Dickson et al.
JOCNote
mmol). The mixture was allowed to swell for 5 min. In a separate
dropwise followed by a solution of 4-(phenylethynyl)phenol (6a)
(750 mg, 3.86 mmol) in THF (10 mL). After the mixture was
stirred at -78 °C for 10 min, the cold bath was removed and the
reaction allowed to warm to rt over 1 h, after which the reaction
was quenched with satd aqueous NH4Cl (20 mL) and parti-
tioned between EtOAc (50 mL) and H2O (50 mL), the layers
were separated, and the aqueous layer was extracted with
EtOAc (3 ꢀ 100 mL). The combined organic extracts were dried
(Na2SO4), filtered, and concentrated under reduced pressure.
The resulting solid was purified by flash chromatography (Et2O/
hexanes, 1:4) to provide 8a (581 mg, 77%) as a white solid: mp
54-56 °C; Rf 0.66 (Et2O/hexanes, 1:3); FT-IR (diamond-ATR,
uncorr) νmax 3238 (br), 3072, 3045, 3009, 1604, 1586, 1509, 1435,
1402, 1192, 1169, 1104 cm-1; 1H NMR (400 MHz, acetone-d6)
flask, Zn(OAc)2 2H2O (2.39 g, 10.9 mmol) was dissolved in
3
DMF (5 mL) followed by addition of 2,20-bipyridine (1.7 g,
10.9 mmol). The resulting solution of zinc(II) bipyridine com-
plex was mixed until it became cloudy white, at which point it
was transferred to the flask containing the resin and DMF.
DBU (1.2 mL, 10.9 mmol) was then added, after which the flask
was sealed with a septum, purged with N2, and then placed on an
orbital shaker and mixed (150 rpm) at 70 °C for 48 h. After being
cooled to rt, the resin was collected by vacuum filtration,
sequentially washed with 2 ꢀ 20 mL of DMF, H2O, THF, hexanes,
THF, and hexanes, and then dried under vacuum (1.0 mmHg) at rt
for 24 h to yield 4b (3.65 g) as a yellow solid: IR (KBr) νmax 3057,
3023, 2915, 2851, 1657, 1596, 1504, 1446, 1165, 754.
Resin-bound (3E)-4-(4-hydroxy-3-methoxyphenyl)but-3-en-2-
one (4a): IR (KBr) νmax 3057, 3023, 2916, 2851, 1655, 1597, 1495,
1448, 1252, 1167, 1022, 970, 818, 751, 692.
δH 8.56 (br s, 1 H), 7.28-7.14 (m, 5 H), 7.09 (d, J = 8.5 Hz, 2 H),
6.70 (d, J = 8.5 Hz, 2 H), 6.53 (d, J = 12 Hz, 1 H), 6.47 (d, J = 12
Hz, 1 H); 13C NMR (125 MHz, d6-acetone) δC 157.7, 138.7,
131.0 (2 C), 130.9, 129.6 (2 C), 129.3, 129.1 (2 C), 128.8, 127.8
115.9 (2 C); HRMS-EI calcd for C14H12O [M]þ 196.0888, found
196.0890.
Resin-Bound 4-(4-Hydroxyphenyl)butan-2-one (5b). A 50 mL
Erlenmeyer flask was charged with resin 4b (0.5 g, 1.05 mmol),
THF (8.0 mL), and triethylsilane (0.24 mL, 1.5 mmol), after
which it was sealed with a septum, purged with N2, and allowed
to swell for 5 min. Separately, solid t-BuOK (22.0 mg, 0.2 mmol)
was added to a solution of PPh3 (52.0 mg, 0.2 mmol) dissolved in
THF (2.0 mL) followed by addition of CuCl (20.0 mg,
0.2 mmol). The contents were mixed at rt for 10 min and then
transferred by cannula to the solution containing the resin. The
flask was then placed in an orbital shaker and mixed (100-
150 rpm) at rt for 16 h. The resin was collected by vacuum
filtration, sequentially washed with 2 ꢀ 10 mL of THF, H2O,
THF, and hexanes, and then dried under vacuum (1.0 mmHg) at
rt for 24 h to yield 5b (0.47 g) as a gray/green solid: IR (KBr) νmax
3057, 3025, 2921, 2851, 1715, 1645, 1600, 1508, 1450, 1422, 1371,
Resin-Bound 4-(Phenylethynyl)phenol (6b). A reactor vial was
sequentially charged with Merrifield resin (10) (2.00 g, 3.4
mmol), DMF (25 mL), 4-(phenylethynyl)phenol (6a) (1.27 g,
6.54 mmol), and K2CO3 (1.0 g, 7.2 mmol). The vial was purged
with N2, capped, and then placed on an orbital shaker (200 rpm)
at 70 °C for 48 h. After being cooled to rt, the resin was collected
by vacuum filtration, washed sequentially with 2 ꢀ 5 mL of
DMF, H2O, THF, H2O, THF, hexanes, CH2Cl2, and hexanes,
and then dried under vacuum (1.0 mmHg) for 24 h at rt to
provide 6b (2.6 g) as a white solid: Volhard titration (0.20 g resin)
0.37 mmol of active Cl/g resin remaining, 77% displaced; FT-IR
(diamond-ATR, uncorr) νmax 3081, 3056, 3026, 2918, 2851,
1594, 1509, 1493, 1451 cm-1; Raman νmax 3056, 3006, 2908,
1306, 1231, 1171 cm-1
.
Resin-bound 4-(4-hydroxy-3-methoxyphenyl)butan-2-one (5a):
IR (KBr) νmax 3058, 3025, 2920, 2849, 1720, 1601, 1491, 1448,
1265, 757, 699.
2856, 2216, 1596, 1450, 1182 cm-1
.
Resin-Bound cis-4-Styrylphenol (8b): Immobilization. Volhard
titration (0.20 g resin) 0.37 mmol of active Cl/g resin remaining,
77% displaced; FT-IR (diamond-ATR, uncorr) νmax 3081,
3056, 3022, 2918, 2848, 1602, 1583, 1509, 1493, 1451, 1263
cm-1; Raman νmax 3053, 3002, 2976, 2906, 2853, 1635, 1602,
Rheosmin (1b). A 50 mL Erlenmeyer flask was charged with
resin 5b (0.5 g, 1.0 mmol) and CH2Cl2 (8.0 mL) and the resin
allowed to swell for 5 min. The flask was sealed with a septum
and purged with N2, after which trifluoroacetic acid (2.0 mL)
was added. The flask was then placed in an orbital shaker and
mixed (150 rpm) for 24 h at rt. The resin was collected by gravity
filtration and washed with CH2Cl2 (2 ꢀ 10 mL). The combined
filtrates were treated with 10 mL of saturated aqueous NaHCO3
and mixed until gas evolution ceased. The organic and aqueous
phases were separated, and the aqueous layer was extracted with
CH2Cl2 (2 ꢀ 10 mL). The combined organic extracts were dried
(Na2SO4) and then concentrated under reduced pressure to
provide 1b as a yellow film (15 mg, 10% based on Volhard
titration of 3b): IR (film) νmax 3372, 3021, 2947, 2923, 2862,
1691, 1610, 1512, 1443, 1366, 1219 cm-1; 1H NMR (400 MHz,
CDCl3) δH 7.01 (d, J = 8.3 Hz, 2 H), 6.77 (d, J = 8.3 Hz, 2 H),
6.60 (br s, 1 H), 2.82 (t, J = 7.0 Hz, 2 H), 2.74 (d, J = 7.0 Hz, 2
H), 2.14 (s, 3 H); 13C NMR (100 MHz, CDCl3) δC 210.5, 154.6,
132.3, 129.4, 115.6, 45.6, 30.3, 29.0.
1583, 1449, 1323, 1265, 1194, 1182, 1155 cm-1
.
Resin-Bound cis-4-Styrylphenol (8b): Ti(II) Reduction. An
oven-dried reactor vial was charged with resin-bound
4-(phenylethynyl)phenol (6b) (0.45 g, 0.55 mmol 6a/g resin as
calculated by Volhard titration), capped with a self-healing seal,
and then placed under an atmosphere of N2. Distilled THF
(15 mL) was added by syringe followed by Ti(i-OPr)4 (1.42 mL,
4.80 mmol) after which the vial was cooled to -78 °C. With
stirring, n-BuLi (4.0 mL, 1.6 M, 6.4 mmol) was added dropwise.
The mixture was allowed to warm to rt and then placed in an
orbital shaker (200 rpm). After the mixture was stirred for 48 h
at rt, H2O (5 mL) was added and the mixture shaken for an
additional 1 h after which the resin was collected by vacuum
filtration, washed sequentially with 2 ꢀ 5 mL of DMF, H2O,
THF, H2O, THF, hexanes, CH2Cl2, and hexanes, and then dried
in an oven (70 °C) for 24 h to provide 8b (0.45 g) as an off-white
solid: Raman νmax 3053, 3002, 2976, 2910, 2854, 1635, 1601,
Zingerone (1a). Resin 5a (0.5 g, 1.0 mmol) was treated in a
similar manner as above to provide 1a as a yellow film (12 mg,
7.3%, based on Volhard titration of 3a): IR (film) νmax 3420,
1584, 1449, 1322, 1265, 1193, 1183, 1155 cm-1
.
3002, 2937, 2845, 1709, 1606, 1516, 1269, 1236, 1157, 1033 cm-1
;
Acknowledgment. We gratefully acknowledge the support of
the National Science Foundation (NSF-CHE-0418902) to the
Center for Authentic Science Practice in Education and the par-
ticipants from the advanced synthetic laboratory course at UIC.
1H NMR (400 MHz, CDCl3) δ 6.82 (d, J = 8.0 Hz, 2 H), 6.69 (d,
J = 2.0 Hz, 1 H), 6.69 (dd, J = 8.0, 1.9 Hz, 1 H), 5.70 (brs, 1 H),
3.86 (s, 3 H), 2.82 (t, J = 7.5 Hz, 2 H), 2.73 (t, J = 7.5 Hz, 2 H),
2.10 (s, 3 H); 13C NMR (125 MHz, CDCl3) δ 208.4, 146.6, 143.8,
133.0, 120.9, 114.5, 111.2, 56.0, 45.6, 30.2, 29.6.
cis-4-Styrylphenol (8a). A flame-dried round-bottom flask,
under an atmosphere of nitrogen, was charged with THF
(40 mL) and Ti(i-OPr)4 (2.3 mL, 7.72 mmol) and then cooled
to -78 °C. n-BuLi (6.2 mL, 2.5 M, 15.4 mmol) was added
Supporting Information Available: Experimental procedures
for 1a, 3a, 4a, 5a, 6a, 8b, and Volhard titrations. NMR data for 1a,
b, 6a, and 8a. Raman data for 8b, 6b, and 10. This material is
9538 J. Org. Chem. Vol. 74, No. 24, 2009