Murai Reaction

In organic chemistry, the Murai reaction is an organic reaction that uses C-H activation to create a new C-C bond between a terminal or strained internal alkene and an aromatic compound using a ruthenium catalyst. The reaction, named after Shinji Murai, was first reported in 1993. While not the first example of C-H activation, the Murai reaction is notable for its high efficiency and scope. Previous examples of such hydroarylations required more forcing conditions and narrow scope.

Scope and regiochemistry

The reaction was initially demonstrated using a ketone as the directing group, but other functional groups have been reported, including esters, imines, nitriles, and imidates. Murai reactions have also been reported with disubstituted alkynes. Bidentate directing groups allow ''ortho'' alkylation of aromatic rings with α,β-unsaturated ketones, which typically are unreactive in Murai reactions.

Early examples of the reaction suffered from side products of alkylation at both ''ortho'' positions. This problem can be partially solved using an ''ortho'' methyl blocking group. Unfortunately, with ortho methyl groups both the rate and generality of the reaction are reduced. Substituents at the ''meta'' position influence regioselectivity. The reaction preferentially adds at the least sterically hindered ''ortho'' position, except when there is a ''meta'' group capable of coordinating with the Ru catalyst. Methoxyacetophenones show preferential reaction at the more hindered position.

Mechanism

A variety of Ru catalysts catalyze the Murai reaction, including RuH₂(CO)(PPh₃)₃, RuH₂(PPh₃)₄, Ru(CO)₂(PPh₃)₃, and Ru₃(CO)₁₂.

Ru(0) catalysts

A detailed mechanism for the Murai reaction has not been elucidated. Experimental and computational studies give evidence for at least two different mechanisms, depending on the catalyst. For catalysts such as u(H)₂(CO)(PR₃)₃which are active as Ru⁰, a combination of computational density functional studies and experimental evidence has resulted in the following proposed mechanism:

It is proposed that at high temperatures RuH₂(CO)(PPh₃)₃ converts to an unsaturated Ru(CO)(PPh₃)_n species. The catalytic cycle is proposed to begin with coordination of the ketone followed by oxidative addition of a C-H bond. The resulting five-coordinated metallocycle is stabilized by an agostic interaction. The C-C bond formation is the rate limiting step.

Ru(II) catalysts

The complex u(''o''-C₆H₄PPh₂)(H)(CO)(PPh₃)₂catalyzes the Murai reaction at room temperature.{{Cite journal, last=Kakiuchi, first=Fumitoshi, last2=Kochi, first2=Takuya, last3=Mizushima, first3=Eiichiro, last4=Murai, first4=Shinji, date=2010-12-22, title=Room-Temperature Regioselective C−H/Olefin Coupling of Aromatic Ketones Using an Activated Ruthenium Catalyst with a Carbonyl Ligand and Structural Elucidation of Key Intermediates, journal=Journal of the American Chemical Society, volume=132, issue=50, pages=17741–17750, doi=10.1021/ja104918f, pmid=21114294, issn=0002-7863 For u(H)₂(H₂)₂(PR₃)₂ the active complex is u(H)₂(PR₃)₂

After the active form of the ruthenium catalyst complex is generated from 1, acetophenone coordinates to the complex via its carbonyl oxygen and agostically via its ''ortho'' C-H bond (2). As in the Ru⁰ proposed mechanism, this agostic interaction leads to the oxidative addition of the ''ortho'' C-H. Reductive elimination releases H₂, which remains coordinated, giving complex 3. Coordination of ethylene and decoordination of the ketone results in complex 4 which then undergoes migratory insertion of ethylene into the hydride to give 5. Following oxidative addition of H₂ (6), the complex reductively eliminates the product to give the product agostically bound to the complex. Coordination of another acetophenone molecule regenerates complex 2.

References

Organic reactions