Enantioselective cinnamic esters

Charrette and Lebel [24] developed a catalytic enantioselective cyclopropa-nation of trans-cinnamate esters with diazomethane. Their procedure involves an argon-flow-mediated diazomethane addition, leading to high yields (up to 80%) in products with up to 80% ee, by using the bis(oxazoHne) arising from phenylglycinol (Scheme 10). 

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

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 Rh(I) salts heterobidentate ligands such as 3 form catalysts of greater activities than homobidentate ligands 4, for enantioselective hydrogenation of acrylate and cinnamate esters. The findings are rationalized in terms of conformational and allosteric effects of the substrates. ... 

Reductive aldol reaction of l-alken-3-ones and cinnamic esters depends on generating Rh enolates and the presence of chiral ligands turns such a process enantioselective. Effective ligands of very different structural types have been identified, and they include TADDOL phosphine 71 and BOX ligand 72. ... 

These parameters were probed in an in-depth study dealing with the epoxidation of cis-cinnamate esters 11, a protocol Jacobsen has used for the enantioselective synthesis of diltiazem (13), a commercial anti-hypertensive agent [94TET4323]. Surprisingly, electronic and steric factors on the phenyl moiety exercise practically no influence on the enantioselectivity (1st step) of the reaction, whereas increasing steric... 

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. 

Owing to the low reactivity of the in situ formed dioxiranes, they suffer decomposition processes to give the corresponding Bayer-VilUger oxidation products. Therefore, new ketones with enhanced stability have been introduced to perform the aforementioned epoxidation. One of these ketones was the fructose derivative 62a [68], which efficiently catalyzed the oxidation of different cinnamate esters with higher yields (40-96%) and improved enantioselectivities (up to 97% ee). Surprisingly, the epoxidation of the related ethyl ( -cinnamate gave a lower result (84%, 44% ee). 

Racemic diphosphines may be resolved by using transition metal complexes that contain optically active olefinic substrates (Scheme 11) (24). When racemic CHIRAPHOS is mixed with an enantiomerically pure Ir(I) complex that has two ( —)-menthyl (Z)-a-(acetam-ido)cinnamate ligands, (S,5)-CHIRAPHOS forms the Ir complex selectively and leaves the R,R enantiomer uncomplexed in solution. Addition of 0.8 equiv of [Rh(norbomadiene)2]BF4 forms a catalyst system for the enantioselective hydrogenation of methyl (Z)-a-(acetamido)cinnamate to produce the S amino ester with 87% ee. Use of the enantiomerically pure CHIRAPHOS-Rh complex produces the hydrogenation product in 90% ee. These data indicate that, in the solution containing both (S,S)-CHIRAPHOS-Ir and (/ ,/ )-CHIRAPHOS-Rh complexes, hydrogenation is catalyzed by the Rh complex only. 

Heterogeneisation of chiral rhodium complex of 1,2-diphosphines already known as very efficient catalysts for enantioselective hydrogenation32 was achieved through amine functionality borne by pyrrolidine molecule. The supported Rh complex revealed as its homogeneous counterpart very high enantioselectivity (<90%) in hydrogenation of a-(acetylamino)cinnamic acid and its methyl ester. 

The first report of an enantioselective photocycloaddition of prochiral conjugated esters involved the introduction of (+ )-2,3-di-0-methyl-erythritol as chiral auxiliary in a diastereoselective and intramolecular photocycloaddition of the bis cinnamate 78 (Scheme 18). Among the isolated isomers, the chiral 8-truxinate (+ )-79 could be obtained as the major product with a de up to 86% [59] (Scheme 18). 

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