A Highly Efficient and Practical Synthesis of Chromene Derivatives Using Ring-Closing Olefin Metathesis

Full text of DOI:10.1021/jo9712198

864
J . Org. Chem. 1998, 63, 864-866
pounds; substituted salicylaldehydes or 2-hydroxy aryl
ketones (Scheme 1, method A).
A High ly Efficien t a n d P r a ctica l Syn th esis
of Ch r om en e Der iva tives Usin g
O-Allylation with allyl bromide was conveniently per-
formed in the presence of K2CO3 and acetone under reflux
conditions. Subsequent filtration of the reaction mixture
followed by removal of the solvent afforded the interme-
diates quantitatively. The R3 group was introduced using
a substituted allyl halide under the same aforementioned
reaction conditions. The O-allylated intermediates were
analytically pure and used in the next olefination reac-
tions without further purification. The Wittig reaction
of the corresponding carbonyl compounds with methyl-
triphenylphosphonium bromide provided the dienes 2a -
j.
Rin g-Closin g Olefin Meta th esis
Sukbok Chang and Robert H. Grubbs*
The Arnold and Mabel Beckman Laboratory of
Chemical, Synthesis, Division of Chemistry and
Chemical Engineering, California Institute of Technology,
Pasadena, California 91125
Received J uly 3, 1997
Chromenes (2H-1-benzopyran derivatives) have been
widely employed as important intermediates in the
synthesis of many natural products and medicinal agents.
There has been recent interest in the use of these
common structural elements for a new family of potas-
sium-channel activating drugs.1 They also serve as the
framework of a range of tannins,2 which are becoming
increasingly important because of their health-promoting
effects found in teas, vegetables, fruits, fruit juices, and
red wines. Despite the several existing methods for the
synthesis of chromene derivatives,3 there still is demand
for general strategies which can efficiently provide vari-
ously substituted chromene systems.
In contrast, dienes with substituents on the R2 position
(2k -l) were efficiently prepared by the Mitsunobu reac-
tion7 of 2-vinylphenol with secondary allyl alcohols
(Scheme 1, method B). Especially noteworthy is that a
chiral center in the R2 position could be introduced using
chiral secondary allyl alcohols, which can be readily
obtained by
a
Sharpless resolution.8 Nonracemic
chromene derivatives could be therefore prepared.
Ring-closing metathesis of the dienes prepared above
was next attempted using ruthenium carbene catalyst 1
[Cl2(PCy3)2RudCHPh].9 Table 1 summarizes the results.
With dienes containing only R1 substituents, cycliza-
tions were nearly quantitative using only 2 mol % of the
complex 1 (CH2Cl2, room temperature, 2 h). All func-
tional groups tested in the R1 position were tolerated
under these reaction conditions. In addition, the elec-
tronic properties of the substituents have little effect on
the efficiency of the ring closure, and chromenes having
substituents such as NO2, Et2N, Br, or MeO could be
prepared with the same efficiency. RCM of naphthyl
vinyl allyl ether diene 2j afforded 2H-naphtho[1,2-b]-
pyran in 89% yield (entry 10).
Cyclization of a diene having another substituent at
the R4 position (2f, entry 6) was equally quantitative
under the same reaction conditions. In contrast, reaction
of dienes with an R3 substituent was slow. For example,
only 45% conversion to the cyclized product was observed
for diene 2g after 24 h using 8 mol % of catalyst 1
(CH2Cl2, room temperature). The reaction rate was
greatly increased at higher temperatures in benzene,
however, and the cyclized product was obtained in
excellent yield to give 3g (6 mol % of 1, 60 °C, 2 h). This
strongly implies that the initial metathesis between
complex 1 and dienes 2a -l is on the O-allylic olefin
rather than the styrenyl double bond. It is noteworthy
that excellent yield of cyclization was observed for
compound 2i, where there is a second allyl ether in the
molecule. The R1 allyl ether undergoes nonproductive
In this note, we report a practical and highly efficient
procedure for preparing diverse chromene derivatives
using ring-closing metathesis (RCM),4 a methodology
emerging as a new tool in synthetic organic chemistry.5,6
Resu lts a n d Discu ssion
A series of 2-styrenyl allyl ethers (2a -j) was easily
prepared in high yields from the readily available com-
(1) (a) Ashwood, V. A.; Buckingham, R. E.; Cassidy, F.; Evans, J .
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Chem. 1996, 49, 1217-1219. (b) van Rensburg, H.; van Heerden, P.
S.; Bezuidenhoudt, B. C. B.; Ferreira, D. Tetrahedron Lett. 1997, 38,
3089-3092. (c) Covington, A. D. Chem. Soc. Rev. 1997, 111-126. (d)
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1997, 387, 561.
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5023-5024. (b) Billeret, D.; Blondeau, D.; Sliwa, H. Synthesis 1993,
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1997, 53, 5573-5580. (d) Dorta, R. L.; Mart´ın, A.; Sua´rez, E.; Betancor,
C. J . Org. Chem. 1997, 62, 2273-2274. (e) Ahrach, M.; Ge´rardin, P.;
Loubinoux, B. Synth. Commun., 1997, 27, 1877-1883.
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5427. (b) Grubbs, R. H.; Miller, S. J .; Fu, G. C. Acc. Chem. Res. 1995,
28, 446-552. (c) Dias, E. L.; Nguyen, S. T.; Grubbs, R. H. J . Am. Chem.
Soc. 1997, 119, 3887-3897.
(5) For most recent synthetic applications of RCM, see: (a) Crim-
mins, M. T.; King, B. W. J . Org. Chem. 1996, 61, 4192-4193. (b) Meng,
D.; Su, D.-S.; Balog, A.; Bertinato, P.; Sorenson, E. J .; Danishefsky, S.
J .; Zheng, Y.-H.; Chou, T.-C.; He, L.; Horwitz, S. J . Am. Chem. Soc.
1997, 119, 2733-2734. (c) Yang, Z.; He, Y.; Vourloumis, D.; Vallberg,
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(6) Recently it has been reported that Ru-carbene catayzed rear-
rangement of styrenyl ethers delivers 2-substituted chromene systems,
see: Harrity, J . P. A.; Visser, M. S.; Gleason, J . D.; Hoveyda, A. H. J .
Am. Chem. Soc. 1997, 119, 1488-1489.
(7) (a) Manhas, M. S.; Hoffman, W. H.; Lai, B.; Bose, A. K. J . Chem.
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S0022-3263(97)01219-X CCC: $15.00 © 1998 American Chemical Society
Published on Web 01/16/1998

Notes
J . Org. Chem., Vol. 63, No. 3, 1998 865
Ta ble 1. Rin g-Closin g Olefin Meta th esis (RCM) of Va r iou s Styr en yl Allyl Eth er Dien es
entry
dienes
cond.a
yield (%)b
1
2
3
4
5
6
7
8
9
2a (R1 ) H, R2 ) H, R3 ) H, R4 ) H)
A
A
A
A
A
A
B
A
A
A
C
C
95
99
99c
97
91
94
93
94
95
89
82
79
2b (R1 ) 6-Br, R2 ) H, R3 ) H, R4 ) H)
2c (R1 ) 7-Et2N, R2 ) H, R3 ) H, R4 ) H)
2d (R1 ) 6-NO2, R2 ) H, R3 ) H, R4 ) H)
2e (R1 ) 7-CH3O, R2 ) H, R3 ) H, R4 ) H)
2f (R1 ) 6-Cl, R2 ) H, R3 ) H, R4 ) CH3)
2g (R1 ) 7-CH3O, R2 ) H, R3 ) CH3, R4 ) H)
2h (R1 ) 8-CH3O, R2 ) H, R3 ) H, R4 ) H)
2i (R1 ) 7-OCH2CHdCH2, R2 ) H, R3 ) H, R4 ) H)
2j (R1 ) 7-(CH)4-8, R2 ) H, R3 ) H, R4 ) H)
2k (R1 ) H, R2 ) CH3, R3 ) H, R4 ) H)
2l (R1 ) H, R2 ) 4-(CH3O)C6H4, R3 ) H, R4 ) H)
10
11
12
a
Condition A: 1 (2 mol %), CH2Cl2 (0.2 M), rt (2 h); condition B: 1 (6 mol %), C6H6 (0.2 M), 60 °C (2 h); condition C: 1 (5 mol %),
CH2Cl2 (0.2 M), rt (10 h). Isolated yields after column chromatography on silica gel except entry 3. c NMR yield due to unstability of the
b
product on silica gel.
evaporated under reduced pressure to give quantitatively O-
allylated benzaldehyde intermediate. In a separate flask con-
taining NaH (prewashed with hexane three times, 360 mg, 15.0
mmol) and THF (30 mL) was added methyltriphenylphospho-
nium bromide (4.6 g, 12.9 mmol) at 0 °C, and it was stirred for
30 min at rt. To the above solution was added a solution of the
O-allylated benzaldehyde prepared above in THF (10 mL), and
the reaction mixture was stirred for 2 h at room temperature.
The crude mixture was extracted with EtOAc (100 mL × 2),
washed with brine (100 mL), and then dried over MgSO4. Silica
gel column chromatography (EtOAc/hexanes ) 1:20) afforded
the diene 2a (1.33 g, 83%)10 as a colorless liquid.
Sch em e 1. P r ep a r a tion of Styr en yl Allyl Eth er
Dien es
2b (92%, R1 ) 6-Br, R2 ) R3 ) R4 ) H) was prepared by the
same procedure from 5-bromosalicylaldehyde: 1H NMR (300
MHz, CD2Cl2) δ 7.61 (d, J ) 2.4 Hz, 1H), 7.31 (dd, J ) 9.0, 2.4
Hz, 1H), 7.02 (dd, J ) 17.7, 11.1 Hz, 1H), 6.75 (d, J ) 8.7 Hz,
1H), 6.07 (m, 1H), 5.75 (dd, J ) 17.7, 0.9 Hz, 1H), 5.43 (dd, J )
17.1, 1.8 Hz, 1H), 5.30 (dd, J ) 11.1, 4.2 Hz, 2H), 4.54 (d, J )
5.1 Hz, 2H); 13C NMR (75 MHz, CD2Cl2) δ 153.5, 145.2, 132.7,
130.9, 130.2, 128.8, 117.0, 115.2, 113.9, 112.9, 69.1; IR (film)
2866, 1624, 1476, 1409, 1241, 1122, 1016, 916 cm-1; HRMS (EI)
calcd for C11H11BrO [M]+ 237.9993, found 237.9991.
metathesis on the time scale of the RCM reaction. Dienes
having R2 substituents such as 2k ,l were also readily
cyclized (entries 11 and 12) under longer reaction times
(5 mol % of 1, CH2Cl2, room temperature, 10 h).
The efficiency of catalytic ring-closing metathesis
combined with ease of preparation of the dienes makes
this strategy an attractive alternative for the formation
of variously substituted chromene systems.
2c (77%, R1 ) 7-Et2N, R2 ) R3 ) R4 ) H) was prepared by
the same procedure from 4-(diethylamino)salicylaldehyde: 1H
NMR (300 MHz, CD2Cl2) δ 7.32 (d, J ) 8.7 Hz, 1H), 6.94 (dd, J
) 17.7, 11.1 Hz, 1H), 6.27 (dd, J ) 8.7, 2.4 Hz, 1H), 6.15 (s, 1H),
6.08 (m, 1H), 5.51 (dd, J ) 17.7, 1.8 Hz, 1H), 5.45 (dd, J ) 17.4,
1.8 Hz, 1H), 5.30 (m, 1H), 4.96 (dd, J ) 11.1, 1.8 Hz, 1H), 4.56
(d, J ) 3.6 Hz, 2H), 3.36 (q, J ) 7.2 Hz, 4H), 1.16 (t, J ) 7.2 Hz,
6H); 13C NMR (75 MHz, CD2Cl2) δ 157.1, 148.8, 134.0, 131.4,
127.1, 116.8, 114.3, 108.7, 104.6, 102.6, 96.2, 69.2, 12.5; IR (film)
Exp er im en ta l Section
2964, 1607, 1559, 1506, 1370, 1269, 1215, 1119, 916 cm-1
.
2d (81%, R1 ) 6-NO2, R2 ) R3 ) R4 ) H) was prepared by the
NMR spectra were recorded on a General Electric QE-300
spectrometer. Chemical shifts are reported in ppm downfield
from TMS with reference to internal solvent. High-resolution
mass spectra were provided by the Southern California Mass
Spectrometry Facility (University of California, Riverside).
Analytical thin-layer chromatography (TLC) was performed
using silica gel 60 F254 precoated plates (0.25 mm thickness)
with a fluorescent indicator. Flash column chromatography was
performed using silica gel 60 (230-400 mesh) from EM Science.
1
same procedure from 2-hydroxy-5-nitrobenzaldehyde: H NMR
(300 MHz, CD2Cl2) δ 8.36 (d, J ) 3.0 Hz, 1H), 8.10 (dd, J ) 9.9,
3.0 Hz, 1H), 7.05 (dd, J ) 17.7, 11.1 Hz, 1H), 6.95 (d, J ) 9.0
Hz, 1H), 6.10 (m, 1H), 5.90 (d, J ) 18.0, 1H), 5.43 (d, J ) 11.1,
1H), 5.38 (m, 2H), 4.69 (d, J ) 5.4 Hz, 2H); 13C NMR (75 MHz,
CD2Cl2) δ 160.4, 141.5, 132.2, 129.8, 127.6, 124.6, 122.0, 118.2,
117.1, 111.7, 69.7; IR (film) 3080, 2925, 1583, 1515, 1336, 1264,
1085, 993, 916 cm-1; HRMS (CI) calcd for C11H15N2O3 [M +
NH4]+ 223.1082, found 223.1088.
2e (91%, R1 ) 7-CH3O, R2 ) R3 ) R4 ) H) was prepared by
the same procedure from 2-hydroxy-5-methoxybenzaldehyde: 1H
NMR (300 MHz, CD2Cl2) δ 7.43 (d, J ) 8.4 Hz, 1H), 7.01 (dd, J
) 17.7, 11.1 Hz, 1H), 6.51 (dd, J ) 8.4, 2.1 Hz, 1H), 6.46 (d, J )
Alkylidenes
1 was prepared according to the published
procedures.9b
Gen er a l P r oced u r e for P r ep a r a tion of Dien es (Meth od
A). To a solution of salicylaldehyde (1.2 g, 10.0 mmol) and allyl
bromide (2.4 g, 19.8 mmol) in acetone (30 mL) was added
potassium carbonate (2.7 g, 19.5 mmol), and the reaction mixture
was stirred at 60 °C for 2 h. After cooling to room temperature,
it was filtered and washed with acetone (50 mL × 2) and then
(10) Okamoto, T.; Kobayashi, K.; Oka, S.; Tanimoto, S. J . Org. Chem.
1988, 53, 4897-4901.

866 J . Org. Chem., Vol. 63, No. 3, 1998
Notes
2.4 Hz, 1H), 6.10 (m, 1H), 5.65 (d, J ) 18.6 Hz, 1H), 5.46 (dd, J
) 17.1, 1.8 Hz, 1H), 5.33 (dt, J ) 10.8, 1.5 Hz, 1H), 5.16 (dd, J
) 12.0, 1.5 Hz, 1H), 4.55 (dd, J ) 4.8, 0.9 Hz, 1H), 3.81 (s, 3H);
13C NMR (75 MHz, CD2Cl2) δ 160.6, 156.8, 133.4, 131.2, 127.1,
119.8, 117.1, 111.8, 105.1, 99.4, 69.1, 55.3; IR (film) 3080, 2935,
matography on silica gel (EtOAc/hexanes ) 1:15) to afford 2k
(357 mg, 82%) as a colorless liquid: 1H NMR (300 MHz, CD2-
Cl2) δ 7.51 (dd, J ) 7.5, 1.5 Hz, 1H), 7.20 (td, J ) 7.8, 1.5 Hz,
1H), 7.12 (dd, J ) 17.1, 11.1 Hz, 1H), 6.93 (t, J ) 8.7 Hz, 1H),
6.91 (d, J ) 6.6 Hz, 1H), 5.97 (m, 1H), 5.76 (dd, J ) 18.0, 1.2
Hz, 1H), 5.29 (dt, J ) 7.5, 0.9 Hz, 1H), 5.26 (t, J ) 1.5 Hz, 1H),
5.18 (dt, J ) 10.5, 0.9 Hz, 1H), 4.85 (qd, J ) 6.3, 6.2 Hz, 1H),
1.47 (d, J ) 6.3 Hz, 3H); 13C NMR (75 MHz, CD2Cl2) δ 154.9,
139.1, 131.6, 128.3, 126.1, 120.5, 116.4, 115.0, 114.3, 113.5, 75.1,
20.8; IR (film) 3074, 2973, 1623, 1592, 1481, 1451, 1410, 1289,
1607, 1501, 1414, 1264, 1196, 1167, 1114, 1027, 925, 901 cm-1
;
HRMS (CI) calcd for
191.1073.
C
12H15O2 [M + H]+ 191.1072, found
2f (94%, R1 ) 8-CH3O, R2 ) R3 ) R4 ) H) was prepared by
1
the same procedure from o-vanilline: H NMR (300 MHz, CD2-
1234, 1102, 996, 915, 747 cm-1; HRMS (CI) calcd for C12H15
O
Cl2) δ 7.13 (d, J ) 7.8 Hz, 1H), 7.04 (dd, J ) 16.5, 8.1 Hz, 1H),
6.84 (d, J ) 8.1, 1H), 6.11 (m, 1H), 5.78 (d, J ) 17.7, 1H), 5.36
(dd, J ) 17.1, 1.5 Hz, 1H), 5.24 (m, 2H), 4.46 (d, J ) 5.7 Hz,
2H), 3.84 (s, 3H); 13C NMR (75 MHz, CD2Cl2) δ 152.7, 144.9,
134.1, 130.9, 123.5, 116.9, 116.5, 114.3, 111.1, 102.6, 73.5, 55.2;
[M + H]+ 175.1123, found 175.1119.
2l (69%, R1 ) H, R2 ) 4-(CH3O)C6H4, R3 ) R4 ) H) was
prepared by the same procedure from 2-vinylphenol and
1-(4-methoxyphenyl)-2-propen-1-ol: 1H NMR (300 MHz, CD2-
Cl2) δ 7.54 (dd, J ) 7.5, 1.8 Hz, 1H), 7.38 (d, J ) 6.6 Hz, 2H),
7.21 (dd, J ) 12.0, 6.6 Hz, 1H), 7.17 (dd, J ) 9.0, 1.8 Hz, 1H),
6.95 (m, 4H), 6.16 (m, 1H), 5.83 (dt, J ) 16.5, 1.2 Hz, 1H), 5.70
(d, J ) 6.0 Hz, 1H), 5.39 (dt, J ) 17.1, 5.4 Hz, 1H), 5.30 (m,
3H), 3.82 (s, 3H); 13C NMR (75 MHz, CD2Cl2) δ 159.4, 154.3,
138.3, 131.8, 128.6, 127.8, 126.4, 121.0, 115.9, 114.0, 107.4, 102.6,
80.8, 55.3; HRMS (CI) calcd for C18H19O2 [M + H]+ 267.1385,
found 267.1383.
IR (film) 3080, 2935, 1573, 1472, 1264, 1066, 988, 916 cm-1
;
HRMS (CI) calcd for C12H15O2 [M + H]+ 191.1072, found
191.1081.
2 g (84%, R1 ) 6-Cl, R2 ) R3 ) H, R4 ) CH3) was prepared by
the same procedure from 5′-chloro-2′-hydroxyacetophenone: 1H
NMR (300 MHz, CD2Cl2) δ 7.20 (m, 2H), 6.80 (d, J ) 9.0 Hz,
1H), 6.06 (m, 1H), 5.40 (dt, J ) 17.4, 1.8 Hz, 1H), 5.29 (dd, J )
10.8, 1.5 Hz, 1H), 5.18 (t, J ) 1.8 Hz, 1H), 5.10 (d, J ) 5.1 Hz,
1H), 2.13 (s, 3H); 13C NMR (75 MHz, CD2Cl2) δ 143.3, 131.1,
129.2, 127.7, 125.3, 117.3, 115.8, 113.5, 109.8, 102.6, 69.3, 22.8;
IR (film) 3080, 2916, 1631, 1588, 1486, 1230, 1109, 1017, 930,
896 cm-1; HRMS (CI) calcd for C12H14ClO [M + H]+ 209.0733,
found 209.0739.
Gen er al P r ocedu r e of Rin g-Closin g Metath esis of Dien es
2a -2l. To a solution of diene 2a (160 mg, 1.0 mmol) in CH2Cl2
(5 mL) was added Ru-benzylidene complex 1 (16.5 mg, 0.02
mmol, 2 mol %), and the reaction mixture was stirred at room
temperature for 2 h. After removal of the solvent, the residue
was purified by silica gel column chromatography (EtOAc/
hexanes ) 1:25) to give the cyclized product 2H-1-benzopyran
3a (126 mg, 95% yield) as a colorless liquid.
2h (85%, R1 ) 7-CH3O, R2 ) H, R3 ) CH3, R4 ) H) was
prepared by the same procedure from 2-hydroxy-5-methoxyben-
zaldehyde and 3-chloro-2-methylpropene: 1H NMR (300 MHz,
CD2Cl2) δ 7.44 (d, J ) 8.4 Hz, 1H), 7.02 (dd, J ) 17.7, 11.1 Hz,
1H), 6.50 (dd, J ) 8.7, 2.4 Hz, 1H), 6.46 (t, J ) 2.4 Hz, 1H), 5.67
(dd, J ) 17.7, 1.5 Hz, 1H), 5.16 (dd, J ) 11.1, 1.8 Hz, 1H), 5.15
(s, 1H), 5.03 (s, 1H), 4.47 (s, 1H), 3.80 (s, 3H), 1.87 (s, 3H); 13C
NMR (75 MHz, CD2Cl2) δ 147.8, 129.8, 118.1, 116.0, 108.7, 108.4,
105.1, 102.2, 88.5, 80.2, 62.2, 19.3; IR (film) 2925, 1607, 1501,
1443, 1259, 1196, 1119, 1046, 901, 824 cm-1; HRMS (EI) calcd
for C13H16O2 [M]+ 204.1150, found 204.1152.
2i (90%, R1 ) 7-OCH2CHdCH2, R2 ) R3 ) R4 ) H) was
prepared by the same procedure from 2,5-dihydroxybenzalde-
hyde using 4 equiv of allyl bromide and potassium carbonate:
1H NMR (300 MHz, CD2Cl2) δ 7.43 (d, J ) 8.1 Hz, 1H), 7.05 (dd,
J ) 18.0, 11.4 Hz, 1H), 6.50 (dd, J ) 11.7, 2.4 Hz, 1H), 6.51 (d,
J ) 2.4 Hz, 1H), 6.09 (m, 2H), 5.68 (dd, J ) 17.7, 1.5 Hz, 1H),
5.50 (m, 1H), 5.43 (m, 1H), 5.35 (m, 1H), 5.31 (m, 1H), 5.20 (dd,
J ) 11.1, 1.5 Hz, 1H), 4.55 (m, 4H); 13C NMR (75 MHz, CD2Cl2)
δ 159.2, 156.6, 132.9, 131.0, 126.9, 120.1, 117.5, 117.1, 112.0,
105.8, 100.2, 68.9, 68.7; IR (film) 3070, 2858, 1607, 1501, 1419,
1259, 1182, 993, 925 cm-1; HRMS (CI) calcd for C14H17O2 [M +
H]+ 217.1229, found 217.1225.
2j (83%, R1 ) 7-(CH)4-8, R2 ) R3 ) R4 ) H) was prepared
from 2-hydroxy-1-naphthylaldehyde: 1H NMR (300 MHz, CD2-
Cl2) δ 8.19 (dd, J ) 7.8, 0.9 Hz, 1H), 7.87 (dd, J ) 7.2, 1.8 Hz,
1H), 7.69 (dd, J ) 26.4, 8.7 Hz, 2H), 7.54 (m, 2H), 7.32 (dd, J )
18.0, 11.1 Hz, 1H), 6.29 (m, 1H), 5.95 (d, J ) 17.7, 1H), 5.60 (dt,
J ) 17.1, 1.5 Hz, 1H), 5.47 (d, J ) 11.4 Hz, 1H), 5.38 (dt, J )
10.5, 1.2 Hz, 1H), 4.57 (dt, J ) 5.4, 1.5 Hz, 2H); 13C NMR (75
MHz, CD2Cl2) δ 152.2, 134.7, 134.0, 131.3, 128.6, 127.9, 126.4,
124.3, 123.2, 117.3, 114.9, 109.8, 102.6, 75.8; IR (film) 3051, 2858,
1626, 1564, 419, 1380, 1240, 1182, 1080. 983, 916 cm-1; HRMS
(CI) calcd for C15H15O [M + H]+ 211.1123, found 211.1111.
Gen er a l P r oced u r e for P r ep a r a tion of Dien es (Meth od
B). To a solution of 2-vinylphenol11 (300 mg, 2.5 mmol),
triphenylphosphine (787 mg, 3.0 mmol), and 3-buten-2-ol (216
mg, 3.0 mmol) in THF (15 mL) was added dropwise a solution
of diethyl azodicarboxylate (523 mg, 3.0 mmol) in THF (5 mL)
at 0 °C. After stirring for 5 h at room temperature, the reaction
mixture was extracted with EtOAc (50 mL × 2), washed with
brine solution (100 mL), and dried over MgSO4. After removal
of the solvent, the residue was purified by flash column chro-
3c (R1 ) 7-Et2N, R2 ) R3 ) R4 ) H) was prepared by the
same procedure from the diene 2c: 1H NMR (300 MHz, CDCl3)
δ 6.87 (d, J ) 8.4 Hz, 1H), 6.40 (d, J ) 9.6 Hz, 1H), 6.24 (dd, J
) 8.4, 2.4 Hz, 1H), 6.19 (s, 1H), 5.54 (dt, J ) 9.6, 3.6 Hz, 1H),
4.80 (dd, J ) 3.3, 1.5 Hz, 2H), 3.36 (q, J ) 7.2 Hz, 4H), 1.19 (t,
J ) 7.2 Hz, 6H); 13C NMR (75 MHz, CDCl3) δ 156.6, 148.9, 127.5,
124.7, 116.3, 104.6, 102.6, 98.8, 65.8, 44.6, 12.8; IR (film) 2965,
2872, 1617, 1561, 1463, 1350, 1267, 1206, 1123, 825, 788 cm-1
;
HRMS (CI) calcd for C13H18NO [M + H]+ 204.1388, found
204.1395.
3g (R1 ) 7-CH3O, R2 ) H, R3 ) CH3, R4 ) H): 1H NMR (300
MHz, CDCl3) δ 6.85 (d, J ) 7.8 Hz, 1H), 6.41 (m, 1H), 6.40 (dd,
J ) 9.0, 2.7 Hz, 1H), 6.13 (d, J ) 1.2 Hz, 1H), 4.68 (s, 2H), 3.78
(s, 3H), 1.79 (d, J ) 1.5 Hz, 3H); 13C NMR (75 MHz, CDCl3) δ
159.9, 153.8, 128.0, 126.3, 118.9, 116.2, 106.7, 101.5, 69.3, 55.4,
18.9; IR (film) 2923, 2830, 1617, 1576, 1504, 1442, 1272, 1190,
1159, 1030, 845 cm-1; HRMS (EI) calcd for C11H12O2 [M]+
176.0837, found 176.0839.
3i (R1 ) 7-OCH2CHdCH2, R2 ) R3 ) R4 ) H): 1H NMR (300
MHz, CDCl3) δ 6.89 (d, J ) 8.1 Hz, 1H), 6.46 (dd, J ) 8.1, 2.4
Hz, 1H), 6.41 (s, 1H), 6.39 (d, J ) 8.1 Hz, 1H), 6.07 (m, 1H),
5.64 (dd, J ) 9.9, 3.3 Hz, 1H), 5.50 (dd, J ) 17.4, 1.8 Hz, 1H),
5.31 (dd, J ) 5.4, 1.5 Hz, 1H), 4.81 (dd, J ) 3.3, 1.5 Hz, 1H),
4.52 (dt, J ) 5.4, 1.5 Hz, 2H); 13C NMR (75 MHz, CDCl3) δ 161.6,
155.3, 133.2, 127.3, 124.3, 119.1, 117.8, 107.7, 102.6, 68.9, 65.7;
IR (film) 2923, 2851, 1612, 1499, 1458, 1308, 1267, 1144, 1020,
932, 835 cm-1; HRMS (EI) calcd for C12H12O2 [M]+ 188.0837,
found 188.0837.
Ack n ow led gm en t. This research was supported by
National Institute of Health.
Registr y No. (registry numbers are provided by the authors).
2a ; 19244-42-9, 3a ; 254-04-6; 3b; 18385-87-0, 3d ; 16336-26-8,
3e; 18385-89-2, 3f; 183907-31-0, 3h ; 16336-25-7, 3j; 230-62-6,
3k ; 2513-24-8, 3l; 41786-36-1.
Su p p or tin g In for m a tion Ava ila ble: Photocopies of 1H
NMR spectra of compounds 2a -l, 3c, 3g, and 3i (15 pages).
This material is contained in libraries on microfiche, im-
mediately follows this article in the microfilm version of the
journal, and can be ordered from the ACS; see any current
masthead page for ordering information.
(11) 2-Vinylphenol was prepared from coumaric acid: (a) Corson,
B. B.; Heintzelman, W. J .; Schwartzman, L. H.; Tiefenthal, H. E.;
Lokken, R. J .; Nickels, J . E.; Atwood, G. R.; Pavlik, F. J . J . Org. Chem.
1958, 23, 544-549. (b) Tsaur, S.-L.; Fitch, R. M. J . Colloid Interface
Sci. 1987, 115, 450-462.
J O9712198