The Journal of Organic Chemistry
Page 6 of 10
3H), 3.68 (t, J = 6.3, 2H), 2.66 (t, J = 7.6, 2H), 1.91ꢀ1.84 (m,
83% yield as a colorless oil with C−N/C−O selectivity of 94:6.
2H), 1.33 (br, 1H); 13C NMR (125 MHz, CDCl3) δ 157.8,
133.9, 129.4, 113.9, 62.3, 55.3, 34.5, 31.2.
1H NMR (500 MHz, CDCl3) δ 5.86 ꢀ 5.77 (m, 1H), 5.03 ꢀ 4.97
(m, 1H), 4.96 ꢀ 4.91 (m, 1H), 3.64 (t, J = 6.6, 2H), 2.07 ꢀ 2.02
(m, 2H), 1.61 ꢀ 1.53 (m, 2H), 1.46 ꢀ 1.24 (m, 13H); 13C NMR
(125 MHz, CDCl3) δ 139.3, 114.2, 63.2, 33.9, 32.9, 29.6,
29.5× 2, 29.2, 29.0, 25.8.
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2ꢀ(4ꢀIsobutylphenyl)propanꢀ1ꢀol 2m8a (entry 12, Table 2).
According to the general procedure, the reaction of methyl 2ꢀ
(4ꢀisobutylphenyl)ꢀN,Nꢀdimethylpropanamide
1m
(0.50
(Z)ꢀOctadecꢀ9ꢀenꢀ1ꢀol 2s8a (entry 18, Table 2). According to
the general procedure, the reaction of N,Nꢀdimethyloleamide
1s (0.50 mmol), EtOH (15.0 mmol) and sodium dispersions
(5.00 mmol) for 20 min at 0 °C, after chromatography (hexꢀ
anesꢀ20% EtOAc/hexane), afforded 2s 111.4 mg in 83% yield
mmol), EtOH (15.0 mmol) and sodium dispersions (5.00
mmol) for 20 min at 0 °C, after chromatography (hexanesꢀ
20% EtOAc/hexane), afforded 2m 59.6 mg in 62% yield as a
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colorless oil with C−N/C−O selectivity of 90:10. H NMR
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(500 MHz, CDCl3) δ 7.17ꢀ7.14 (m, 2H), 7.14ꢀ7.10 (m, 2H),
3.69 (d, J = 6.9, 2H), 2.98ꢀ2.90 (m, 1H), 2.46 (d, J = 7.3, 2H),
1.92ꢀ1.81 (m, 1H), 1.28 (d, J = 6.9, 3H), 0.92 (d, J = 6.6, 6H);
13C NMR (125 MHz, CDCl3) δ 140.8, 140.1, 129.4, 127.2,
68.8, 45.1, 42.1, 30.3, 22.5, 17.7.
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as a colorless oil with C−N/C−O selectivity of 94:6. H NMR
(500 MHz, CDCl3) δ 5.38ꢀ5.31 (m, 2H), 3.65 (t, J = 6.8, 2H),
2.05ꢀ2.00 (m, 4H), 1.61ꢀ1.55 (m, 2H), 1.39ꢀ1.22 (m, 23H),
0.89 (t, J = 7.1, 3H); 13C NMR (125 MHz, CDCl3) δ 130.1,
129.9, 63.2, 32.9, 32.0, 29.9, 29.8, 29.6× 2, 29.5, 29.4× 2,
29.3, 27.3× 2, 25.8, 22.8, 14.2.
2ꢀMethylꢀ3ꢀphenylpropanꢀ1ꢀol 2n12 (entry 13, Table 2). Acꢀ
cording to the general procedure, the reaction of N,N,2ꢀ
trimethylꢀ3ꢀphenylpropanamide 1n (0.50 mmol), EtOH (15.0
mmol) and sodium dispersions (5.00 mmol) for 20 min at 0
°C, after chromatography (hexanesꢀ30% EtOAc/hexane), afꢀ
forded 2n 54.1 mg in 72% yield as a colourless oil with
2ꢀ(1HꢀIndolꢀ3ꢀyl)ethanol 2t6b (entry 19, Table 2). According
to the general procedure, the reaction of 2ꢀ(1Hꢀindolꢀ3ꢀyl)ꢀ
N,Nꢀdimethylacetamide 2t (0.50 mmol), EtOH (15.0 mmol)
and sodium dispersions (5.00 mmol) for 20 min at 0 °C, after
preparative TLC (20% EtOAc/Hexane), afforded 2t 68.5 mg
in 85% yield as a brown oil with C−N/C−O selectivity of
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C−N/C−O selectivity of 94:6. H NMR (400 MHz, CDCl3) δ
7.32ꢀ7.26 (m, 2H), 7.24ꢀ7.17 (m, 3H), 3.55 (dd, J = 10.7, 5.8,
1H), 3.49 (dd, J = 10.7, 6.0, 1H), 2.77 (dd, J = 13.6, 6.3, 1H),
2.44 (dd, J = 13.6, 8.2, 1H), 2.02ꢀ1.91 (m, 1H), 1.38 (br, 1H),
0.93 (d, J = 6.9, 3H); 13C NMR (100 MHz, CDCl3) δ 140.7,
129.2, 128.3, 126.0, 67.8, 39.8, 37.9, 16.5.
1ꢀAdamantanemethanol 2o6b (entry 14, Table 2). According
to the general procedure, the reaction of N,Nꢀ
dimethyladamantaneꢀ1ꢀcarboxamide 1o (0.50 mmol), EtOH
(15.0 mmol) and sodium dispersions (5.00 mmol) for 20 min
at 0 C, after chromatography (hexanesꢀ20% EtOAc/hexane),
afforded 2o 59.0 mg in 71% yield as a white solid with
C−N/C−O selectivity of 82:18. Mp 117ꢀ118 °C; 1H NMR (500
MHz, CDCl3) δ 3.21 (s, 2H), 2.03ꢀ1.98 (m, 3H), 1.77ꢀ1.71 (m,
3H), 1.69ꢀ1.63 (m, 3H), 1.54ꢀ1.50 (m, 6H), 1.27 (br, 1H); 13C
NMR (125 MHz, CDCl3) δ 74.0, 39.1, 37.3, 34.6, 28.3.
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90:10. H NMR (500 MHz, CDCl3) δ 8.08 (br, 1H), 7.65ꢀ7.63
(m, 1H), 7.41ꢀ7.39 (m, 1H), 7.24ꢀ7.21 (m, 1H), 7.17ꢀ7.14 (m,
1H), 7.11ꢀ7.09 (m, 1H), 3.93 (t, J = 6.3, 2H), 3.06 (m, 2H),
1.59 (br, 1H); 13C NMR (125 MHz, CDCl3) δ 136.5, 127.5,
122.6, 122.3, 119.6, 118.9, 112.4, 111.3, 62.7, 28.8.
3ꢀ(4ꢀMethoxyphenyl)propanꢀ1ꢀol 2l6b (entry 20, Table 2).
According to the general procedure, the reaction of (E)ꢀ3ꢀ(4ꢀ
methoxyphenyl)ꢀN,Nꢀdimethylacrylamide 1u (0.50 mmol),
EtOH (15.0 mmol) and sodium dispersions (5.00 mmol) for 20
min at
0
°C, after chromatography (hexanesꢀ20%
EtOAc/hexane), afforded 2l 75.6 mg in 91% yield as a colourꢀ
less oil with C−N/C−O selectivity of 91:9. Spectroscopic
properties matched those previously described.
4ꢀ(Ethylamino)butanꢀ1ꢀol 2v13 (entry 21, Table 3). Accordꢀ
ing to the general procedure, the reaction of 1ꢀethylpyrrolidinꢀ
2ꢀone 1v (0.50 mmol), EtOH (15.0 mmol) and sodium disperꢀ
sions (5.00 mmol) for 20 min at 0 °C, after chromatography
(30% EtOAc/hexaneꢀ100% EtOAc), afforded 2v 45.7 mg in
78% yield as a colorless oil with C−N/C−O selectivity of
90:10. DCM was used as the extracting solvent instead of
Et2O. 1H NMR (400 MHz, CDCl3) δ 3.79 (br, 2H), 3.56 (t, J =
4.6, 2H), 2.70ꢀ2.63 (m, 4H), 1.72ꢀ1.59 (m, 4H), 1.12 (t, J =
7.2, 3H); 13C NMR (125 MHz, CDCl3) δ 62.6, 49.4, 43.7,
32.7, 29.0, 14.8.
3ꢀCyclopentylpropanꢀ1ꢀol 2p8a (entry 15, Table 2). Accordꢀ
ing to the general procedure, the reaction of 3ꢀcyclopentylꢀ
N,Nꢀdimethylpropanamide 1p (0.500 mmol), EtOH (15.0
mmol) and sodium dispersions (5.00 mmol) for 20 min at 0
°C, after chromatography (hexanesꢀ20% EtOAc/hexane), afꢀ
forded 2p 48.7 mg in 76% yield as a colorless oil with
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C−N/C−O selectivity of 85:15. H NMR (400 MHz, CDCl3) δ
3.65 (t, J = 6.6, 2H), 1.82ꢀ1.71 (m, 3H), 1.65ꢀ1.46 (m, 6H),
1.43ꢀ1.33 (m, 3H), 1.14ꢀ1.04 (m, 2H); 13C NMR (100 MHz,
CDCl3) δ 63.4, 40.0, 32.8, 32.2, 32.1, 25.3.
Decanꢀ1ꢀol 2q12 (entry16, Table 2). According to the genꢀ
eral procedure, the reaction of N,Nꢀdimethyldecanamide 1q
(0.50 mmol), EtOH (15.0 mmol) and sodium dispersions (5.00
mmol) for 20 min at 0 °C, after chromatography (hexanesꢀ
20% EtOAc/hexane), afforded 2q 57.8 mg in 73% yield as a
colorless oil with C−N/C−O selectivity of 92:8. 1H NMR (400
MHz, CDCl3) δ 3.65 (t, J = 6.3, 2H), 1.61ꢀ1.53 (m, 2H), 1.40ꢀ
1.21 (m, 15H), 0.89 (t, J = 6.9, 3H); 13C NMR (100 MHz,
CDCl3) δ 63.2, 32.9, 32.0, 29.7, 29.6, 29.5, 29.4, 25.8, 22.8,
14.2.
Undecꢀ10ꢀenꢀ1ꢀol 2r8a (entry 17, Table 2). According to the
general procedure, the reaction of N,Nꢀdimethylundecꢀ10ꢀ
enamide 1r (0.50 mmol), EtOH (15.0 mmol) and sodium disꢀ
persions (5.00 mmol) for 20 min at 0 °C, after chromatogꢀ
raphy (hexanesꢀ20% EtOAc/hexane), afforded 2r 70.7 mg in
(4ꢀMethoxyphenyl)methanol 2x6b (entry 22, Table 3). Acꢀ
cording to the general procedure, the reaction of 4ꢀmethoxyꢀ
N,Nꢀdimethylbenzamide 1x (0.50 mmol), EtOH (15.0 mmol)
and sodium dispersions (5.00 mmol) for 20 min at 0 °C, after
chromatography (hexaneꢀ10% EtOAc/hexane), afforded 2x
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49.7 mg in 72% yield as a colorless oil. H NMR (400 MHz,
CDCl3) δ 7.28 (m, 2H), 6.88 (m, 2H), 4.60 (s, 2H), 3.80 (s,
3H); 13C NMR (125 MHz, CDCl3) δ 159.2, 133.2, 128.7,
114.0, 65.0, 55.3.
General Procedure for the Reductive Deuteration of
Tertiary Amides by Na/EtODꢀd1. To a solution of amides
(0.500 mmol) in hexane (2.5 mL), was added EtODꢀd1 (15.0
mmol, 876 ꢁL), followed by sodium dispersions (34.5 wt %,
5.00 mmol) under N2 at 0 °C and the mixture was stirred vigꢀ
orously. The reaction mixture was stirred at 0 °C for 20 min
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