Coupling reactions involve joining two molecules together using a metal catalyst. There are two main types of coupling reactions: cross-coupling reactions where two different molecules react to form a new molecule, and homocoupling where two similar molecules couple together. Common metal catalysts include palladium, zinc, nickel, copper, boron, and tin. Important coupling reactions include Kumada, Heck, Sonogashira, Negishi, Stille, Suzuki, Hiyama, Buchwald-Hartwig, and Fukuyama reactions.

1. COUPLING
REACTIONS

2. 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.

3. 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.

4. Some thing about Palladium

5. Important coupling reactions
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

6. Kumada coupling reaction
 Cross coupling between aryl or alkyl
Grignard with aryl or vinyl halocarbon.
 The first Pd or Ni catalysed coupling
reaction

7. Kumada coupling

8. Kumada coupling

9. Heck coupling
 Pdcatalyzed coupling between aryl or
vinyl halides with activated alkene in
basic media.

10. Heck coupling

11. Sonogashira coupling
 Terminal alkynes with aryl or vinyl
halides (triflate).
 Pd as a catalyst, Cu as co-catalyst and
an amine as a base.

12. Sonogashira coupling

13. Sonogashira coupling

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

15. Nigishi coupling

16. Stille coupling
 Using tin (stannes) alkyl compounds, wide range
of R groups, but?????
 Less polar, more toxic???

17. Stille coupling

18. Suzuki coupling
 Usingboronic acids or esters B(OR)3 .
 Needs base to activate boron species

19. Suzuki coupling

20. Suzuki coupling

21. Hyiama coupling
 Organosilanes (Si), with organohalids.
 Needs base or fluoride ion to activate
 Fluorinated, methoxyleted silanes more
reactive than alkyl ones.

22. Hyiama coupling

23. Buchwald-Hartwig coupling
 Pd catalyzed synthesis of aryl secondry
or tertiary amines.
 Using primary or secondry amins and
aryl halides (or triflates)

24. Buchwald-Hartwig coupling

25. Buchwald-Hartwig coupling

26. Fukuyama Coupling*
 Pd catalyzed coupling of organozinc with
thioesters to form ketones.