Regioselectivity oxidant-controlled

Aryl-Aryl Coupling via Cross-Dehydrogenative-Coupling Reactions 

Further studies have come from the DeBoef group on oxidant-controlled regioselectivity, in which both benzofuran and indole arylations were examined in different solvent parameters. They surmised that solvent had little overall effect on regioselectivity compared to oxidant choice, and both DeBoef and Fagnou reasoned that site selectivity is most likely due to the formation of polymetallic clusters during catalysis.  

These co-catalyst oxidants are sometimes needed to help prevent bulk Pd from falling out of solution. They are often strong oxidants that can readily re-oxidize Pd(0) back to Pd(ii) before it falls out of solution. Transition metal salts, such as Sn(OAc)2, Ag20, Cu(OTf)2 and 

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Scheme 61 Pd-catalyzed cross-dehydrogenative arylation of 1-pivaloyl-1H-indoles via oxidant-controlled regioselectivity, AgOAc versus Cu(OAc)2 (Scheme 40).

The formation of 66 by reaction of acetylenes with (f/ -CsHs) (PhjP)Co(acetylene) has been investigated in detail. Kinetic studies indicate the intermediacy of ( / -C5H5)Co(acetylene)2 (Scheme 24), which cy-clizes to a coordinatively unsaturated cobaltacyclopentadiene by a spontaneous oxidative coupling. Regioselectivity of the cyclization process is controlled by steric rather than by electronic character of substituents. 

Gaunt and coworkers were able to affect a solvent-controlled regioselective intermolecular oxidative Heck reaction between indole and a range of alkenes (Scheme... 

The high regioselectivity ( stereoelectronic control ) in the ring cleavage by chlorination of sulfur was anticipated. It had been found before that in corresponding bicyclic systems such as in the scheme below oxidation of the sulfur atom always led to the undesired cleavage of the S—Cg bond. This was rationalized through the observation on molecular models that... 

The increase in thermodynamic stability of 85 is achieved by easy ring opening (01H127). This knowledge allows one to control the regioselectivity of the oxidative amination of the 6-aryl-l,2,4-tiiazine 4-oxides 53, obtaining either (i) the 5-amino-1,2,4-triazine 4-oxides 56 in the reaction of 53 with amines at low temperature in the presence of the oxidant or (ii) the 3-amino-1,2,4-triazine 4-oxides 88, provided the reaction is carried out in two steps (addition and oxidation) at room temperature or higher. 

Control experiments do not provide evidence for oxidation of the secondary alcohol groups in the glycoside or for degradation of the ligand backbone. A similar regioselectivity was also observed in a benzyl alcohol/1-phenylethanol model system that showed no proof for the oxidation of the secondary alcohol by formation of acetophenone (18, 23,26). 

The reaction proceeds via electrogenerated cationic species as its seen with the nonfluorinated amines, carbamates, and amides (Scheme 6.14). However, the regiochemistry of this anodic methoxylation is not governed by the stability of the cationic intermediates B and B (thermodynamic control) since the main products are formed via the less stable intermediates B. Indeed, this remarkable promotion effect and unique regioselectivity can be explained mainly in terms of a-CH kinetic acidities of the cation radicals formed by one-electron oxidation of the amines since the stronger the acidity of the methylene hydrogen, the easier the deprotonation. 

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