imino]phenyliodinane (64) and an asymmetric copper catalyst to yield (/ )-Ar-(p-toluenesulphonyl)-2-phenylaziridine [(/ )-65] in 97% yield with an ee of 61%, the catalyst being the complex formed in situ in chloroform from the chiral bis[(5 ) 4-ferf-butyloxazoline] [(S,S)-66] and copper triflate (CuOTf)56, the reaction proceeding by way of a nitrene transfer57. 

Iodine was found to be an efficient catalyst for the aziridination of alkenes (Scheme 6) utilizing chloramine-T (A-chloro-A-sodio-p-toluenesulfonamide) as the nitrogen source. For example, when 2 equiv. of styrene (45a) were added to chloramine-T in the presence of a catalytic amount of iodine (10mol%) in a 1 1 solvent mixture of acetonitrile and neutral buffer, the corresponding aziridine (46) was obtained in 91% yield. The reaction proved to work with other acyclic and cyclic alkenes, such as oct-l-ene and cyclohexene. The aziridination of para-substituted styrene derivatives (45b-e) demonstrated that, as expected for an electrophilic addition, electron-rich alkenes reacted faster than electron-poor alkenes. However, with 1 equiv. of I2, mainly iodohydrin (47) was formed. A catalytic cycle has been proposed to account for the fact that only a catalytic amount of iodine is required (Scheme 1) ... 

A chiral D4-manganese(III) porphyrin catalyst, Mn(P )(MeOH)(OH) [H2P = 5, 10, 15,20-tetrakis(l,2,3,4,5,6,7,8-octahydro-l,4 5,8-dimethanoanthracene-9-yl)porphyrin], has been shown to catalyse the asymmetric aziridination of substituted styrenes (105) with enantiomeric excess of 43-68% (Scheme 40). ... 

Stance, although Mn(TPP)Cl-catalyzed reaction of 19 with styrene affords aziridine derivative in 80% yield (Eq. 13), significantly lower yields are obtained with other olefins. Allylic insertion by the metal nitrenoid is frequently the major side reaction encountered during olefin aziridination (88TL1927) (Eq. 14). 

Various epoxides and aziridines undergo smooth ring opening with water in presence of bismuth triflate (10 mol%) to provide the corresponding v/c-diols and p-amino alcohols with excellent regioselectivity [35]. Reaction of styrene oxide with water in the presence of Bi(OTf)3 affords styrene 1,2-diols (Fig. 7). Similarly,... 

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. 

---