Benzylic substrates, oxidation

Besides having smaller oxidation potential values than substituted benzyl alcohols (E° > 1.4 V/NHE), the DMAs have larger energy values (90-92 kcalmoD ) for the NC—H bond with respect to C—H bond energies around 75-85 kcalmoD of the benzyl alcohols (Scheme 12). Both factors disfavour the operation of the radical HAT route for PINO with the DMAs, and cause a mechanistic changeover to the ET route, as opposed to the reactions with the benzylic substrates listed in Table 4. 

These systems are also described as normal copper proteins due to their conventional ESR features. In the oxidized state, their color is light blue (almost undetectable) due to weak d-d transitions of the single Cu ion. The coordination sphere around Cu, which has either square planar or distorted tetrahedral geometry, contains four ligands with N and/or 0 donor atoms [ 12, 22]. Representative examples of proteins with this active site structure (see Fig. 1) and their respective catalytic function include galactose oxidase (1) (oxidation of primary alcohols) [23,24], phenylalanine hydroxylase (hydroxy-lation of aromatic substrates) [25,26], dopamine- 6-hydroxylase (C-Hbond activation of benzylic substrates) [27] and CuZn superoxide dismutase (disproportionation of 02 superoxide anion) [28,29]. 

LiBr has been reported to catalyse the dihydroxylation of alkenes (1) to afford syn-and anh -diols (2/3) with excellent diastereoselectivity, depending on the use of NaKTt (30 mol%) or PhI(OAc)2 (1 equiv.), respectively, as the oxidant.28 The authors claim that oxidation of non-benzylic halides was achieved for the first time to afford the corresponding diols in excellent yields 28 is not really justified as the development of the silver-free Prevost-Woodward dihydroxylation for non-benzylic substrates had... 

Suitable alkylbenzene side chains are oxidized at the benzylic position under the action of mCPBA, air, and NaHC03 to generate the corresponding ketones. The oxygen-centered radical formed from mCPBA, abstracts the benzylic hydrogen atom of the benzylic substrate (68) to form a benzylic radical, and then it reacts with molecular oxygen... 

Cunninghamella elegans has shown a degree of generality in the oxidation of benzylic substrates. For example the tetrahydroquinoline (88) is converted to the derivative (89 equation 30), but the degree of enantioselectivity is not known." Similarly triprolidine (90) is converted to the alcohol (91 equation 31) in respectable yield. 

Compounds containing active hydrogen atoms (pK = 11-25) could be brominated when DBU was added dropwise into a mixture of substrate (phenylacetylene, diethyl butylmalonate, indene, or fluorene) and BrCClj in benzene (78CL73). Compounds with lower acidity (pK 29) exhibited no reaction. With more acidic derivatives (diethyl malonate and benzyl cyanide), oxidative dimerization also occurred. Oxidative dimerization also took place when BrCClj was added dropwise into a solution of active methylene compound and DBU in benzene. The ratio of the reaction products depended on the ratio of DBU and BrCCIj. 

A remarkably efficient FeCl2-catalyzed intermolecular amination of simple benzylic substrates has been described (Fig. 15) [76]. These same authors have also noted the ability of CuBr to operate in a similar capacity [77]. iV-Bromosucci-mide (NBS) is used as the oxidant together with either a carboxamide or sulfonamide starting material. The /V-brominated amide purportedly reacts with FeCF to generate an Fe nitrene species that is capable of oxidizing benzylic C-H bonds, though evidence for such a mechanism is absent from the discussion. If a nitrenoid pathway is indeed operative, one might expect isocyanate formation to compete... 

While the majority of Rh-catalyzed C-H amination processes employ hyperva-lent iodine oxidants and sulfonamide derivatives, Lebel and coworkers have demonstrated that /V-tosyloxycarbamates will engage with catalytic Rh2(02CCPh3)4 and K2CC>3 to afford products of intramolecular C-H insertion (Fig. 22) [104, 5, 105]. Similar to Du Bois earlier work involving oxidative cyclization with 1 ° carbamates [94], the /V-tosyloxy derivatives display a strong bias for oxazolidinone formation. Selectivity trends and other mechanistic data support a reaction pathway involving a Rh-nitrene oxidant. Intermolecular amination of simple benzylic substrates... 

Scheme 15.1 (Top) LCo(lll)N02- and Lewis acid-catalyzed aerobic oxidation of benzyl alcohol and cycloheptanol. (Bottom) Proposed mechanism for substrate oxidation.

Alkyl halides other than benzylic substrates have also been reported to undergo Cocatalyzed double carbonylation to give corresponding a-keto acids, but in some cases more drastic conditions are necessary and the selectivity for a-keto acid is not high. Styrene oxides are doubly carbonylated to furandiones catalyzed by Co2(CO)8 in the presence of Mel and NaOH in a phase transfer system. 

A number of different types of benzyl substrates, diethyl benzylphosphonate, benzyl methyl sulfide, benzyl phenyl sulfide, benzyl benzoate, benzyl phenyl ether, and benzyloxytrimethylsilane were also reacted with Mn. Unfortunately, according to TLC and/or gas chromatography analyses, no oxidative addition occurred with these substrates. 

Decarboxylation of the acyloxy radical then competes with electron transfer (k f) for formation of ion pairs. The rates of electron transfer for both substituted 1-naphthylmethyl 2 and benzyl substrates 6 follow Marcus theory in both the normal and inverted region when correlated with the oxidation potential of the arylmethyl radical. The meta-methoxy compounds give high yields of ion-derived products because the oxidation potentials of their arylmethyl radicals place them near the maximum on the Marcus plot therefore, kg is competitive with fcco2- This work has been reviewed in the previous volume of this Handbook and in other places." ... 

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