Oxazoline allylic oxidation

Pfaltz and co-workers (108) reported that the allylic oxidation of cyclohexene proceeds in moderate selectivity using stoichiometric amounts of semicorrin-Cu(II) complexes. In catalytic reactions, the enantioselectivity decreased drastically. Better results were realized using bis(oxazolines) as ligands. Upon... 

Tris(oxazoline) complexes have also been investigated as ligands in the allylic oxidation reaction. Katsuki and co-workers (116) observed that Cu(OTf)2 com-plexed to the tris(oxazoline) 160 is a more selective catalyst than one derived from CuOTf, Eq. 99, in direct contrast to results observed with bis(oxazohnes) or pyridyl bis(oxazohnes) as ligands (cf. Section III.A.3). When the reaction is conducted at -20°C, the cyclopentenyl benzoate is delivered in 88% ee albeit in only 11% yield after 111 h. Larger cycloalkenes are less selective (cyclohexene 56% ee, cyclohep-tene 14% ee, cyclooctene 54% ee). 

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. 

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

Copper-catalyzed allylic oxidation allows the functionalization of unactivated alkenes into chiral allylic carboxylates.1347 The use of oxazoline-containing ligands give good enantioselectivities, but the reaction is extremely slow.1348-1351 Chiral bipyridine complexes, in turn, are much more active and give products in good yields and enantioselectivities up to 70% when applied in benzoyloxylation of cycloalkenes with rm-butyl perbenzoate.1352,1353... 

Allylic oxidation of a variety of cyclic alkenes with copper complexes of different pybox ligands (8) and with various peresters shows high enantioselectivity (80-96% ee). Use of phenylhydrazine as an additive and acetone as solvent accelerates the reaction. It has been suggested that the phenylhydrazone is responsible for the observed acceleration. Using EPR spectra, it has been shown that the Cu(II) species is reduced to Cu(I) by phenylhydrazine and phenylhydrazone. It has been found that the presence of a gem-diphenyl group at C(5) and a secondary or tertiary alkyl substituent at the chiral centre at C(4) of the oxazoline rings is crucial for high enantioselectivity. 

From Cu(OTf)2 or Cu(OTf) and the chiral Cj-symmetric tris(oxazoline) ligand 9, copper complexes are obtained that are capable of catalyzing the allylic oxidation of cyclopentene by /er/-butyl perbenzoate in up to 84 % ee [12]. Even today, for most oxidations with chiral or achiral ligand systems, the structures of the real active metal catalysts are unknown. Because of this it is difficult to give a scientific rationale for the selectivities and inductions observed. 

The reaction of an isocyanide containing an acidic hydrogen with copper(I) oxide and an activated olefin or a ketone [Eq. (123)] provides a synthesis of either pyrrolines or oxazolines, respectively (251,252). Addition of allyl bromide gave the coupling product with the allyl carbanion derived from allyl isocyanide. Oxazolines are obtained in yields as high as 957o> not pyrrolines because of competing dimerization... 

Oxidations. A widely used method for allylic oxidation is the Kharash-Sosnovsky reaction using a peroxide and a copper(I) salt system. Enantioselective allylic oxidations of cycloalkenes such as cyclopentene, cyclohexene and cycloheptene with tert-butyl peibenzoate were investigated with a variety of catalysts derived from bis(oxazoline) ligands and copper(I) triflate complexes (eq 18). The ligand-copper(I) complexes from the /-Bu-... 

Allylic Oxidation. The Kharasch-Sosnovsky reaction involves oxidation of the allylic position while the olefin remains intact. In the presence of catalytic copper (II) salts, treatment of olefins with peresters affords acylated allylic alcohols. When (S)-(—)-4-(2-methylpropyl)-2-(2-pyridyl)-2-oxazoline was involved, (R)-cyclohexenyl benzoate was isolated in 57% yield and 28% ee (eq 6). ... 

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. ... 

In 1995, three different chiral oxazoline derivatives were introduced as chiral ligands which remarkably improved enantioselectivity in allylic oxidation [19]. Pfaltz et al. reported that copper(I)-bis(oxazoline) (15) complex show good to high enantioselectivity (up to 84% ee at -20 °C) in the oxidation of cyclopentene (Scheme 11) [19a], Enantioselectivity is dependent on the solvent used, and acetonitrile gives... 

Allylic Oxidation. Chiral CuOTf-bis(oxazoline) complexes catalyze the asymmetric Kharasch acyloxylation of cyclopentene, cyclohexene, and cycloheptene with f-butyl perbenzoate with good yields but moderate enantioselectivities (eq 125). ... 

Structural variants of the chiral bis(oxazoline) ligands have been described for the CuOTf-catalyzed asymmetric JQiarasch reaction. Thus, a chiral CuOTf-tris(oxazoline) complex catalyzes the allylic oxidation of cyclopentene in 67% yield and with 66% ee. Cu(OTf)2 is, however, moderately more effective (68% yield, 74% ee). Ruorous bis(oxazolines), in which two... 

Oxazolines are nowadays essential ligands in asymmetric catalysis and also important synthons for stereoselective synthesis [8]. The success of the Cj-symmetric bis(oxazolines) ( BOX ) and pyridine-bis(oxazolines) ( Pybox ) discovered in the early 1990s has established them as a privileged class of ligands [9]. In contrast, the development and application of trisoxazolines lagged behind for a long time. Katsuki and collaborators [10] reported the first example of a chiral trisoxazoline in 1995 and their use in the allylic oxidation of alkenes (Kharasch-Sosnovsky reaction), as well as the enantioselective addition of diethylzinc to aldehydes. 

Oxazoline formation from 5-vinyloxazolidinones promoted by palladium (0) is also known. Oxidative insertion of palladium with loss of CO2 results in a pair of equihbrating 71-allyl palladium complexes. The stereochemistry of the vinyl group is therefore not important. Ring closure from the thermodynamically more stable transition state accounts for the trans-isomer as the major product. Depending on the exact substitution, diastereoselectivities ranging from 2.5 1 to 16 1 can be obtained (Scheme 8.68). 

Three research groups discovered almost at the same time that non-C2-symmetrical oxazolines of the type 32 can be even more effective ligands for asymmetric catalysis than type 4 ligands (Fig. 11). For the palladium-catalyzed allylic substitutions on 62, record selectivities could be reached using 32 (X = PPhj) [30]. It seems that not only steric but also electronic factors, which cause different donor/acceptor qualities at the coordination centers of the ligand, seem to play a role here [31]. The reaction products can subsequently be converted to interesting molecules, for example 63 (Nu = N-phthalyl) can be oxidized to the amino acid ester 64 [32]. 

Catalytic enantioselective versions of the inverse electron demand cycloaddition have also been reported. For example, the C-(diisopropylamino)carbonyl A -phenyl nitrone reacted with 7-substituted allylic alcohols in the presence of diethylzinc, iodine, pyridine A -oxide, and a catalytic amount of enantiopure DIPT to afford 3,5-m-disubstituted isoxazolidines with high enantioselectivity (Scheme 124) <2002CL302>. Enantioselective cycloaddition of nitrones to enol ethers was achieved in the presence of chiral binaphthol-aluminium and chiral copper-bis(oxazoline) catalysts <1999JA3845, 1999CC811, 1999JOC2353, 2000JOC9080>. 

One of the exciting developments of the Wacker-type oxidation is the asymmetric synthesis of the reaction. For instance, using a new chiral bis(oxazoline) ligand L = 3,3 -Disubstituted 2,2 -bis(oxazolyl)-l,r-binaphthyls (boxax), a catalytic asymmetric Wacker -type cyclization converted allyl-phenol 55 to dihydrofuran 74 with 67% ee.ss... 

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