Styrene complexes, aziridination

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). 

Jacobsen reported in 1990 that Mnm complexes of chiral salen ligands (41) were the most efficient catalysts available for the enantioselective epoxidation of alkyl- and aryl-substituted olefins.118 This stimulated a rapid development in the chemistry and applications of chiral SB complexes, which offer promising catalytic applications to several organic reactions, such as enantioselective cyclopropanation of styrenes, asymmetric aziridination of olefins, asymmetric Diels-Alder cycloaddition, and enantioselective ring opening of epoxides.4,119... 

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. 

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. 

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... 

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. 

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. 

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. 

Copper complexes catalyze formally related aziridination of olefins with ]7V-(p-toluenesulfonyl)imino]phenyliodinane, a nitrene precursor (219b). As exemplified in Scheme 98, catalysts formed from Cu(I) tri-flate and optically active bis(oxazolines) effect enantioselective reaction of styrene (Scheme 98) (218b, 219a). 

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],... 

Metalloporphyrin complexes serve as catalysts for aziridination in the presence of PhI=NTs [73], Che et al. have reported the chiral version of metalloporphyrin-catalyzed aziridination (Scheme 6B.36) [81], The reaction of styrene derivatives with a D4-manganese(III) porphyrin complex 34 proceeds with fairly good enantioselectivity, up to 68% ee. This reaction is proposed to proceed through a Mn(IV)-PhINTs adduct 35 on the basis of EPR analysis. 

A review has appeared on the synthesis of enantiomerically enriched aziridines by the addition of nitrenes to alkenes and of carbenes to imines.45 A study of the metal-catalysed aziridination of imines by ethyl diazoacetate found that mam group complexes, early and late transition metal complexes, and rare-earth metal complexes can catalyse the reaction.46 The proposed mechanism did not involve carbene intermediates, the role of the metal being as a Lewis acid to complex the imine lone pah. Ruthenium porphyrins were found to be efficient catalysts for the cyclopropana-tion of styrenes 47 High diastereoselectivities in favour of the //-product were seen but the use of chiral porphyrins gave only low ees. 

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. 

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. 

Table 6.5 Asymmetric aziridination of rran -substituted styrene derivatives with complex 15 Olefin Conditions Aziridine Yield (%) ee (%)...

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. 

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>. 

Aziridination Reactions. CuOTf-bis(oxazoline) complexes are efficient catalysts for the aziridination of olefins. Olefins with aryl substituents have proven to be the most efficient substrates for this reaction. For styrene, the corresponding Ai-tosylaziridine was obtained in good yield (89%), but only moderate enantiomeric ex-... 

Aziridination. The bis(triflate) complex (2) catalyzes the az-iridination of styrene derivatives in the presence of [iV-(p-toluene-sulfonyl)imino]phenyliodinane (eq 1). Spectroscopic studies revealed that catalysts prepared from both Cu OTf and Cu (OTf)2 were identical under the reaction conditions, thus leading to the conclusion that the Cu(II) complex is the catalytically active species. 

Styrene cyclopropanation continues to attract much interest. Cationic complex CpFe(CO)2(THF) BF4" mediates carbene transfer from ethyl diazoacetate with high cis selectivity cis trans = 85 15) [38]. On the other hand, Tp Cu(C2H4), where Tp is hydrotris(3,5-dimethyl-l-pyrazolyl)borate, is one of the rare catalysts to promote carbene transfer from ethyl diazoacetate to alkenes and also to alkynes. While cyclopropanes are formed in high yield, cyclopropenes are obtained only in moderate yield [39]. The same complex also catalyzes nitrene transfer from PhI=NTs to alkenes to produce aziridines in high yields. 

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