Table 1 Ligand effects and catalyst loading optimization of nickel-catalyzed intramolecular reductive coupling of N-alkynone (1a)

From: Pyrrolidines and piperidines bearing chiral tertiary alcohols by nickel-catalyzed enantioselective reductive cyclization of N-alkynones

Entriesa

Ligand

X (mol%)

Y (mol%)

T (oC)

Solvent

Yield (%)b

er (%)c

1

PPh 3

10

10

25

Dioxane

98

0

2

PCy 3

10

10

25

Dioxane

82

0

3

Ru-Phos

10

10

25

Dioxane

95

0

4

S-Phos

10

10

25

Dioxane

98

0

5

X-Phos

10

10

25

Dioxane

85

0

6

(R)-MONOPHOS

10

10

25

Dioxane

0

ND

7

(R)-BINAP

10

5

25

Dioxane

< 5

ND

8

(R)-(S)-JosiPhos

10

5

25

Dioxane

< 5

ND

9

(R)-Me-DuPhos

10

5

25

Dioxane

0

ND

10

(R)-Binapine

10

5

25

Dioxane

0

ND

11

(R)-DTBM-SEGPhos

10

5

25

Dioxane

< 5

ND

12

L1

10

10

25

Dioxane

0

ND

13

L2

10

10

25

Dioxane

68

89:11

14

L3

10

10

25

Dioxane

98

97:3

15

L4

10

5

25

Dioxane

98

99:1

16

L3

1

1

25

Dioxane

40

97:3

17

L4

1

0.5

25

Dioxane

98

99:1

18

L4

0.1

0.05

25

Dioxane

45d

99:1

19

L4

0.1

0.05

60

Dioxane

98 d

99:1

  1. The reaction scheme is shown in Fig 2
  2. a Unless otherwise specified, the reactions were performed under nitrogen in dioxane (0.5 mL) for 12 h with 1a (0.2 mmol), Ni(cod)2 (X mol %), ligand (Y mol %), and triethylsilane (0.6 mmol); product 2a was the only observed product. The R absolute configuration of 2a was assigned on the basis of the absolute configuration of 3a determined by X-ray crystallography
  3. b Isolated yields
  4. c The enantiomeric excess was determined by chiral HPLC on a Chiralcel AD-H column
  5. d The reactions were performed under nitrogen in dioxane (2.5 mL) for 12 h with 1a (2 mmol), Ni(cod)2 (2 μmol, 0.1 mol%), L4 (1 μmol, 0.05 mol%), and triethylsilane (6 mmol). Text in italics (entry 19) indicates optimised conditions
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