Oxidation reactions allylic derivatives

Dialkylindolines and 1,3-dialkylindoles are formed in poor yield (<10%) from the reaction of ethyl- or phenymagnesium bromide with 2-chloro-N-methyl-N-allylaniline in the presence of catalytic quantities of (bistriphenylphosphine)nickel dichloride.72 In a modification of this procedure, the allyl derivatives can be converted by stoichiometric amounts of tetrakis(triphenylphosphine)nickel into 1,3-dialkylindoles in moderate yield72 (Scheme 43) an initial process of oxidative addition and ensuing cyclization of arylnickel intermediates is thought to occur. In contrast to the nickel system,72 it has proved possible to achieve the indole synthesis by means of catalytic quantities of palladium acetate.73 It is preferable to use... 

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). 

The reaction sequence Is based on the readiness with which a-pinene undergoes oxidation predominantly to the tertiary acetate with Pb(OAc)4.3 4 Dichromate oxidation of the derived alcohol proceeds by way of a second allylic rearrangement to give verbenone without affecting the neighboring stereogenic centers. 

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 addition of allylic boron reagents to carbonyl compounds first leads to homoallylic alcohol derivatives 36 or 37 that contain a covalent B-O bond (Eqs. 46 and 47). These adducts must be cleaved at the end of the reaction to isolate the free alcohol product from the reaction mixture. To cleave the covalent B-0 bond in these intermediates, a hydrolytic or oxidative work-up is required. For additions of allylic boranes, an oxidative work-up of the borinic ester intermediate 36 (R = alkyl) with basic hydrogen peroxide is preferred. For additions of allylic boronate derivatives, a simpler hydrolysis (acidic or basic) or triethanolamine exchange is generally performed as a means to cleave the borate intermediate 37 (Y = O-alkyl). The facility with which the borate ester is hydrolyzed depends primarily on the size of the substituents, but this operation is usually straightforward. For sensitive carbonyl substrates, the choice of allylic derivative, borane or boronate, may thus be dictated by the particular work-up conditions required. 

T he oxidation of olefins by selenium dioxide has received much atten-- tion because of the unique characteristics of the reaction that produces an allylic derivative of the olefin (ester, alcohol, or ether, depending upon the solvent) and elemental selenium as the final reduced state of the oxidant. 

The first example of Pd-catalyzed enantioselective allylation to be reported was the reaction of l-(l -acetoxyethyl)cyclopentene and the sodium salt of methyl benzenesulfonylacetate in the presence of 10 mol % of a DIOP-Pd complex, which led to the condensation product in 46% ee (Scheme 85) (200). This reaction used a racemic starting material, but the enantioselection was not a result of kinetic resolution of the starting material, because the chemical yield was above 80%. However, in certain cases, the selectivity is controlled at the stage of the initial oxidative addition to a Pd(0) species. In a related reaction, a BINAP-Pd(0) complex exhibits excellent enantioselectivity the chiral efficiency is affected by the nature of the leaving group of the allylic derivatives (Scheme 85) (201). It has been suggested that this asymmetric induction is the result of the chiral Pd catalyst choosing between two reactive conformations of the allylic substrate. 

In 1997, the first truly catalytic enantioselective Mannich reactions of imines with silicon enolates using a novel zirconium catalyst was reported [9, 10]. To solve the above problems, various metal salts were first screened in achiral reactions of imines with silylated nucleophiles, and then, a chiral Lewis acid based on Zr(IV) was designed. On the other hand, as for the problem of the conformation of the imine-Lewis acid complex, utilization of a bidentate chelation was planned imines prepared from 2-aminophenol were used [(Eq. (1)]. This moiety was readily removed after reactions under oxidative conditions. Imines derived from heterocyclic aldehydes worked well in this reaction, and good to high yields and enantiomeric excesses were attained. As for aliphatic aldehydes, similarly high levels of enantiomeric excesses were also obtained by using the imines prepared from the aldehydes and 2-amino-3-methylphenol. The present Mannich reactions were applied to the synthesis of chiral (3-amino alcohols from a-alkoxy enolates and imines [11], and anti-cc-methyl-p-amino acid derivatives from propionate enolates and imines [12] via diastereo- and enantioselective processes [(Eq. (2)]. Moreover, this catalyst system can be utilized in Mannich reactions using hydrazone derivatives [13] [(Eq. (3)] as well as the aza-Diels-Alder reaction [14-16], Strecker reaction [17-19], allylation of imines [20], etc. 

In view of the Zr-catalyzed enantioslective carbomagnesation-elimination tandem reaction of allylic derivatives discussed earlier, a similar process with EtjAl might be expected and has indeed been developed recently [29]. As a representative example, the reaction of 2,5-dihydro-furan with 3 equiv. of Et3Al in the presence of (i )-(EBTHI)Zr[B[NOL-(5)] (8) and (NMTHI)ZrCpCl2 (9) produced, after hydrolysis, (S)-2-ethyl-3-buten-1 -ol in 90 and 67% yields, respectively. The enantioselectivity observed with 8 was >99% ee, whereas that observed with 9 was 85-90% ee. Upon deuterolysis of the organoaluminum products, a mixture of monodeuterated and nondeuterated products was obtained and the extent of D incorporation increased to 94% with neat Et3Al without any solvent. The results indicate that the reaction must produce two organoaluminum products, 10 and 11 (Scheme 4.18). On oxidation with 02 only... 

Nitrile oxides react with the methyl enol ethers of (Rs)-l -fluoro-alkyl-2-(p-tolylsulfinyl)ethanones to produce (45,5/f,/fs)-4,5-dihydroisoxazoles with high regio-and diastereo-selectivity.87 In the 1,3-dipolar cycloaddition of benzonitrile oxide with adamantane-2-thiones and 2-methyleneadamantanes, the favoured approach is syn, as predicted by the Cieplak s transition-state hyperconjugation model.88 The 1,3-dipolar cycloaddition reaction of acetonitrile oxide with bicyclo[2.2.l]hepta-2,5-diene yields two 1 1 adducts and four of six possible 2 1 adducts.89 Moderate catalytic efficiency, ligand acceleration effect, and concentration effect have been observed in the magnesium ion-mediated 1,3-dipolar cycloadditions of stable mesitonitrile oxide to allylic alcohols.90 The cycloaddition reactions of acryloyl derivatives of the Rebek imide benzoxazole with nitrile oxides are very stereoselective but show reaction rates and regioselectivities comparable to simple achiral models.91. 

The two sidechains of the prostaglandin are readily introduced by the reaction of norbomene with an allylpalladium compound followed by reaction within an optically active lithium acetylide. The key step of the overall reaction depends on the selective oxidation of the allylic derivative 42 to an aldehyde 43 (Scheme 11.11).46 The reaction exploits the fact that ozone is able to selectively oxidize a carbon-carbon double bond in the presence of an acetylene.46 This is achieved by reaction at -78°C in dichloromethane in the presence of pyridine to moderate the reactivity of ozone. 

We also observed similar phenomena in the reaction of silyl enol ethers with cation radicals derived from allylic sulfides. For example, oxidation of allyl phenyl sulfide (3) with ammonium hexanitratocerate (CAN) in the presence of silyl enol ether 4 gave a-phenylthio-Y,5-un-saturated ketone 5. In this reaction, silyl enol ether 4 reacts with cation radical of allyl phenyl sulfide CR3 to give sulfonium intermediate C3, and successive deprotonation and [2,3]-Wittig rearrangement affords a-phenylthio-Y,6-unsaturated ketone 5 (Scheme 2). Direct carbon-carbon bond formation is so difficult that nucleophiles attack the heteroatom of the cation radicals. 

Oxidation reactions of this nature are common in the literature. For example, selenium dioxide in refluxing etiumolic solution brought about the allylic oxidative rearrangement geranyl acetate, which was further functionalized in a synthesis of the norsesquiterpenoid gytinidal (equation 46). This trans formation was also used in a total synthesis of phytol. Similarly, an a, -unsaturated aldehyde was obtained undm similar conditions in studies of a synthesis of pentalenic acid derivatives (equation 47). ... 

In contrast to the oxidation of unactivated stannanes, allylic derivatives are expected to be more reactive, and mild conditions and oxidizing agents can be employed successfully. A particularly useful reaction involves the conversion of an allylstannane to die allylic alcdiol, and die commercially available, solid, easily handled m-chloroperbenzoic acid (MCPBA) is die reagent of choice for oxidations employing organic solvents such as dichloromethane. Under these conditions epoxystannanes cannot be isolated and allylic alcohols form direcdy (equation 6). °- ... 

Bicyclic A(0-Mti-homonucleoside analogues such as 591 were synthesized through 1,3-dipolar cycloaddition of an enantiopure 3-hydroxy-l-pyrroline A -oxide and protected allyl alcohol and subsequent introduction of thymine by a Mitsunobu reaction <2003T5231>. Furthermore, isoxazole, isoxazoline, and isoxazolidine analogues of (7-nucleo-sides such as 592-594 were synthesized by 1,3-dipolar cycloaddition of nitrile oxides and nitrones derived from uracil-5-carbaldehydes with suitable dipolarophiles <2003T4733, 2006T1494>. 

This synthetic project makes provision for the regioselective oxidation of allylic hydroxyl of 13h with Jones s reactant in acetone this reaction provided the keto derivative 13i quantitatively only when we operates with small substrate quantities (few milligrams). Then the hydroxyl at C-4 has been esterified with methanesulfonyl chloride the mesylation reaction has been led in methylene chloride in presence of triethylamine at 0°C and it has brought to the formation of product 131. Then it has been substituted azide for mesyl group by the treatment of mesyl derivative 131 with sodium azide in dimethylformamide at SOX, so obtaining product 13m. 

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