Asymmetric reactions allylic oxidation

Sn(OTf)2 can function as a catalyst for aldol reactions, allylations, and cyanations asymmetric versions of these reactions have also been reported. Diastereoselective and enantioselective aldol reactions of aldehydes with silyl enol ethers using Sn(OTf)2 and a chiral amine have been reported (Scheme SO) 338 33 5 A proposed active complex is shown in the scheme. Catalytic asymmetric aldol reactions using Sn(OTf)2, a chiral diamine, and tin(II) oxide have been developed.340 Tin(II) oxide is assumed to prevent achiral reaction pathway by weakening the Lewis acidity of Me3SiOTf, which is formed during the reaction. 

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. 

The asymmetric oxidation of organic compounds, especially the epoxidation, dihydroxylation, aminohydroxylation, aziridination, and related reactions have been extensively studied and found widespread applications in the asymmetric synthesis of many important compounds. Like many other asymmetric reactions discussed in other chapters of this book, oxidation systems have been developed and extended steadily over the years in order to attain high stereoselectivity. This chapter on oxidation is organized into several key topics. The first section covers the formation of epoxides from allylic alcohols or their derivatives and the corresponding ring-opening reactions of the thus formed 2,3-epoxy alcohols. The second part deals with dihydroxylation reactions, which can provide diols from olefins. The third section delineates the recently discovered aminohydroxylation of olefins. The fourth topic involves the oxidation of unfunc-tionalized olefins. The chapter ends with a discussion of the oxidation of eno-lates and asymmetric aziridination reactions. 

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). 

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. 

Analogous reactions have been achieved recently with molecular oxygen as the sole stoichiometric oxidant by employing (-)-sparteine (sp) as the chiral ligand [153,163]. Stoltz and coworkers demonstrated asymmetric oxidative cychzation of a 2-allylphenol substrate (Eq. 34). A stoichiometric quantity of the sp hgand was necessary, perhaps because it also serves as a base in the reaction. Enantioselective oxidative tandem cychzation of 2-allyl anilides was achieved by Yang and coworkers (Eq. 35). The reactions proceed exclusively to the five-membered exocyclization products. 

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... 

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... 

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. 

Step. In fact, several asymmetric reactions via this process have recently been reported for the preparation of chiral allylic alcohols. In this section, typical results of asymmetric [2,3]sigmatropic rearrangement via chiral allylic selen-oxides to afford the corresponding chiral allylic alcohols are described. 

The Sharpless asymmetric epoxidation is an enantioselective reaction that oxidizes alkenes to epoxides. Only the double bonds of allylic alcohols—that is, alcohols having a hydroxy group on the carbon adjacent to a C=C —are oxidized in this reaction. 

Several methods are now available for allylic oxidation. Among them, the ene-type oxidation reaction with, e.g., Se02 or 02 oxidation have been the most widely used for the purpose [15] but their asymmetrization has not met with success. Another widely used method is the Kharash-Sosnovsky reaction using a peroxide and Cu(I) salt system [16]. This reaction has been considered to proceed through a Cu(III)-allyl complex 7 (Scheme 6) [17]. 

Other enantioselective reactions. Several asymmetric reactions worth mentioning are the Cu-cataly/.ed allylic oxidation in the presence of 105, 106, or 107- - with t-butyl perbenzoate, oxidation of sulfides (/-BuOOH-Ti ) in the presence of a 4,4 -dimer of B-aromatic l-hydroxyestrane,-" the reductive amination by chiral t-butylsulfinamidc,- the glyoxylate ene reaction promoted by Yb(OTf), and ent-l ) C-arylation ol phenols with aryllcad reagents under the influence of brucine,- and the C—H bond insertion by Rh-carbenoids."-"... 

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