Shilov chemistry

Synthetic organic chemistry applications employing alkane C-H functionalizations are now well established. For example, alkanes can be oxidized to alkyl halides and alcohols by the Shilov system employing electrophilic platinum salts. Much of the Pt(ll)/Pt(rv) alkane activation chemistry discussed earlier has been based on Shilov chemistry. The mechanism has been investigated and is thought to involve the formation of a platinum(ll) alkyl complex, possibly via a (T-complex. The Pt(ll) complex is oxidized to Pt(iv) by electron transfer, and nucleophilic attack on the Pt(iv) intermediate yields the alkyl chloride or alcohol as well as regenerates the Pt(n) catalyst. This process is catalytic in Pt(ll), although a stoichiometric Pt(rv) oxidant is often required (Scheme 6).27,27l 2711... 

The authors point out that the dependence of the site of electrophilic attack on the ligand trans to the hydride in the model systems may be important with respect to alkane activation. If the information is transferable to Pt-alkyls, protonation at the metal rather than the alkyl should be favored with weak (and hard ) a-donor ligands like Cl- and H20. These are the ligands involved in Shilov chemistry and so by the principle of microscopic reversibility, C-H oxidative addition may be favored over electrophilic activation for these related complexes. 

Recently, Sames and co-workers showed an interesting application, in which it was demonstrated that the Shilov chemistry permits heteroatom-directed functionalization of polyfunctional molecules [16]. The amino acid valine (10) was allowed to react in an aqueous solution of the oxidation catalyst PtCU and Cu(ii) chloride as stoichiometric oxidant (Scheme 3). At temperatures >130 °C a catalytic reaction was observed, and a regioselective C-H functionalization delivered the hydroxyvaline lactone 11 as a 3 1 mixture of anti/syn isomers. It was noted that the hydroxylation of amino acid substrates occurred with a regioselectivity different from those for simple aliphatic amines and carboxylic acids. The authors therefore proposed that the amino acid functionalization proceeded through a chelate-directed C-H activation. 

Shilov chemistry, developed from 1970, employs [Pt(II)CLt] salts to oxidize alkanes RH to ROH or RCl with modest efficiency. Pt(IV) is an efficient (but economically impractical) primary oxidant that makes the process catalytic. This discovery strongly contributed to the continuing activity in CH activation. Periana developed a related and much more efficient system for methane oxidation to methanol using 2,2 -bipyrimidine ligands and sulfuric acid as solvent. In this case, the sulfuric acid is the primary oxidant and the methanol formed is protected by being converted in situ to MeOSOsH, an ester that strongly resists further oxidation. This area is more fully described under the entry Alkane Carbon-Hydrogen Bond Activation. 

The activation and functionalization of C-H bonds by the Pt" ion is particularly attractive because of the unusual regioselectivity, high oxidation level specificity, and mildness of reaction conditions. Moreover, Sen has recently reported that, in the presence of copper chloride at 120-160 °C, Shilov chemistry can be made catalytic with dioxygen as the ultimate oxidant [39]. A number of aliphatic acids were tested, and turnover numbers of up to 15/hour with respect to platinum were observed. H/D exchange studies also confirm the marked preference for the activation of primary C-H bonds in the presence of weaker secondary C-H bonds. This study constituted the first example of the direct use of dioxygen in the catalytic oxidation of unactivated primary C-H bonds under mild conditions that does not involve the use of a co-reductant (e. g., sacrificial metals, 2H + 2e", dihydrogen, or carbon monoxide see below). 

Such a reaction could be quite useful on an industrial scale, but unfortunately, it is stoichiometric in highly expensive Pt complex. Since its discovery in 1972, Shilov chemistry has been the focus of numerous investigations, many of which have sought to replace the Pt(IV) stoichiometric oxidant with a cheaper alternative. In the course of this research, the mechanism of the Shilov C-H bond activation has been elucidated. The following scheme shows the catalytic cycle involved. 

Shilov Chemistry and Related Electrophilic Systems for Homogeneous Alkane Oxidation... 

As both nucleophiles, Z and Y , can participate in a reductive elimination reaction, a mixture of reaction products, R-Z and R-Y, forms. Such behavior is observed in the Shilov reaction (Fig. 2). Formation of a mixture of methanol and methyl chloride is considered in Shilov chemistry as a result of occurrence of two concurrent S 2 processes with water and chloride anion as competing nucleophiles [18, 19]. The rate of the formation of chloromethane in aqueous solutions of [MePt Clsl in this reaction was shown to be first order in chloride ion concentration. 

M. Lin, C. Shen, E.A. Garcia-Zayas, A. Sen, Catalytic shilov chemistry platinum chloride-catalyzed oxidation of terminal methyl groups by dioxygen, J. Am. Chem. Soc. 123 (2001) 1000-1001. 

The tremendous impact this transformation made justifies the prominent status acquired by Shilov system in C-H bond activation even in this era of rapid technological advances. For several years Shilov Chemistry did not obtain the recognition that it deserved. However, recent developments mainly by Bercaw et have brought about resurgence in understanding and improving the scope of the system. ... 

The first example of a metal-catalyzed oxygen atom insertion into the C-H bond was the reaction found by Shilov and Shteinman and their coworkers in 1972 (for reviews, see References Ih and 5). These authors demonstrated that Pt Cl4 ion could catalyze H/D exchange in methane in a D2O/CD3COOD solution and, if Pt Cls " is added, the latter oxidizes methane to methanol (Shilov chemistry). The catalytic cycle in which ct-methyl complexes of platinum(ll) and platinum(lV) are involved is shown in Fig. 1.1. 

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