Evans aziridination reaction

The use of sulfonylimino(aryl)iodanes, especially [(tosylimino)iodo]benzene (41), as nitrene-transfer agents has undergone considerable development during the past decade. Much of this effort is based on the finding in the early 1990s that tosylaziridinations of alkenes with Phi = NTs, previously demonstrated with Mn(III)- and Fe(III)-porphyrin catalysts, can be achieved more generally and efficiently with copper(I) and copper(II) salts i.e., the Evans aziridination reaction [172,173]. Standard conditions for preparative aziridinations of this type were developed, and applied to cyclic and acyclic alkenes, arylalkenes, and a, / -... 

In a study published concurrently with the Evans bis(oxazoline) results, Jacobsen and co-workers (82) demonstrated that diimine complexes of Cu(I) are effective catalysts for the asymmetric aziridination of cis alkenes, Eq. 66. These authors found that salen-Cu [salen = bis(salicylidene)ethylenediamine] complexes such as 88b Cu are ineffective in the aziridination reaction, in spite of the success of these ligands in oxo-transfer reactions. Alkylation of the aryloxides provided catalysts that exhibit good selectivities but no turnover. The optimal catalyst was found to involve ligands that were capable only of bidentate coordination to copper. 

Evans,D.A., Eaul,M.M.and Bilodeau, M.T. (1994) Development ofthe copper-catalysed olefin aziridination reaction. Journal of the American Chemical Society, 116, 2742-2753. 

Significant recent interest in the transition metal catalyzed reactions of imidoiodanes was initiated in the 1990s by the pioneering works of Evans [586, 763, 764] and Jacobsen [765,766] on the asymmetric aziridination of olefins using copper catalysts (2-10 mol%) with chiral dinitrogen ligands and PhD JTs as the nitrene precursor. Since these initial publications, research activity in this area has surged and the copper-catalyzed aziridination of alkenes has been utilized in numerous syntheses. For example, Dodd and coworkers applied the Evans aziridination procedure to 2-substituted acrylates and cinnamates 649 [767] and to steroids 650 (Scheme 3.257) [768]. 

Evans DA, Paul MM, Bilodeau MT. Development of the copper-catalyzed olefin aziridination reaction. 7. Am. Chem. Soc. 1994 116(7) 2742-2753. 

The use of the bisoxazolinylanthracene ligand AnBOX in an Evans-like aziridination of chalcones has thrown up the interesting observation that the sense of enantiodiscrimination is inverted in relation to the reaction carried out with a traditional BOX ligand with similar stereogenicity (Scheme 4.17) [16]. 

Decomposition of sulfonyl azides was shown to be catalyzed by copper in 1967 (72, 73). In the presence of alkenes, the reaction provides both aziridines and the C-H insertion products, albeit in low yields (73). In 1991, Evans et al. (74, 75) illustrated that both Cu(I) and Cu(II) salts were effective catalysts for nitrenoid transfer from [A-(/Moluenesulfonyl)imino]phenyliodinane (PhI=NTs) to a variety of acceptor alkenes. In the absence of ancillary ligands, reactions proceed best in polar aprotic solvents such as acetonitrile. Similar results are observed using both Cu(MeCN)4C104 and Cu(acac)2 as precatalysts, Eq. 53. 

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 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. 

In 1991, Evans et al. reported that cationic Cu(I) ions catalyzed the nitrene-transfer reaction smoothly (Scheme 6B.29) [74]. Since then, many studies on asymmetric aziridination have been carried out with chiral copper(I) complexes as catalysts. 

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. 

Attempts to aziridinate alkenes with iron catalysts in an asymmetric manner have met with only limited success to date [101], In an early report on the use of various chiral metal salen complexes, it was found that only the Mn complex catalyzed the reaction whereas all other metals investigated (Cr, Fe, Co, Ni etc.) gave only unwanted hydrolysis of the iminoiodinane to the corresponding sulfonamide and iodoben-zene [102], Later, Jacobsen and coworkers and Evans et al. achieved good results with chiral copper complexes [103]. 

With this ligand, aziridination of chromene 7.40 (X = O, R = Me, R = 4-CN) takes place at -78°C with an ee superior to 98% and aziridination of 7.40 (X = CH2, R=R =H) takes place with 87% ee. From other olefins, disappointing results are observed. Evans and coworkers recommended bis-oxazolines 3.28 (R = Ph, R = H, R" = Me) as copper ligands for asymmetric aziridination of cinnamic esters [965] (Figure 7.35). These reactions take place in benzene at room temperature in the presence of molecular sieves. However, other olefinic substrates again do not give high selectivities. 

During the course of their pioneering work on the copper-catalyzed cyclopropanation reaction of alkenes [25], the copper-catalyzed aziridination of alkenes using PhI=NTs was also discovered by Evans et al. in 1991 [26], A wide range of alkenes can be smoothly converted to the corresponding aziridines in the presence of Cu(I) and Cu(II) salts, such as Cu(MeCN)4C104 and Cu (acac)2, respectively (Scheme 2.16). Notably, aliphatic alkenes afforded the desired aziridines without allylic C-H amidation products. In the hterature, only one example of the enantioselective aziridination of styrene using chiral bis (oxazoline)-based copper catalyst was demonstrated. At the... 

Evans et al. had expanded their previous copper-catalyzed aziridination using CuOTf with chiral bis(oxazoline) hgand 11 [28]. This catalyst system was particularly effective for the aziridination of cinnamate esters to achieve an excellent enantioselectivity (Scheme 2.17). Indeed, because both CuOTf and Cu(OTf)2 afforded similar results, it was indicated that copper worked as a catalyst in the 2-1- oxidation state. Contrarily, the reactions using CuCl or CuBr as a catalyst instead of CuOTf were very slow and gave low enantioselectivity. These results showed that counter ions such as triilate anion play an effective role in accelerating the highly electronegative reactions. 

Around the same time as the Evans work, Jacobsen and coworkers also independently reported the enantioselective alkene aziridination employing a chiral CuOTf catalyst [29]. The most effective catalyst was prepared from CuOTf with bis-((2,6-dichlorobenzylidene)-diamino)cyclohexane ligand 12, which afforded the excellent enantioselectivity in the reaction of 6-cyano-2,2-dimethylchromane with the iminoiodinane (Scheme 2.18). Reactions of styrenes also proceeded in moderate to high enantioselectivities. However, tetradentate (salen)Cu complexes such as 13 decreased both the product yields and enantioselectivities, which indicated that the existence of multiple open coordination sites on a copper center was essential to enhance the catalytic activity [30]. 

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