The Journal of Organic Chemistry
Note
confirmation of reaction completion by TLC analysis, the reaction
mixture was quenched by adding saturated aqueous NH4Cl (100 mL)
and then transferred to a separatory funnel. Extraction with Et2O,
washing of the organic layers with water and brine, drying over
Na2SO4, filtration, and evaporation of solvents gave the desired
alcohol, which was purified by flash chromatography using an
appropriate hexane/EtOAc gradient.
1010.6, 998.6, 949.7, 825.7, 806.7, 767.7, 748.5, 698.5 cm−1; HRMS
(ES-TOF) m/z calcd for C17H15BrO3Na [M + Na]+ 369.0102, found
369.0102.
Alcohol 26. White solid (0.315 g, 85% yield); mp 51.0−53.4 °C.
Data for the E isomer: 1H NMR (CDCl3, 400 MHz) δ 7.51 (d, J = 8.3
Hz, 2H), 7.24 (d, J = 8.3 Hz, 2H), 6.89 (dd, J = 15.6, 4.8 Hz, 1H), 6.05
(dd, J = 15.8, 2.0 Hz, 1H), 5.32 (br t, J = 4.6 Hz, 1H), 2.10 (d, J = 3.4
Hz, 1H), 1.48 (s, 9H); 13C NMR (CDCl3, 100 MHz) δ 165.5, 146.5,
140.0, 131.9, 128.2, 122.7, 122.2, 80.8, 72.9, 28.1; FT-IR (neat) 3440.8,
2982.8, 1683.7, 1652.8, 1588.9, 1482.8, 1454.8, 1393.8, 1365.7, 1340.7,
1315.8, 1299.8, 1257.7, 1234.7, 1149.5, 1092.7, 1066.7, 1045.7, 1007.6,
979.6, 822.5, 762.7 cm−1; HRMS (ES-TOF) m/z calcd for
C14H17BrO3Na [M + Na]+ 335.0259, found 335.0259.
General Procedure for Dess−Martin Periodinane Oxida-
tion.20 To a dry 100 mL flask with a stir bar were added the Dess−
Martin periodinane reagent (1.2 equiv) and dichloromethane (∼1 M).
To the mixture was added a solution of the allylic alcohol (1.0 equiv)
in minimal dichloromethane. The reaction mixture was allowed to stir
for 30 min and then monitored by TLC to confirm complete
transformation of the alcohol to the ketone. Following this, an equal
volume of ether was added, and the mixture was transferred to a
separatory funnel containing a saturated NaHCO3 solution. The
organic layer was washed with Na2S2O3 solution, saturated bicarbonate
solution, water, and then brine. Evaporation of the solvents gave the
desired ketoester in nearly quantitative yield, free of detectable side
products.
Alcohol 19.32 Colorless oil (2.1 g, 58% yield); H NMR (CDCl3,
1
400 MHz) δ 7.36−7.33 (m, 2H), 7.28−7.25 (m, 3H), 6.00−5.92 (m,
1H), 5.27 (td, J = 17.2, 1.4 Hz, 1H), 5.16 (td, J = 10.5, 1.3 Hz, 1H),
4.40−4.35 (br m, 1H), 2.93−2.88 (m, 1H), 2.84−2.79 (m, 1H); 13C
NMR (CDCl3, 100 MHz) δ 140.1, 137.7, 129.6, 128.5, 126.6, 115.0,
73.7, 43.8; FT-IR (neat) 3376.8, 3063.9, 3027.9, 2919.9, 1644.9,
1603.9, 1495.8, 1454.8, 1424.8, 1117.8, 1076.8, 1029.6, 990.6, 921.6,
854.8, 744.5, 697.3, 668.6 cm−1.
Alcohol 20.33 Brown oil (1.95 g, 68% yield); 1H NMR (CDCl3, 400
MHz) δ 7.42 (d, J = 8.4 Hz, 2H), 7.19 (d, J = 8.2 Hz, 2H), 5.98−5.90
(m, 1H), 5.29 (td, J = 17.1, 1.2 Hz, 1H), 5.16 (td, J = 10.3, 1.2 Hz,
1H), 5.10 (br, 1H), 2.04 (br s, 1H); 13C NMR (CDCl3, 100 MHz) δ
141.5, 139.8, 131.6, 128.0, 1221.6, 115.7, 74.7; FT-IR (neat) 3342.8,
2981.9, 2871.9, 1640.9, 1591.8, 1485.6, 1401.7, 1241.8, 1191.8, 1100.8,
1070.6, 1033.7, 1009.4, 986.5, 924.4, 815.5, 794.5, 719.6 cm−1.
General Procedure for Grubbs Metathesis. For other meta-
thesis reactions, the same procedure as used for the synthesis of
alcohol 18 was followed using the appropriate acrylate and olefin
reactants.
Ketoester 27.26 Pale-yellow oil (0.111 g, 94% yield); 1H NMR
(CDCl3, 400 MHz) δ 7.37−7.29 (m, 2H), 7.30 (obscured d, 1H), 7.21
(obscured d, 2H), 7.12 (d, J = 16.1 Hz, 1H), 6.74 (d, J = 16.1 Hz, 1H),
3.92 (s, 2H), 3.79 (s, 3H); 13C NMR (CDCl3, 100 MHz) δ 196.5,
165.8, 138.6, 132.8, 131.1, 129.5, 128.9, 127.4, 52.4, 48.8; FT-IR (neat)
2952.8, 1723.5, 1687.5, 1603.8, 1496.7, 1454.7, 1438.6, 1414.8, 1348.7,
1310.5, 1256.4, 1213.6, 1199.5, 1170.4, 1077.6, 1029.7, 1011.6, 981.4,
940.7, 915.6, 858.6, 739.5, 700.4 cm−1.
Alcohol 21.26 Pale-yellow oil (0.300 g, 87% yield); 1H NMR
(CDCl3, 400 MHz) δ 7.37−7.33 (m, 2H), 7.30−7.23 (m, 3H), 7.03
(dd, J = 15.7, 4.1 Hz, 1H), 6.09 (dd, J = 15.7, 1.8 Hz, 1H), 4.57−4.54
(br m, 1H), 3.76 (s, 1H), 2.99−2.95 (m, 1H), 2.84−2.78 (m, 1H); 13C
NMR (CDCl3, 100 MHz) δ 166.9, 149.1, 136.7, 129.5, 128.7, 127.0,
120.2, 71.7, 51.7, 43.2; FT-IR (neat) 3446.9, 3028.9, 2950.9, 1704.5,
1658.7, 1602.9, 1495.8, 1454.8, 1435.7, 1309.6, 1273.5, 1195.6, 1166.5,
1100.6, 1076.7, 1030.6, 983.6, 926.7, 855.7, 823.8, 746.6, 698.3 cm−1.
Alcohol 22. Pale-yellow oil (0.380 g, 80% yield). Data for the E
1
Ketoester 28. Yellow oil (0.256 g, 99% yield); H NMR (CDCl3,
1
isomer: H NMR (CDCl3, 400 MHz) δ 7.28−7.21 (m, 6H), 7.18−
400 MHz) δ 7.43−7.37 (m, 5H), 7.35−7.29 (m, 3H), 7.21−7.20 (br,
2H), 7.15 (d, J = 15.9 Hz, 1H), 6.68 (d, J = 15.9 Hz, 1H), 5.32 (s, 2H),
3.92 (s, 2H); 13C NMR (CDCl3, 100 MHz) δ 196.5, 165.2, 138.9,
135.2, 132.8, 131.2, 129.5, 128.9, 128.7, 128.5, 128.4, 127.4, 67.2, 48.7;
FT-IR (neat) 3031.9, 2961.9, 1722.5, 1696.5, 1636.8, 1496.8, 1454.7,
1376.8, 1274, 1212.6, 1165.4, 1073.7, 975.5, 732.5, 695.2 cm−1; HRMS
(ES-TOF) m/z calcd for C18H16O3Na [M + Na]+ 303.0997, found
303.0997.
7.11 (m, 4H), 6.95 (dd, J = 15.6, 4.5 Hz, 1H), 6.02 (dd, J = 15.6, 1.7
Hz, 1H), 5.09 (s, 2H), 4.46−4.40 (br m, 1H), 2.87−2.83 (m, 1H),
2.71−2.65 (m, 1H); 13C NMR (CDCl3, 100 MHz) δ 166.2, 149.5,
136.7, 135.9, 129.5, 128.7, 128.5, 128.2, 128.1, 127.0, 120.3, 71.8, 66.3,
43.2; FT-IR (neat) 3421.9, 3030.9, 2942.9, 1715.5, 1655.7, 1603.9,
1454.7, 1377.8, 1302.6, 1266.5, 1159.4, 1100.6, 1077.7, 1027.6, 982.6,
908.8, 855.8, 735.5, 695.2 cm−1; HRMS (ES-TOF) m/z calcd for
C18H18O3Na [M + Na]+ 305.1154, found 305.1154.
1
Ketoester 29. Yellow oil (0.152 g, 86% yield); H NMR (CDCl3,
Alcohol 23. Off-white solid (0.326 g, 78% yield); mp 65.0−71.9 °C;
1H NMR (CDCl3, 400 MHz) δ 7.37−7.33 (m, 2H), 7.29−7.24 (m,
3H), 6.92 (dd, J = 15.6, 4.7 Hz, 1H), 6.00 (dd, J = 15.6, 1.7 Hz, 1H),
4.54−4.49 (br m, 1H), 2.99−2.94 (m, 1H), 2.82−2.76 (m, 1H), 1.51
(s, 9H); 13C NMR (CDCl3, 100 MHz) δ 165.7, 147.6, 136.9, 129.5,
128.7, 126.9, 122.5, 80.5, 71.8, 43.3, 28.1; FT-IR (neat) 3486.8, 2977.8,
1693.5, 1656.6, 1602.8, 1493.9, 1454.8, 1391.8, 1367.7, 1326.7, 1297.6,
1252.7, 1213.7, 1151.6, 1111.6, 1071.8, 1011.7, 995.7, 981.7, 941.7,
863.7, 848.8, 746.7, 710.7, 698.4 cm−1; HRMS (ES-TOF) m/z calcd
for C15H20O3Na [M + Na]+ 271.1310, found 271.1310.
400 MHz) δ 7.36−7.33 (m, 2H), 7.30−7.28 (br d, 1H), 7.22−7.20 (br
d, 2H), 7.02 (d, J = 15.7 Hz, 1H), 6.67 (d, J = 15.5 Hz, 1H), 3.91 (s,
2H), 1.50 (s, 9H); 13C NMR (CDCl3, 100 MHz) δ 196.9, 164.6,
137.7, 133.6, 133.0, 129.5, 128.9, 127.3, 82.1, 48.5, 27.9; FT-IR (neat)
2979.8, 1695.5, 1636.8, 1496.8, 1476.8, 1455.8, 1393.8, 1368.6, 1305.5,
1257.6, 1148.2, 1071.7, 1031.8, 976.5, 841.7, 730.6, 697.4 cm−1;
HRMS (ES-TOF) m/z calcd for C15H19O3 [M + H]+ 247.1333, found
247.1334.
General Procedure for MnO2 Oxidation. Activated MnO2 (10
equiv, obtained from Sigma-Aldrich and heated at 100 °C overnight
before use) was added to a flask containing the alcohol (1 equiv) in
CH2Cl2 (∼1 M). The reaction mixture was allowed to stir for 12 h as
the conversion was monitored by TLC analysis. The mixture was
filtered through a pad of Celite and washed with Et2O. The solvents
were evaporated to give the pure product, typically in high yield and
free of detectable side products.
Alcohol 24.26 Brown oil (0.351 g, 91% yield); H NMR (CDCl3,
1
400 MHz) δ 7.50 (d, J = 8.5 Hz, 2H), 7.21 (d, J = 8.4 Hz, 2H), 7.00
(dd, J = 15.6, 4.9 Hz, 1H), 6.15 (dd, J = 15.6, 1.7 Hz, 1H), 5.30 (br d, J
= 4.88 Hz, 1H), 3.73 (s, 3H); 13C NMR (CDCl3, 100 MHz) δ 166.8,
148.3, 139.8, 131.9, 131.9, 128.2, 122.3, 120.1, 72.8, 51.8; FT-IR (neat)
3419.8, 2951.8, 1703.5, 1658.6, 1590.8, 1486.7, 1436.6, 1401.7, 1274.5,
1274.5, 1166.5, 1091.5, 1070.5, 1039.6, 1009.4, 980.5, 924.7, 879.8,
825.5, 761.7, 719.7 cm−1.
Ketoester 30.34 Amber solid (0.311 g, 83% yield); mp 70.3−74.6
°C; 1H NMR (CDCl3, 400 MHz) δ 7.62 (d, J = 15.4 Hz, 1H), 7.28 (d,
J = 8.8 Hz, 2H), 7.08 (d, J = 8.7 Hz, 2H), 6.91 (d, J = 15.4 Hz, 1H),
3.85 (s, 3H); 13C NMR (CDCl3, 100 MHz) δ 188.3, 165.8, 135.9,
135.3, 132.6, 132.3, 130.3, 129.3, 52.4; FT-IR (neat) 2952.8, 1721.6,
1666.6, 1626.7, 1581.6, 1485.8, 1438.7, 1396.7, 1324.7, 1301.5, 1220.7,
1194.7, 1170.5, 1067.5, 1007.7, 993.6, 943.6, 833.6, 821.6, 755.4, 661.7
cm−1.
Alcohol 25. Pale-yellow solid (0.350 g, 86% yield); mp 63.5−65.7
1
°C; H NMR (CDCl3, 400 MHz) δ 7.50 (d, J = 8.6 Hz, 2H), 7.38−
7.33 (m, 5H), 7.23 (d, J = 8.1 Hz, 2H), 7.04 (dd, J = 15.6, 5.0 Hz, 1H),
6.20 (dd, J = 15.6, 1.7 Hz, 1H), 5.35 (br t, J = 3.6 Hz, 1H), 5.19 (s,
2H), 2.10 (d, J = 4.0 Hz, 1H); 13C NMR (CDCl3, 100 MHz) δ 166.0,
148.3, 139.7, 135.7, 132.0, 128.5, 128.3, 128.2, 122.4, 120.4, 72.9, 66.4;
FT-IR (neat) 3461.8, 2987.8, 1685.6, 1646.7, 1589.8, 1482.1, 1454.8,
1395.7, 1382.7, 1326.7, 1280.6, 1218.7, 1181.6, 1106.7, 1088.6, 1069.6,
Ketoester 31. Yellow solid (0.250 g, 77% yield); mp 97.2−101.3
°C; 1H NMR (CDCl3, 400 MHz) δ 7.88 (d, J = 5.8 Hz, 1H), 7.86 (d, J
E
dx.doi.org/10.1021/jo4023606 | J. Org. Chem. XXXX, XXX, XXX−XXX