Coupling reactions 2

COUPLING REACTIONS

Coupling Reactions

Coupling reactions occur between organometallic with organic halide with the aid of a metal containing catalyst.

Coupling reactions can be divided into two main classes, cross couplings in which two different molecules react to form one new molecule.

The other type of coupling is homocoupling, in this reaction two similar molecules coupling together to form a new molecule.

Main features

Common metal used in this field is Pd, in addition to Zn, Ni, Cu, B, and Sn.

Most of coupling reactions are air and water sensitive ??

But, some coupling reactions can be carried out in aqueous solutions.

Some thing about Palladium

Reaction Year Reactant 1 Reactant 2 Catalyst

Kumada 1972 R-MgBr RX Pd or Ni

Heck 1972 Alkene RX Pd

Sonogashira 1973 Alkyne RX Pd or Cu

Nigishi 1977 R-Zn-X RX Pd or Ni

Stille 1977 R-Sn-R3` RX Pd

Suzuki 1979 R-B(OR)2 RX Pd

Hyiama 1988 R-Si-R3 RX Pd

Buchwald-Hartwig 1994 R2-N-R RX Pd

Important coupling reactions

Kumada coupling reaction

Cross coupling between aryl or alkyl Grignard with aryl or vinyl halocarbon.

The first Pd or Ni catalysed coupling reaction

Kumada coupling

Kumada coupling

Heck coupling

Pd catalyzed coupling between aryl or vinyl halides with activated alkene in basic media.

Heck coupling

Sonogashira coupling

Terminal alkynes with aryl or vinyl halides (triflate).

Pd as a catalyst, Cu as co-catalyst and an amine as a base.

Sonogashira coupling

Sonogashira coupling

Nigishi coupling

Pd or Ni catalyzed coupling organozinc compounds with aryl, vinyl, benzyl halids.

Nigishi coupling

Stille coupling

Using tin (stannes) alkyl compounds, wide range of R groups, but?????

Less polar, more toxic???

Stille coupling

Suzuki coupling

Using boronic acids or esters B(OR)3 . Needs base to activate boron species

Suzuki coupling

Suzuki coupling

Hyiama coupling

Organosilanes (Si), with organohalids.Needs base or fluoride ion to activate Fluorinated, methoxyleted silanes more

reactive than alkyl ones.

Hyiama coupling

Buchwald-Hartwig coupling

Pd catalyzed synthesis of aryl secondry or tertiary amines.

Using primary or secondry amins and aryl halides (or triflates)

Buchwald-Hartwig coupling

Buchwald-Hartwig coupling

Fukuyama Coupling*

Pd catalyzed coupling of organozinc with thioesters to form ketones.