Styrene, chiral aziridination

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... 

Scheme 9.22 Chiral aziridination of styrene over a chiral copper bis-oxazoline complex supported in zeolite Y (from reference 59).

In a shorter synthesis of dihydrexidine [9], synthetic intermediate 51 was obtained via an FC reaction of a chiral aziridine intermediate 60 (Scheme 2.8). Styrene 58 was prepared from a Wittig reaction of aldehyde 57 as a mixture of diastereomers ( 7Z=78 22) and treated with PhINNs in the presence of the BOX ligand 59 and Cu(OTf)2. It was found that Cu(OTf)., was a dual catalyst for the enantioselective aziridination and FC reaction. The E/Z mixture of styrenes 58 provided exclusively tran5-2-amino-l-phenyltetralin 51 in 87% ee, which could be increased up to 99% after crystallization. The c/s-cyclized product was not detected. 

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... 

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. 

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. 

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). ... 

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. 

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 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. 

Solvent CHjCN, styrene PhI=NTs = 5 1 molar ratio Isolated yield of aziridine based on PhI=NTs. Values in parentheses indicate yields obtained from homogeneous reactions Enantioselectivity determined by chiral HPLC styrene was used as solvent, e0 °C, f25°C, Absolute configurations of major products, determined by optical rotation, are (S) for trans-P-niethylstyrene and trans-P-methylcinnamate, (R) for styrene. 

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>. 

A one-pot procedure designed for the aziridination of a series of styrene derivatives employs commercially available iodobenzene diacetate [PhI(OAc)2] and sulfonamides (427, RSO2NH2) to generate the nitrene precursors [iV-(arene/methanesulfonyl)imino]phenyliodanes (RS02N=IPh) in situ. The reaction is carried out in the presence of the chiral catalyst CuIMeCNIaClOa-L (436 L = 2,2-bis[2-[(4A)-/-butyl-l,3-oxazolinyl]]propane) to give aziridine 437 (Scheme 113) <2004TL3965>. 

Alkenes undergo diastereoselective aziridination in the presence of chiral 3-acetoxyaminoquinazolinones (e.g., 715), prepared in situ by acetoxylation of the corresponding 3-aminoquinazolinones. Thus, trimethylsilyl styrene 716... 

Although asymmetric aziridination of styrenes was attempted by Burrow and Katsuki and their coworkers using manganese salen complexes in the presence of PhI=NTs, low asymmetric induction was observed ". Nishikori and Katsuki later employed a salen complex synthesized from (/ ,/f)-2,3-diaminobutane and ( i-biphenol, and found that the chirality at the 3,3 -positions is more important for the asymmetric induction (equation 85) . Carreira conducted the stoichiometric amination of enol ethers and alkenes using a manganese nitride salen complex. Komatsu extended the methodology to the catalytic process and attained 94% ee for aziridination of / -isopropylstyrene. ... 

Although a large number of chiral porphyrin catalysts has been developed for study in asymmetric epoxidation chemistry [12], to date only one example has been applied to aziridination. In that instance, Lai and coworkers reported the use of the Halterman porphyrin catalyst in the aziridination of styrene derivatives with moderate enantioselectivity (Scheme 5) [13]. 

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-... 

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