Cross-coupling reaction

Source: Wikipedia, the free encyclopedia.

In

catalysts
. One important reaction type is this:

R−M + R'−X → R−R' + MX (R, R' = organic fragments, usually
aryl; M = main group center such as Li or MgX; X = halide
)

These reactions are used to form carbon–carbon bonds but also carbon-heteroatom bonds.[1][2][3][4] Cross-coupling reaction are a subset of coupling reactions.

Akira Suzuki were awarded the 2010 Nobel Prize in Chemistry for developing palladium-catalyzed coupling reactions.[5][6]

Mechanism

Many mechanisms exist reflecting the myriad types of cross-couplings, including those that do not require metal catalysts.[7] Often, however, cross-coupling refers to a metal-catalyzed reaction of a nucleophilic partner with an electrophilic partner.

Aryl
).

In such cases, the

transmetallation with a source of R'−. The final step is reductive elimination
of the two coupling fragments to regenerate the catalyst and give the organic product. Unsaturated substrates, such as C(sp)−X and C(sp2)−X bonds, couple more easily, in part because they add readily to the catalyst.

Catalysts

Mechanism proposed for the Sonogashira coupling.

Catalysts are often based on palladium, which is frequently selected due to high

Heterogeneous catalysts based on Pd are also well developed.[9]

Copper-based catalysts are also common, especially for coupling involving heteroatom-C bonds.[10][11]

Iron-,[12] cobalt-,[13] and nickel-based[14] catalysts have been investigated.

Leaving groups

The

pseudohalide have been used. Chloride is an ideal group due to the low cost of organochlorine compounds. Frequently, however, C–Cl bonds are too inert, and bromide or iodide leaving groups are required for acceptable rates. The main group metal in the organometallic partner usually is an electropositive element such as tin, zinc, silicon, or boron
.

Carbon–carbon cross-coupling

Many cross-couplings entail forming carbon–carbon bonds.

Reaction Year Reactant A Reactant B Catalyst Remark
Cadiot–Chodkiewicz coupling 1957 RC≡CH sp RC≡CX sp Cu requires base
Castro–Stephens coupling 1963 RC≡CH sp Ar-X sp2 Cu
Corey–House synthesis 1967 R2CuLi or RMgX sp3 R-X sp2, sp3 Cu Cu-catalyzed version by Kochi, 1971
Kumada coupling 1972 RMgBr sp2, sp3 R-X sp2 Pd or Ni or Fe
Heck reaction 1972 alkene sp2 Ar-X sp2 Pd or Ni requires base
Sonogashira coupling 1975 ArC≡CH sp R-X sp3 sp2 Pd and Cu requires base
Negishi coupling 1977 R-Zn-X sp3, sp2, sp R-X sp3 sp2 Pd or Ni
Stille cross coupling
 1978 R-SnR3 sp3, sp2, sp R-X sp3 sp2 Pd or Ni
Suzuki reaction 1979 R-B(OR)2 sp2 R-X sp3 sp2 Pd or Ni requires base
Murahashi coupling[15] 1979 R-Li sp2, sp3 R-X sp2 Pd or Ru
Hiyama coupling 1988 R-SiR3 sp2 R-X sp3 sp2 Pd requires base
Fukuyama coupling 1998 R-Zn-I sp3 RCO(SEt) sp2 Pd or Ni see Liebeskind–Srogl coupling, gives ketones
Liebeskind–Srogl coupling 2000 R-B(OR)2 sp3, sp2 RCO(SEt) Ar-SMe sp2 Pd requires
CuTC
, gives ketones
Cross dehydrogenative coupling 2004 R-H sp, sp2, sp3 R'-H sp, sp2, sp3 Cu, Fe, Pd etc. requires oxidant or dehydrogenation
Decarboxylative cross-coupling 2000s R-CO2H sp2 R'-X sp, sp2 Cu, Pd Requires little-to-no base

The restrictions on carbon atom geometry mainly inhibit

β-hydride elimination when complexed to the catalyst.[16]

Carbon–heteroatom coupling

Many cross-couplings entail forming carbon–heteroatom bonds (heteroatom = S, N, O). A popular method is the

Buchwald–Hartwig reaction
:

The Buchwald–Hartwig reaction
The Buchwald–Hartwig reaction

 

 

 

 

(Eq.1)

Reaction Year Reactant A Reactant B Catalyst Remark
Ullmann-type reaction 1905 ArO-MM, ArNH2,RS-M,NC-M sp3 Ar-X (X = OAr, N(H)Ar, SR, CN) sp2 Cu
Buchwald–Hartwig reaction[17]
 1994 R2N-H sp3 R-X sp2 Pd N-C coupling,
second generation free amine
Chan–Lam coupling[18] 1998 Ar-B(OR)2 sp2 Ar-NH2 sp2 Cu

Miscellaneous reactions

Palladium-catalyzes the cross-coupling of

aryl halides with fluorinated arene. The process is unusual in that it involves C–H functionalisation at an electron deficient arene.[19]

Fluoroarene coupling
Fluoroarene coupling

Applications

Cross-coupling reactions are important for the production of pharmaceuticals,[4] examples being montelukast, eletriptan, naproxen, varenicline, and resveratrol.[20] with Suzuki coupling being most widely used.[21] Some polymers and monomers are also prepared in this way.[22]

Reviews

References

  1. PMID 31184483
    .
  2. PMID 16836296
    .
  3. ISBN 978-1-84973-896-5
  4. ^
    ISBN 978-3-540-01603-8
    .
  5. ^ "The Nobel Prize in Chemistry 2010 - Richard F. Heck, Ei-ichi Negishi, Akira Suzuki". NobelPrize.org. 2010-10-06. Retrieved 2010-10-06.
  6. S2CID 20582425
    .
  7. PMID 25184859
    .
  8. ^ Thayer, Ann (2005-09-05). "Removing Impurities". Chemical & Engineering News. Retrieved 2015-12-11.
  9. S2CID 36974481
    .
  10. PMID 16836296
    .
  11. PMID 18698737
    .
  12. PMID 25916260
    .
  13. PMID 20148539
    .
  14. PMID 21133429
    .
  15. ISSN 0022-3263
    .
  16. ^ Clayden, J.; Greeves, N.; Warren, S. Organic Chemistry, 2nd ed.; Oxford UP: Oxford, U.K., 2012. pp. 1069-1102.
  17. PMID 27689804
    .
  18. ISBN 9783527639328
    .
  19. PMID 16819868
    .
  20. ISBN 9783527328970
    .
  21. PMID 21504168
    .
  22. ISBN 1-891389-53-X
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