Evans asymmetric aziridination

Cycloadditions. The scope of the Evans asymmetric aziridination is broadened by the ready availability of nitrene precursor 4-02NCjH S02N=IPh. The oxazolidinone-Af-acetic acid derived from (+)-cw-2-amino-l,2-diphenylethanol participates in p-lactam formation with imines. The predominant products (>99 1) have the (3/f,45)-configuration. The intramolecular [2+2]photocycloaddition involving a chiral allenylsilane moiety is an excellent method for accessing optically active methylenecyclobutane derivatives. ... 

In 1995, aziridination with 1,3-dienes 10 by treatment with PhI=NTs 9 was developed (Scheme 2.4) [10] on the foundation of pioneering works by Jacobsen and Evans on copper-catalyzed asymmetric aziridination of isolated alkenes [11]. 

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. 

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. 

Given the significant existing knowledge-base in asymmetric catalytic cyclo-propanation (Chap. 16), the discovery that metal ions useful for catalysis of carbene transfer to alkenes were also effective for nitrene transfer to the same substrates opened a clear new direction for research in asymmetric aziridination. Brief mention of the asymmetric catalysis of the aziridination of styrene was made in two early reports on (bisoxazoline)copper-catalyzed asymmetric cyclopropanations [20,21], and subsequently new methods for copper-catalyzed asymmetric aziridination were revealed in two independent studies published simultaneously by Jacobsen and Evans [22,23]. 

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. 

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]. 

In more recent years, a number of discoveries involving the use of nitre-noid or carbenoid intermediates have been made [35-37]. In 1993, Evans [139] and Jacobsen [140] independently described the asymmetric aziridination of olefins with Phi = NTs mediated by Cu(I) catalysts [141]. The chiral ligands included bisoxazoline 173 (Equation 29) [139] and diimine 176 (Equation 30) [140]. The methods displayed complementary substrate... 

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. 

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]. 

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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