An Investigation of the Enolization and Isomeric Products Distribution in the Water Promoted Aldol Reaction of Tropinone and Granatanone
Table 3
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 granatanone 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 (4a)
Gas/neat
A
4.27
0.08
6.58
89.07
11 : 89
11 : 89 (45)
0
B
9.41
0.11
6.52
83.97
16 : 84
54
Water
A
0.67
0.03
37.13
62.17
38 : 62
39 : 61 (21)
4
B
2.52
0.03
33.44
64.01
36 : 64
12
p-NO2-C6H4 (4b)
Gas/neat
A
2.98
0.15
14.36
82.51
17 : 83
20 : 80 (90)
18
B
12.13
0.11
0.00
87.76
12 : 88
45
Water
A
0.23
0.02
40.75
59.01
41 : 59
49 : 51
28
B
1.33
0.03
38.80
59.84
40 : 60
31
p-F-C6H4 (4c)
Gas/neat
A
2.59
0.05
10.92
86.45
14 : 86
18 : 82
26
B
6.27
0.06
49.29
44.37
56 : 44
480
Water
A
0.00
0.01
37.73
62.26
38 : 62
45 : 55
25
B
2.75
0.03
39.62
57.60
42 : 58
11
p-Cl-C6H4 (4d)
Gas/neat
A
1.92
0.04
22.21
75.82
24 : 76
17 : 83
54
B
5.82
0.14
16.16
77.88
22 : 78
38
Water
A
0.23
0.02
54.27
45.48
55 : 45
45 : 55
49
B
1.96
0.03
48.28
49.74
50 : 50
22
p-CF3-C6H4 (4e)
Gas/neat
A
1.27
0.06
13.94
84.73
15 : 85
20 : 80 (61)
29
B
23.12
0.40
57.94
18.54
81 : 19
1605
Water
A
0.06
0.01
27.08
72.85
27 : 73
17 : 83 (58)
81
B
0.87
0.01
70.17
28.95
71 : 29
1095
m-MeO-C6H4 (4f)
Gas/neat
A
2.51
0.04
11.90
85.55
14 : 86
10 : 90
47
B
12.55
0.10
11.79
75.56
24 : 76
184
Water
A
0.31
0.02
49.90
49.77
50 : 50
39 : 61
56
B
3.37
0.05
54.03
42.55
57 : 43
107
α-Naphth (4g)
Gas/neat
A
0.24
0.00
3.80
95.96
4 : 96
2 : 98
104
B
1.53
0.00
4.44
94.02
6 : 94
213
Water
A
0.06
0.00
24.81
75.13
25 : 75
35 : 65
38
B
0.38
0.00
34.48
65.13
35 : 65
0
MAD 6-31g(d)
40
MAD 6-311++g(3d,3p)
278
Reaction [23]: gas/neat (2 mmol aldehyde, 1 mmol granatanone, and 18 μL H2O); water (2 mmol aldehyde, 1 mmol granatanone, and 2.5 mL H2O). 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 was monitored by 1H NMR spectroscopy; reaction time: up to 4 days (over 4 days significant amounts of elimination products were formed). Isolated yield of all aldols (amount of anti and syn aldols). Calculated as . No solid product precipitated under these conditions in 2 h. Extension of the reaction time to 24 h resulted in formation of solid and change in selectivity anti/syn 5 : 95 and yield (93%). Conversion determined by 1H NMR spectroscopy. Pure product was not isolated because of low conversion.
