Ambident Reactivity of Medium-Ring Cycloalkane-1,3-dione Enolates

Article abstract of DOI:10.1021/jo971515k

Cycloalkane-1,3-diones with ring sizes 7-10 have been converted to their enolates and subjected to a variety of ethylation and methylation reagent/solvent systems. The greatest amount of O-alkylation was encountered using ethyl tosylate in HMPA. The O/C alkylation ratios decreased with almost every reagent/solvent system as the ring size was increased. This trend is consistent with greater steric strain in the conjugated enolate resonance contributor, resulting in diminished O-attack as the ring size is increased.

Full text of DOI:10.1021/jo971515k

1098
J . Org. Chem. 1998, 63, 1098-1101
Am bid en t Rea ctivity of Med iu m -Rin g Cycloa lk a n e-1,3-d ion e
En ola tes1
Glenn S. Thompson and J erry A. Hirsch*
Department of Chemistry, Seton Hall University, South Orange, New J ersey 07079
Received August 13, 1997
Cycloalkane-1,3-diones with ring sizes 7-10 have been converted to their enolates and subjected
to a variety of ethylation and methylation reagent/solvent systems. The greatest amount of
O-alkylation was encountered using ethyl tosylate in HMPA. The O/C alkylation ratios decreased
with almost every reagent/solvent system as the ring size was increased. This trend is consistent
with greater steric strain in the conjugated enolate resonance contributor, resulting in diminished
O-attack as the ring size is increased.
Sch em e 15
The ability of enols and enolate anions to function as
ambident species is an important aspect in many syn-
thetic applications.2,3 For the enols and enolates derived
from 1,3-diones, the understanding of ambident behavior
is complicated by the various conformations of the enone
segments and the contribution of chelated or intramo-
lecularly hydrogen-bonded species.2 As part of a study
of enone equilibria in medium-ring cycloalkenones,4
preparation of 7- to 10-membered 3-alkoxycycloalkenones
(1, 2) became essential in order to probe the effect of
strongly electron-donating groups on these equilibria. If
O-alkylation of cycloalkane-1,3-diones (3, n ) 3-6) could
be performed in high yield, the desired compounds could
be prepared in a straightforward manner.
Since Pirrung6 reported a 43% yield of 3-ethoxy-2-
cyclooctenone (1, n ) 4) using potassium tert-butoxide
and triethyloxonium fluoroborate (TEO) in DME, initial
attempts were addressed to using this system to O-
alkylate the 10-membered dione (3, n ) 6). The results
were poor yields of a complex mixture of products. It was
therefore decided to perform a more systematic investi-
gation of the alkylation of these four 1,3-diones.
The desired medium-ring cycloalkane-1,3-diones (3, n
) 3-6) were prepared (Scheme 1) by the ring expansion
method developed by Ito5 for the 7- and 9-membered rings
and modified by Pirrung6 for the 8-membered ring.7
A starting point was the work of Sraga and Hrnciar,8
who studied the methylation of the 5-, 6-, and 7-mem-
bered 1,3-diones. They reported that the ratio of O-
methylated product to C-methylated product was much
greater in the 5-membered ring than in the 6-membered
ring and was greater in the 6-membered ring than in the
7-membered ring. They reported 57-65% total yields of
7-membered ring products, with 80% O-methylation from
diazomethane in methanol and total O/C ratios9 of 0.8,
0.2, 0.1, 0.2, and 0.9 using methyl iodide and anhydrous
potassium carbonate in ether, THF, acetone, acetonitrile,
and DMF, respectively. These results followed the
expected trends.2,3 Polar aprotic solvents increase O-
alkylation, while nonpolar and hydrogen-bonding sol-
vents decrease O-alkylation. The harder the electrophilic
center in the alkylating agent, the greater the preference
for O-alkylation.10 Thus, leaving group effects for O-
alkylation should be in the order iodide < bromide <
chloride < tosylate < ether.2
(1) Taken from: Thompson, G. S. Ph.D. Dissertation, Seton Hall
University, 1995.
(2) House, H. O. Modern Synthetic Reactions, 2nd ed.; W. A.
Benjamin, Inc.: Menlo Park, CA, 1972; Chapter 9.
(3) Carey, F. A.; Sundberg, R. J . Advanced Organic Chemistry, 2nd
ed.; Plenum Press: New York, 1983; Part B, Chapter 1.7.
(4) Eskola, P.; Hirsch, J . A. J . Org. Chem. 1997, 62, 5732 and
previous papers in the series.
(5) Ito, Y.; Fujii, S.; Nakatsuka, M.; Kawamoto, F.; Saegusa, T. Org.
Synth. 1979, 59, 113. Ito, Y.; Fujii, S.; Saegusa, T. J . Org. Chem. 1976,
41, 2073.
(6) Pirrung, M. C.; Webster, N. J . G. J . Org. Chem. 1987, 52, 3606.
(7) Other syntheses of 3. n ) 3: (a) Maclean, I.; Sneeden, R. P. A.
Tetrahedron 1965, 21, 31. (b) Eistert, B.; Haupter, F.; Schank, K.
J ustus Liebig Ann. Chem. 1963, 665, 55. (c) Bhushan, V.; Chan-
drasekaran, S. Synth. Commun. 1984, 14, 339. n ) 3, 4, and 8: (d)
Suzuki, M.; Watanabe, A.; Noyori, R. J . Am. Chem. Soc. 1980, 102,
2095. n ) 3-5: (e) Nishiguchi, I.; Hirashima, T.; Shono, T.; Sasaki, M.
Chem. Lett. 1981, 551. n ) 4-8: (f) Schank, K.; Eistert, B.; Felzmann,
J . H. Chem. Ber. 1966, 99, 1414. Eistert, B.; Schank, K. Tetrahedron
Lett. 1964, 8, 429. n ) 6 and 7: (g) Beccalli, E. G.; Majori, L.;
Marchesini, A. J . Org. Chem. 1981, 46, 222. n ) 7-11 and 13: (h)
Hunig, S.; Hoch, H. Tetrahedron Lett. 1966, 42, 5215; Liebigs Ann.
Chem. 1968, 716, 68. (i) Kirrmann, A.; Wakselman, C. Bull. Soc. Chim.
Fr. 1967, 10, 3772. n ) 11: Reference 5. n ) 3-5 with 2-methyl
substituent: (j) Brooks, D. W.; Mazdiyasni, H.; Sallay, P. J . Org. Chem.
1985, 50, 3411.
(8) Sraga, J .; Hrnciar, P. Chem. Zvesti 1981, 35, 119.
(9) O/C ratios are the amount of 2-alkoxyenone (1 + 2) plus any
1,3-dialkoxydiene (9) relative to the total amount of 2-alkyl (6), 2,2-
dialkyl (7), 2,2,4-trialkyl 1,3-dione (10), and 2-alkyl-3-alkoxy enone (8).
S0022-3263(97)01515-6 CCC: $15.00 © 1998 American Chemical Society
Published on Web 01/30/1998

Medium-Ring Cycloalkane-1,3-dione Enolates
J . Org. Chem., Vol. 63, No. 4, 1998 1099
Ta ble 1. O/C Ra tios for th e Alk yla tion of
Ta ble 3. Alk yla tion of Cycloocta n e-1,3-d ion e (3, n ) 4)
Cyclod eca n e-1,3-d ion e (3, n ) 6)
system (equiv)a
3b
1
6
7
O/C ratio9
O/C ratio9 (% O-alkylated producta)
DME/EtI (5X)
6
11
1
54
77
80
40
90
89
21
4
5
31
2
3
17
0.1
0.2
24
0.5
0.8
1.4
19
15
0.7
36
23
solvent
RIb
Me2SO4 Et tosylate Et3OBF4
DME/Et3OBF4 (1.2X)
THF/Et3OBF4 (1.2X)
HMPA/EtI (5X)
DME
<0.1 (4) <0.1 (4)
0.1 (6)
1.6 (23)c
1.3 (35)
1.1 (33)
0.9 (30)
80%DME/20%HMPA
DMSO
d
0.5 (27)
0.8 (38)
1.9 (31)
0.7 (38)
1.8 (61)
3.1 (70)
HMPA/EtTos (2.5X)c
HMPA/EtTos (2.5X)c,d
<0.1 (1)
0.1 (8)
HMPA
a
A solution of potassium tert-butoxide (1.2 equiv) was added
to a stirred solution of cyclooctane-1,3-dione (0.4-0.6 mmol) in 10
mL of solvent under N2. The alkylating agent was added after 15
min of stirring and the reaction monitored by GC. All were at rt
a
b
cis-3-Ethoxy- or -3-methoxy-2-cyclodecenone (1, n ) 6). EtI
d
or MeI. c Includes THF data. Not determined.
Ta ble 2. Alk yla tion of Cyclon on a n e-1,3-d ion e (3, n ) 5)
b
except Et3OBF4 were at 0°C. Percent cyclooctane-1,3-dione re-
system (equiv)a
3b
1
9
6
7
O/C ratio9
maining. c Product mixture contained 5% of an unknown compo-
d
nent. Reaction used 6.1 mmol of dione.
DME/EtI (5X)
2
57
38
88
89
0.2
0.1
0.7
4
34
44
4
6
15
2
1.4
0.6
15
HMPA/EtI (10X)
HMPA/EtTos (2.5X)c
HMPA/EtTos (2.3X)d
3
<1
<1
Ta ble 4. Alk yla tion of Cycloh ep ta n e-1,3-d ion e (3, n ) 3)
3
3
16
system (equiv)a
3b
1
9
6
7
8
O/C ratio9
DME/EtI (10X)c
45 43
12
4
1
1
1
3.6
2.4
29
a
A solution of potassium tert-butoxide (1.1-1.2 equiv) was
added to a stirred solution of cyclononane-1,3-dione (0.7 mmol) in
10 mL of solvent under N2 at rt. The alkylating reagent was added
after stirring for 15 min and the reaction monitored by GC.
DME/EtI (10X)d
3
1
2
67
60 26
50 29
16
5
2
5
HMPA/EtTos (2.5X)d,e,f
HMPA/EtTos (2.5X)d,f
HMPA/EtTos (2.5X)d,g,h
THF/Et3OBF4 (3X)
13f
h
Percent cyclononane-1,3-dione (3) remaining. c Reaction per-
formed using 3.2 mmol dione. Reaction performed using 6.3 mmol
b
1
70
d
49 36
2
0.5
18
dione.
a
A solution of potassium tert-butoxide was added to a stirred
solution of cycloheptane-1,3-dione (0.5 mmol) in 10 mL of solvent
under N2 at rt (at 0°C for Et3OBF4). Alkylating agent was added
We chose to compare the reactions of ethyl iodide,
methyl iodide, dimethyl sulfate, ethyl tosylate, and TEO
in the presence of potassium tert-butoxide in DME, THF,
DMSO, HMPA, and 80% DME/20% HMPA. The results
for cyclodecane-1,3-dione (3, n ) 6) are summarized in
Table 1 (see the Supporting Information for details:
Tables 5-8). Increasing solvent polarity (HMPA most
polar)11 produced significant increases in O-alkylation,
especially with ethyl tosylate and dimethyl sulfate. The
highest yield of the desired 3-alkoxycyclodecane-1,3-dione
(3, n ) 6) was obtained with ethyl tosylate in HMPA.
Unexpectedly, TEO did not show this trend, nor were
yields high. This was the result of the typical presence
of about 40% of unreacted 1,3-dione starting material
even when large amounts of TEO were utilized. On the
other hand, the largest amount of 2-alkylated product
(6, n ) 6) was usually found with the alkyl iodide, and
the largest amount of 2,2-dialkylated material (7, n ) 6)
was observed with either methyl iodide or dimethyl
sulfate in DMSO, with the number of equivalents of base
used being an additional variable in the formation of 7.
b
after 15 min stirring and the reaction monitored by GC. Percent
of cycloheptane-1,3-dione remaining. c 0.5 equiv of base. 1.0 equiv
d
of base. e Used 2.5 mmol of dione. f Contained two unidentified
trialkylated products in 7.5% and 2% yield, which are ignored in
g
calculating the O/C ratio. Continuation of previous experiment
with an additional 0.5 equiv of base added after 1.5 h. Contained
two unidentified trialkylated products corresponding to 19% and
4% yield.
h
approximately 90% of 3-ethoxy-2-cyclononenone (1, n )
5) and 3-ethoxy-2-cyclooctenone (1, n ) 4) with O/C
ratios9 of 16 and 30, respectively. The results with ethyl
tosylate/HMPA and cycloheptane-1,3-dione were compli-
cated by the large amount of 1,3-diethoxy-1,3-cyclohepta-
diene (9, n ) 3) formed. All of the reagent/solvent
systems preferred O-alkylation in the 7-membered ring
1,3-dione.
One notable trend is the decrease in the O/C ratio with
almost every reagent/solvent system as the ring size was
increased. In the case of ethyl tosylate in HMPA, this
ratio decreased from 30 in the 8-membered ring to 16 in
the 9-membered ring to 3 in the 10-membered ring. As
the ring size increases, the steric requirement to have a
coplanar arrangement of a conjugated enone system
becomes more severe. This results in an increasing
preference for 3-cycloalkenones over 2-cycloalkenones4,12
as ring size increases from 7 to 10. In the current work,
the destabilization with increasing ring size of the
conjugated enone resonance contributor 11 in the enolate
anion from the 1,3-dione results in increasing importance
of the carbon acid resonance contributor 12. The result
is greater C-alkylation with increasing ring size as long
as the same reagent/solvent system is compared. These
results also parallel the kinetic studies of Rhoads11 on
the isopropylation of 2-carbalkoxycycloalkanones with
ring sizes 5-8 and 10, where the rates of attack on carbon
relative to attack on oxygen in DMSO and in HMPA
increased with increasing ring size. However, Rhoads’
system involves different mixes of enolate conformations
Limited comparisons were performed in the 9-, 8-, and
7-membered rings (Tables 2-4, respectively), but the
trends were similar. Ethyl tosylate in HMPA produced
(10) Ho, T. L. Hard and Soft Acids and Bases Principle in Organic
Chemistry; Academic Press: New York, 1977.
(11) Rhoads, S. J .; Hasbrouck, R. W. Tetrahedron 1966, 22, 3557.
Rhoads, S. J .; Decora, A. W. Tetrahedron 1963, 19, 1645. Rhoads, S.
J .; Holder, R. W. Tetrahedron 1969, 25, 5443.
(12) Heap, N.; Whitham, G. H. J . Chem. Soc. B 1966, 164. Whitham,
G. H.; Zaidlewicz, M. J . Chem. Soc., Perkin Trans. 1 1972, 1509.

1100 J . Org. Chem., Vol. 63, No. 4, 1998
Thompson and Hirsch
or reduced pressure, and the residue was vacuum-distilled
using a short-path distillation column, yielding the 1,2-bis-
(trimethylsiloxy)cycloalkene.
because one of their carbonyls is external to the ring. In
addition, Rhoads pointed out the possibility of their
working near the isokinetic temperature.
Gen er a l P r oced u r e for th e Syn th esis of 1, (n + 3)-
Bis(tr im eth ylsiloxy)bicyclo[n + 1.1.0]a lk a n es 5.5,6 A solu-
tion of diethylzinc (2.0-2.8 equiv) in toluene (Aldrich, 15 wt
% (1.1 M)) was added dropwise over 1 h to a mechanically
stirred solution of 1,2-bis(trimethylsiloxy)cycloalkene (4) and
diiodomethane (2.4-2.7 equiv) (Aldrich, 99%) in dried toluene
at 0 °C (ice bath) under a dried N2 atmosphere. After the
addition of the diethylzinc solution was complete, the reaction
mixture was stirred at rt for 2-2.5 h. Next, the reaction
mixture was slowly poured into 100 mL of cold saturated
aqueous NH4Cl. Quenching the excess diethylzinc in this
manner minimized bubbling resulting from the liberation of
ethane. The mixture was vacuum-filtered, and the white
precipitate was washed with 100 mL of n-hexane. The filtered
aqueous layer was extracted with the hexane wash from above
and was extracted twice more with 100 mL of n-hexane. The
combined organic layers were washed with 100 mL of satu-
rated aqueous NH4Cl and 100 mL of saturated aqueous brine.
The hexane layer was dried (anhyd Na2SO4), and after
filtration, the solvent was removed under reduced pressure.
The residue was vacuum-distilled using a short-path distilla-
tion column to afford the desired compound.
Gen er a l P r oced u r e for th e Syn th esis of Cycloa lk a n e-
1,3-d ion es 3.5,6,7j,15 Anhydrous FeCl3 (4 equiv) (MCB, sublimed,
reagent) was quickly transferred to a round-bottom flask under
an N2 atmosphere. Since anhyd FeCl3 dissolves exothermi-
cally, the dried DMF was added slowly with mechanical
stirring to the ice bath-cooled flask. A solution of the bicy-
cloalkane 5 in dried DMF was added to the stirred mixture,
and the reaction was stirred for 3-3.5 h at 60-70 °C. The
cooled reaction mixture was poured into 100 mL of cold 10%
aqueous HCl, and the mixture was extracted with 100 mL of
CHCl3 four times. The combined CHCl3 extracts were washed
with 100 mL of 10% aqueous HCl two to three times and then
with 100 mL of saturated aqueous brine. The organic layer
was dried over anhyd Na2SO4 or MgSO4 and suction-filtered
and the solvent removed under reduced pressure. If necessary,
the residue was reextracted with 50 mL of CHCl3 and 3 × 50
mL of aqueous HCl to remove residual DMF, followed by
washing with 50 mL of brine. The CHCl3 solution was dried
with anhyd Na2SO4 and filtered and the solvent removed
under reduced pressure. The crude dione was distilled (bulb-
to-bulb) under reduced pressure and then purified by chro-
matography.
Exp er im en ta l Section
The NMR spectra were obtained in solutions of deuterio-
chloroform (CDCl3) with 0.03% tetramethylsilane (TMS) except
for the trimethylsiloxy compounds, which were obtained in
CDCl3. Ultraviolet spectra were obtained in n-hexane (HPLC
grade) unless otherwise noted. GC-MS data were obtained
with a J &W DB-1 (30 m × 0.25 mm i.d., 0.25 µm film
thickness) column or a Hewlett-Packard HP1 (12 m × 0.2 mm
i.d., 0.33 µm film thickness) column. GC analyses were
performed with a J &W DB-1 (30 m × 0.53 mm i.d., 5 µm film
thickness) column, a J &W DB-1 (15 m × 0.555 mm i.d., 1.5
µm film thickness) column, or an XF1150 6 ft × 4 mm glass
column. Elemental analysis was performed by Analytische
Laboratorium, Elbach, Germany. Flash column chromatog-
raphy was performed utilizing E. M. Sciences silica gel 60
(particle size 0.040-0.063 mm) with suitable solvents in glass
columns with 1.5, 2, or 3 cm i.d. TLC analyses were performed
on Merck silica gel 60 F254 precoated glass plates (layer
thickness 0.25 mm) with detection by either shortwave UV,
vanillin spray, or iodine chamber. All syntheses were per-
formed using oven-dried glassware under a nitrogen atmo-
sphere. Both DME and THF were distilled from Na/benzophe-
none prior to use, while DMF was stored over BaO and was
distilled from either BaO or CaH2 under reduced pressure (20
mmHg) prior to use. The DMSO was stored over BaO, distilled
under reduced pressure, and further dried by refluxing over
CaH2 followed by distillation under reduced pressure. The
HMPA was refluxed over BaO under reduced pressure with
an N2 atmosphere followed by distillation. The HMPA was
then refluxed and distilled from Na under reduced pressure
with an N2 atmosphere. Toluene was refluxed and distilled
from either Na or CaH2 prior to use. Trimethylsilyl chloride
(TMSCl) (Aldrich, 98%) was distilled from CaH2 prior to use.
Reagents were generally used as obtained from the supplier.
Details on individual experiments are found in the Supporting
Information.
3-Eth oxy-2-cycloh ep ten -1-on e (1, n ) 3, R ) Et). Modi-
fying the procedure of Pirrung and Webster,6 15.5 mL (15.5
mmol) of potassium tert-butoxide (1.0 M in THF) was added
to a solution of 1.56 g (12.4 mmol) of cycloheptane-1,3-dione
(3, n ) 3) in 35 mL of dried THF at 0 °C. After the yellow-
orange suspension was stirred for 1 h at 0 °C, 20 mL (20 mmol)
of triethyloxonium tetrafluoroborate (TEO) (1.0 M in CH2Cl2,
Aldrich) was added to the reaction. The reaction was stirred
for 30 min at 0 °C. The potassium tert-butoxide and TEO
solutions were added to the reaction a second (8 mmol each)
and third (10 mmol each) time to drive the reaction toward
completion. The reaction mixture was diluted with 40 mL of
diethyl ether and then filtered through a 20 g plug of neutral
alumina. The solvents were removed under reduced pressure
to give a dark yellow liquid, which was dissolved in 10 mL of
ether and filtered through a 5 g plug of neutral alumina. After
removal of solvents and purification by flash chromatography
(95 CH2Cl2/5 ether), the residue was distilled (bulb-to-bulb,
80-100 °C, 5 mmHg) to yield 0.89 g (47%, GC purity 88%) of
a colorless liquid: GC-MS m/z 156, 155, 154 (M+), 126, 125,
109, 98, 97 (base), 84, 82, 81, 69, 67, 55, 41, 39. Repeated flash
chromatography (same conditions) resulted in 0.65 g (34%) of
pure product (GC purity 99%): IR (neat) 3450, 3230, 3040,
Gen er a l P r oced u r e for th e Syn th esis of 1,2-Bis(tr i-
m eth ylsiloxy)cycloa lk en es 4.5,7j,13 A solution of the dimeth-
ylalkanediester in dried toluene was slowly added, dropwise,
to a stirred solution of cleaned Na sand and TMSCl in dried
toluene at the temperature specified in the individual proce-
dure. The cleaned Na was prepared14 by heating pieces of Na
in toluene until melted and pouring the molten Na into dried
toluene. The clean Na balls were easily separated from the
oxidized Na residues. The Na sand14 was prepared in the
reaction flask by vigorously stirring (5-10 min) the weighed,
clean Na balls in refluxing toluene until a fine suspension of
Na was obtained. A Hershberg-type wire paddle was utilized
to stir the Na. The heat was removed with continued stirring
until the Na suspension solidified. After addition of the diester
was complete, the stirred mixture was refluxed until the
reaction was complete and then cooled to room temperature.
Generally, the reaction turned deep purple upon addition of
the diester. The mixture was vacuum-filtered using a sintered
glass funnel, and the purple precipitate was rinsed with 100-
200 mL of dried toluene. The precipitate, containing excess
Na, was carefully treated with 2-propanol. The toluene was
removed from the combined toluene filtrates at atmospheric
1
1625, 1590, 1441, 1368, 1230, 1174 cm-1; H NMR (CDCl3) δ
(13) Ruhlmann, K. Synthesis 1971, 236.
(14) Fieser, L. F.; Fieser, M. Reagents for Organic Synthesis; J ohn
Wiley and Sons: New York, 1967; pp 1022-1023. preparation of a fine
and clean Na sand is critical.
(15) Lewicka-Piekut, S.; Okamura, W. H. Synth. Commun. 1980,
10, 415.

Medium-Ring Cycloalkane-1,3-dione Enolates
J . Org. Chem., Vol. 63, No. 4, 1998 1101
5.38 (s, 1H), 3.80 (q, J ) 7, 2H), 2.59 (m, 4H), 1.84 (m, 4H),
1.34 (t, J ) 7, 3H); 13C NMR (CDCl3) δ 202.1, 176.0, 105.7,
64.0, 41.6, 33.0, 23.5, 21.2, 14.1.
added to a stirred solution of potassium tert-butoxide (1.1-
1.2 equiv, 1.0 M in THF, Aldrich) and the cycloalkane-1,3-dione
in dried HMPA under an N2 atmosphere. The reaction was
stirred for 2-3 h at rt and then was extracted with 75 of mL
n-hexane and 3 × 50 mL water. To optimize the yields, the
aqueous layers were combined and reextracted with 100 mL
of n-hexane. This hexane layer was extracted with 3 × 50
mL water, and the hexane layers were combined. After drying
(anhyd Na2SO4) and filtration, the solvent was removed under
reduced pressure, yielding a mixture of product and unreacted
ethyl tosylate. Generally, an initial purification was performed
by flash chromatography to remove the ethyl tosylate. Sub-
sequent purifications utilized flash chromatography with
different solvent systems until a suitably pure material was
obtained.
The byproduct 2-ethylcycloheptane-1,3-dione (6, n ) 3, R )
Et) was observed by GC-MS: m/z 155, 154 (M+), 126, 111,
98, 97 (base), 84, 83, 69, 55, 41, 39. The dialkylated byproduct
2-ethyl-3-ethoxy-2-cyclohepten-1-one (8, n ) 3, R ) Et) was
observed in the same GC-MS: m/z 184, 183, 182 (M+, base),
167, 154, 153, 139, 138, 137, 136, 135, 126, 125, 123, 121, 113,
111, 110, 109, 108, 107, 97, 95, 94, 93, 91, 85, 84, 83, 82, 81,
79, 77, 69, 68, 67, 65, 57, 55, 53, 43, 41, 39. It was
subsequently isolated from the ensuing flash chromatography
1
in 65% GC purity: H NMR (CDCl3) δ 3.98 (q, 2H), 2.55 (m,
4H, partially overlapped by m from starting material 3 present
as 9% impurity), 2.31 (q, 2H), 1.78 (m, 4H), 1.34 (t, 3H), 0.95
(t, 3H).
When the 3-ethoxy compound 1 (n ) 3) was prepared from
312 mg of 3 (n ) 3) using the general procedure for the larger
rings (see below), column chromatography (75 CH2Cl2/20
n-hexane/5 ether) resulted in 156 mg (41%) of 1 (n ) 3) as a
colorless liquid: GC purity 99%; TLC (as for column) short
wave UV: one trace spot, vanillin: four trace spots, possible
on-plate decomposition; UV (n-hexane) λmax 242 nm (ꢀ 14 800),
311 nm (ꢀ 88).
Su p p or tin g In for m a tion Ava ila ble: Experimental pro-
cedures for specific compounds, spectral data, and Tables 5-8
with details on alkylations of cyclodecane-1,3-dione (3, n ) 6)
(18 pages). This material is contained in libraries on micro-
fiche, immediately follows this article in the microfilm version
of the journal, and can be ordered from the ACS; see any
current masthead page for ordering information.
J O971515K
Gen er a l P r oced u r e for th e Syn th esis of th e 8-, 9-, a n d
10-Mem ber ed 3-Eth oxy-2-cycloa lk en -1-on es 1, (n ) 4-6,
R
) Et). Ethyl tosylate was prepared according to the
(16) Schrapler, U.; Ruhlmann, K. Chem. Ber. 1964, 97, 1383.
(17) Reference 14, p 1180.
procedure of Fieser and Fieser.17 This material (2.5 equiv) was