Table 1 Optimization of the Mannich/Acylation/Wittig reaction conditionsa

From: Development of bifunctional organocatalysts and application to asymmetric total synthesis of naucleofficine I and II

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Entry

Catalyst

T [ºC]

Additive

t [h]

Yield [%]b

ee [%]c

1

Cat 1

0

-

8

21

51

2

Cat 1

0

PhCO2H

8

8

−1.1

3

Cat 1

0

PTS

8

12

−57

4

Cat 1

0

Et 3 N

4

51

91

5

Cat 1

0

DMAP

20

29

87

6

Cat 1

0

DBU

20

47

86

7

Cat 1

−5

Et3N

10

48

88

8

Cat 1

−10

Et3N

10

45

89

9

Cat 2

0

Et3N

48

7

3

10

Cat 3

0

Et3N

48

12

8

11

Cat 4

0

Et3N

48

<5

32

12

Cat 5

0

Et3N

48

<5

18

13

Cat 6

0

Et3N

48

<5

14

14

Cat 7

0

Et3N

48

NDd

NDd

15

Cat 8

0

Et3N

30

15

20

16

Cat 9

0

Et3N

6

26

68

17

Cat 10

0

Et3N

48

20

69

18

Cat 11

0

Et3N

48

<5

67

19

Cat 12

0

Et3N

48

6

20

20

Cat 13

0

Et3N

48

9

29

  1. a Unless otherwise noted, all reactions were carried with 2a (0.1 mmol), acetaldehyde (0.3 mmol), catalyst (0.02 mmol), and additive (0.05 mmol), in 0.5 mL DCE and 0.5 mL H2O; after the reaction is complete, the solution was evaporated, then DCM (1 mL), K2CO3 (0.2 mmol), acyl halide 3 (0.15 mmol), and Wittig reagent 4 (0.2 mmol) was added sequentially to the reaction system
  2. b Isolated yield over three steps
  3. c Determined by HPLC analysis
  4. d No reaction detectable
  5. DBU 1,8-diazabicyclo[5.4.0]undec-7-ene, DMAP 4-dimethylaminopyridine, PTS p-toluenesulfonic acid, DCE 1,2-dichloroethane, DCM dichloromethane
  6. Bold values represent the optimal condition
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