The Nobel Prize in Chemistry 2010 "for palladium-catalyzed cross couplings in organic synthesis". Photo: University of Delaware, USA Photo: Purdue University, USA Photo: Hokkaido University, Japan Richard F. Heck Ei-ichi Negishi Akira Suzuki

The Heck reaction (From Wikipedia) The Heck reaction (after Richard F. Heck, Nobel prize 2010, in chemistry, also called the Mizoroki-Heck reaction) is the chemical reaction of an unsaturated halide (or triflate) with an alkene and a base and palladium catalyst to form a substituted alkene.chemical reactionhalidetriflatealkenebasepalladiumcatalyst Together with the other palladium-catalyzed cross-coupling reactions, this reaction is of great importance, as it allows one to do substitution reactions on planar centers. It is named after Tsutomu Mizoroki and Richard F. Heck.cross-coupling reactionsTsutomu MizorokiRichard F. Heck

Heck Reaction Mechanism: The catalytic cycle for the Heck reaction involves a series of transformations around the palladium catalyst. The palladium(0) compound required in this cycle is generally prepared in situ from a palladium(II) precursor.catalytic cyclein situ This cycle is not limited to vinyl compounds, in the Sonogashira coupling one of the reactants is an alkyne and in the Suzuki coupling the alkene is replaced by an aryl boronic acid and in the Stille reaction by an aryl stannane. The cycle also extends to the other group 10 element nickel for example in the Negishi coupling between aryl halides and organozinc compounds. Platinum forms strong bonds with carbon and does not have a catalytic activity in this type of reaction.Sonogashira couplingalkyneSuzuki couplingboronic acidStille reactionstannanegroup 10 elementnickelNegishi coupling

The Suzuki reaction The Suzuki reaction (after Akira Suzuki, Nobel prize 2010, in chemistry) is the organic reaction of an aryl- or vinyl-boronic acid with an aryl- or vinyl-halide catalyzed by a palladium(0) complex.organic reactionarylvinylboronic acidarylvinylhalide palladium(0) complex The reaction also works with pseudohalides, such as triflates (OTf), instead of halides, and also with boron-esters instead of boronic acids.pseudohalidestriflateshalides Relative reactivity: R 2 -I > R 2 -OTf > R 2 -Br >> R 2 -Cl First published in 1979 by Akira Suzuki, the Suzuki reaction couples boronic acids (containing an organic part) to halides. The reaction relies on a palladium catalyst such as tetrakis(triphenylphosphine)palladium(0) to effect part of the transformation. The palladium catalyst (more strictly a pre-catalyst) is 4-coordinate, and usually involves phosphine supporting groups.Akira Suzukicouplespalladiumcatalysttetrakis(triphenylphosphine)palladium(0) phosphine In many publications this reaction also goes by the name Suzuki-Miyaura reaction. It is also often referred to as "Suzuki Coupling".

Mechanism of the Suzuki reaction

Negishi coupling The Negishi coupling (After Ei-ichi Negishi, Nobel prize, 2010 in chemistry) is a cross coupling reaction in organic chemistry involving an organozinc compound, an organic halide and a nickel or palladium catalyst creating a new carbon-carbon covalent bond (first published in 1977).cross coupling reactionorganic chemistryorganozinc compoundhalidenickelpalladiumcatalystcovalent bond The halide X can be chloride, bromine or iodine but also a triflate or acetyloxy group with as the organic residue R alkenyl, aryl, allyl, alkynyl or propargyl (H-CC-CH 2 -).chloridebromineiodinetriflateacetyloxyalkenylarylallylalkynylpropargyl The halide X' in the organozinc compound can be chloride, bromine or iodine and the organic residue R' is alkenyl, aryl, allyl or alkyl.chloridebromineiodinealkenylarylallylalkyl The metal M in the catalyst is nickel or palladium.nickelpalladium The ligand L in the catalyst can be triphenylphosphine, dppe [1,2- bis(diphenylphosphino)ethan], BINAP or chiraphos.ligandtriphenylphosphinedppeBINAPchiraphos The active catalyst in this reaction is zerovalent (M 0 ) and the reaction in general proceeds through an oxidative addition step of the organic halide followed by transmetalation with the zinc compound and then reductive elimination:zerovalentoxidative additiontransmetalationreductive elimination

The Stille reaction The Stille reaction (also known as Stille Coupling) is a chemical reaction coupling an organotin compound with an sp 2 -hybridized organic halide catalyzed by palladium. The reaction is widely used in organic synthesis.chemical reaction organotin compoundhalidepalladiumorganic synthesis X is typically a halide, such as Cl, Br, I. Additionally, X can be a pseudohalide such as a triflate, CF 3 SO 3 -.halideClBrIpseudohalide triflateCF SO The Stille reaction was discovered in 1977 by John Kenneth Stille and David Milstein, a post-doctorate in his laboratory. Stille reactions were used in 50% of all cross-coupling reactions published in The reaction continues to be exploited industrially, especially for pharmaceuticals.John Kenneth StilleDavid Milsteinpharmaceuticals The Sonogashira coupling is a coupling reaction of terminal alkynes with aryl or vinyl halides. This reaction was first reported by Kenkichi Sonogashira and Nobue Hagihara in 1975.coupling reactionalkynesarylvinyl halidesKenkichi Sonogashira

Mechanism of the Sonogashira coupling: Typically, two catalysts are needed for this reaction: a zerovalent palladium complex and a halide salt of copper(I). The palladium complex activates the organic halides by oxidative addition into the carbon-halogen bond. Phosphine-palladium complexes such as tetrakis(triphenylphosphine)palladium(0) are used for this reaction, but palladium(II) complexes are also available because they are reduced to the palladium(0) species by the consumption of terminal alkynes in the reaction medium. The oxidation of triphenylphosphine to triphenylphosphine oxide can also lead to the formation of Pd(0) in situ when catalysts such as bis(triphenylphosphine)palladium(II) chloride are used. In contrast, copper(I) halides react with the terminal alkyne and produce copper(I) acetylide, which acts as an activated species for the coupling reactions.catalystspalladiumcopper(I)oxidative additioncarbonhalogenbond Phosphine tetrakis(triphenylphosphine)palladium(0)triphenylphosphine oxidebis(triphenylphosphine)palladium(II) chloridecopper(I) acetylide