Cycloalkanes oxidative coupling

Recently, the C-H bond of nitrogen heteroaromatics has been shown to become activated upon the conversion of the heteroaromatic to its corresponding /V-oxide derivative (for recent examples of direct functionalization of pyridine /V-oxides and /V-iminopyridiniuin ylides, see [63-67]). Li and co-workers demonstrated that tert-butyl peroxides can mediate the oxidative coupling between pyridine /V-oxides 67 and cycloalkanes 62 (Scheme 36) [68]. 

A protocol for cross-dehydrogenative oxidative coupling of the 2-arylpyridine 4 with the cycloalkane 5 under ruthenium catalysis was elegantly developed by Li and... 

Cycloalkanes R R R H and chelating arenes ArH were oxidatively cross-conpled to Ar R R R by [RuClj(p-cymene)]2/TBHP/135°C (the reactants were the solvent) thus 2-phenylpyridine and cyclo-octane were cross-coupled cf. mech. Ch. 1. Other complexes (Ru(acac)3, [RuCl CCOD)] and RuHj(CO)(PPh3)3) also catalysed the reaction [78]. 

Scheme 36 Oxidative cross-coupling of pyridine N-oxide derivatives with cycloalkanes...

A ruthenium(II)-catalysed oxidative cross-coupling of phenylpyridine substrates with cycloalkanes has been reported (Scheme 31) [22]. The proposed mechanism involves directed metalation of phenylpyridine and formation of a ruthenium alkyl species in the presence of ferf-butyl peroxide as an oxidizing reagent. The reaction required an excess of oxidizing reagent (4 equiv. with respect to phenylpyridine) as... 

Scheme 31 Ruthenium-catalysed oxidative cross-coupling of chelating arenes with cycloalkanes...

The rate of combination of trifluoromethyl radicals to form hexafluoro-ethane has been measured by the flash photolysis of trifluoromethyl iodide coupled with rapid-scan i.r. spectroscopy in the absence of an inert diluent (At, N2, or COt) carbon tetrafluoride and tetrafluoroethylene were also formed, presumably via fluorine atom abstraction from trifluoroiodomethane by hot trifluoromethyl radicals (c/. ref. 27). Photolysis of trifluoroiodomethane has been used in studies on (i) the direction of radical attack on 1,3,3,3-tetrafluoropropene [- CFj CHI CHFCF, (75%) + (CFa)jCH CHFl (25%)] (ii) the rates of hydrogen abstraction from ammonia, ammonia-ethylene oxide, silane, trimethylsilane, tetramethylsilane, and cycloalkanes and (iiQ the competitive addition of the CFj- radical to ethylene and vinylidene fluoride. Radicals formed by photolysis of the fluoroalkyl iodides CFJ, C FJ, n-C,F,I, (CF,)jCFI, (CFaljCHI, (CFalaCDI, (CFa)jCClI, and (CFa)iCPhI (the last was synthesized by treatment of CFs CPh CTj with CsF and iodine in DMF) have been... 

In a seminal contribution, C.-J. Li reported in 2007 the first iron-catalyzed CDC reaction between alkanes and activated methylene derivatives such as p-ketoesters or p-diketones. A simple FeCl2 catalytic system (20 mol%) can promote the coupling reaction in the presence of 2 equiv. of di-fert-butyl peroxide ( BuOO Bu) as the oxidant in an alkane as the solvent (Scheme 4.2). The CDC reaction is efficient with cycloalkanes and p-ketoesters (48-88% yields). It is worth mentioning that linear alkanes such as n-hexane produce moderate yields (42%) with a mixture of two regio-isomers in a 1.2 1 ratio. By contrast, the reaction with p-diketones is a more difficult task, and only low yields (10-15%) are obtained. 

Scheme 8.24 Transition metal free cross-coupling of pyridine-JV-oxide with cycloalkanes.

A similar situation exists in the hydroxymercuration and thallium(m) oxidation of cycloalkenes and cycloalkanes, the rate laws showing strict second-order behaviour for both metal ions. In the thallium(ni) reactions two products have been observed, a 1,2-diol and a ketone or aldehyde. Two-electron coupling with trifluoroacetate has been shown to promote oxidative phenol coupling. The mechanism of oxidation of olefins by palladium(n) has been investigated. In the presence of PdClg in aqueous media, the data conform to the rate expression... 

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