Allylic oxidation, asymmetric

Scheme 6.97 Copper-catalyzed asymmetric allylic oxidation of bridged bicyclic alkenes.

DattaGupta and Singh45 report the results of bis(oxazolinyl)pyridine induced asymmetric allylic oxidation. The reaction proceeds with 59% yield and 56% ee (Scheme 8-16). 

Except for a 1976 report in the patent literature (100a), the first true catalytic asymmetric allylic oxidation using copper was reported in 1991 by Muzart (100b). Of the various amino acids investigated as ligands for Cu(II), (S) proline was found... 

Asymmetric allylic oxidation and benzylic oxidation (Kharasch-PSosnovsky reaction) are important synthetic strategies for constructing chiral C—O bonds via C—H bond activation.In the mid-1990s, the asymmetric Kharasch-Sosnovsky reaction was first studied by using chiral C2-symmetric bis(oxazoline)s. " Later various chiral ligands, based mainly on oxazoline derivatives and proline derivatives, were used in such asymmetric oxidation. Although many efforts have been made to improve the enantioselective Kharasch-Sosnovsky oxidation reaction, most cases suffered from low to moderate enantioselectivities or low reactivities. 

The efficiency of a new chiral non-racemic and C2-symmetric 2,2-bipyridyl ligand (6) in copper(I)-catalysed asymmetric allylic oxidation reactions of the cyclic alkenes with f-butyl peroxybenzoate has been evaluated. On performing the reaction of cyclopentene, cyclohexene, and cycloheptene in acetonitrile the corresponding product, (lS)-cycloalk-2-enyl benzoate, was isolated in up to 69% yield and in 91% ee 29... 

Asymmetric allylic oxidation of alkenes using peresters is possible when the ligand L of the Cu(III) intermediate is chiral. Copper complexes of chiral bis(pyri-dine)- and bis(oxazoline)-type ligands have been used with fert-butyl perbenzoate to obtain optically active allylic benzoates. 

Asymmetric allylic oxidation is not yet perfected. Although many systems have been scrutinized, both chemical and optical yields need to be improved greatly. An example worth mentioning is the delivery of 2-cyclopenten-l-yl benzoate using a Cu(II)-tris(oxazoline) complex as catalyst in 30% yield and 93% ee. ... 

Scheme 14. Asymmetric allylic oxidation using /err-butyl perbenzoate [12]...

Scheme 13. Asymmetric allylic oxidation using 19 as the chiral auxiliary...

Cu(OTf)2 in the presence of the ligand ( )-N-((naphthalen-7-yl)methylene) benzenamine and C6H5NHNH2 catalyses selective oxidation of benzylic C(sp )-H bonds to C(sp )-0 bonds with t-butyl perbenzoate (TBPB) in acetone. Cu(MeCN)4PF5 catalyses asymmetric allylic oxidation of acyclic olefins by TBPB in acetone in the presence of spiro bisoxazoline ligands (8) the product allyl esters are formed with excellent regioselectivity (>20 1 in most cases) and up to 67% ee. °°... 

Bayardon and Sinou have reported the synthesis of chiral bisoxazolines, which also proved to be active ligands in the asymmetric allylic alkylation of l,3-diphenylprop-2-enyl acetate, as well as cyclopropanation, allylic oxidations and Diels-Alder reactions. [62] The ligands do not have a fluorine content greater than 60 wt% and so are not entirely preferentially soluble in fluorous solvents, which may lead to a significant ligand loss in the reaction system and in fact, all recycling attempts were unsuccessful. However, the catalytic results achieved were comparable with those obtained with their non-fluorous analogues. 

Mechanistic studies showed that metalacycle la is competent to be a catalyst in asymmetric allylic substitution reactions. The reaction of benzylamine with methyl ciimamyl carbonate catalyzed by a mixture of LI and [Ir(COD)Cl]2 occurs with an induction period and forms product in 84% yield and 95% ee, whereas the same reaction catalyzed by a mixture of metalacycle la and [Ir(COD)Cl]2 occurs without an induction period in just 2 hours to form the substitution product in 81% yield and 97% ee. The latter reaction was conducted with added [Ir(COD)Cl]2 to trap the -bound LI after dissociation. This ligand must dissociate to provide a site for oxidative addition of the allylic carbonate. 

HayasM et al. achieved high catalytic activity by using axially chiral iV-oxide catalyst 27. As compared to other organic catalysts, the reaction proceeded much faster, and high enantioselectivities were obtained with 0.01-0.1 mol% catalyst loading [53-55]. In 2005, Hoveyda and Snapper used a novel proline-based ahphatic A-oxide 28 for an asymmetric allylation (Scheme 19) [56],... 

Intermediate for the preparation of vinyloxazolines for stereoselective nitrile oxide cycloaddition Intermediate for polymer 225 supported catalyst for asymmetric allylic alkylation... 

Feringa reported an enantioselective allylic oxidation of cyclohexene to optically active 2-cyclohexenyl propionate 25 by using a chiral copper complex prepared from Cu(OAc)2 and (S)-proline, as chiral catalyst (Scheme 9.14) [32], In the absence of additives, a negative NLE was observed, whereas in the presence of a catalytic amount of anthraquinone, a positive NLE (asymmetric amplification) was observed. Moreover, higher enantioselectiv-ity was attained when enantiopure (S)-proline was used. However, the role of the additive remains elusive. 

The suitability of a different type of organocatalyst, chiral N-oxides, for asymmetric allylation was discovered by the Nakajima group [176]. On the basis of the knowl-... 

A related N-oxide organocatalyst of type 178, developed by Maikov and Kocovsky et al., has been used for successful asymmetric allylation of aldehydes [178]. It is worthy of note that the corresponding N,N -dioxide gave less satisfactory results. In the presence of 7 mol% N-monoxide 178, aromatic aldehydes have been con-... 

A terpene-derived pyridine N-oxide catalyses the asymmetric allylation of aldehy- des with allyl- and crotyl-trichlorosilane at —40 C, and the ees hold up well even at ambient temperature.189... 

Several chiral 2,2 -bipyridine ligands when reacted with [Mo(CO)6] give complexes 18, 19 (R = H, Me), and 20 usable as catalysts in asymmetric allylic substitution, allylic oxidation, and cyclopropanation (01OM673). 

Examples of oxidative coupling to vinyl derivatives remain limited in number, however, because the reaction takes a different course whenever allylic hydrogen atoms are present in a substrate (Scheme3, f andg). Under these conditions allylic sp3 C-H bonds are activated and such reactions are therefore allylic oxidations (SectionIV.1.2.4). In recent years, however, several examples of reactions of type g (Scheme 3) have been performed enantioselectively and called asymmetric... 

Sharpless asymmetric epoxidation of allylic alcohols, asymmetric epoxidation of conjugated ketones, asymmetric sulfoxidations catalyzed, or mediated, by chiral titanium complexes, and allylic oxidations are the main classes of oxidation where asymmetric amplification effects have been discovered. The various references are listed in Table 4 with the maximum amplification index observed. 

Allylic oxidation (acyloxylation) can also be achieved with copper catalysts and stoichiometric amounts of peresters or an alkylhydroperoxide in a carboxylic acid as solvent [108], via a free radical mechanism (Fig. 4.40). The use of water-soluble ligands [109] or fluorous solvents [110] allows recycling of the copper catalyst. In view of the oxidants required, this reaction is economically viable only when valuable (chiral) products are obtained using asymmetric copper catalysts [111-113]. The scope of the reaction is rather limited however. 

In the group of Backvall a method was developed involving palladium and benzoquinone as cocatalyst (Fig. 4.42) [103]. The difficulty of the catalytic reaction lies in the problematic reoxidation of Pd(0) which cannot be achieved by dioxygen directly (see also Wacker process). To overcome this a number of electron mediators have been developed, such as benzoquinone in combination with metal macrocycles, heteropolyacids or other metal salts (see Fig. 4.42). Alternatively a bimetallic palladium(II) air oxidation system, involving bridging phosphines, can be used which does not require additional mediators [115]. This approach would also allow the development of asymmetric Pd-catalyzed allylic oxidation. 

Chiral epoxides are important intermediates in organic synthesis. A benchmark classic in the area of asymmetric catalytic oxidation is the Sharpless epoxidation of allylic alcohols in which a complex of titanium and tartrate salt is the active catalyst [273]. Its success is due to its ease of execution and the ready availability of reagents. A wide variety of primary allylic alcohols are epoxidized in >90% optical yield and 70-90% chemical yield using tert-butyl hydroperoxide as the oxygen donor and titanium-isopropoxide-diethyltartrate (DET) as the catalyst (Fig. 4.97). In order for this reaction to be catalytic, the exclusion of water is absolutely essential. This is achieved by adding 3 A or 4 A molecular sieves. The catalytic cycle is identical to that for titanium epoxidations discussed above (see Fig. 4.20) and the actual catalytic species is believed to be a 2 2 titanium(IV) tartrate dimer (see Fig. 4.98). The key step is the preferential transfer of oxygen from a coordinated alkylperoxo moiety to one enantioface of a coordinated allylic alcohol. For further information the reader is referred to the many reviews that have been written on this reaction [274, 275]. 

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