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. Author manuscript; available in PMC: 2015 Apr 1.
Published in final edited form as: Tetrahedron Lett. 2015 Apr 1;56(14):1911–1914. doi: 10.1016/j.tetlet.2015.02.116

Table 1. Identification of the most active organocatalyst and best-suited reaction conditions for the asymmetric synthesis of 3a.

graphic file with name emss-63354-t0003.jpg

Entry Cat. (mol %) Solvent Base T (°C) t (h) 3aa (%) 4b (%) erc (±)
1 A1 (20%) CH2Cl2 K2CO3 (5 equiv) 25 24d 58 10–15 48:52
2 A1 (20%) CH2Cl2 – 25 24 60 15–20 48:52
3 A2 (20%) CH2Cl2 – 25 24d 30 15–20 55:45
4 A3 (20%) CH2Cl2 – 25 24 58 15–20 50:50
5 A4 (20%) CH2Cl2 – 25 24d 20b 15–20 50:50
6 A5 (20%) CH2Cl2 – 25 24d 39 20 (17)a 42:58
7 A5 (20%) CH2Cl2 K2CO3 (5 equiv) 25 24d 47 15–20 (15)a 44:56
8 B1 (10%) CH2Cl2 – 25 40d 39 n.d. 37:63
9 C1 (20%) Toluene – 25 40d 25 n.d. 34:66
10 D1 (20%) CH2Cl2 – 25 40 80 n.d. 64:36
11 D2 (20%) CH2Cl2 – 25 40 78 n.d. 66:34
12 E1 (20%) CH2Cl2 – 25 40 80 n.d. 38:62
13 E2 (20%) CH2Cl2 – 25 40 83 n.d. 30:70
14 E3 (20%) CH2Cl2 – 25 40 79 n.d. 50:50
15 E4 (20%) CH2Cl2 – 25 40 70 n.d. 42:58
16 F1 (20%) CH2Cl2 – 25 40d 66 n.d. 50:50
17 F2 (20%) CH2Cl2 – 25 40d 67 n.d. 47:53
18 E2 (20%) Toluene – 25 40d 62 n.d. 33:67
19 E2 (20%) MTBE – 25 40 78 n.d. 41:59
20 E2 (20%) CHCl3 – 25 40 70e n.d. 26:74
21 E2 (10%) CHCl3 – 25 40d 34 n.d. 26:74
22 E2 (5%) CHCl3 – 25 40d 32 n.d. 34:66
23 E2 (40%) CHCl3 – 25 40 85 n.d. 30:70
24 E2 (20%) CHCl3 – 0 72d 52 n.d. 25:75
25 E2 (20%) CHCl3 – 40 40 57 n.d. 27:73
a

Isolated yield.

b

Determined by 1H NMR of the crude reaction product.

c

Determined by HPLC using a chiral stationary phase.

d

Less than 90% conversion of 1a.

e

Using 2 equiv of 2 gave 3a in 75% yield and the same enantioselectivity.