3-Aryl-5-methyl- -4-oxid

The modified Sharpless reagent was also successfully applied288 for the asymmetric oxidation of a series of 1,3-dithiolanes 248 to their S-monooxides 249 (equation 134). It was observed that the optical induction on sulphur (e.e. from 68 to 83%) is not significantly affected by the substituents R1 and R2. Asymmetric oxidation of a few aryl methyl sulphides by organic hydroperoxides in the presence of a catalytic amount of the optically active Schiff base-oxovanadium(IV) complexes gave the corresponding sulphoxides with e.e. lower than 40%289. 

Kinetic studies of the oxidation of diaryl sulfoxides by Crvi led to the proposition of a single electron transfer67 as in the case of aryl methyl sulfoxides68. These reactions were performed in aqueous acetic acid/perchloric acid medium, HCr03+ being the active... 

Electrophilic substitution of the ring hydrogen atom in 1,3,4-oxadiazoles is uncommon. In contrast, several reactions of electrophiles with C-linked substituents of 1,3,4-oxadiazole have been reported. 2,5-Diaryl-l,3,4-oxadiazoles are bromi-nated and nitrated on aryl substituents. Oxidation of 2,5-ditolyl-l,3,4-oxadiazole afforded the corresponding dialdehydes or dicarboxylic acids. 2-Methyl-5-phenyl-l,3,4-oxadiazole treated with butyllithium and then with isoamyl nitrite yielded the oxime of 5-phenyl-l,3,4-oxadiazol-2-carbaldehyde. 2-Chloromethyl-5-phenyl-l,3,4-oxadiazole under the action of sulfur and methyl iodide followed by amines affords the respective thioamides. 2-Chloromethyl-5-methyl-l,3,4-oxadia-zole and triethyl phosphite gave a product, which underwent a Wittig reation with aromatic aldehydes to form alkenes. Alkyl l,3,4-oxadiazole-2-carboxylates undergo typical reactions with ammonia, amines, and hydrazines to afford amides or hydrazides. It has been shown that 5-amino-l,3,4-oxadiazole-2-carboxylic acids and their esters decarboxylate. 

The use of furylhydroperoxides[1] has facilitated an operationally simple procedure, alternative to the one reported by Kagan[2]. Oxidation takes place rapidly and very high e.e.s have been obtained, especially in the case of aryl methyl sulfides, while overoxidation to sulfone can be reduced to a great extent (<3 %) under the proposed experimental conditions. 

The influence of steric effects on the rates of oxidative addition to Rh(I) and migratory CO insertion on Rh(III) was probed in a study of the reactivity of a series of [Rh(CO)(a-diimine)I] complexes with Mel (Scheme 9) [46]. For a-diimine ligands of low steric bulk (e.g. bpy, L1, L4, L5) fast oxidative addition of Mel was observed (103-104 times faster than [Rh(CO)2l2] ) and stable Rh(III) methyl complexes resulted. For more bulky a-diimine ligands (e.g. L2, L3, L6) containing ortho-alkyl groups on the N-aryl substituents, oxidative addition is inhibited but methyl migration is promoted, leading to Rh(III) acetyl products. The results obtained from this model system demonstrate that steric effects can be used to tune the relative rates of two key steps in the carbonylation cycle. 

Table 10 Oxidation and peak potentials of aryl methyl chalcogenides X— —E-Me ...

Unlike the aryl methyl selenides, the alkyl aryl selenides with alkyl groups of two carbons or more are able to undergo scission of the radical cation at the Cgp-Se bond, yielding the ArSe radical (Fig. 35). This can impact product distribution, particularly under conditions in which water is not present to react with the radical cation. Trends in ease of oxidation typically seen in series of chalcogen compounds can still be observed, and are consistent with trends in the diaryl chalcogenides and aryl methyl chalcogenides. 

In the oxidation of aryl methyl sulfides catalyzed by chloroperoxidase from Caldariomyces fumago with racemic 1-phenylethyl hydroperoxide instead of H2O2 as oxygen donor, it was found that (k)-sulfoxides, the (S)-hydroperoxides and the corresponding (k)-alcohol are produced in moderate to good enantiomeric excesses by double stereodifferentiation of the substrate and oxidant (Eq. 2, Table 3) [68]. 

Table 3. CPO-catalyzed oxidations of aryl methyl sulfides with racemic hydroperoxides... 

Preparation of various enantiomerically pure sulfoxides by oxidation of sulfides seems feasible in the cases where asymmetric synthesis occurs with ee s in the range of 90% giving crystalline products which can usually be recrystallized up to 100% ee. Aryl methyl sulfides usually give excellent enantioselectivity during oxidation and are good candidates for the present procedure. For example, we have shown on a 10-mmol scale that optically pure (S)-(-)-methyl phenyl sulfoxide [a]p -146 (acetone, o 1) could be obtained in 76% yield after oxidation with cumene hydroperoxide followed by flash chromatographic purification on silica gel and recrystallizations at low temperature in a mixed solvent (ether-pentane). Similarly (S)-(-)-methyl o-methoxyphenyl sulfoxide, [a]p -339 (acetone, o 1.5 100% ee measured by HPLC), was obtained in 80% yield by recrystallizations from hexane. 

Very recently, Lattanzi and coworkers reported on the use of enantiomericaUy pure camphor derived hydroperoxide 61 for the Ti(OPr-/)4 catalyzed chemoselective asymmetric oxidation of aryl methyl sulfides (equation 59) . The corresponding sulfoxides could be obtained in moderate yields (39-68%) and ee values up to 51%. The sulfoxidation to the sulfoxides is accompanied by further oxidation of the sulfone (kinetic resolution, yields of sulfone up to 9%). This process is stereodivergent with respect to the sulfoxidation step, which was found for the first time. Although the obtained enantioselectivities for the sulfoxides were only moderate, they proved to be among the best reported at that time with the use of enantiopure hydroperoxides as the only asymmetric inductor. The... 

Stereoselective catalytic oxidation of Aryl methyl sulfides. 300... 

STEREOSELECTIVE CATALYTIC OXIDATION OF ARYL METHYL SULFIDES... 

Oxidation of enamines.1 Oxidation of enamines of cyclic ketones in the presence of BFj etherate results in a Favorski type rearrangement to esters of contracted cycloalkanoic acids. A related reaction also occurs with enamines of aryl methyl ketones. 

Use of this coupling for synthesis of a number of isoquinoline alkaloids also has been published.2 VOF is usually used in this coupling, but this reagent can lead to overoxidation and oxidative demcthylation of aryl methyl ether groups. 

The three-step sequence used to convert enone 65 to miltirone (56) is shown in Scheme 5.7 and consists of, first, a Wolff-Kishner reduction to convert the C(5) carbonyl moiety into a methylene, followed by deprotection of the aryl methyl ethers and oxidation to an ortho-quinone using ceric ammonium nitrate. The physical and spectroscopic data of our synthetic miltirone are identical with those reported for the natural material. 

Ring and aryl methyl group oxidation were the initial toluene-degradation routes speculated on for the nitrate-reducing enrichment obtained by Kuhn etal. (1988) and the metabolically diverse iron-reducing bacterium Geobacter metallireducens (Lovley Lonergan, 1990). The speculation was consistent with the fact that both of these cultures could metabolize the appropriate suite of putative intermediates. However, conclusive evidence as to which pathway was actually involved was not obtained. 

Chiral sulfoxides (12, 92). Kagan et al.3 have reviewed the asymmetric oxidation of sulfides by a water-modified Sharpless reagent. Optical yields are generally highest in the oxidation of aryl methyl sulfides (—75-90%). 

Table 6C. 1 lists representative results for the asymmetric oxidation of thio ethers with r-butyl hydroperoxide under the standard conditions (in dichloromethane at -20°C). Enantioselectivi-ties are especially good (80-95% ee) for the oxidation of aryl methyl sufoxides (Table 6C.1). A substantial decrease in enantioselectivity is observed for oxidation of aryl-S-alkyl-type sulfides in which an alkyl group is larger than methyl such as n-propyl an n-butyl.

The Schiff base-oxovanadium(IV) complex formulated as 19 was found to catalyze the asymmetric oxidation of sulfides with cumene hydroperoxide (Scheme 6C.8) [70]. Various aryl methyl sulfides were used for this process (room temperature in dichloromethane and 0,1 mol equiv. of the catalyst). Chemical yields were excellent, but enantioselectivities were not higher than 40% for the resulting methyl phenyl sulfoxide, Complex 16a, where [Ti] was replaced by VO, was also examined in the oxidation of sulfides, but the reactions gave only racemic sulfoxides [68],... 

Biological oxidation of sulfides involves cytochromes P-450 or flavin-dependent oxygenases. A chiral flavin model was prepared by Shinkai etal. and used as the catalyst in the oxidation of aryl methyl sulfides [87]. Flavinophane 30 (Scheme 6C.10) is a compound with planar chirality. It catalyzes the oxidation of sulfides with 35% H202 in aqueous methanol at -20°C in the dark. 

The use of Mn-salen catalysts for asymmetric epoxidation has been reviewed.30 Oxo(salen)manganese(V) complexes, generated by the action of PhIO on the corresponding Mn(III) complexes, have been used to oxidize aryl methyl sulfides to sulfoxides.31 The first example of C—H bond oxidation by a (/i-oxo)mangancsc complex has been reported.32 The rate constants for the abstraction of H from dihydroanthracene correlate roughly with O—H bond strengths. 

The oxidation of an aryl methyl ketone, with selenium dioxide [Method (a)] in a suitable solvent, to an aryl 1,2-ketoaldehyde is illustrated by the preparation... 

Finally, iron catalysts based on salen-type ligands have been used. These iron(III)-salen complexes were regarded as enzyme models, using PhIO as oxidant (Scheme 3.52) [162]. Initially, the corresponding active iron-oxo complexes were formed by reaction with PhIO and isolated before use. A stoichiometric amount of the iron-oxo complex allowed the efficient oxidation of a variety of aryl methyl sulfides in moderate to good yields. 

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