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DOI: 10.1055/s-2008-1078216
An Efficient Iodine-Catalyzed Benzylation Reaction of 1,3-Dicarbonyl Compounds
Publikationsverlauf
Publikationsdatum:
22. August 2008 (online)
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Abstract
Under mild conditions, iodine promotes the direct alkylation of 1,3-dicarbonyl compounds with benzylic alcohols or benzylic acetates.
Key words
iodine - catalysis - benzylation - Friedel-Crafts - C-H activation
- Supporting Information for this article is available online:
- Supporting Information
- 1
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References and Notes
General Procedure
All
procedures were carried out under air. To a 10 mL flask, benzylic
alcohols or benzylic acetates (0.5 mmol), 1,3-dicarbonyl compounds,
MeNO2 (2 mL), and molecular iodine (13 mg, 0.05 mmol)
were added successively. The mixture was magnetically stirred at
80 ˚C. After completion of the reaction (by GC), the solvent
was concentrated under reduced pressure by an aspirator, and the
residue was purified by preparative TLC using PE-EtOAc
(10:1) as an eluent to afford products.
Selected Spectroscopic
Data
All prepared compounds were known and identified
by ¹H NMR, ¹³C
NMR, and MS.
Compound 3a: ¹H
NMR (400 MHz, CDCl3): δ = 7.31-7.27 (m,
2 H), 7.22-7.18 (m, 3 H), 4.04 (d, J = 11.3
Hz, 1 H), 3.63-3.55 (m, 1 H), 2.56 (s, 3 H), 1.83 (s, 3
H), 1.21 (d, J = 6.9
Hz, 3 H). ¹³C NMR (100 MHz, CDCl3): δ = 203.5, 203.4,
143.0, 128.8, 127.3, 127.0, 76.7, 40.4, 29.8, 29.7, 20.8. ESI-MS: m/z = 227.0 [M + Na+].
Compound 3b: ¹H NMR (400 MHz,
CDCl3): δ = 7.28-7.25 (m,
2 H), 7.15-7.12 (m, 2 H), 4.00 (d, J = 11.3
Hz, 1 H), 3.61-3.57 (m, 1 H), 2.26 (s, 3 H), 1.87 (s, 3
H), 1.19 (d, J = 6.9
Hz, 3 H). ¹³C NMR (100 MHz, CDCl3): δ = 203.0, 202.9,
141.5, 132.6, 128.9, 128.6, 76.5, 39.6, 29.8, 29.6, 20.7. ESI-MS: m/z = 261.1 [M + Na+].
Compound 3c: ¹H NMR (400 MHz,
CDCl3): δ = 7.12-7.08 (m,
2 H), 6.84-6.82 (m, 2 H), 3.98 (d, J = 11.3
Hz, 1 H), 3.78 (s, 3 H), 3.57-3.53 (m, 1 H), 2.26 (s, 3
H), 1.84 (s, 3 H), 1.18 (d, J = 6.9
Hz, 3 H). ¹³C NMR (100 MHz, CDCl3): δ = 203.6,
203.5, 158.4, 134.9, 128.2, 114.1, 76.9, 55.1, 39.7, 29.8, 29.6,
20.9. ESI-MS: m/z = 257.0 [M + Na+].
Compound 3d: ¹H NMR (400 MHz,
CDCl3): δ = 7.22-7.18 (m,
2 H), 7.14-7.12 (m, 1 H), 6.97 (d, J = 7.8
Hz, 2 H), 6.88 (s, 1 H), 6.69 (s, 1 H), 5.48 (d, J = 11.7
Hz, 1 H), 4.94 (d, J = 11.7
Hz, 1 H), 2.55 (s, 3 H), 2.29 (s, 3 H), 2.20 (s, 3 H), 1.99 (s,
3 H), 1.83 (s, 3 H). ¹³C NMR (100 MHz,
CDCl3): δ = 203.7,
203.0, 141.1, 137.3, 136.7, 136.7, 134.9, 131.3, 129.6, 128.4, 126.9,
126.1, 70.5, 43.0, 30.3, 28.9, 21.7, 20.9, 20.7. Anal. Calcd for:
C, 81.78; H, 7.84. Found: C, 81.74; H, 7.93.
Compound 3e: ¹H NMR (400 MHz,
CDCl3): δ = 7.22-7.18 (m,
2 H), 7.14-7.11 (m, 1 H), 6.94 (d, J = 7.9
Hz, 2 H), 6.88 (s, 1 H), 5.67 (d, J = 11.3
Hz, 1 H), 4.94 (d, J = 11.3
Hz, 1 H), 2.46 (s, 3 H), 2.34 (s, 3 H), 2.28 (s, 3 H), 2.08 (s,
3 H), 1.88 (s, 3 H), 1.72 (s, 3 H). ¹³C
NMR (100 MHz, CDCl3): δ = 203.8,
202.8, 142.0, 137.9, 135.3, 134.1, 133.8, 133.1, 131.3, 128.5, 126.8,
126.0, 71.9, 43.3, 29.8, 29.2, 21.5, 20.4, 17.1, 16.8. Anal. Calcd
for: C, 81.95; H, 8.13. Found: C, 81.64; H, 8.37.
Compound 3f: ¹H NMR (400 MHz,
CDCl3): δ = 7.32
(d, J = 8.4
Hz, 2 H), 6.88 (s, 1 H), 6.84 (d, J = 8.3
Hz, 2 H), 6.71 (s, 1 H), 5.40 (d, J = 11.6
Hz, 1 H), 4.89 (d, J = 11.6
Hz, 1 H), 2.53 (s, 3 H), 2.29 (s, 3 H), 2.21 (s, 3 H), 1.98 (s,
3 H), 1.83 (s, 3 H). ¹³C NMR (100 MHz,
CDCl3): δ = 203.3,
202.6, 140.4, 137.3, 137.0, 136.6, 134.4, 131.5 (2C), 129.8, 128.8, 120.0,
70.4, 42.5, 30.3, 29.0, 21.7, 21.0, 20.7. Anal. Calcd for: C, 65.12;
H, 5.99. Found: C, 65.03; H, 6.04.
Compound 3g: ¹H
NMR (400 MHz, CDCl3): δ = 7.01
(d, J = 8.0
Hz, 2 H), 6.87-6.85 (m, 3 H), 6.69 (s, 1 H), 5.42 (d, J = 11.7 Hz,
1 H), 4.92 (d, J = 11.7
Hz, 1 H), 2.55 (s, 3 H), 2.29 (s, 3 H), 2.26 (s, 3 H), 2.21 (s,
3 H), 2.01 (s, 3 H), 1.82 (s, 3 H). ¹³C
NMR (100 MHz, CDCl3): δ = 204.0,
203.2, 138.1, 137.3, 136.8, 136.7, 135.7, 135.1, 131.4, 129.7, 129.1,
126.9, 70.8, 42.9, 30.2, 28.9, 21.8, 21.0, 20.9, 20.8. ESI-MS: m/z = 345.2 [M + Na+].
Compound 3h: ¹H NMR (400 MHz,
CDCl3): δ = 4.19
(s, 5 H), 4.16-4.05 (m, 4 H), 3.59 (d, J = 9.7
Hz, 1 H), 3.29-3.25 (m, 1 H), 2.15 (s, 3 H), 1.87 (s, 3
H), 1.26 (d, J = 6.5
Hz, 3 H). ¹³C NMR (100 MHz, CDCl3): δ = 204.5,
203.4, 91.7, 77.3, 68.8, 68.7, 67.8, 67.6, 65.4, 34.6, 32.0, 29.4,
18.3. Anal. Calcd for: C, 65.40; H, 6.46. Found: C, 65.40; H, 6.54.
Compound 3i: ¹H NMR (400 MHz,
CDCl3): δ = 7.50
(s, 1 H), 7.40 (s, 5 H), 2.43 (s, 3 H), 2.29 (s, 3 H). ¹³C
NMR (100 MHz, CDCl3): δ = 205.7,
196.6, 142.7, 139.9, 132.8, 130.7, 129.7, 129.0, 31.7, 26.5. ESI-MS: m/z = 211.0 [M + Na+].
Compound 3k: ¹H NMR (400 MHz,
CDCl3): δ = 8.10-8.08 (m,
1 H), 7.49-7.04 (m, 9 H), 4.94 (d, J = 10.9
Hz, 1 H), 3.90-3.86 (m, 1 H), 1.90 (s, 3 H), 1.21 (d, J = 6.8 Hz,
3 H). ¹³C NMR (100 MHz, CDCl3): δ = 203.1,
195.2, 143.2, 137.2, 133.9, 128.9, 128.8, 128.5, 127.5, 127.0, 70.8,
41.0, 28.0, 21.6.
Another diastereomer: ¹H
NMR (400 MHz, CDCl3): δ = 7.80-7.78
(m, 1 H), 7.49-7.04 (m, 9 H), 4.50 (d, J = 11.0 Hz,
1 H), 3.90-3.86 (m, 1 H), 2.23 (s, 3 H), 1.30 (d, J = 7.0 Hz,
3 H). ¹³C NMR (100 MHz, CDCl3): δ = 203.6,
195.2, 143.5, 137.0, 133.4, 128.9, 128.6, 128.5, 127.4, 126.6, 71.4, 40.4,
27.6, 20.3.
Compound 3l: ¹H
NMR (400 MHz, CDCl3): δ = 8.05-8.02 (m,
2 H), 7.74 (d, J = 7.4
Hz, 2 H), 7.57-7.53 (m, 1 H), 7.46-7.39 (m, 3
H), 7.29-7.25 (m, 4 H), 7.19-7.15 (m, 2 H), 7.09-7.05
(m, 1 H), 5.61 (d, J = 10.1
Hz, 1 H), 4.10-4.06 (m, 1 H), 1.34 (d, J = 7.0
Hz, 3 H). ¹³C NMR (100 MHz, CDCl3): δ = 195.0,
194.6, 143.8, 137.2, 136.9, 133.6, 133.0, 128.9, 128.8, 128.5, 128.5,
128.4, 127.7, 126.6, 64.9, 41.2, 20.2. ESI-MS: m/z = 351.3 [M + Na+].
Compound 3m: ¹H NMR (400 MHz,
CDCl3): δ = 7.27-7.20 (m,
3 H), 7.14-7.12 (m, 2 H), 3.79 (q, J = 7.0
Hz, 1 H), 2.53-2.46 (m, 2 H), 2.19-2.10 (m, 1
H), 1.97-1.92 (m, 1 H), 1.86 (s, 3 H), 1.84-1.79
(m, 2 H), 1.67-1.55 (m, 2 H), 1.30 (d, J = 7.1
Hz, 3 H). ¹³C NMR (100 MHz, CDCl3): δ = 208.6, 205.9,
141.4, 128.7, 128.3, 127.0, 72.1, 42.7, 42.4, 28.2, 26.7, 25.9,
22.2, 17.4. ESI-MS: m/z = 267.1 [M + Na+].
Another
diastereomer: ¹H NMR (400 MHz, CDCl3): δ = 7.28-7.24
(m, 4 H), 7.21-7.19 (m, 1 H), 3.89 (q, J = 7.4 Hz,
1 H), 2.38-2.34 (m, 2 H), 2.16-2.07 (m, 1 H),
2.12 (s, 3 H), 1.67-1.65 (m, 1 H), 1.63-1.60 (m,
1 H), 1.47-1.43 (m, 1 H), 1.42-1.40 (m, 2 H),
1.16 (d, J = 7.4
Hz, 3 H). ¹³C NMR (100 MHz, CDCl3): δ = 209.2,
205.4, 141.9, 129.9, 127.8, 126.7, 72.1, 42.3, 41.5, 29.4, 27.1,
25.5, 21.9, 16.2. ESI-MS: m/z = 267.1 [M + Na+].
Compound 3n: ¹H NMR (400 MHz,
CDCl3): δ = 7.30-7.26 (m,
2 H), 7.23-7.7.19 (m, 3 H), 3.87 (q, J = 7.1
Hz, 2 H), 3.81-3.73 (m, 1 H), 3.57-3.52 (m, 1
H), 1.93 (s, 3 H), 1.23 (d, J = 6.9
Hz, 3 H), 0.94 (t, J = 7.2
Hz, 3 H). ¹³C NMR (100 MHz, CDCl3): δ = 202.4,
168.6, 143.1, 128.7, 127.4, 126.9, 67.0, 61.5, 40.1, 29.9, 20.6,
14.1. ESI-MS: m/z = 257.1 [M + Na+].
Another
diastereomer: ¹H NMR (400 MHz, CDCl3): δ = 7.30-7.26
(m, 2 H), 7.23-7.7.19 (m, 3 H), 4.23 (q, J = 7.1
Hz, 2 H), 3.81-3.73 (m, 1 H), 3.57-3.52 (m, 1
H), 2.30 (s, 3 H), 1.30 (d, J = 6.9
Hz, 3 H), 1.29 (t, J = 7.2
Hz, 3 H). ¹³C NMR (100 MHz, CDCl3): δ = 202.4,
168.2, 143.3, 128.4, 127.5, 126.8, 67.6, 61.1, 39.8, 29.5, 20.4,
13.7. ESI-MS: m/z = 257.1 [M + Na+].
Compound 3o: ¹H NMR (400 MHz,
CDCl3): δ = 7.35-7.32 (m,
2 H), 7.28-7.25 (m, 3 H), 5.27 (s, 1 H), 5.22-5.18
(q, J = 6.4
Hz, 1 H), 2.47-2.43 (m, 2 H), 2.30-2.26 (m, 2
H), 1.98-1.90 (m, 2 H), 1.57 (d, J = 6.4
Hz, 3 H). ¹³C NMR (100 MHz, CDCl3): δ = 199.7,
176.5, 141.3, 128.8, 128.0, 125.3, 104.6, 76.6, 36.6, 29.3, 23.6,
21.1.
Compound 5a: ¹H
NMR (400 MHz, CDCl3): δ = 7.26-7.21 (m,
2 H), 7.17-7.12 (m, 3 H), 6.81 (s, 2 H), 4.63 (q, J = 7.3 Hz,
1 H), 2.25 (s, 3 H), 2.10 (s, 6 H), 1.64 (d, J = 7.3
Hz, 3 H). ¹³C NMR (100 MHz, CDCl3): δ = 145.5,
140.1, 136.6, 135.4, 130.0, 128.2, 126.9, 125.3, 37.9, 21.1, 20.8,
16.9.
Compound 5b: ¹H
NMR (400 MHz, CDCl3): δ = 7.28-7.21 (m,
4 H), 7.17-7.14 (m, 1 H), 5.83 (s, 1 H), 3.89 (q, J = 7.2 Hz,
1 H), 2.20 (s, 3 H), 2.14 (s, 3 H), 1.50 (d, J = 7.3
Hz, 3 H). ¹³C NMR (100 MHz, CDCl3): δ = 149.2,
146.6, 144.7, 128.4, 127.1, 125.9, 124.1, 106.0, 35.6, 22.1, 13.6,
11.7.
Compound 5c: ¹H
NMR (400 MHz, CDCl3): δ = 7.27-7.23 (m,
2 H), 7.19-7.12 (m, 3 H), 6.50 (s, 1 H), 4.08 (q, J = 7.2 Hz,
1 H), 2.35 (s, 3 H), 2.25 (s, 3 H), 1.54 (d, J = 7.2
Hz, 3 H). ¹³C NMR (100 MHz, CDCl3): δ = 146.3,
141.5, 135.1, 130.2, 128.4, 127.3, 125.9, 125.3, 38.3, 22.1, 15.4,
13.0. ESI-MS: m/z = 239.4 [M + Na+].