THE MURAI REACTION

According to isotope studies the rate-determining step of this sequence is the reductive elimination, and all other reactions (C-H activation, insertion of alkene) are reversible. The first indication of this behaviour was the H/D exchange of the ortho proton of acetophenone. Secondly, and perhaps useful for many other systems, was the kinetic isotope effect observed for 13C natural 

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This synthetically useful process, termed the Murai reaction and treated in detail in the next section for C-H activations of r/T-hybridizcd carbon atoms, was extended to other substrates (Equation (47)). 

Effectively, this is another example of the addition of a functional aromatic compound to an alkene, as the Murai reaction, but the mechanism is different. Alkyl substituted pyridine derivatives are interesting molecules for pharmaceutical applications. The a-bond metathesis reaction is typical of early transition metal complexes as we have learnt in Chapter 2. 

The Murai reaction (Scheme 4), the replacement of an ortho-CH on an aromatic ketone by an alkyl group derived from a substrate olefin, is catalyzed by a variety of Ru complexes. This C bond formation occurs via chelate directed C-H bond activation (cyclometalation) in the first step, followed by alkene insertion into RuH and reductive elimination of the alkylated ketone. In a recent example of the use of a related cyclometalation in complex organic synthesis, Samos reports catalytic arylation (Suzuki reaction) and alkenylation (Heck reaction) of alkyl segments of a synthetic intermediate mediated by Pd(II). 

Cyclometalation/ one of the earliest reactions involving CH oxidative addition, has been reviewed recently. Apart from the Murai reaction, cyclometalation has also been incorporated into a number of other catalytic reactions of interest in organic synthesis." ... 

An important catalytic process that relies on cyclometalation is the Murai reaction [136]. This involves heteroatom directed cyclometalation of an arene followed by insertion of an alkene and reductive elimination to give a net alkylation of the arene. The most common catalyst is RuH2(CO)(PPh3)3. An example of transformation brought about by this catalyst is shown in Eq. 2.51. 

In 1993, Murai et al. [75] built upon these promising results and designed a highly efficient and selective rutheniumotalyzed catalytic ortho-C-H alkylation of aromatic ketones with olefins (Scheme 19.49). The Murai reaction is very usefiil... 

Scheme 19.67 Mechanism of the Murai reaction cataiyzed by RuH2(CO)(PPhj)3.

Lim and coworkers [102] examined the reaction of aldimines and ketimines with aikenes in the presence of [Rh(coe)2Cl]2/PCy3 (Scheme 19.71). Acidic hydrolysis of the produced imine provided the corresponding arylketone, ultimately rendering the overall transformation analogous to the Murai reaction. With this active catalytic system, the mono- and/or the dialkylated products were obtained in moderate to... 

Cyclometalation has been applied to synthesis in the Murai reaction. The substrate has to contain a group, a ketone in Eq. 14.42, that binds the metal complex. Cyclometalation gives an intermediate aryl that undergoes insertion with a vinyl silane followed by reductive elimination to give the product the result is a C-H addition across a C=C bond. ... 

The proposed mechanism (Scheme 8) involves initial coordination of the pyridine to direct sp C-H bond oxidative addition to the Ru(0) centre followed by alkene insertion into a Ru-H bond and reductive elimination as for the Murai reaction involving sp C-H bond alkylation [3]. 

Show a plausible detailed mechanism for the Murai reaction of Eq. 14.37, showing the intermediates in full. 

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