An Investigation of the Enolization and Isomeric Products Distribution in the Water Promoted Aldol Reaction of Tropinone and Granatanone
Table 2
Calculated (method A: B3LYP/6-31g(d) CPCM and method B: B3LYP/6-311++g(3d,3p) CPCM) distributions of products (for terminology see Figure 3) and experimental results for the aldol reaction of tropinone with aldehydes at 25°C.
R1 (Aldol)
Reaction medium
Method
Anti HB-O (%)
Syn HB-O (%)
Anti HB-N (%)
Syn HB-N (%)
Calculateddr anti : syn
Experimental dr anti : syn (yield )
Deviation of calculated from experimental [%]
Ph (3a)
Gas/neat
A
1.87
0.02
8.65
89.46
11 : 89
10 : 90 (84)
11
B
9.06
0.03
8.34
82.57
17 : 83
84
Water
A
0.38
0.01
40.20
59.41
41 : 59
41 : 59
0
B
2.67
0.01
43.84
53.47
46 : 54
23
p-NO2-C6H4 (3b)
Gas/neat
A
1.11
0.02
17.51
81.36
19 : 81
22 : 78 (76)
17
B
4.91
0.04
19.19
75.85
24 : 76
12
Water
A
0.16
0.01
50.70
49.13
51 : 49
64 : 36 (95)
39
B
0.55
0.01
54.82
44.63
56 : 44
25
p-F-C6H4 (3c)
Gas/neat
A
2.15
0.02
11.16
86.68
14 : 86
20 : 80 (75)
35
B
11.29
0.04
13.24
75.42
24 : 76
26
Water
A
0.33
0.01
38.55
61.11
39 : 61
46 : 54 (43)
25
B
2.11
0.02
44.82
53.05
47 : 53
4
p-Cl-C6H4 (3d)
Gas/neat
A
1.39
0.03
9.87
88.72
12 : 88
14 : 86 (90)
16
B
8.55
0.07
13.44
77.94
22 : 78
73
Water
A
0.27
0.01
37.92
61.81
38 : 62
45 : 55 (69)
25
B
1.74
0.02
43.35
54.89
45 : 55
0
p-CF3-C6H4 (3e)
Gas/neat
A
2.05
0.07
14.94
82.93
17 : 83
17 : 83 (92)
0
B
7.48
0.01
11.52
80.99
19 : 81
15
Water
A
0.17
0.01
66.10
33.72
66 : 34
55 : 46 (77)
62
B
1.00
0.02
47.29
51.70
48 : 52
23
m-MeO-C6H4 (3f)
Gas/neat
A
1.71
0.02
11.61
86.66
13 : 87
10 : 90 (73)
34
B
10.09
0.05
14.20
75.66
24 : 76
184
Water
A
0.38
0.01
46.83
52.77
47 : 53
39 : 61 (46)
39
B
2.08
0.02
46.74
51.16
49 : 51
50
α-Naphth (3g)
Gas/neat
A
0.52
0.00
8.81
90.67
9 : 91
5 : 95 (51)
88
B
1.65
0.00
9.16
89.19
10 : 90
111
Water
A
0.06
0.00
32.62
67.32
33 : 67
33 : 67 (34)
0
B
0.54
0.00
46.22
53.24
46 : 54
73
MAD 6-31g(d)
28
MAD 6-311++g(3d,3p)
50
Reaction [23]: gas/neat (2 mmol aldehyde, 1 mmol tropinone, and 18 μL H2O); water (2 mmol aldehyde, 1 mmol tropinone, and 2.5 mL H2O). Calculated and experimental data in part taken from the literature [24]. Diastereoisomer ratio given as a ratio of the sum of both anti forms to both syn forms. Calculated in the gas phase for the neat reaction. The progress of reactions were monitored by 1H NMR spectroscopy (reaction time: 1–14 days). Yield of all aldols (amount of anti and syn aldols). Calculated as . No solid product precipitated under these conditions. When formation of solid was observed the selectivity anti/syn rose to >95 : 5 and yield to 75%.
