Murahashi Coupling on:
[Wikipedia]
[Google]
[Amazon]
The Murahashi Coupling is a 
cross coupling reaction
In organic chemistry, a cross-coupling reaction is a reaction where two different fragments are joined. Cross-couplings are a subset of the more general coupling reactions. Often cross-coupling reactions require metal catalysts. One important reac ...
. The coupling partner In cross-coupling reactions, the component reagents are called cross-coupling partners or simply coupling partners. These reagents can be further classified according to their nucleophilic vs electrophilic character:
:R-X + R'-Y → R-R' + X ...
s are organolithiums and organic halides. Transition metal
In chemistry, a transition metal (or transition element) is a chemical element in the d-block of the periodic table (groups 3 to 12), though the elements of group 12 (and less often group 3) are sometimes excluded. The lanthanide and actinid ...
catalysts
Catalysis () is the increase in reaction rate, 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 ...
are required. The reaction was first reported by Shun-Ichi Murahashi in 1974. This reaction is notable for using organolithiums as opposed to other cross-coupling reactions which utilize various metal-carbon compounds (metal = tin, magnesium, boron, silicon, zinc). Since the production of these other coupling reagents relies heavily upon organolithiums (especially in the case of organozinc and organomagnesium compounds), in bypassing these intermediates, this process is much more efficient. It has further been shown that the Murahashi reaction proceeds with greater selectivity, faster reaction times, and lower reaction temperatures than other similar coupling reactions while maintaining similar or higher yields.
History
Murahashi first reported C(sp2)—C(sp3) coupling in 1974. These reactions were not metal catalyzed but were promoted by solvent,THF
Tetrahydrofuran (THF), or oxolane, is an organic compound with the formula (CH2)4O. The compound is classified as heterocyclic compound, specifically a cyclic ether. It is a colorless, water-miscible organic liquid with low viscosity. It is ma ...
. The following year, Murahashi showed that coupling can occur between organolithium and alkenyl halides in the presence of tetrakis(triphenylphosphine)palladium catalyst. In 1979, Murahashi published the catalytic version of this reaction.
Mechanism
Palladium catalysis
The catalytic cycle of the Murahashi coupling is comparable to that of other extensively studied palladium-catalyzed cross-coupling reactions. The cycle proposed by Murahashi involves four intermediates and two oxidation states of palladium, palladium(0) and palladium(II). At the start of the cycle, oxidative addition occurs between the Pd(0) catalyst (1) and an organo-halide to form an organo-Pd(II) complex (2). A transmetallation then occurs between (2) and an organo-lithium to yield the trans-hetero-organometallic complex (3) and the lithium-halide. In order to perform the reductive elimination that ultimately yields the final coupled product, a trans-cis-isomerization of (3) must occur to bring the ligands cis to each other, resulting in the cis-hetero-organometallic complex (4). Finally, reductive elimination of (4) regenerates the Pd(0) catalyst and creates the C(sp2)--C(sp3) bond in the coupled product.Murahashi, S.; Yamamura, M.; Yanagisawa, K.; Mita, N.; Kondo, K. Stereoselective Synthesis of Alkenes and Alkenyl Sulfides from Alkenyl Halides Using Palladium and Ruthenium Catalysts. J. Org. Chem. 1979, 44 (14), 2408–2417. https://doi.org/10.1021/jo01328a016.
Conditions limitations
Organolithium reagent
In organometallic chemistry, organolithium reagents are chemical compounds that contain carbon–lithium (C–Li) bonds. These reagents are important in organic synthesis, and are frequently used to transfer the organic group or the lithium atom ...
s pose some danger because they are highly pyrophoric.Schwindeman, J. A.; Woltermann, C. J.; Letchford, R. J. Safe Handling of Organolithium Compounds in the Laboratory. Chem. Health Saf. 2002, 9 (3), 6–11. https://doi.org/10.1016/S1074-9098(02)00295-2.
The reaction is typically carried out in toluene as a solvent . The mixture is often carried out between 0–80 °C and quenched with acid to deactivate any remaining organolithium.
Ruthenium catalysis
While Pd(0)-catalyzed reactions are highly efficient for the cross-coupling of organo-halides and organolithium reagents, ruthenium catalysts have also been demonstrated.
See also
*Heck reaction
The Heck reaction (also called the Mizoroki–Heck reaction) is the chemical reaction of an unsaturated halide (or triflate) with an alkene in the presence of a base and a palladium catalyst to form a substituted alkene. It is named after T ...
* Hiyama coupling
The Hiyama coupling is a palladium-catalyzed cross-coupling reaction of organosilanes with organic halides used in organic chemistry to form carbon–carbon bonds (C-C bonds). This reaction was discovered in 1988 by Tamejiro Hiyama and Yasuo Ha ...
* Suzuki reaction
The Suzuki reaction or Suzuki coupling is an organic reaction that uses a palladium complex catalyst to cross-couple a boronic acid to an organohalide. It was first published in 1979 by Akira Suzuki, and he shared the 2010 Nobel Prize in Chemi ...
* Negishi coupling
The Negishi coupling is a widely employed transition metal catalyzed cross-coupling reaction. The reaction couples organic halides or triflates with organozinc compounds, forming carbon–carbon bonds (C–C) in the process. A palladium (0) s ...
* Petasis reaction
The Petasis reaction (alternatively called the Petasis borono–Mannich (PBM) reaction) is the multi-component reaction of an amine, a carbonyl, and a vinyl- or aryl- boronic acid to form substituted amines.
Reported in 1993 by Nicos Petasis ...
* Stille reaction
The Stille reaction is a chemical reaction widely used in organic synthesis. The reaction involves the coupling of two organic groups, one of which is carried as an organotin chemistry, organotin compound (also known as organostannanes). A variet ...
* Sonogashira coupling
The Sonogashira reaction is a cross-coupling reaction used in organic synthesis to form carbon–carbon bonds. It employs a palladium catalyst as well as copper co-catalyst to form a carbon–carbon bond between a terminal alkyne and an aryl or vi ...
* Kumada coupling
In organic chemistry, the Kumada coupling is a type of cross coupling reaction, useful for generating carbon–carbon bonds by the reaction of a Grignard reagent and an organic halide. The procedure uses transition metal catalysts, typically ...
Citations
{{Reflist Carbon-carbon bond forming reactions Name reactions