Aziridination, of styrene

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. 

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. 

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. 

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. 

Catalytic methods are suitable for nitrene transfer," and many of those found to be effective for carbene transfer are also effective for these reactions. However, 5- to 10-times more catalyst is commonly required to take these reactions to completion, and catalysts that are sluggish in metal carbene reactions are unreactive in nitrene transfer reactions. An exception is the copper(ll) complex of a 1,4,7-triaza-cyclononane for which aziridination of styrene occurred in high yield, even with 0.5 mol% of catalyst. Both addition and insertion reactions have been developed. 

Evans and co-workers were the first to report that 4,4 -disubstituted bisoxazolines 29 are excellent chiral ligands for enantioselective aziridination (Scheme 6B.30) [74,75]. Aryl-substi-tuted olefins, especially cinnamate esters, are good substrates for this aziridination. The best reaction conditions, however, vary with the substrates used. For the reactions of cinnamate esters, bisoxazoline 29a and benzene are the ligand and solvent of choice. Under these conditions, enantioselectivity up to 97% ee is observed. For the aziridination of styrene, bisoxazoline 29b and acetonitrile are the appropriate ligand and solvent. 

Lowenthal and Masamune also reported that the copper complex bearing a bisoxazoline ligand 30 was an effective catalyst for aziridination of styrene (88% ee) (Scheme 6B.31) [76], However, Evans et al. later claimed that this result was not reproducible [75],... 

Enantioselectivity of copper-catalyzed aziridination is dependent on the nitrene precursor used (Scheme 6B.32) [77]. Although the precursor of choice varies with the substrates, /j-Me0C6H4S02N=lPh orp-02NC6H4S02N=IPh is superior to TsN=IPh in many cases. For example, the aziridination of styrene in the presence of copper-bisoxazoline complex 29b gives the product with 78% ee using p-Me0C6H4S02N=IPh as the nitrene precursor, whereas the enantioselectivity is 52% ee when TsN=IPh is used as the precursor. 

Another bisoxazoline ligand 31 was prepared from tartrate and applied to asymmetric aziridination. However, enantioselectivity observed was modest (Scheme 6B.33) [78], Bisaz-iridine ligand 32 was prepared, but its copper complex showed only modest enantioselectivity in the aziridination of styrene (Scheme 6B.34) [79],... 

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 major advantage of the use of CuHY as a catalyst for this reaction is the ease with which it can be recovered from the reaction mixture by simple filtration if used in. a batch reactor (alternatively it can be used in a continuous flow fixed bed reactor). We have carried out the heterogeneous asymmetric aziridination of styrene until completion, filtered and washed the zeolite then added fresh styrene, PhI=NTs and solvent, without further addition of chiral bis(oxazoline), for several consecutive experiments. The yield and the enantioselectivity decline slightly on reuse we have found that adsorbed water can build up within the pores of the zeolite on continued use and we believe that this is the cause of loss of activity and enantioselection. However, full enantioselectivity and yield can be recovered if the catalyst is simply dried in air prior to reuse, or alternatively the catalyst can be recalcined and fresh oxazoline ligand added. 

Hydrotris(3,5-dimethyl-l-pyrazolyl)borato](ethylene)copper(I) catalyzed the aziridination of styrene (90% yield), 1-hexene (40%) and cfv-cyclooctene (75%) with C6H5I = NTs under anhydrous conditions (CH2C12, molecular sieves)120. 

Chiral salen-iron(III)49 and -manganese(III)50 complexes were also tested as catalysts for the aziridination of styrene and (Z)-l-phenylpropene with C6H5I = NTs, but the enantioselectivities and/or the yields were low. 

Relative rates of the aziridination of styrene 397 versus a series of ra-substituted styrenes 398 furnishing the respective aziridines 401 and 402 have been determined using Tp Cu(C2H4) (Tp =hydridotris(3,5-dimethyl-l-pyr-azolyl)borate) 400 as the copper precatalyst in combination with PhI=NTs 399 as the nitrene source. The experimental data of the aziridination reaction can be fit with a two-term equation of the type log(>fx/ H) = -t-p cr" a are Jackson s radical substituent constants) leading to the values =—0.28 0.06 (polar contribution) and p = 0.34... 

Experimental observations of the aziridination of styrene-type alkenes, catalyzed by CuPF6 in the presence of chiral diimine ligands (such as (lR,2R,A i4A i4)-A A -bis(2,6-dichlorobenzylidene)cyclohexane-l,2-diamine 425), have been taken as evidence of the intermediacy of a discrete, monomeric Cu(lll)-nitrene complex, (diimine)Cu=NTs 423. Variation of the steric properties of the aryl group in the oxidant TsN=IAr (Ar = Ph, 2-/-Bu, 5,6-Me3C6H) has no effect on the enantioselectivities in forming the aziridination products 424 (Scheme 108) <1995JA5889>. 

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>. 

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