Styrene with aziridine

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 ...

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.

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... 

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. 

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). 

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... 

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). 

Scheme 9. Copper-catalyzed aziridination of styrene with CT 3H20.

Asymmetric Aziridination of Styrene with Nitrido Complex... 

Scheme 18. Aziridination of styrene with complex 15 and Ts20 the reaction pathway and regeneration of complex 15 from recovered Mn111 complex.

Table 6.1 Effect of pyridine N-oxide for the aziridination of styrene with complex 15.

The nitrido complexes 16-21, as shown in Section 6.3, which bear various substituents on the para (R1) and/or ortho (R2) positions of a benzene ring of complex 15 were employed in the asymmetric aziridination of styrene (Table 6.2). The reaction of styrene with complex 16 or 17 gave lower product yields and enantioselectivities compared to the reaction with the complex 15. Complex 18 decreased the yield of the aziridination, but the enantioselectivity was not affected however, when complex 19 was employed, the yield and the selectivity were low. In the case of 20, the enantioselectivity was moderate but the yield was very low complex 21, which bears Jacobsen s ligand, showed a similar result with complex 20. Thus far, complex 15 is the best nitrogen source for the asymmetric aziridination of styrene. 

The reaction of thiophene with the styrene-derived aziridine 44 with I11CI5 catalysis involves attack mainly at the more hindered and benzylic carbon, although ca. 10% of product formation derives from terminal attack (Scheme 33) <2002TL1565>. Similarly, In(OTf)3 can be used to promote the reaction of 44 with reactive benzenes, with the same regioselectivity <2001TL8067>. 

The asymmetric copper-catalyzed aziridination of styrene with /i-toluenesulfonamide, iodosylbenzene, and 2,2-bis[(4d )-/-butyl-l,3-oxazolin-2-yl]propane catalyst (Evans catalyst) provided the aziridine product with an ee comparable with that previously obtained (Scheme 110) <2001JA7707>. 

Another method to synthesize tetramizole starts with the reaction of styrene oxide (18) with aziridine to form N-(2-hydroxy-2-phenylethyl)aziridine (19) which is converted into the desired product as shown in scheme 2 [18,19]. 

Levamisole has also been prepared by synthesizing optically active N-(2-hy-droxy-2-phenylethyl)aziridine (19) which is heated with thiourea in aqueous sulphuric acid at lOO C for 3 hours to give the title compound. Compound (R)-19, in turn, was obtained by reaction of (R)-styrene oxide with aziridine (r/. Scheme 2) [29]. 

The more thoroughly developed salen-based catalysts have also been studied in the context of aziridination, albeit with limited success. While Burrows observed no measurable enantioselection in the aziridination of styrene derivatives using simple chiral (salen)Mn catalysts derived from 1,2-phenylethylenedi-amine [14], Katsuki encountered some success (up to 28% ee in the azidination of styrene) with more complex derivatives of the same diamine [15]. Substantially improved enantioselectivities were observed with a less hindered diamine backbone associated with highly optimized chiral salicylide elements. Thus, up to 94% ee has been obtained in the aziridination of styrene with a 2,3-diaminob-utane-derived catalyst (Scheme 6) [16]. Incorporation of catalytic levels of a py-... 

Xanthenyliumsodium (from sodamide and xanthene) reacts with aziridines to give a mixture of 9-mono- (271) or 9,9-di-substituted xanthenes (272).Addition of perchloric acid to unsymmetric allenes such as the 9-xanthylidene derivative (273) (prepared by a new route from 9,9-dichloroxanthene and an alkene) gave a red xanthylium salt (274), which was converted into a colourless spiro-indene (275) on heating.Full details have now been published of the properties and of the reactions of 9-diazoxanthene (276) and 9-xanthylidene (278) with methyl acrylate, substituted styrenes, several ketones, and alkyl-benzenes. The kinetics of the reaction with styrenes were studied and the conversion of (276) into (278) was achieved by photolysis of the tosylhydrazone (277) at —25 °C. 

The asymmetric synthesis of aziridines can be achieved by a number of methods. The best alkene substrates are typically a,3-unsaturated esters, styrenes or chromenes, with aziridination by PhI=NTs and a metal-chiral ligand complex. For example, aziridination of tert-butyl cinnamate 73 occurs highly enantioselec-tively with copper(I) triflate and a bisoxazoline ligand (5.77). 

Nitridomanganese complex was first applied to asymmetric aziridination reactions of alkenes by Komatsu and coworkers in 1998 [9]. The reaction of styrene with the chiral nitridomanganese 3 [10] in the presence of pyridine, TS2O,... 

Since the work of Cenini and coworkers the aziridination reaction of alkenes with azide using various types of metal-loporphyrin-based catalyst has been broadly studied. Zhang and coworkers developed the Co(TPP)-catalyzed aziridination of styrenes with diphenylphosphoryl azide (DPPA) (Scheme 2.9) [14a]. In continuing their work on the cobalt-porphyrin catalyst, the asymmetric alkene aziridinations with DPPA catalyzed by the cobalt(ll) complexes with D2-sym-metric chiral porphyrin ligands were also reported [14b]. 

Recently, inexpensive and biocompatible iron complexes have attracted much attention as a transition-metal catalyst in organic synthesis. Iron porphyrins are easy to handle and now commercially available. Liu and Che reported that [Fe (F2o-tpp)Cl] (F2o-tpp = mejo-tetrakis(pentalluoro-phenyl)porphyrinato dianion) 6 is a highly reactive catalyst for aziridination of various alkenes with sulfonyl and aryl azides (Scheme 2.11) [16, 17]. In particular, aliphatic alkenes, which have lower reactivity than styrenes for aziridination, could also be applied in this reaction system. 

Mansuy et al. discovered the nitrene transfer reactions from iminoiodinanes to C=C double bond afrbrding aziridines in 1984 [22]. The reaction of styrene with PhI=NTs in the presence of a catalytic amount of Fe(TPP)(Cl) or Mn(TPP) (Cl) complex in dichloromethane at room temperature provided the corresponding aziridine products as shown in Scheme 2.14. TheiV-tosylaziridination proceeded in a stereoselective manner, where the more stable trans products were obtained from either cis- or tranr-stilbene. Those characteristics are totally different from the Fe(TPP)Cl-catalyzed alkene epoxidation using Phl=0, which proceeds in a stereospecific manner. 

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