B. M. Bocknack et al. / Tetrahedron 61 (2005) 6266–6275
6273
3
h. After cooling to room temperature, the reaction was
3.5.3. Mono(diketone) 1f. A solution of (C)-camphor
(5.02 g, 33.0 mmol, 200 mol%) in anhydrous THF
(100 mL) was cooled to K78 8C. tert-Butyllithium (1.7 M
solution in pentane, 20 mL, 34 mmol, 207 mol%) was added
dropwise over a period of 15 min. The mixture was stirred at
K788C for 1 h, at which point the ester 9 (4.35 g,
16.4 mmol, 100 mol%) was added. Notwithstanding these
deviations, the general procedure for Claisen condensation
was followed as described above. The crude product was
isolated as a yellow oil, which was purified by flash
carefully poured into ice water (150 mL) and the resulting
mixture was extracted with DCM (3!50 mL). The
combined organic extracts were washed with brine (1!
5
0 mL) and dried (Na SO ). After filtration, removal of the
2 4
volatiles in vacuo, the crude product was isolated as a dark
orange oil. Purification by flash chromatography (SiO2:
2
acetic ester 9 (8.626 g, 32.54 mmol, 76% yield) as a pale
.5:97.5 Et O/hexanes) afford the a-difluorinated phenyl-
2
1
yellow oil. H NMR (300 MHz, CDCl ): d 7.77 (s, 1H), 7.64
3
(
7
d, JZ7.9 Hz, 1H), 7.56 (d, JZ7.9 Hz, 1H), 7.35 (t, JZ
chromatography (SiO : 2.5:97.5 ethyl acetate/hexanes) to
2
1
3
.9 Hz, 1H), 3.87 (s, 3H). C NMR (75 MHz, CDCl ): d
yield a mixture of keto and enol tautomers of 14 (4.54 g,
11.8 mmol) in 72% yield as a pale purple oil. [a] C72.68
3
2
7
1
64.0, 134.6, 134.2, 130.3, 128.6, 124.2, 122.7, 112.4, 53.7.
F NMR (282 MHz, CDCl ): d K104.3 (s). IR (film): 2959,
767, 1425, 1302, 1252, 1112, 1076, 1017, 818, 796,
D
1
9
1
(cZ1.13, CHCl ). H NMR (300 MHz, CDCl ): d 11.80 (s,
3
3
3
1
7
2
1H), 7.71 (s, 1H), 7.60 (d, JZ8.1 Hz, 1H), 7.50 (d, JZ
8.1 Hz, 1H), 7.32 (t, JZ8.1 Hz, 1H), 2.99 (m, 1H), 2.08 (m,
1H), 1.73 (m, 1H), 1.43 (m, 2H), 0.99 (s, 3H), 0.96 (s, 3H),
K1
28 cm . HRMS: Calcd for C H BrF O [MC1]
9
8
2
2
64.9676, Found 264.9679.
.5. Preparation of bis(1,3-diketones) 2a–2c
.5.1. Mono(diketone) 1e. A solution of LDA in anhydrous
1
3
0
.81 (s, 3H). C NMR (75 MHz, CDCl ): d 214.4, 155.3,
3
3
3
136.7, 133.7, 130.1, 128.6, 124.1, 122.6, 116.4, 115.7, 57.8,
9.1, 47.3, 30.2, 26.9, 20.4, 18.4, 8.6. IR (film): 3456, 2967,
4
K1
1680, 1640 cm . HRMS: Calcd for C18
385.0615, Found 385.0614.
H20BrF O [MC1]
2 2
THF was prepared as described above. Monoketone 8
1.51 g, 9.30 mmol, 100 mol%) and (3.746 g,
4.13 mmol, 152 mol%) were then reacted according to
(
1
9
3.5.4. Bis(diketone) 2b. Compound 1f (0.504 g, 1.31 mmol,
100 mol%) and hexamethylditin (0.219 g, 0.670 mmol,
58 mol%) were dissolved in dry toluene (10 mL, 0.13 M
with respect to 1f). The reaction vessel was sealed with a
rubber septum, and the solution was sparged with argon for
the general acylation procedure. The crude product was
isolated as an orange-brown oil, which was purified by flash
chromatography (SiO : 1:4 DCM/hexanes) to yield a
mixture of keto- and enol-tautomers of 1e (1.16 g,
2.93 mmol) in 32% yield as a dark purple, viscous oil.
The overall yield based on recovered 8 (707 mg,
2
1 min, at which point Pd(PPh ) (100 mg, 0.09 mmol,
3 4
7 mol%) was added. The mixture was heated to 100 8C
with stirring under argon for 17 h. The reaction mixture was
evaporated onto silica gel. Purification by flash chromato-
2
6
1
4
NMR (300 MHz, CDCl ): d 12.78 (s, 1H), 7.73 (s, 1H), 7.62
.36 mmol) was 59%. [a]D C22.18 (cZ1.13, CHCl ). H
3
3
(
7
(
d, JZ7.9 Hz, 1H), 7.53 (d, JZ7.9 Hz, 1H), 7.34 (t, JZ
.9 Hz, 1H), 3.26 (m, 1H), 2.67 (s, 1H), 2.50 (m, 3H), 2.42
m, 1H), 1.76 (m, 4H), 1.44 (m, 4H). C NMR (75 MHz,
graphy (SiO
2b (0.256 g, 0.419 mmol) in 45% yield as a pale purple
: SiO ; 20:80 ethyl acetate/hexanes) provides
2 2
1
3
27
1
solid. Mp 187–1898C. [a]
NMR (300 MHz, CDCl ): d 11.85 (s, 2H), 7.77 (s, 2H), 7.57
C10.28 (cZ0.98, CHCl ). H
D 3
CDCl ): d 217.7, 158.4, 136.4, 133.7, 130.1, 128.7, 124.2,
3
3
1
2
4
22.5, 115.4, 114.8, 55.6, 50.0, 47.5, 47.4, 45.1, 44.0, 33.4,
(m, 4H), 3.01 (m, 2H), 2.08 (m, 2H), 1.75 (m, 2H), 1.45 (m,
4H), 0.99 (s, 6H), 0.96 (s, 6H), 0.83 (s, 6H). C NMR
1
9
13
7.9, 27.3. F NMR (282 MHz, CDCl ): d K100.9 (d, JZ
3
K1
.0 Hz). IR (film): 3446, 2955, 1680, 1635 cm . HRMS:
(75 MHz, CDCl ): d 214.4, 155.3, 136.7, 133.7, 130.1,
3
Calcd for C H BrF O [MC1] 395.0458, Found
1
128.6, 124.1, 122.6, 116.4, 116.4, 57.8, 49.1, 47.4, 30.2,
9
18
2
2
K1
3
95.0454.
26.9, 20.4, 18.4, 8.6; IR (film): 3460, 2975, 1675, 1635 cm .
HRMS: Calcd for C H F O [MC1] 611.2784, Found
611.2793.
3
6 39 4 4
3
1
0
.5.2. Bis(diketone) 2a. Compound 1e (530 mg,
.34 mmol, 100 mol%) and hexamethylditin (255 mg,
.78 mmol, 58 mol%) were dissolved in dry toluene
3.5.5. Friedel–Craft acylation of dibenzofuran. To a
solution of dibenzofuran (172 mg, 1.02 mmol, 100 mol%)
(
10 mL, 0.13 M with respect to 1e). The reaction vessel
was sealed with a rubber septum, and the solution was
sparged with argon for 1 min, at which point Pd(PPh3)4
(73 mg, 0.063 mmol, 5 mol%) was added. The mixture was
heated to 100 8C with stirring under argon for 17 h. The
in DCM (5.20 mL, 0.20 M) at 0 8C was added AlCl (1.67 g,
3
12.5 mmol, 1250 mol%) followed by ethyl chlorooxo-
acetate (670 mL, 6.0 mmol, 600 mol%). The reaction
mixture was allowed to stir for 2 h and was allowed to
reach ambient temperature, at which point ice water
(10 mL) was added to reaction mixture. The reaction
mixture was transferred to a separatory funnel and the
aqueous layer was extracted with DCM (3!10 mL). The
combined organic extracts were washed with brine (50 mL),
dried (Na SO ), filtered and evaporated to afford the crude
reaction mixture was evaporated onto silica gel. Purification
by flash chromatography (SiO : 1:4 DCM/hexanes) pro-
vides 2a (0.189 g, 0.30 mmol) in 45% yield as a pale purple
2
2
8
1
oily solid. [a]D K94.48 (cZ0.90, CHCl3). H NMR
300 MHz, CDCl ): d 13.82 (s, 2H), 7.80 (s, 2H), 7.72 (m,
(
3
2
1
2
1
2
H), 7.57 (m, 4H), 3.31 (m, 2H), 2.68 (s, 2H), 2.51 (m, 8H),
2
4
1
3
.73 (m, 8H), 1.48 (m, 4H). C NMR (75 MHz, CDCl3):
17.7, 159.0, 140.7, 135.2, 130.4, 130.3, 129.4, 129.2,
24.6, 114.7, 55.7, 50.0, 47.6, 47.4, 45.2, 44.1, 33.4, 28.0,
reaction product as a yellow oil. Purification by flash
chromatography (SiO : 1:4 EtOAc/hexanes) provides the
2
bis(oxoacetic) ester (150 mg, 0.41 mmol) in 40% yield as a
yellow solid. Mp 97–99 8C. H NMR (CDCl , 400 MHz): d
1
9
1
7.3. F NMR (282 MHz, CDCl ): d K100.6 (s, 2F),
3
3
K100.8 (s, 2F). IR (film): 2926, 2872, 2854, 1680,
8.71 (d, JZ1.5 Hz, 1H), 8.25 (dd, JZ8.7, 1.8 Hz, 2H), 7.70
(d, JZ8.7 Hz, 2H), 4.54 (q, JZ7.2 Hz, 4H), 1.49 (t, JZ
K1
1
6
624 cm . HRMS: Calcd for C H F O [MC1]
38 34 4 4
30.2393, Found 630.2399.
1
7.2 Hz, 6H). C NMR (CDCl , 100 MHz): d 185.0, 163.6,
3
3