The Journal of Organic Chemistry
Article
−
1
23
1
2
9
2
H), 3.65 (qd, J = 10.9, 3.9 Hz, 3H), 3.23 (d, J = 5.5 Hz, 2H), 2.97−
.80 (m, 2H), 2.69−2.62 (m, 1H), 2.62−2.46 (m, 8H), 2.41 (dt, J =
.9, 4.9 Hz, 2H), 2.21 (d, J = 12.3 Hz, 1H), 2.16 (d, J = 11.9 Hz, 2H),
.05−1.98 (m, 1H), 1.85−1.74 (m, 2H), 1.60−1.07 (m, 71H), 1.03 (d,
2954, 2935, 2865, 1710, 1693, 1667, 1251, 1161 cm ; [α] +20.9,
D
[α]23 + 22.7, [α]
23
+ 21.4, [α]
23
+ 40.4 (c = 0.6, MeOH);
HRMS (ESI-TOF) m/z: [M] Calcd for C H O 279.1596; Found
577
546
435
−
16
23
4
279.1595.
J = 6.9 Hz, 6H), 1.01 (d, J = 7.1 Hz, 6H), 0.98−0.87 (m, 16H), 0.85
Preparation of Potassium Oxalate 72. A round-bottom flask
was charged with S7 (81 mg, 0.28 mmol, 1.0 equiv), 1:1 THF:H O
13
(
d, J = 6.5 Hz, 6H), 0.83 (d, J = 6.5 Hz, 4H), 0.80−0.71 (m, 6H);
C
2
NMR (151 MHz, C D ) δ 172.8, 172.3, 104.7, 103.2, 102.0, 101.0,
(1.4 mL, 0.2 M), and a stir bar under ambient atmosphere. The
resulting biphasic mixture was cooled to 0 °C. Next, 0.85 N KOH (aq)
(320 μL, 1.0 equiv) was added dropwise. The mixture was then stirred
vigorously at 0 °C for 5 min. The stir bar was removed and
homogeneous solution was concentrated by use of a rotary evaporator
with water bath warmed gradually from rt to 45 °C. The resulting
colorless solid was washed with pentanes (3 × 5 mL) and dried further
6
6
8
3
2
1
1
0.9, 80.4, 75.6, 75.4, 61.1, 58.9, 49.2, 49.1, 44.8, 41.5, 40.9, 40.8, 40.5,
7.7, 37.6, 37.2, 36.8, 36.7, 35.4, 35.3, 32.2, 32.1, 28.7, 28.6, 27.1, 27.0,
5.8, 23.9, 23.6, 23.1, 22.52, 22.47, 22.45, 22.4, 22.03, 21.95, 21.4, 21.1,
6.54, 16.46; IR (thin film) 3463, 3438, 2924, 2867, 1704, 1636, 1367,
−1
21
21
21
546
21
435
152 cm ; [α] +101, [α]
+ 101, [α]
+ 112, [α]
+ 159
D
577
+
(c = 0.15, CHCl ); HRMS (ESI-TOF) m/z: [M+Na] Calcd for
3
C H O Na 475.3399; Found 475.3395.
under high vacuum to yield product 72 as a colorless solid (86 mg,
2
7
48
5
1
Preparation of Dioxabicyclo[3.3.0]octan-3-one 68. A 2-dram
0.28 mmol, 99% yield); H NMR (600 MHz, CD OD) 4.93−4.89 (m,
3
scintillation vial was charged with lactol 67 (34 mg, 0.075 mmol, 1.0
equiv), 1:1 4 M HCl (aq):THF (3 mL, 0.025 M), and a magnetic stir
bar under ambient atmosphere. The resulting biphasic mixture was
stirred vigorously at rt for 30 min. The reaction mixture was
2H), 2.49−2.38 (m, 2H), 2.31 (d, J = 12.9 Hz, 1H), 1.93−1.84 (m,
1H), 1.84−1.69 (m, 5H), 1.48−1.44 (m, 3H), 1.41 (q, J = 12.3, 11.4
Hz, 1H), 1.25 (d, J = 13.8 Hz, 1H), 1.00 (t, J = 2.5 Hz, 3H), 0.95−0.91
(m, 3H); 13C NMR (151 MHz, CD OD) δ 166.9, 166.5, 152.8, 117.0,
3
transferred to a separatory funnel and extracted with Et O (3 × 10
97.2, 58.7, 52.0, 38.7, 38.6, 37.2, 37.1, 34.3, 30.0, 26.5, 25.3, 22.4; IR
2
−1
23
mL). The combined organic layers were dried over Na SO4 and
(thin film) 3608, 1713, 1663, 1641, 1233, 893 cm ; [α]
+14.6,
2
D
[α]23 + 14.9, [α]
23
+ 16.7, [α]
23
+ 31.2 (c = 1.7, MeOH);
concentrated by use of a rotary evaporator. The residue was purified
by flash column chromatography on silica gel using 10:90 ethyl
acetate:hexanes →25:75 ethyl acetate:hexanes as eluent to yield
577
546
435
−
HRMS (ESI/TOF) m/z calculated for C H O [M] 279.1596,
16
23
4
−
observed 269.1598. HRMS (ESI-TOF) m/z: [M] Calcd for
product 68 as a colorless solid (11 mg, 0.046 mmol, 61% yield): R =
C H O 279.1596; Found 279.1598.
f
16 23
4
0
.30 (30:70 ethyl acetate:hexanes, stained with ceric ammonium
Preparation of Lactone 70 from 69. On the bench under
ambient atmosphere, 1-dram scintillation vial was charged with 69 (86
mg, 0.30 mmol, 1.0 equiv), ent-59 (82 mg, 0.30 mmol, 1.0 equiv),
Ir[dF(CF )ppy] (dtbbpy)PF (7 mg, 0.006 mmol, 0.02 equiv),
3
1
molybdate). Spectral data were consistent with reported values.
Preparation of Methyl Oxalate S7. A round-bottom flask was
charged with 54 (560 mg, 2.7 mmol, 1.0 equiv), DMAP (33 mg, 0.27
mmol, 0.1 equiv), dichloromethane (13 mL, 0.20 M), and a stir bar
3
2
6
tetrahydrofuran (500 μL, 0.6 M), H O (27 μL, 1.5 mmol, 5 equiv),
2
under ambient atmosphere. Next, Et N (0.45 mL, 3.2 mmol, 1.2
and a stir bar. The vial was then sealed with screw cap bearing Teflon
septum. The septum of the vial was pierced with a 21 gauge × 1.5″
needle that was inserted just barely through the septum with the tip of
the needle kept above the fluid level inside the vial. A separate 22
gauge x 3″ needle attached to a flow of argon was also pierced through
the septum, and the tip of the needle was pushed to the bottom of the
vial and submersed in the fluid. The reaction mixture was degassed by
sparging with argon for 15 min. Both needles were removed, and the
sealed vial was then placed on a stir plate equipped with 2 × 34 W blue
LED lamps and a rack to hold the vial inside of a cardboard box to
block light pollution from entering the lab. The vial was placed
approximately 4 cm from the lamps and stirred vigorously. The sample
was irradiated by the lamps for 18 h inside the closed box, allowing the
temperature of the reaction mixture to rise to 60 °C and the air inside
the box to 40−45 °C because of heat given off from the LEDs. The
3
equiv) and methyl chlorooxoacetate (0.30 mL, 3.2 mmol, 1.2 equiv)
were added sequentially. The resulting yellow solution was maintained
at rt for 10 min, at which point TLC analysis (10:90 ethyl
acetate:hexanes, stained with p-anisaldehyde) indicated complete
consumption of the starting material. The reaction was quenched via
addition of sat. NH Cl (aq) (15 mL). The resulting biphasic mixture
4
was transferred to a separatory funnel and extracted with CH Cl (3 ×
2
2
2
5 mL). Combined organic layers were dried over MgSO4 and
concentrated by use of a rotary evaporator. The crude product was
purified by flash column chromatography on silica gel using 5:95 ethyl
acetate:hexanes as eluent to yield the desired product S7 as a clear oil
(
720 mg, 2.45 mmol, 91% yield): Rf = 0.43 (10:90 ethyl
1
acetate:hexanes, stained with p-anisaldehyde); H NMR (500 MHz,
CDCl ) δ 4.92 (d, J = 2.3 Hz, 1H), 4.86 (d, J = 2.3 Hz, 1H), 3.88 (s,
3
3
H), 3.20 (dd, J = 8.1, 1.7 Hz, 1H), 2.44 (dddd, J = 12.0, 10.1, 3.4, 1.6
Hz, 1H), 2.38−2.26 (m, 2H), 1.92−1.72 (m, 4H), 1.69−1.59 (m, 2H),
.49 (s, 3H), 1.45−1.31 (m, 1H), 1.25 (dt, J = 14.3, 3.5 Hz, 1H), 0.98
s, 3H), 0.91 (s, 3H); 13C NMR (126 MHz, CDCl ) δ 159.3, 157.1,
reaction was allowed to cool to rt, diluted with Et O (1 mL) and
2
filtered over MgSO . The filtrate was concentrated by use of a rotary
4
1
(
evaporator. The crude product was purified by flash column
chromatography on silica gel using 2:98 ethyl acetate:hexanes as
eluent to yield the desired product 70 as a thick colorless foam (102
3
1
50.2, 117.2, 99.7, 57.7, 53.5, 50.9, 37.6, 37.3, 36.2, 35.9, 33.9, 28.7,
2
6.1, 24.3, 21.7; IR (thin film) 2953, 2937, 2867, 1766, 1739, 1154
mg, 0.22 mmol, 73% yield): R = 0.33 (5:95 ethyl acetate:hexanes,
f
−1
23
23
23
23
+
1
cm ; [α] +11.5, [α]
=
C H O Na 317.1729; Found 317.1732.
+ 13.6, [α]
+ 14.4, [α]
+ 29.1 (c
stained with p-anisaldehyde); H NMR (600 MHz, CDCl ) δ 5.59 (d,
D
577
546
435
3
1.0, CHCl ); HRMS (ESI-TOF) m/z: [M+Na] Calcd for
J = 3.3 Hz, 1H), 4.87 (s, 1H), 4.62 (s, 1H), 3.59 (td, J = 10.7, 4.7 Hz,
1H), 2.68−2.59 (m, 2H), 2.36 (dd, J = 12.3, 5.4 Hz, 1H), 2.26−2.17
(m, 1H), 2.14 (d, J = 11.1 Hz, 1H), 2.05 (q, J = 9.8 Hz, 1H), 1.83−
1.73 (m, 5H), 1.73−1.57 (m, 5H), 1.45−1.34 (m, 2H), 1.28 (dd, J =
12.4, 6.7 Hz, 2H), 1.03−0.97 (m, 4H), 0.97−0.92 (m, 7H), 0.92−0.86
(m, 4H), 0.84 (s, 3H), 0.80 (d, J = 6.0 Hz, 3H); 13C NMR (151 MHz,
3
1
7
26
4
Preparation Lithium Oxalate 69. A round-bottom flask was
charged with S7 (700 mg, 2.38 mmol, 1.0 equiv), 1:1 THF:H O (4.8
mL, 0.5 M), and a stir bar under ambient atmosphere. The resulting
biphasic mixture was cooled to 0 °C. Next, 0.5 N LiOH (aq) (4.8 mL,
1
2
.0 equiv) was added dropwise. The mixture was then stirred
CDCl ) δ 172.6, 153.4, 115.2, 101.9, 77.7, 60.9, 55.7, 53.7, 52.2, 48.1,
3
vigorously at 0 °C for 5 min. The stir bar was removed and
homogeneous solution was concentrated by use of a rotary evaporator
with water bath warmed gradually from rt to 45 °C. The resulting
colorless solid was washed with pentanes (3 × 5 mL) and dried further
47.9, 40.0, 37.7, 37.4, 37.0, 36.5, 34.5, 31.6, 28.9, 25.8, 25.7, 25.4, 23.2,
22.5, 21.2, 21.1, 15.7; IR (thin film) 2953, 2922, 2868, 1789, 1364
−
1
23
23
23
23
+
cm ; [α] −52.0, [α]
− 54.3, [α]
− 65.8, [α]
− 104 (c
D
577
546
435
= 0.6, CHCl ); HRMS (ESI-TOF) m/z: [M+Na] Calcd for
3
under high vacuum to yield product 69 as a colorless solid (680 mg,
C H ClO Na 487.2955; Found 487.2971.
28
45
3
1
2
.38 mmol, 100% yield); H NMR (500 MHz, CD OD) δ 4.91 (d, J =
Preparation of Lactone 70 from 72. On the bench under
3
2
.6 Hz, 1H), 4.86 (d, J = 2.6 Hz, 1H), 2.51−2.37 (m, 2H), 2.35−2.27
ambient atmosphere, 1-dram scintillation vial was charged with 72 (63
mg, 0.20 mmol, 1.0 equiv), ent-59 (55 mg, 0.20 mmol, 1.0 equiv),
Ir[dF(CF )ppy] (dtbbpy)PF (5 mg, 0.004 mmol, 0.02 equiv),
(
1
m, 1H), 1.95−1.84 (m, 1H), 1.84−1.67 (m, 5H), 1.46 (s, 3H), 1.43−
13
.34 (m, 1H), 1.31−1.15 (m, 1H), 1.00 (s, 3H), 0.93 (s, 3H);
C
3
2
6
NMR (126 MHz, CD OD) δ 167.0, 166.3, 152.7, 116.8, 97.0, 58.5,
tetrahydrofuran (330 μL, 0.6 M), H O (18 μL, 1.0 mmol, 5 equiv),
3
2
5
1.9, 38.6, 38.5, 37.0, 36.9, 34.2, 29.8, 26.4, 25.1, 22.2; IR (thin film)
and a stir bar. The vial was then sealed with screw cap bearing Teflon
O
J. Org. Chem. XXXX, XXX, XXX−XXX