3618 J . Org. Chem., Vol. 66, No. 10, 2001
Notes
Ta ble 1. In vestiga tion of Rea ction Con d ition sa
was used without purification: 1H NMR (CDCl3) 2.23 (s, 3 H),
5.35 (s, 1 H), 7.35-7.47 (m, 5 H).
product ratio, %b
equiv of additive reaction
t-BuOK (equiv) condition
To a solution of the crude R-chloroketone 3 (119.6 g) in toluene
(700 mL) were added neopentyl glycol (105.4 g) and p-toluen-
ensulfonic acid (2.57 g). Then the mixture was refluxed for 7 h
in a Dean-Stark apparatus with continuous removal of sepa-
rated water. After cooling to room temperature, n-hexane (1000
mL) was added, and the resulting solid was removed by filtration
and washed with n-hexane. The filtrate was washed with diluted
NaHCO3 solution, water, and saturated NaCl solution succes-
sively and dried over anhydrous Na2SO4. Removal of the drying
agent and concentration afforded crude acetal 4 (174.3 g,
containing a small amount of toluene), which was used without
purification: 1H NMR (CDCl3) 0.80 (s, 3 H), 0.99 (s, 3 H), 1.41
(s, 3 H), 3.48 (dd, J ) 11.4 Hz, 1.7 Hz, 1 H), 3.50 (dd, J ) 11.7
Hz, 1.7 Hz, 1 H), 3.62 (d, J ) 11.4 Hz, 1 H), 3.63 (d, J ) 11.7
Hz, 1 H), 4.97 (s, 1 H), 7.20-7.35 (m, 3 H), 7.45-7.55 (m, 2 H).
This crude acetal 4 (174.3 g, containing a small amount of
toluene) was dissolved in chloroform (1400 mL), and pyridinium
hydrobromide perbromide (230.0 g) was added. After refluxing
for 30 min, it was cooled to room temperature, and then water
(1000 mL) was added. The aqueous layer was extracted with
chloroform, and the combined extracts were washed with water,
saturated NaHCO3 solution, and saturated NaCl solution suc-
cessively and dried over anhydrous Na2SO4. Removal of the
drying agent and concentration afforded a crude product, which
was recrystallized from n-hexane to give the desired compound
1 (148.2 g, 66%): mp 81-82 °C; IR (KBr) 2959, 2868, 1472, 1453,
1426, 1395, 1208, 1129, 1265, 1020, 988, 766, 704; 1H NMR
(CDCl3) 0.77 (s, 3 H), 0.81 (s, 3H), 3.38-3.65 (m, 5H), 3.94 (d, J
) 11.7 Hz, 1H), 5.29 (s, 1H), 7.25-7.40 (m, 3 H), 7.45-7.60 (m,
2 H); 13C NMR (CDCl3) 21.66, 21.69, 27.21, 29.07, 62.94, 70.44,
70.61, 97.25, 127.20, 127.93, 129.24, 135.94. Anal. Calcd for
C14H18BrClO2: C, 50.40; H, 5.44; Br, 23.59; Cl, 10.63. Found:
C, 50.30; H, 5.37; Br, 23.71; Cl, 10.34.
2-P h en ylcyclop r op en on e 2,2-d im eth yl-1,3-p r op a n ed iyl
Aceta l 6. To a solution of potassium tert-butoxide (672 mg) in
DMI (5 mL) was added dihalide 1 (1.0 g) in THF (5 mL) at 0 °C.
After stirring for 4 h at 0 °C, water (20 mL) was added, and
then the aqueous solution was extracted with n-hexane three
times. The combined extracts were washed with saturated NaCl
solution and dried over anhydrous Na2SO4. Removal of the
drying agent and concentration gave a crude product, which was
purified by flush column chromatography (5% ethyl acetate/n-
hexane) to afford the titled compound (453 mg, 70%): mp 54
°C; IR (CCl4) 3100, 2250, 1960, 1900, 1810, 1720, 1470, 1260;
1H NMR (CDCl3) 1.08 (s, 3 H), 1.15 (s, 3 H), 3.75 (s, 4 H), 7.35-
7.47 (m, 3 H), 7.60-7.67 (m, 2 H), 7.69 (s, 1 H); 13C NMR (CDCl3)
21.78, 22.00, 29.95, 77.26, 82.69, 114.12, 125.45, 128.29, 129.13,
129.52, 135.18. Anal. Calcd for C14H16O2: C, 77.75; H, 7.46.
Found: C, 77.64; H, 7.54.
entry
solvent
THF
1
5
6
7
1
2
3
4
5
6
7
8
2.0
2.6
2.0
2.0
2.0
2.0
2.0
2.0
none
none
none
none
none
DMI (1.0) rt, 1 h
DMF (3.0) rt, 1 h
rt, 3 h
rt, 5 h
rt, 15 h
rt, 3 h
rt, 3 h
32
0
100
0
0
8
0 36 32
THF
0
0
0
0
100
0
t-BuOH
NMPc
DMI
THF
THF
22 66 12
23 72
5
4
0
0
0
88
72 13
40 39
15
21
THF
TMEDA
(3.0)
rt, 3 h
9
THF-DMI
2.0
none
rt, 5 h
0
11 86
3
All reactions were performed in 0.30 mmol scale. b Determined
a
by 1H NMR. c Reaction mixture became red quickly.
Sch em e 3
The effect of additives was also examined, and 1 equiv
of DMI in THF gave a satisfactory result (entry 6), but
no satisfactory result was obtained by the use of DMF
or TMEDA (entries 7 and 8). Alternatively, a 1:1 mixture
of THF and DMI also gave an excellent result (entry 9).
Next we confirmed the isolated yield. The dihalide 1
was treated with 2 equiv of potassium tert-butoxide in
THF and DMI (1:1), and the crude product was purified
by column chromatography to afford the desired cyclo-
propenone acetal 6 in 70% yield (Scheme 3), which is
comparable to the isolated yield 61% by treatment of 1
with sodium amide in liquid ammonia. Alternatively, the
recrystallization of the crude product from n-heptane
gave the pure product in 40% yield.
In summary, we developed a convenient method to
synthesize 2-phenylcyclopropenone acetals, which are the
key intermediates for some biologically active compounds
containing a cyclopropenone moiety. As this reaction
proceeds in THF containing 1 equiv of DMI or in a THF-
DMI mixture in good yield and the experimental proce-
dure is very simple in comparison to the previously
reported methods,3,4 it will be useful especially for a
small-scale preparation.
2-Ch lor o-2-p h en ylcyclop r op a n on e 2,2-d im eth yl-1,3-p r o-
p a n ed iyl Aceta l 5. mp 87 °C; IR (KBr) 2961, 2872, 1473, 1445,
1422, 1364, 1343, 1310, 1258, 1242, 1171, 1088, 1071, 1042,
1
1020, 984, 953, 916, 735, 700, 658, 648, 617; H NMR (CDCl3)
0.85 (s, 3 H), 1.15 (s, 3 H), 1.68 (d, J ) 8.2 Hz, 1 H), 2.07 (d, J
) 8.2 Hz, 1 H), 3.19 (s, 2 H), 3.68 (d, J ) 11 Hz, 1 H), 3.84 (d,
J ) 11 Hz, 1 H), 7.25-7.40 (m, 3 H), 7.45-7.60 (m, 2 H). Anal.
Calcd for C14H17ClO2: C, 66.53; H, 6.78; Cl, 14.03. Found: C,
66.17; H, 6.69; Cl, 13.90.
Exp er im en ta l Section
Gen er a l. All 1H NMR spectra taken at 250 MHz were
measured on a Bruker AC-250 instrument and are reported in
parts per million from internal tetramethylsilane. 13C NMR
spectra taken at 75 MHz were measured on a Bruker ARX-300
instrument and are reported in parts per million. IR spectra
were recorded on a J ASCO FT/IR-5300 instrument; absorptions
are reported in cm-1. Most of reagents were purchased from
Tokyo Chemical Industry and used without further purification.
2-Br om om et h yl-2-(ch lor op h en ylm et h yl)-5,5-d im et h yl-
1,3-d ioxa n e 1. Phenylacetone 2 (90.56 g) was dissolved in
dichloromethane (500 mL), and sulfuryl chloride (66.0 mL) was
added slowly at 0 °C. After stirring at room temperature for 7
h, water (400 mL) was added, and the separated aqueous layer
was extracted twice with dichloromethane. Then the combined
extracts were washed with saturated NaCl solution and dried
over anhydrous MgSO4. Removal of the drying agent and
concentration afforded crude R-chloroketone 3 (119.6 g), which
2-ter t-Bu toxy-3-p h en ylcyclop r op a n on e 2,2-d im eth yl-1,3-
p r op a n ed iyl Aceta l 7. mp 75-76 °C; IR (KBr) 2984, 2961,
2868, 1603, 1495, 1474, 1458, 1393, 1366, 1192, 1165, 1123,
1
1082, 1065, 1049, 897, 883, 696, 630; H NMR (CDCl3) 0.72 (s,
3 H), 1.20 (s, 3 H), 1.27 (s, 9 H), 2.25 (d, J ) 4.9 Hz, 1 H), 3.04
(d, J ) 10.8 Hz, 1 H), 3.32 (dd, J ) 10.8 Hz, 2.1 Hz, 1 H), 3.62
(d, J ) 10.7 Hz, 1 H), 3.66 (d, J ) 4.9 Hz, 1 H), 3.72 (dd, J )
10.7 Hz, 2.1 Hz, 1 H), 7.10-7.25 (m, 3 H), 7.25-7.35 (m, 2 H);
13C NMR (CDCl3) 21.44, 22.25, 27.49, 30.57, 37.91, 61.44, 74.82,
75.15, 90.72, 125.12, 126.22, 127.76, 136.44. Anal. Calcd for
C18H26ClO3: C, 74.45; H, 9.02. Found: C, 74.54; H, 9.09.
Ack n ow led gm en t. The authors wish to thank Prof.
Eiichi Nakamura, The University of Tokyo, for helpful
discussions.
J O001722B