Vinyl Phosphate/â-Keto Phosphonate Rearrangements
J . Org. Chem., Vol. 63, No. 8, 1998 2617
a solution of enone 1613 (75 mg, 0.90 mmol) in THF (10 mL)
at -78 °C. After 1 h, diisobutyl phosphorochloridate (267 mg,
mmol), 2-methyl-2-propanol (118 mg, 1.59 mmol), n-BuLi (1.00
mL, 1.59 M in hexanes), and diethyl phosphorochloridate (686
mg, 3.98 mmol). Standard workup and purification by flash
column chromatography (20 to 25% EtOAc in hexanes) gave
compound 25a (407 mg, 51%): 1H NMR δ 4.69-4.59 (m, 4H),
1
.17 mmol) in 1 mL of THF was added, and the mixture was
allowed to warm to room temperature. After 35 min, the
reaction was quenched (NH Cl) and extracted with ether. The
organic layer was washed with H O and brine, dried (MgSO ),
4
1
3
2
4
4.29-4.19 (m, 4H),), 1.37 (td, J ) 6.9, J HP ) 1.2 Hz, 6H);
C
and concentrated in vacuo. The resulting oil was purified by
flash column chromatography (14 to 20% EtOAc in hexanes)
NMR δ 142.3 (d, J CP ) 7.6 Hz), 95.0 (d, J CP ) 10.6 Hz), 74.6,
3
1
70.1, 64.9, 64.8, 15.5 (d, J CP ) 6.0 Hz, 2C); P NMR δ -6.1.
Anal. Calcd for C P‚0.5H O: C, 31.09; H, 4.89.
Found: C, 31.10; H, 4.58.
-Br om o-3-[(d iisobu toxyp h osp h in yl)oxy]-2,5-d ih yd r o-
fu r a n (25b). According to the general procedure bromo ketone
4 (533 mg, 3.23 mmol) was treated with KH (78 mg, 1.9
1
to obtain phosphate 20 (99 mg, 40%): H NMR δ 5.26-5.24
8
H
14BrO
5
2
(
2
1
m, 1H), 3.86 (td, J ) 6.6, 0.9 Hz, 4H), 2.49-2.42 (m, 2H),
.35-2.27 (m, 1H), 2.04-1.88 (m, 4H), 0.96 (d, J ) 6.7 Hz,
4
13
2H); C NMR δ 150.1 (d, J CP ) 7.6 Hz), 109.1 (d, J CP ) 6.0
Hz), 74.1, 74.0, 31.4 (d, J CP ) 5.3 Hz), 29.0, 28.9, 28.0 (t, J CD
2
3
1
)
20.0 Hz), 20.7, 18.5 (4C); P NMR δ -5.44; GCMS, m/z (rel
mmol), 2-methyl-2-propanol (411 mg, 1.94 mmol), n-BuLi (1.22
mL, 1.59 M in hexanes), and diisobutyl phosphorochloridate
+
intensity) 277 (M , 3), 221 (2), 165 (100), 99 (31), 84 (59), 67
(37), 57 (25), 41 (30).
(884 mg, 3.88 mmol). Standard workup and purification by
Rea r r a n gem en t of Vin yl P h osp h a te 20. Compound 20
89 mg, 0.32 mmol) in THF (0.5 mL) was added to a solution
flash column chromatography (20 to 25% EtOAc in hexanes)
(
gave compound 25b (508 mg, 44%): 1H NMR δ 4.69-4.59 (m,
of LDA (3.5 equiv) in THF (2 mL) at -78 °C, and the resulting
mixture was allowed to warm to room temperature. After 1.5
4
H), 3.93 (td, J ) 6.6, 1.2 Hz, 4H), 2.09-1.94 (m, 2H), 0.97 (d,
13
J ) 6.7 Hz, 12H); C NMR δ 140.3, 95.6 (d, J CP ) 10.6 Hz),
h, the reaction was quenched by addition of saturated NH
The aqueous phase was extracted with ether, and the com-
bined organic layer was washed with brine, dried over MgSO
4
Cl.
7
6
4
5.1 (d, J CP ) 3.8 Hz), 75.0 (d, J CP ) 2.3 Hz), 73.4 (d, J CP
)
.0 Hz), 70.5, 28.8 (d, J CP ) 6.8 Hz, 2C), 18.3 (d, J CP ) 7.6 Hz,
4
,
31
C); P NMR δ -6.0; HR FAB-MS: calcd for C12
21 5
H O BrP (M
and concentrated in vacuo. Purification by flash column
chromatography (25 to 50% EtOAc in hexanes) afforded a
mixture of keto phosphonates 19 and 21 (62 mg, 70%). The
+
2
) , 355.0310; found, 355.0302.
+
H - H
2
-B r o m o -1-[(d i i s o b u t o x y p h o s p h i n y l)o x y ]c y c lo -
h exen e (27). According to the general procedure for conjugate
addition, 2-bromo-2-cyclohexen-1-one14 (240 mg, 1.37 mmol)
was treated with L-Selectride (1.51 mL, 1 M in THF) and
diisobutyl phosphorochloridate (406 mg, 1.78 mmol). Standard
workup and purification by flash column chromatography (20
to 25% EtOAc in hexanes) gave compound 27 (455 mg, 88%):
1
H NMR spectrum was generally indistinguishable from that
reported for compound 19, except for the CHP(O) resonance.
This signal appeared as a six-line pattern interpreted as a
doublet of triplets (the resonance from the minor isomer 21
where the R-hydrogen is coupled to phosphorus and two
adjacent H’s) overlapping a doublet of doublets (the resonance
from the major isomer 19 where the R-hydrogen is coupled to
phosphorus and one adjacent H). Overlap of these key
resonances prevented determination of the isomer ratio from
1
H NMR δ 3.92 (t, J ) 6.3 Hz, 4H), 2.54-2.43 (m, 4H), 2.06-
1
.93 (m, 2H), 1.81-1.65 (m, 4H), 0.97 (d, J ) 6.7 Hz, 12H);
C NMR δ 143.9 (d, J CP ) 3.0 Hz), 107.0 (d, J CP ) 7.6 Hz),
3.7 (d, J CP ) 6.8 Hz, 2C), 33.9, 28.7 (d, J CP ) 6.0 Hz, 2C),
1
3
7
2
1
the H spectrum. In an inverse gated broadband decoupled
3
1
8.5, 23.4, 22.1, 18.1 (4C); P NMR δ -6.4. Anal. Calcd for
P: C, 45.54; H, 7.10. Found: C, 45.68; H, 7.16.
-(Diisob u t ylp h osp h in yl)cycloh exa n on e (28). To a
1
3
C NMR spectrum, the integrated intensity of signals at δ
14 4
C H26BrO
4
6.7 and 46.8, and those at δ 38.9 and 38.8, was 5:1, with the
2
major resonances corresponding to those observed for com-
pound 19. For the mixture of phosphonates 19 and 21:
1
a
1
3
cooled solution (-90 °C) of 2-bromovinyl phosphate 27 (229
mg, 0.620 mmol) in THF (12 mL) was added n-BuLi (0.834
mL, 1.63 M in hexanes) dropwise. After 3.5 h at -90 °C, the
reaction was quenched by addition of NH
phase was extracted with ether, and the combined organic
layer was washed with brine, dried (MgSO ), and concentrated
C
NMR (125 MHz) δ 212.0 (d, J CP ) 12.5 Hz), 72.3 (d, J CP ) 6.3
Hz), 72.1 (d, J CP ) 7.5 Hz), 46.8 (d, J CP ) 136.3 Hz), 46.7 (d,
4
Cl. The aqueous
J
CP ) 137.5 Hz), 38.9 (d, J CP ) 3.8 Hz), 38.8 (d, J CP ) 3.8 Hz),
2
3
8
9.2 (d, J CP ) 3.8 Hz), 29.1 (d, J CP ) 3.8 Hz), 25.4 (d, J CP
.8 Hz), 25.2 (td, J CD ) 20 Hz, J CP ) 3.8 Hz), 21.6 (d, J CP
)
)
4
3
1
in vacuo. Flash column chromatography (33 to 50% EtOAc
.8 Hz), 21.4 (td, J CD ) 21.3 Hz, J CP ) 7.5 Hz), 18.6 (4C).
P
1
+
in hexanes) gave phosphonate 28 (55 mg, 31%): H NMR δ
NMR δ +23.23; GCMS, m/z (rel intensity) 278 (M + 1, 0.2),
22 (11), 166 (100), 110 (59), 83 (91), 68 (14), 57 (25), 41 (34).
-Br om o-3-h yd r oxytetr a h yd r ofu r a n (23). Recrystal-
3
2
.89-3.81 (m, 4H), 3.01 (dt, J HP ) 23.4 Hz, J ) 5.8 Hz, 1H),
.71-2.60 (m, 1H), 2.43-2.34 (m, 1H), 2.33-1.57 (m, 8H), 0.95
2
4
1
3
(
(
J
J
d, J ) 3.1 Hz, 6H), 0.93 (d, J ) 3.1 Hz, 6H); C NMR δ 206.1
d, J CP ) 7.6 Hz), 72.2, 72.1, 50.1 (d, J CP ) 132.1 Hz), 41.5 (d,
lized N-bromosuccinimide (11.44 g, 64.27 mmol) was added
as a solid to a solution of 2,5-dihydrofuran (4.29 g, 61.2 mmol)
CP ) 2.3 Hz), 29.2, 29.1, 27.9 (d, J CP ) 5.3 Hz), 26.5, 22.5 (d,
in distilled H
with ether. The combined organic layer was washed with
brine, dried (MgSO ), and concentrated in vacuo to give
2
O (275 mL). After 6 h, the solution was extracted
CP ) 6.8 Hz), 18.6 (4C); 31P NMR δ +27.64, +23.68 (keto-
+
enol tautomerism); HRFAB calcd for C14
313.1545, found 313.1544.
27 4
H O P (M + Na)
4
1
compound 23 (6.03 g, 66%) as a yellow oil: H NMR δ 4.58-
4
9
.57 (m, 1H), 4.42 (dd, J ) 10.5, 4.5 Hz, 1H), 4.26 (dd, J )
.9, 4.2 Hz, 1H), 4.21-4.19 (m, 1H), 4.08 (dd, J ) 10.5, 2.4
3-Br om o-4,6,6-t r im et h ylb icyclo[3.1.1]-3-h ep t en -2-on e
(30). Sodium bromide (0.895 g, 8.70 mmol) was added to a
vigorously stirring solution of oxone (5.35 g, 8.70 mmol) in
1
3
Hz, 1H), 3.81 (dd, J ) 10.2, 0.6 Hz, 1H); C NMR δ 78.6, 74.2,
7
3.3, 51.5.
carbon tetrachloride (25 mL) and H
resulting mixture was heated to 45 °C and (-)-verbenone
(0.653 g, 4.35 mmol) in CH Cl (1.5 mL) was added. After 1
2
O (5 mL) at 0 °C. The
Keton e 24. Pyridinium dichromate (20.74 g, 55.12 mmol)
and molecular sieves (21 g) were added in portions to a solution
of bromohydrin 23 (3.68 g, 22.1 mmol) in CH Cl (200 mL) and
2
2
2
2
h, the reaction was cooled to 0 °C, and triethylamine (0.880 g,
8.70 mmol) was added dropwise. The reaction was allowed to
allowed to stir overnight. The resulting mixture was filtered
through a 2 cm pad of Celite, and the pad was rinsed
warm to room temperature, quenched (NH
with CH Cl . The combined organic layer was washed with
brine, dried (MgSO ), and concentrated in vacuo. Purification
4
Cl), and extracted
thoroughly with CH
2
Cl
2
. After the filtrate was concentrated
2
2
in vacuo, the resulting oil was purified by flash column
4
chromatography (3:1 hexanes/EtOAc) to give bromo ketone 24
of the residue by radial chromatography (4:1 hexanes/EtOAc)
gave compound 30 (0.498 g, 50%) along with some of the
intermediate dibromide. Treatment of the dibromide with
triethylamine gave an additional batch of the desired product
(0.245 g), raising the total yield to 75%: 1H NMR δ 2.90-2.78
(m, 2H), 2.64 (dd, J ) 6.6, 5.4 Hz, 1H), 2.19 (s, 3H), 2.17 (d, J
) 9.0 Hz, 1H), 1.50 (s, 3H), 1.00 (s, 3H); 13C NMR δ 195.5,
1
(
1.82 g, 75%): H NMR δ 4.53 (ddd, J ) 10.8, 6.0, 0.9 Hz, 1H),
4
1
1
.36 (td, J ) 5.7, 0.6 Hz, 1H), 4.23 (ddd, J ) 10.8, 5.1, 0.6 Hz,
H), 4.13 (dd, J ) 17.4, 0.9 Hz), 3.99 (dd, J ) 17.4, 0.6 Hz,
1
3
H); C NMR δ 207.2, 73.8, 68.9, 42.3. Anal. Calcd for C
: C, 29.12; H, 3.05. Found: C, 28.90; H, 3.10.
-Br om o-3-[(d ie t h oxyp h osp h in yl)oxy]-2,5-d ih yd r o-
fu r a n (25a ). According to the general procedure bromo ketone
4 (437 mg, 2.65 mmol) was treated with KH (64 mg, 1.6
4 5
H -
BrO
2
4
166.6, 116.7, 57.2, 54.7, 51.5, 40.0, 26.0, 23.7, 21.8; HR FAB
+
2
MS calcd for C10
H
14BrO (M + H) 229.0228, found 229.0223.