C-H activation alkyl

Rh(TMP)- under these conditions, and in fact the selective activation of methane in benzene solution is a distinctive and unusual feature of this system, given that aryl C—H activation ought to be thermodynamically favored over alkyl C—H activation. The proposed linear transition state proposed in Fig. 8 is the key to this different reactivity. The corresponding trimolecular transition state for an arene would be expected to be bent, and this would be precluded by the bulky TMP... 

An unusual C — H activation on orf/zo-methoxy groups was observed by Dyker et al., in the reaction of methoxyiodoarenes such as 144 leading elegantly to 6//-dibenzo[/ , /]pyrans such as 145 (Scheme 3-38) [190,191]. Under the same conditions, 2-rert-butyliodobenzene (146) with various aryl halides gave the benzocyclobutene derivatives 147, the formation of which also involves an alkyl C — H activation [190e]. 

Some hydrometalation reactions have been shown to be catalyzed by zirconocene. For instance, CpiZrCf-catalyzed hydroaluminations of alkenes [238] and alkynes [239] with BU3AI have been observed (Scheme 8-34). With alkyl-substituted internal alkynes the process is complicated by double bond migration, and with terminal alkynes double hydrometalation is observed. The reaction with "PrjAl and Cp2ZrCl2 gives simultaneously hydrometalation and C-H activation. Cp2ZrCl2/ BuIi-cat-alyzed hydrosilation of acyclic alkenes [64, 240] was also reported to involve hydrogen transfer via hydrozirconation. 

There has been little insight into potential decomposition pathways for the Ni(II) system due to sparse experimental evidence. Polymerization results with catalysts bearing different alkyl and fluorinated substituents have suggested that a C-H activation process analogous to that occuring with the Pd(II) catalysts is unlikely with Ni(TT) [28], Instead, side reactions between Ni and the aluminum coactivator, present as it is in such large excess, have been implicated. The formation of nickel dialkyl species and their subsequent reductive elimination to Ni(0) is one possible deactivation mechanism [68]. 

The existence of tr-complex intermediates in C-H activation chemistry has been suggested to explain inverse kinetic isotope effects in reductive elimination processes whereby alkanes are formed from alkyl metal hydrides (Scheme 3).9... 

Alkyl groups of compounds other than alkanes can be regioselectively functionalized using C-H activation chemistry. For example, acyclic and cyclic ethers can be activated by Ir(m) complexes to yield carbene complexes (Equation (25)).35... 

The C-H insertion into alkanes described above is a surrogate of enolate alkylation (Figure 2). The two strategic reactions are complementary, because enolate alkylation is preferred at primary alkyl halides while the C-H activation tends to preferentially occur at tertiary C-H bonds. 

Rhodium(n) carboxamidates are clearly superior to all other types of catalysts in effecting highly chemo-, regio-, diastereo-, and enantioselective intramolecular C-H activation reactions of carbenoids derived from diazoacetates. Specifically, Rh2(4Y-MPPIM)4 is the catalyst of choice for C-H activation reactions of simple primary and secondary alkyl diazoacetates. Likewise, Rh2(4Y-MACIM)4 thus far has been the most successful catalyst with tertiary alkyl diazoacetates, whereas for primary acceptor-substituted diazoacetates with a pendant olefin side chain, Rh2(4A-MEOX)4 has proved to be highly selective. 

The ruthenium-, rhodium-, and palladium-catalyzed C-C bond formations involving C-H activation have been reviewed from the reaction types and mechanistic point of view.135-138 The activation of aromatic carbonyl compounds by transition metal catalyst undergoes ortho-alkylation through the carbometallation of unsaturated partner. This method offers an elegant way to activate C-H bond as a nucleophilic partner. The rhodium catalyst 112 has been used for the alkylation of benzophenone by vinyltrimethylsilane, affording the monoalkylated product 110 in 88% yield (Scheme 34). The formation of the dialkylated product is also observed in some cases. The ruthenium catalyst 113 has shown efficiency for such alkylation reactions, and n-methylacetophenone is transformed to the ortho-disubstituted acetophenone 111 in 97% yield without over-alkylation at the methyl substituent. 

For the C-H activation sequence, the different possibilities to be considered are shown in Scheme 5 (a) direct oxidative addition to square-planar Pt(II) to form a six-coordinate Pt(IV) intermediate and (b, c) mechanisms involving a Pt(II) alkane complex intermediate. In (b) the alkane complex is deprotonated (which is referred to as the electrophilic mechanism) while in (c) oxidative addition occurs to form a five-coordinate Pt(IV) species which is subsequently deprotonated to form the Pt(II) alkyl product. 

The question of which pathway is preferred was very recently addressed for several diimine-chelated platinum complexes (93). It was convincingly shown for dimethyl complexes chelated by a variety of diimines that the metal is the kinetic site of protonation. In the system under investigation, acetonitrile was used as the trapping ligand L (see Fig. 1) which reacted with the methane complex B to form the elimination product C and also reacted with the five-coordinate alkyl hydride species D to form the stable six-coordinate complex E (93). An increase in the concentration of acetonitrile led to increased yields of the methyl (hydrido)platinum(IV) complex E relative to the platinum(II) product C. It was concluded that the equilibration between the species D and B and the irreversible and associative1 reactions of these species with acetonitrile occur at comparable rates such that the kinetic product of the protonation is more efficiently trapped at higher acetonitrile concentrations. Thus, in these systems protonation occurs preferentially at platinum and, by the principle of microscopic reversibility, this indicates that C-H activation with these systems occurs preferentially via oxidative addition (93). 

The classic platinum(O) approach to C-H activation, yielding platinum(II) alkyl hydrides as the oxidative addition products, contributed significantly to our understanding of C-H activation. However, the platinum(II)/(IV) approach has proven capable of achieving oxidative functionalization of hydrocarbons, and so this review focuses on the higher oxidation state. 

Another effective way of staying clear of the thermodynamic barriers of C-H activation/substitution is the use of the c-bond metathesis reaction as the crucial elementary step. This mechanism avoids intermediacy of reactive metal species that undergo oxidative additions of alkanes, but instead the alkyl intermediate does a o-bond metathesis reaction with a new substrate molecule. Figure 19.13 illustrates the basic sequence [20],... 

In closely related experiments it was shown that sp C—H activation takes place reversibly within the coordinahon sphere of the electron-rich Ir(I)-diphosphine complex 58 (Scheme 6.9) to form an alkyl-amino-hydrido derivative 57 reminiscent of the CCM intermediate 24 the solid-state structure of 57 is shown in Figure 6.13 [40]. It appears that C—H activation only takes place after coordination of the amine function to the Ir(I) center (complex 58, NMR characterized). Amine coordination allows to break the chloro bridge of 59 and to augment the electron density of the metal center, thus favoring oxidative addihon of the C—H bond. Most importantly, the microscopic reverse of this C—H activation process (i.e. C—H reductive elimination) models the final step of the CCM cycle (see Scheme 6.1) indeed, the reaction of Scheme 6.10 is cleanly reversible at 373 K. 

A very elegant synthetic approach was reported a year later by Davies et al., leveraging asymmetric C-H activation chemistry to accomplish a one-pot synthesis of d-threo methyiphenidate (Scheme 17.10) (Davies et al., 1999). A-Boc piperidine (33) was selectively alkylated by the carbene formed by decomposition of diazoester 34 in a reaction mediated by 25 mol% of chiral Rh (II) catalyst 35, giving the A-Boc protected (2R,2 R) isomer in a single step. TFA was added to accomplish removal of the Boc group after the C-H insertion reaction was complete, affording (R,R)-methylphenidate (2) with an ee of 86% in 52% overall yield. 

This then was the first report of a compound in which alkyl C—H bond activation by a transition metal had occurred. In the solid state, this equilibrium is also in favor of the hydrido complex (V), and its crystal structure has recently been determined (15). It shows compound V to be a dimer (VI), the oxidative addition of the methyl group of a ligand on each ruthenium atom being to a second ruthenium atom. Presumably one reason why this occurs is because the product of intramolecular ring closure would contain a highly strained three-membered Ru—P—C ring (i.e., in monomer V). 

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