In
organic chemistry
Organic chemistry is a subdiscipline within chemistry involving the science, scientific study of the structure, properties, and reactions of organic compounds and organic matter, organic materials, i.e., matter in its various forms that contain ...
, the Murai reaction is an
organic reaction
Organic reactions are chemical reactions involving organic compounds. The basic organic chemistry reaction types are addition reactions, elimination reactions, substitution reactions, pericyclic reactions, rearrangement reactions, mechanistic organ ...
that uses
C-H activation to create a new
C-C bond
CC, cc, or C-C may refer to:
Arts, entertainment, and media Fictional characters
* C.C. (''Code Geass''), a character in the ''Code Geass'' anime series, pronounced "C-two"
* C.C. Babcock, a character in the American sitcom ''The Nanny''
* Co ...
between a terminal or strained internal
alkene
In organic chemistry, an alkene, or olefin, is a hydrocarbon containing a carbon–carbon double bond. The double bond may be internal or at the terminal position. Terminal alkenes are also known as Alpha-olefin, α-olefins.
The Internationa ...
and an
aromatic compound
Aromatic compounds or arenes are organic compounds "with a chemistry typified by benzene" and "cyclically conjugated."
The word "aromatic" originates from the past grouping of molecules based on odor, before their general chemical properties were ...
using a
ruthenium
Ruthenium is a chemical element; it has symbol Ru and atomic number 44. It is a rare transition metal belonging to the platinum group of the periodic table. Like the other metals of the platinum group, ruthenium is unreactive to most chem ...
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
In organic chemistry, a ketone is an organic compound with the structure , where R and R' can be a variety of carbon-containing substituents. Ketones contain a carbonyl group (a carbon-oxygen double bond C=O). The simplest ketone is acetone ( ...
as the
directing group
In organic chemistry, a directing group (DG) is a substituent on a molecule or ion that facilitates chemical reaction, reactions by interacting with a reagent. The term is usually applied to C–H activation of hydrocarbons, where it is defined a ...
, but other functional groups have been reported, including
ester
In chemistry, an ester is a compound derived from an acid (either organic or inorganic) in which the hydrogen atom (H) of at least one acidic hydroxyl group () of that acid is replaced by an organyl group (R). These compounds contain a distin ...
s, imines, nitriles, and imidates. Murai reactions have also been reported with disubstituted
alkynes
\ce
\ce
Acetylene
\ce
\ce
\ce
Propyne
\ce
\ce
\ce
\ce
1-Butyne
In organic chemistry, an alkyne is an unsaturated hydrocarbon containing at least one carbon—carbon triple bond. The simplest acyclic alkynes with only one triple bond and no ...
.
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 Alkylation is a chemical reaction that entails transfer of an alkyl group. The alkyl group may be transferred as an alkyl carbocation, a free radical, a carbanion, or a carbene (or their equivalents). Alkylating agents are reagents for effecting al ...
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 RuH
2(CO)(PPh
3)
3, RuH
2(PPh
3)
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
Catalysis () is the increase in rate of a chemical reaction due to an added substance known as a catalyst (). Catalysts are not consumed by the reaction and remain unchanged after it. If the reaction is rapid and the catalyst recycles quick ...
.
For catalysts such as
2(CO)(PR3)3">u(H)2(CO)(PR3)3which are active as Ru
0, a combination of computational
density functional studies and experimental evidence has resulted in the following proposed mechanism:
It is proposed that at high temperatures RuH
2(CO)(PPh
3)
3 converts to an unsaturated Ru(CO)(PPh
3)
n species.
The catalytic cycle is proposed to begin with coordination of the
ketone
In organic chemistry, a ketone is an organic compound with the structure , where R and R' can be a variety of carbon-containing substituents. Ketones contain a carbonyl group (a carbon-oxygen double bond C=O). The simplest ketone is acetone ( ...
followed by
oxidative addition
Oxidative addition and reductive elimination are two important and related classes of reactions in organometallic chemistry. Oxidative addition is a process that increases both the oxidation state and coordination number of a metal centre. Oxidat ...
of a C-H bond. The resulting five-coordinated
metallocycle is stabilized by an
agostic interaction
In organometallic chemistry, agostic interaction refers to the intramolecular interaction of a coordinatively-unsaturated transition metal with an appropriately situated C−H bond on one of its ligands. The interaction is the result of two ele ...
. The C-C bond formation is the rate limiting step.
Ru(II) catalysts
The complex
6H4PPh2)(H)(CO)(PPh3)2">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
2(H2)2(PR3)2">u(H)2(H2)2(PR3)2 the active complex is
2(PR3)2">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 Ru
0 proposed mechanism, this agostic interaction leads to the oxidative addition of the ''ortho'' C-H. Reductive elimination releases H
2, 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 H
2 (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