Suzuki-Miyaura Cross-Coupling Reaction

Suzuki-Miyaura reaction is a palladium catalyzed cross-coupling reaction between organic boron compounds and organic halides.1) The reaction requires an additional base for the activation of the boron compound and proceeds under mild conditions. This relatively simple and versatile C-C bond formation reaction can be extended to various substrates and therefore finds wide application for the synthesis of pharmaceuticals and total synthesis of complex natural products.

The usefulness of this reaction has been well documented by the synthesis of biaryl compounds in 1981,3) triggered by the initial synthesis of dienes using the vinyl-type boron compounds initiated in 1979.2) Eventually the reaction also proved applicable to the coupling reaction of alkyl halides and alkylboranes. Organotrifluoroborates also represent an effective alternative to boronic acids and boronate esters being stable towards numerous reagents and allow the manipulation of functional groups within them.4)
N-Heterocyclic carbenes prepared from imidazolium and imidazolinium salts can also be efficiently employed as ligands in addition to organophosphine compounds.5) Recently, the synthesis of biaryl compounds without the aid of ligands has also been accomplished.6)
It has been recently reported that nickel can also catalyze the above reaction with the same efficiency as the expensive palladium catalysts specially in case of difficult substrates like aryl chlorides in which reaction does not proceed easily with conventional palladium as the catalyst. In addition to being inexpensive, nickel catalysts can also be removed much easily from the reaction system.7)
Proper choice of metals, ligands, bases and solvents enable the widespread application of the Suzuki-Miyaura cross-coupling reaction to various substrates and different synthetic sequences. We provide a wide range of organic boron compounds as coupling partners. In this section, we introduce different varieties of reaction partners in addition to the organoboron compounds, such as metal catalysts and phosphine ligands to explore the versatile applicability of the Suzuki-Miyaura cross-coupling reaction.

Palladium Catalyst

Nickel Catalyst

Phosphine Ligands

N-Heterocyclic Carbene Ligands

Others

Bases & Additives

Palladium Catalyst

A1479 A1479 B2029 B2029 B2018 B2018
B1676 B1676 B1668 B1668 B1374 B1374
B2161 B2161 B2026 B2026 B3161 B3161
B2055 B2055 B2042 B2042 B1667 B1667
B3224 B3224 C2407 C2407 C2387 C2387
C2406 C2406 C2372 C2372 D2604 D2604
P1490 P1490 P1491 P1491 P1785 P1785
P1528 P1528 A1424 A1424 P1489 P1489
P1425 P1425 S0540 S0540 T1350 T1350
T2184 T2184 B3160 B3160 B2064 B2064
B2016 B2016 B2192 B2192 B2031 B2031
A1479 Allylpalladium(II) Chloride Dimer
B2029 Benzylbis(triphenylphosphine)palladium(II) Chloride
B2018 Bis(2,4-pentanedionato)palladium(II)
B1676 Bis(acetonitrile)palladium(II) Dichloride
B1668 Bis(benzonitrile)palladium(II) Dichloride
B1374 Bis(dibenzylideneacetone) Palladium(0)
B2161 Bis(methyldiphenylphosphine)palladium(II) Dichloride
B2026 Bis(tri-o-tolylphosphine)palladium(II) Dichloride
B3161 Bis(tri-tert-butylphosphine)palladium(0)
B2055 Bis(tricyclohexylphosphine)palladium(II) Dichloride
B2042 Bis(triphenylphosphine)palladium(II) Diacetate
B1667 Bis(triphenylphosphine)palladium(II) Dichloride
B3224 Bis[1,2-bis(diphenylphosphino)ethane]palladium(0)
C2407 Chloro[[1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene](4'-methoxyacetanilide)palladium(II)]
C2387 Chloro[[1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene](acetanilide)palladium(II)]
C2406 Chloro[[1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene](N,N-dimethyl-3,5-dimethoxybenzylamine)palladium(II)]
C2372 Chloro[[1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene](N,N-dimethylbenzylamine)palladium(II)]
D2604 Dichloro(1,5-cyclooctadiene)palladium(II)
P1490 Palladium 5% on Carbon (wetted with ca. 55% Water)
P1491 Palladium 10% on Carbon (wetted with ca. 55% Water)
P1785 Palladium 10% on Carbon (wetted with ca. 55% Water) [Useful catalyst for coupling reaction, etc.]
P1430 Palladium Catalyst Set Palladium(II) Acetate / Allylpalladium(II) Chloride Dimer / Bis(benzonitrile)palladium(II) Dichloride / Bis(dibenzylideneacetone)palladium(0) / [1,1'-Bis(diphenylphosphino)ferrocene]palladium(II) Dichloride Dichloromethane Adduct / Bis(triphenylphosphine)palladium(II) Dichloride / Tetrakis(triphenylphosphine)palladium(0) (includes useful 7 Palladium catalysts)
P1528 Palladium Hydroxide 20% on Carbon (wetted with ca. 50% Water)
A1424 Palladium(II) Acetate
P1489 Palladium(II) Chloride
P1425 Poly[N-isopropylacrylamide-co-4-(diphenylphosphino)styrene] Palladium(II) Dichloride (ratio, acrylamide:phosphine=20:2)
S0540 Sodium Tetrachloropalladate(II)
T1350 Tetrakis(triphenylphosphine)palladium(0)
T2184 Tris(dibenzylideneacetone)dipalladium(0)
B3160 [1,1'-Bis(di-tert-butylphosphino)ferrocene]palladium(II) Dichloride
B2064 [1,1'-Bis(diphenylphosphino)ferrocene]palladium(II) Dichloride Dichloromethane Adduct
B2016 [1,2-Bis(diphenylphosphino)ethane]palladium(II) Dichloride
B2192 [1,3-Bis(diphenylphosphino)propane]palladium(II) Dichloride
B2031 [1,4-Bis(diphenylphosphino)butane]palladium(II) Dichloride
Page Top

Nickel Catalyst

N0096 N0096 B3534 B3534 B1571 B1571
B2226 B2226 B2225 B2225 B1313 B1313
N0096 Bis(2,4-pentanedionato)nickel(II) Hydrate
B3534 Bis(tricyclohexylphosphine)nickel(II) Dichloride
B1571 Bis(triphenylphosphine)nickel(II) Dichloride
S0487 Skeletal Nickel Catalyst slurry in Water [Active catalyst for Hydrogenation]
B2226 [1,1'-Bis(diphenylphosphino)ferrocene]nickel(II) Dichloride
B2225 [1,2-Bis(diphenylphosphino)ethane]nickel(II) Dichloride
B1313 [1,3-Bis(diphenylphosphino)propane]nickel(II) Dichloride
Page Top

Phosphine Ligands

B1113 B1113 B1112 B1112 B1406 B1406
D2535 D2535 B1405 B1405 D2536 D2536
B2711 B2711 B2710 B2710 B2027 B2027
B1137 B1137 B1138 B1138 B1246 B1246
B1960 B1960 B1959 B1959 D3387 D3387
D3389 D3389 D3388 D3388 B2709 B2709
D2766 D2766 B1982 B1982 B2867 B2867
D3940 D3940 D2411 D2411 E0519 E0519
T1643 T1643 T1912 T1912 T0361 T0361
T0519 T0519 T1614 T1614 T1024 T1024
T1025 T1025 T0861 T0861 T0862 T0862
B1113 (2R,3R)-(-)-1,4-Bis(diphenylphosphino)-2,3-O-isopropylidene-2,3-butanediol
B1112 (2S,3S)-(+)-1,4-Bis(diphenylphosphino)-2,3-O-isopropylidene-2,3-butanediol
B1406 (R)-(+)-2,2'-Bis(diphenylphosphino)-1,1'-binaphthyl
D2535 (R)-N,N-Dimethyl-1-[(S)-2-(diphenylphosphino)ferrocenyl]ethylamine
B1405 (S)-(-)-2,2'-Bis(diphenylphosphino)-1,1'-binaphthyl
D2536 (S)-N,N-Dimethyl-1-[(R)-2-(diphenylphosphino)ferrocenyl]ethylamine
B2711 1,1'-Bis(di-tert-butylphosphino)ferrocene
B2710 1,1'-Bis(diisopropylphosphino)ferrocene
B2027 1,1'-Bis(diphenylphosphino)ferrocene
B1137 1,2-Bis(diphenylphosphino)ethane
B1138 1,3-Bis(diphenylphosphino)propane
B1246 1,4-Bis(diphenylphosphino)butane
B1960 1,5-Bis(diphenylphosphino)pentane
B1959 1,6-Bis(diphenylphosphino)hexane
D3387 2-(Di-tert-butylphosphino)biphenyl
D3389 2-(Dicyclohexylphosphino)-2'-(dimethylamino)biphenyl
D3388 2-(Dicyclohexylphosphino)biphenyl
B2709 4,5-Bis(diphenylphosphino)-9,9-dimethylxanthene
D2766 4-Diphenylphosphinomethyl Polystyrene Resin cross-linked with 2% DVB (200-400mesh) (0.5-1.0mmol/g)
B1982 Bis(diphenylphosphino)methane
B2867 Bis[2-(diphenylphosphino)phenyl] Ether
D3940 Di-tert-butylphenylphosphine
D2411 Dicyclohexylphenylphosphine
E0519 Ethyldiphenylphosphine
T1643 Tri(2-furyl)phosphine
T1912 Tri-tert-butylphosphine
T0361 Tributylphosphine
T0519 Triphenylphosphine
T1614 Tris(2,6-dimethoxyphenyl)phosphine
T1024 Tris(2-methylphenyl)phosphine
T1025 Tris(3-methylphenyl)phosphine
T0861 Tris(4-methoxyphenyl)phosphine
T0862 Tris(4-methylphenyl)phosphine
Page Top

N-Heterocyclic Carbene Ligands

B3158 B3158 B3465 B3465 B3506 B3506
B3157 B3157 D3611 D3611 D3472 D3472
D3711 D3711 D3870 D3870 D3446 D3446
B3158 1,3-Bis(2,4,6-trimethylphenyl)imidazolinium Chloride
B3465 1,3-Bis(2,6-diisopropylphenyl)imidazol-2-ylidene
B3506 1,3-Bis(2,6-diisopropylphenyl)imidazolidin-2-ylidene
B3157 1,3-Bis(2,6-diisopropylphenyl)imidazolinium Chloride
D3611 1,3-Bis(2,6-diisopropylphenyl)imidazolium Chloride
D3472 1,3-Di-tert-butylimidazol-2-ylidene
D3711 1,3-Di-tert-butylimidazolium Tetrafluoroborate
D3870 1,3-Dimesitylimidazol-2-ylidene
D3446 1,3-Dimesitylimidazolium Chloride
Page Top

Others

T0508 T0508
T0508 Triphenylarsine
Page Top

Bases & Additives

P0221 P0221 P0081 P0081 B1018 B1018
M0508 M0508 B0468 B0468 B2695 B2695
D0905 D0905 C2430 C2430 C2204 C2204
L0222 L0222 D1599 D1599 S0485 S0485
B0709 B0709 T0054 T0054 T0057 T0057
P0221 1,10-Phenanthroline Monohydrate
P0081 1,10-Phenanthroline Hydrochloride Monohydrate
B1018 1,8-Bis(dimethylamino)naphthalene [for Dehydrohalogenation]
M0508 1-Methylimidazole
B0468 2,2'-Bipyridyl
B2695 Bathophenanthroline (refined product of D0905)
D0905 Bathophenanthroline
C2430 Cesium Acetate
C2204 Cesium Fluoride
L0222 Lithium Chloride (2.3% in Tetrahydrofuran, ca. 0.5mol/L)
D1599 N,N-Diisopropylethylamine
S0485 Sodium Methoxide
B0709 tert-Butylamine
T0054 Tetrabutylammonium Bromide
T0057 Tetrabutylammonium Iodide
Page Top

Classes of Boron Compounds

Page Top

Literature

1) Review: A. Suzuki, Chem. Commun., 2005, 4759 [DOI]; A. Suzuki, Yuki Gosei Kagaku Kyokaishi (J. Synth. Org. Chem. Jpn.), 2005, 63, 312; A. Suzuki, Proc. Jpn. Acad., Ser. B, 2004, 80, 359 [DOI]; N. Miyaura, A. Suzuki, Chem. Rev., 1995, 95, 2457 [DOI].
2) N. Miyaura, K. Yamada, A. Suzuki, Tetrahedron Lett., 1979, 20, 3437 [DOI].
3) T. Yanagi, N. Miyaura, A. Suzuki, Synth. Commun., 1981, 11, 513 [DOI].
4) Review: G. A. Molander, N. Ellis, Acc. Chem. Res., 2007, 40, 275 [DOI].
5) Review: E. A. B. Kantchev, C. J. O'Brien, M. G. Organ, Angew. Chem. Int. Ed., 2007, 46, 2768 [DOI].
6) T. Maegawa, Y. Kitamura, S. Sako, T. Udzu, A. Sakurai, A. Tanaka, Y. Kobayashi, K. Endo, U. Bora, T. Kurita, A. Kozaki, Y. Monguchi, H. Sajiki, Chem. Eur. J., 2007, 13, 5937 [DOI].
7) Review: T. Kamikawa, Fain Kemikaru, 2006, 35, 53.

Page Top
90ac4m0000001x7m