4676
D.E. White et al. / Tetrahedron 66 (2010) 4668e4686
bath, becoming very viscous at this time. The enol carbonate
solution was then transferred via syringe to the catalyst solution at
11 ꢁC, washing the original flask with deoxygenated anhydrous
benzene (6.5 mL, allowed to cool briefly before transferring). The
reaction, which turned green, was then stirred at 11 ꢁC for 24 h.
Solvent was removed under reduced pressure. The residue was
suspended in Et2O and filtered through filter paper to remove
precipitated Pd. The filtrate was then concentrated under reduced
pressure. The residue was suspended in 5% Et2O/petroleum ether
(some solid precipitates) and applied to a silica gel column
(12ꢅ5 cm). Flash chromatography (5% Et2O/petroleum ether
12.3 mmol) was added dropwise over 10 min via syringe. An exo-
therm was observed, and the liquid phase turned yellow. After
stirring for 35 min at ꢂ78 ꢁC, chloroalkene (þ)-12 (1.286 g,
4.14 mmol) in anhydrous THF (5 mL) was added dropwise over
3 min via syringe, washing the original flask with THF (2ꢅ4 mL).
The reaction was stirred for 30 min at ꢂ78 ꢁC and then placed in an
ice bath. After stirring an additional 68 min at 0 ꢁC, 10 wt % HCl (aq)
(52 mL) was added, during which time a significant exotherm was
observed. The mixture was then allowed to warm to 23 ꢁC as it was
stirred for 66 min. The reaction mixture was extracted with Et2O
(3ꢅ150 mL), and the combined organic layers were washed with
brine (2ꢅ250 mL) and dried over MgSO4. Solvent was removed
under reduced pressure. Flash chromatography over silica gel
(10ꢅ4 cm, 15% Et2O/pentane eluent until product begins to elute,
then 30% Et2O/pentane eluent) then provided (þ)-laurencenone B
((þ)-7) (929 mg, 89%) as a white powder. Discrepancies existed
between the published 1H NMR data reported in the original iso-
lation paper2g and that of the synthetic material. IR data matched
that reported for the natural product. No 13C NMR or optical rota-
tion data were reported. 1H NMR, 13C NMR, and IR data matched
that reported for semisynthetic material obtained from the degra-
dation of elatol.10 The optical rotation matched in sign, but not in
eluent) then provided
a
,u
-diene (ꢂ)-13 (1.488 g, 82%) as a highly
viscous, slightly yellow oil. Observed 87% ee as determined by chiral
HPLC analysis (ChiralpakÒ AD,1% EtOH/hexanes,1 mL/min, 254 nm,
tR (minor)¼6.1 min; tR (major)¼6.7 min). Rf 0.06 (5% Et2O/petro-
24
leum ether eluent); [
(500 MHz, CDCl3)
a
]
D
ꢂ10.55 (c 0.995, CHCl3); 1H NMR
d 5.30 (br s, 1H), 5.28 (s, 1H), 5.23 (s, 1H),
4.67e4.71 (m, 1H), 4.64e4.68 (m, 1H), 3.59 (dd, J¼9.5, 6.6 Hz, 1H),
3.54 (dd, J¼9.3, 6.8 Hz, 1H), 2.94e3.18 (br m, 1H), 2.46e2.83 (br m,
1H), 2.57 (br d, J¼15.6 Hz, 1H), 2.12e2.38 (br m, 1H), 2.12e2.26 (m,
1H), 1.88e2.12 (br m, 1H), 2.01 (app. septet, J¼6.7 Hz, 1H), 1.71 (s,
3H), 1.50e1.82 (br m, 2H), 1.21 (br s, 3H), 1.11 (s, 3H), 0.97 (d,
J¼6.8 Hz, 6H); 13C NMR (126 MHz, CDCl3)
d
202.6, 172.9, 146.2, 141.7
magnitude. These comparisons are outlined in the Supplementary
24
(br), 116.7, 109.5, 100.2 (br), 74.5, 54.6, 43.1, 38.9, 37.4 (br), 32.9,
data. Rf 0.26 (30% Et2O/petroleum ether eluent); [
a
]
þ47.08 (c
D
28.3, 27.7, 24.8, 24.6, 22.8, 19.0; IR (neat film, NaCl)
n
3073, 2963,
0.36, CHCl3); 1H NMR (500 MHz, CDCl3)
d 5.89 (s, 1H), 2.50e2.69 (br
2939, 2877, 1651, 1622, 1471, 1449, 1431, 1406, 1383, 1367, 1298,
1222,1206,1172,1157,1134,1069,1009, 967, 956, 884, 845, 767, 752,
692, 656, 624 cmꢂ1; HRMS (EIþ) m/z calcd for C20H31ClO2 [M]þ:
338.2013, found 338.2009.
m, 2H), 2.26 (br d, J¼18.3 Hz, 1H), 2.13e2.23 (br m, 1H), 1.99e2.14
(br m, 2H), 1.98 (d, J¼0.98 Hz, 3H), 1.93 (ddd, J¼12.3, 12.3, 5.4, Hz,
1H), 1.81 (br s, 3H), 1.72e1.80 (m, 1H), 1.06 (s, 3H), 0.97(s, 3H); 1H
NMR (500 MHz, acetone-d6)
d 5.80 (s, 1H), 2.52e2.69 (br m, 2H),
2.31 (dd, J¼18.1, 0.98 Hz, 1H), 2.19e2.27 (br m,1H), 2.02e2.16 (br m,
1H), 1.88e2.02 (m, 2H), 1.98 (d, J¼1.2 Hz, 3H), 1.76e1.88 (br m, 1H),
1.80 (br s, 3H), 1.09 (s, 3H), 0.96 (s, 3H); 13C NMR (126 MHz, CDCl3)
4.2.6. Chloroalkene (þ)-12. To a flame-dried 100 mL round-bot-
tomed flask equipped with a magnetic stir bar was added catalyst
49 (124.9 mg, 0.219 mmol). After attaching an oven-dried
condenser and sealing with a septum, the flask was placed under
high vacuum and refilled with Ar. Anhydrous benzene (26 mL,
deoxygenated prior to use by sparging with N2 in a flame-dried
flask for ꢃ1 h) was added via syringe. To the resulting solution was
d
198.2,168.6,129.6,127.5,126.2 (br), 48.8, 46.3, 40.4, 36.3, 30.4 (br),
30.1, 24.8, 23.9 (two overlapping CH3 peaks as determined by
gHSQC and DEPT NMR spectroscopy; second peak appears as an
upfield shoulder), 19.7; IR (neat film, NaCl)
n 3025, 2963, 2933,
2855,1667,1612,1462,1439,1417,1392,1375,1350,1331,1319,1306,
1282, 1257, 1207, 1192, 1171, 1150, 1137, 1125, 1106, 1070, 1048, 1023,
1010, 988, 972, 954, 930, 913, 869, 834, 818, 684 cmꢂ1; HRMS (EIþ)
m/z calcd for C15H21ClO [M]þ: 252.1281, found 252.1270.
added
a
,u
-diene (ꢂ)-13 (1.483 g, 4.38 mmol) in deoxygenated an-
hydrous benzene (6 mL) via syringe, washing the original flask with
deoxygenated anhydrous benzene (2ꢅ6 mL). The reaction was
placed in a 60 ꢁC oil bath and stirred for 18 h. After cooling to 23 ꢁC,
solvent was removed under reduced pressure. Flash chromatogra-
phy over silica gel (12ꢅ5 cm, 20% Et2O/petroleum ether eluent until
product begins to elute, then 30% Et2O/petroleum ether eluent)
4.3. Procedures for the synthesis of the proposed structure
of (L)-laurencenone B ((L)-7)
then provided chloroalkene (þ)-12 (1.313 g, 97%) as an off-white
4.3.1.
the preparation of
0.783 mmol) was converted to
a
,
u
-Diene (þ)-13. Following a similar procedure to that for
24
waxy powder. Rf 0.38 (20% Et2O/petroleum ether eluent); [
a
]
a,u
-diene (ꢂ)-13, enol carbonate 26 (299.9 mg,
D
þ99.27 (c 1.005, CHCl3); 1H NMR (500 MHz, CDCl3)
d
5.19e5.23 (m,
a
,u
-diene (þ)-13 (240.2 mg, 90%)
1H), 3.59 (dd, J¼9.3, 6.3 Hz, 1H), 3.52 (dd, J¼9.5, 6.6 Hz, 1H),
2.50e2.70 (br m, 1H), 2.47 (br d, J¼17.1 Hz, 1H), 2.19e2.33 (br m,
1H), 1.61e2.14 (br m, 5H), 2.01 (app. septet, J¼6.7 Hz, 1H), 1.76 (br s,
3H), 1.06 (s, 3H), 0.97 (d, J¼6.8 Hz, 6H), 0.95 (s, 3H); 13C NMR
using phosphinooxazoline ligand (ꢂ)-41 (52.3 mg, 0.0884 mmol),
bis(3,5,30,50-dimethoxydibenzylideneacetone)palladium(0)
(63.7 mg, 0.0781 mmol), and deoxygenated anhydrous benzene
(24 mL total) at 12 ꢁC. Observed 87% ee as determined by chiral
HPLC analysis (ChiralpakÒ AD,1% EtOH/hexanes,1 mL/min, 254 nm,
tR (major)¼6.0 min; tR (minor)¼6.6 min). 1H NMR data matched
(75 MHz, CDCl3)
d 202.3, 172.5, 127.3, 125.5 (br), 99.7, 74.5, 52.6,
41.5, 37.5, 34.4 (br), 29.5, 27.7, 25.7 (br), 24.1, 23.8, 19.7, 19.1; IR (neat
film, NaCl) 2961, 2931, 2876, 2838, 1657, 1618, 1470, 1434, 1404,
n
that of
a
,u
-diene (ꢂ)-13. [
a]
25 þ10.46 (c 1.005, CHCl3).
D
1383, 1365, 1344, 1297, 1220, 1169, 1137, 1045, 1008, 965, 908, 858,
830, 817, 742, 685, 621 cmꢂ1; HRMS (FABþ) m/z calcd for C18H28ClO2
[MþH]þ: 311.1778, found 311.1789.
4.3.2. Chloroalkene (ꢂ)-12. Following a similar procedure to that
for the preparation of chloroalkene (þ)-12,
a,
u
-diene (þ)-13
(229.7 mg, 0.678 mmol) was converted to chloroalkene (ꢂ)-12
4.2.7. Proposed structure of (þ)-laurencenone B ((þ)-7)29. In a glo-
vebox, anhydrous CeCl3 (3.973 g, 16.1 mmol) was added to a flame-
dried 250 mL round-bottomed flask equipped with a magnetic stir
bar. The flask was sealed with a septum and removed from the
glovebox. The flask was placed under high vacuum and refilled with
Ar. Anhydrous THF (39 mL) was added via syringe, and the
suspension was stirred for 3 h at 23 ꢁC. The suspension was cooled
to ꢂ78 ꢁC over 15 min, and MeLi (1.37 M in Et2O, 9.0 mL,
(204.7 mg, 97%) using catalyst 49 (19.3 mg, 0.0338 mmol) and de-
oxygenated anhydrous benzene (7 mL total). 1H NMR data matched
26
that of chloroalkene (þ)-12. [
a
]
ꢂ101.03 (c 1.0, CHCl3).
D
4.3.3. Proposed structure of (ꢂ)-laurencenone B ((ꢂ)-7). Following
a similar procedure to that for the preparation of the proposed
structure of (þ)-laurencenone B ((þ)-7), chloroalkene (ꢂ)-12
(99.9 mg, 0.321 mmol) was converted to the proposed structure of