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For Palladium-Catalysed C–N And C–C Cross-Couplings.

Air and moisture insensitive auxiliary ligands for highly efficient palladium catalysts. These ultra-low loading (high TONs or TOFs) catalysts have shown excellent activity in Suzuki cross-coupling with aryl bromides and chlorides, Heck vinylation, Heck-Sonogashira alkynylation and allylic amination of allyl acetates (Tsuji–Trost type reactions). Low loadings of the catalysts ensure minimal contamination of the final compounds with palladium and simplify the purification procedures. High stability of the allows to store them for unlimited time without special precautions.

Tetraphos Fc(P)4
EN400-15231

Triphos Fc(P)3
EN400-15232

Triphos Fc(P)2PiPr
EN400-15233

Tetraphos Fc(P)2(P’)2
EN400-15234

Diphos Fc(P)2
EN400-15235

Diphos Fc(PFuMe)2
EN400-15236

Ligands are available in milligram and multigram quantities.
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EXAMPLES & NOTES:
(J.-C. Hierso et al. Organometallics (2003), 22(22), 4490-4499.)

  • Suzuki cross-coupling with aryl bromides at ultra-low catalyst loadings (L = Tetraphos Fc(P)4 EN400-15231)

R1
R2
Ratio S/Cat.
Yield, %

R1

C(=O)Me

R2

H

Ratio S/Cat.

100 000

Yield, %

100 (94)a

R1

CN

R2

H

Ratio S/Cat.

100 000

Yield, %

100 (87)a

R1

CF3

R2

H

Ratio S/Cat.

100 000

Yield, %

100

R1

OMe

R2

H

Ratio S/Cat.

100 000

Yield, %

77

R1

OMe

R2

H

Ratio S/Cat.

10 000

Yield, %

100 (92)a

a - isolated yield, conditions: 1 Pd / 1 Tetraphos Fc(P)4: 10-2 - 10-4 mol%; DMF or xylene, K2CO3, 130 °C, 20h.


  • Suzuki cross-coupling with aryl chlorides (L = Tetraphos Fc(P)4 EN400-15231)

R1
R2
Ratio S/Cat.
Yield, %

R1

C(=O)Me

R2

OMe

Ratio S/Cat.

1000

Yield, %

98 (88)a

R1

C(=O)Me

R2

OMe

Ratio S/Cat.

10 000

Yield, %

74

R1

CN

R2

OMe

Ratio S/Cat.

1000

Yield, %

89 (83)a

a - isolated yield, conditions: 1 Pd / 1 Tetraphos Fc(P)4 : 10-1 - 10-2 mol%; DMF or xylene, K2CO3, 130 °C, 20h.


  • Heck reaction at ultralow catalyst loadings (L = Tetraphos Fc(P)4 EN400-15231)

Aryl Halide
Alkene
Ratio S/Cat.
Yield, %
Time, h

Aryl Halide

PhI

Alkene

n-BuOCOCH=CH2

Ratio S/Cat.

1000 000

Yield, %

100 (85)a

Time, h

48

Aryl Halide

4-MeOC6H4Br

Alkene

n-BuOCOCH=CH2

Ratio S/Cat.

10 000

Yield, %

100 (88)a

Time, h

48

Aryl Halide

4-MeOC6H4Br

Alkene

C6H5CH=CH2

Ratio S/Cat.

100 000

Yield, %

65a

Time, h

20

Aryl Halide

4-CH(O)C6H4Br

Alkene

n-BuOCH=CH2

Ratio S/Cat.

250

Yield, %

100 (83)a

Time, h

20

Aryl Halide

4-CH(O)C6H4Br

Alkene

n-BuOCH=CH2

Ratio S/Cat.

1000

Yield, %

41a

Time, h

20

a - isolated yield, conditions: 1 Pd / 1 Tetraphos Fc(P)4, Xylene, K2CO3, 130 °C.


  • Alkynylation of aryl halides (Heck-Sonogashira reaction) under low (10-1 to 10-4 mol%) catalyst loadings in the presence of a Triphos Fc(P)2PiPr EN400-15233 with TONs up to 250000. Copper-free coupling using phenyl- acetylene is also accessible in good yield.

    J.-C. Hierso, V. Ivanov et al., Organic Letters (2004), 6(20), 3473-3476.
    H. Doucet, J.-C. Hierso, Angewandte Chemie International Edition (2007), 46, 834-871.

Aryl Halide
Alkene
Ratio S/Cat.
Yield, %

Aryl Halide

PhI

Alkene

phenylacetylene

Ratio S/Cat.

100 000

Yield, %

95

Aryl Halide

4-Bromoacetophenone

Alkene

phenylacetylene

Ratio S/Cat.

100 000

Yield, %

94

Aryl Halide

4-Bromobenzonitrile

Alkene

phenylacetylene

Ratio S/Cat.

10 000

Yield, %

89

Aryl Halide

4-Chlorobenzonitrile

Alkene

phenylacetylene

Ratio S/Cat.

250

Yield, %

86a

Aryl Halide

4-Bromoanisole

Alkene

phenylacetylene

Ratio S/Cat.

250

Yield, %

93

Aryl Halide

4-Bromoacetophenone

Alkene

but-1-yn-4-ol

Ratio S/Cat.

250

Yield, %

92b

aReaction performed without CuI. bReaction performed at 100 °C / Conditions: catalyst {Pd(C3H5)Cl}2/Triphos Fc(P)2Pi-Pr 1/2, aryl halide (1 mmol), alkyne (2 mmol), CuI (0.05 mmol), K2CO3 (2 mmol), DMF, 130 °C, 20 h, isolated yields.
  • Selective Amination of allylic acetates under low catalyst loadings in the presence of ferrocenyldiphosphine Diphos Fc(PFuMe)2 EN400-15236

    J.-C. Hierso et al. Advanced Synthesis and Catalysis (2005), 347(9), 1198-1202.
    J.-C. Hierso, H. Doucet et al. Tetrahedron (2005), 61, 9759-9766.

Acetate
Amine
Ratio S/Cat.
Conditions
Conversion, %
Selectivity
TOF (h-1)

Acetate

Allyl acetate

Amine

aniline

Ratio S/Cat.

100

Conditions

Rt, 1h

Conversion, %

100

Selectivity

96/4

TOF (h-1)

10 000

Acetate

Allyl acetate

Amine

piperidine

Ratio S/Cat.

10 000

Conditions

Rt, 1h

Conversion, %

100

Selectivity

-

TOF (h-1)

5 000

Acetate

Allyl acetate

Amine

morpholine

Ratio S/Cat.

10 000

Conditions

Rt, 2h

Conversion, %

85

Selectivity

100

TOF (h-1)

4 250

Acetate

Allyl acetate

Amine

diisopropylamine

Ratio S/Cat.

1 000

Conditions

80 °C 2h

Conversion, %

96

Selectivity

100

TOF (h-1)

480

Acetate

Hex-2-en-1-yl acetate

Amine

pyrrolidine

Ratio S/Cat.

1 000

Conditions

50 °C, 20h

Conversion, %

100

Selectivity

93/7(lin/br)

TOF (h-1)

-

Acetate

Hex-2-en-1-yl acetate

Amine

morpholine

Ratio S/Cat.

1 000

Conditions

50 °C, 20h

Conversion, %

98

Selectivity

94/6(lin/br)

TOF (h-1)

-

Acetate

Cinnamyl acetate

Amine

pyrrolidine

Ratio S/Cat.

1 000

Conditions

50 °C, 20h

Conversion, %

100

Selectivity

94/6(lin/br)

TOF (h-1)

2 600

Acetate

Cinnamyl acetate

Amine

morpholine

Ratio S/Cat.

1 000

Conditions

50 °C, 20h

Conversion, %

100

Selectivity

93/7(lin/br)

TOF (h-1)

4 800

Acetate

Cinnamyl acetate

Amine

diethylamine

Ratio S/Cat.

1 000

Conditions

Rt, 20h

Conversion, %

100

Selectivity

94/6(lin/br)

TOF (h-1)

7 600

Acetate

Geranyl acetate

Amine

morpholine

Ratio S/Cat.

1 000

Conditions

80 °C, 3h

Conversion, %

100

Selectivity

98

TOF (h-1)

33

Catalyst {Pd(C3H5)Cl}2 / Diphos Fc(PFuMe)2 Conditions: S/C = 250-10000, T = 25°C-50 °C, 2 equiv. amine, 1 to 20 h.

 

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