Table 1 Optimization studies for enantioselective alkynylation of C–P bond with terminal alkynes

From: Diversity-oriented synthesis of P-stereogenic and axially chiral monodentate biaryl phosphines enabled by C-P bond cleavage

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Entry

Ligand

Additive

Solvent

Base

3a

Yield (%)a

e.e. (%)b

dr

1

L1

CuI

2-Me-THF

Cs2CO3

65

51

>25:1

2

L2

CuI

2-Me-THF

Cs2CO3

18

54

>25:1

3

L3

CuI

2-Me-THF

Cs2CO3

93

8

>25:1

4

L4

CuI

2-Me-THF

Cs2CO3

>99

86

>25:1

5

L5

CuI

2-Me-THF

Cs2CO3

42

82

>25:1

6

L6

CuI

2-Me-THF

Cs2CO3

86

91

>25:1

7

L6

CuBr

2-Me-THF

Cs2CO3

90

91

>25:1

8

L6

CuCl

2-Me-THF

Cs2CO3

47

90

>25:1

9

L6

CuBr

TBME

Cs2CO3

19

95

>25:1

10

L6

CuBr

DME

Cs2CO3

55

91

>25:1

11

L6

CuBr

Toluene

Cs2CO3

16

89

>25:1

12

L6

CuBr

CH3CN

Cs2CO3

Trace

N.D.

N.D.

13

L6

CuBr

2-Me-THF

K2CO3

78

93

>25:1

14

L6

CuBr

2-Me-THF

K3PO4

76

93

>25:1

15

L6

CuBr

2-Me-THF

DBU

30

90

>25:1

16

L6

CuBr

2-Me-THF

Et3N

0

N.D.

N.D.

17c

L6

CuBr

2-Me-THF

Cs2CO3

98

92

>25:1

18c,d

L6

CuBr

2-Me-THF

Cs2CO3

>99 (83)

93

>25:1

  1. The enantioselective alkynylation of C–P bond was performed by using 1a (0.2 mmol), 2a (0.4 mmol), [Pd(allyl)Cl]2 (5 mol%), chiral phosphine (22 mol%), additive (0.75 equiv), and base (2.0 equiv) in solvent (2.0 mL) at 60 °C for 12 h.
  2. N.D. not detected.
  3. aThe yield was determined by 1H NMR using CH2Br2 as the internal standard. Isolated yields are reported in parentheses.
  4. bee values of the major isomers are shown and determined by chiral HPLC analysis. dr values were determined by 1H NMR analysis of the crude reaction mixtures.
  5. c[Pd(allyl)Cl]2 (2.5 mol%), L6 (11 mol%) and the reaction was performed at 45 °C for 36 h.
  6. dCuBr (1 equiv) was used.
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