Organic chemistry

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.