Cinnamate esters, aziridination

Recently, Scott et al. have reported that a Cu complex bearing an axially chiral ligand (49) is an excellent catalyst for aziridination of 2,2-dimethylchromene and cinnamate esters (Scheme 36), though it is also less efficient for the reactions of simple olefins.157,158 On the basis of DFT investigation of the nitrenoid intermediate (50), one of the oxygen atoms of the A -sulfonyl group has been proposed to be interacting with the nitrene N-atom.158... 

The first highly enantioselective aziridination was reported in 1993 (76). Evans et al. found that cinnamate esters are excellent substrates for 55d CuOTf catalyzed... 

Optimal selectivities of cinnamate aziridines are provided by the phenyl-substituted bis(oxazoline) (55d). In contrast, /ra .v-p-mcthyl styrene proved to be most selective with ferf-butyl substituted 55c and acetonitrile as solvent, Eq. 56, conditions that afford the cinnamate ester-derived aziridine in only 19% ee. Styrene is a poor substrate for this catalyst and provides the opposite antipode as the major enantiomer from the same ligand, Eq. 57. 

TABLE 9.34 AZIRIDINATION OF CINNAMATE ESTERS, 575 TABLE 9.35 BIS(OXAZOLINE)-MEDIATED ALLYLIC OXIDATION, 577 TABLE 9.36 HYDROSILYLATION OF ACETOPHENONE, 578... 

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. 

Jacobsen and co-workers have reported that chiral diimine 33a serves as an effective chiral auxiliary for the copper-catalyzed aziridination of aryl-substituted Z-olefins (Scheme 6B.35) [80], For example, the aziridination of 6-cyanochromene proceeds with high enantioselectivity (>98% ee). Comparison of ligands 33a-33c has revealed that the o-substituents in the ligands sterically and electronically influence the enantioselectivity of the reaction, that is, the introduction of chlorines at o-positions not only prolongs catalyst lifetime but also enhances enantioselectivity. The reactions of other Z-substrates and cinnamate esters catalyzed by 33a show moderate-to-high enantioselectivity, whereas that of -stilbene gave low enantioselectivity (Table 6B.3). 

The Evans system employs chiral bisoxazoline ligands with copper(I) triflate. Exceptionally high levels of enantioselection were observed in the aziridination of cinnamate ester derivatives (Scheme 8),but thus far no other substrate classes have been demonstrated to undergo aziridination with synthetically-useful levels of stereoinduction. 

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. 

When the ligand (5,5)-70 was used, methyl cinnamate (71) was converted to the corresponding aziridine (S,S)-72 in 63% yield with an ee of 94% , but the optimal conditions for the aziridination of the cinnamate esters cannot be reliably extrapolated to other acyclic olefins . Reductive ring opening of (S,S)-72 by transfer hydrogenation afforded the corresponding (/f)-methyl iV-(p-toluenesulphonyl)phenylalaninate [(R)-73] and established the absolute configuration of (S,5 )-72 . This latter reaction and other reactions of the... 

Reactions of A-tosyliminophenyliodinanes (PhI=NTs) as nitrene source with alkenes in the presence of chiral ligands also present a valuable method to achieve asymmetric aziridination reactions. Cinnamate esters 73 yield enantiomeric aziridinate products in good selectivities on reaction with chiral bisoxazolines 23 and Al-tosyliminophenyliodinanes in the presence of copper salts (Scheme 29) [87]. Biaryl Schiff bases 74 can also be used as ligands in the enantioselective aziridination of ciimamate esters, chromenes and st5renes [88]. Chiral C2-symmetric salen-type ligands 75 were also found to be highly effective for 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. 

The asymmetric synthesis of aziridines can be achieved by a number of methods. The best alkene substrates are typically a,3-unsaturated esters, styrenes or chromenes, with aziridination by PhI=NTs and a metal-chiral ligand complex. For example, aziridination of tert-butyl cinnamate 73 occurs highly enantioselec-tively with copper(I) triflate and a bisoxazoline ligand (5.77). 

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