Rhodium(ii)-carbenoid C-H insertion reactions in the synthesis of β-oxospirane systems

Article abstract of DOI:10.1039/b001988g

A simple one-pot procedure is described for the preparation of spiro[4.4]nonane-2,7-dione derivatives from open chain bis(α-diazoketones) by two consecutive intramolecular Rh(II)-catalyzed carbenoid insertion reactions. With 1-diazo-4-(3-oxocycloalkyl)butan-2-ones as substrates, the methodology provides 2,7-dioxospiranes with. a cyclopentane ring spiroannulated onto a five-, six- or seven-membered cycloalkane. The Royal Society of Chemistry 2000.

Full text of DOI:10.1039/b001988g

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Rhodium(II)-carbenoid C–H insertion reactions in the synthesis
of ꢀ-oxospirane systems
Pompiliu S. Aburel and Kjell Undheim*
1
Department of Chemistry, University of Oslo, N-0315 Oslo, Norway
Received (in Cambridge, UK) 13th March 2000, Accepted 10th April 2000
Published on the Web 25th May 2000
A simple one-pot procedure is described for the preparation of spiro[4.4]nonane-2,7-dione derivatives from
open chain bis(α-diazoketones) by two consecutive intramolecular Rh()-catalyzed carbenoid insertion reactions.
With 1-diazo-4-(3-oxocycloalkyl)butan-2-ones as substrates, the methodology provides 2,7-dioxospiranes with
a cyclopentane ring spiroannulated onto a five-, six- or seven-membered cycloalkane.
dicarboxylic acids, pimelic acid and methyl-substituted
Introduction
homologs by way of their acid chlorides and subsequent
reactions with diazomethane or diazoethane in diethyl ether
solution (Scheme 1). The diazo ketones 2 were isolated after
Spiranes constructed from small to medium sized rings are
characterized by a stiff framework and may therefore serve as a
rigid scaffold for stereocontrol of pharmacophoric groups in
bioorganic molecules. Appropriately substituted and enantio-
meric spiranes may also be envisaged as chiral auxiliaries in
dissymmetric catalytic operations. We have therefore initiated
work on the preparation of selected spiranes and some studies
of chemical transformations in these systems. In particular,
we have reported on the use of α,αЈ-dioxospiro[3.3.0]nonane
as substrates in palladium-catalyzed carbosubstitutions.1,2 In
this report we describe work on the construction of β,βЈ-
dioxocarbospiranes. The products are functionalized substrates
which are useful for further manipulations of the spirane
system via oxo group activations.
Several synthetic routes are available for the preparation of
α,αЈ-diones such as via spiro[4.4]nonane-1,6-diones and α,β-
unsaturated derivatives thereof.3,4 In contrast, the spiro[4.4]-
nonane-2,7-dione system had received little attention when this
work was begun. The parent compound 4a had been prepared
by a multistep synthesis involving reductive cyclization of mer-
curial α,β-unsaturated cyclopentanone derivatives.5 Part of our
initial work on spiro[4.4]spirane-2,7-diones has been disclosed
in a recent preliminary report.6 Another recent report describes
the preparation of spiro[4.4]nonane-2,7-dione and spiro[4.5]-
decane-2,7-dione by a SmI2 reductive cleavage reaction of
appropriate cyclopropane derivatives,7 and finally the latter
compound as well as spiro[5.5]undecane-2,8-dione have been
prepared by an acid catalyzed cyclization procedure.8
Scheme 1 Reagents and conditions: (i) Et2O, 0 ЊC, 3 h; (ii) CH2Cl2,
20 ЊC, 14 h.
Results and discussion
flash chromatography in good yields. Dirhodium tetraacetate
was used as the catalyst for the intramolecular C–H insertion
reactions which were run in dichloromethane solutions at
ambient temperature. The spiranes 4 were isolated after flash
chromatography in 27–35% overall yield. The methyl deriv-
atives 4b and 4c were diastereomeric mixtures because racemic
methyl-substituted pimeloyl chlorides 1b and 1c were used as
substrates for exploring the methodology. The spirane 4d,
which has methyl groups in the two α,αЈ-positions, was not
obtained by this procedure presumably because of unfavor-
able steric interactions in the formation of the spiro center.
An α-methyl derivative, however, is available indirectly from an
α-carboxylate derivative such as 13a (see Scheme 4).
We have based our construction of spiranes on carbenoid
rhodium intramolecular C–H insertion reactions leading
to spiroannulations. In Rh()-carbenoid C–H insertions the
usual order of reactivity observed is methine > methylene >
methyl.9–11 Furthermore, the C–H insertion is normally site
selective in that five-membered ring formation is normally
favored and will generally take preference over the above
considerations.9,12,13 With this information to hand, we have
constructed a convenient and practical method for the prep-
aration of the spiro[4.4]nonane system from aliphatic α,αЈ-
diazo-dicarbonyl reagents in
a “one-pot” intramolecular
Rh()-carbenoid insertion reaction.6 The substrates for the
cyclization reactions, the open chain α,αЈ-diazo-dicarbonyl
derivatives 2 were readily available from the corresponding
Intramolecular Rh()-carbenoid insertion into the C–H
bond in methylene groups generally favors formation of five-
DOI: 10.1039/b001988g
J. Chem. Soc., Perkin Trans. 1, 2000, 1891–1896
This journal is © The Royal Society of Chemistry 2000
1891

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membered rings (vide supra). Therefore the cyclopentanone 3
would be expected to be the first formed product. The latter
possesses a methine C–H bond in a position suitable for a
second five-membered ring formation, and would be expected
to undergo insertion at the methine carbon with spiroannu-
lation faster than formation of the intermediate cyclopentanone
3. In accordance with this postulate we did not isolate any
intermediate corresponding to the cyclopentanone 3.
The assumption that the initial product in the overall
spirocyclization was a cyclopentanone led us to extend this
approach to the use of appropriately substituted five-, six- and
seven-membered cycloalkanones 10 and 11 (see Scheme 3) as
substrates for the dirhodium() tetraacetate catalyzed C–H
insertion. Because of the strong tendency for formation of five-
membered rings over any other ring size, no attempts were made
to prepare side-chains in the cycloalkanone for spiroannulation
of smaller or larger rings. The methodology presented provides
2,7-dioxospiranes with a cyclopentane ring spiroannulated onto
a five-, six- or seven-membered cycloalkane.
Scheme 3 Reagents and conditions: (i) CH2Cl2, 20 ЊC, 12 h.
Preparation of intermediate substrates for the spiroannu-
lation is shown in Scheme 2. α,β-Unsaturated cycloalkanones
dioxospiranes 4 (Scheme 1) the overall yields were in the range
27–35%. For the simplest member, 4a, the yield was 27% which
would correspond to an average 52% yield in each cyclization
step (2a→3a→4a).
The direct spiroannulation methodology had failed (vide
supra) to yield the α,αЈ-dimethyl derivative 4d (Scheme 1).
α-Methylation, however, would seem likely in the carboxylates
13 because the ester group would direct enolate formation
towards the α-carbon. Subsequent treatment with an alkylating
agent would lead to α-substitution. The monomethyl ester 15
was prepared in this manner from the spiro[4.4]nonane 13a
(Scheme 4). Subsequent ester hydrolysis and decarboxylation
provided the monomethyl derivative 16.
Scheme 4
Scheme 2 Reagents and conditions: (i) tBuOK, THF, Ϫ20 ЊC; (ii)
H2, 5% Pd/C, AcOH, 20 ЊC; (iii) LiOH, MeOH, 20 ЊC; (iv) (COCl)2,
benzene, 40 ЊC; (v) Et2O, 0 ЊC, 4 h; (vi) neat, 40–60 ЊC, 7 h.
In conclusion, we have developed a simple “one-pot” pro-
cedure for the preparation of spiro[4.4]nonane-2,7-dione
derivatives from readily available open chain α,αЈ-
bis(diazo)diketones. The cyclizations are effected by intra-
molecular Rh()-carbenoid insertion into a methylene C–H
bond with cyclopentane formation and a subsequent cyclo-
pentane spiroannulation by insertion into a methine C–H bond.
In a more general method, the substrates for cyclization by
the dirhodium() acetate catalyzed C–H insertion were cyclo-
alkanones which were appropriately β-functionalized for
spiroannulation onto cyclopentanones.
were β-alkylated by a Michael addition reaction using metal-
lated 3-nitropropionate. Concurrent elimination to the acrylate
6 occurred under the conditions of the reaction.14 Saturation of
the olefinic double bond by catalytic hydrogenation and ester
hydrolysis yielded the propionic acid 8.15 Subsequent treatment
with oxalyl chloride furnished the acid chlorides 9 which were
to become substrates for the formation of the diazoketones 10
and 11 in reactions with diazomethane and diazoacetate,
respectively. Diazomethane was more reactive, with ethyl
diazoacetate requiring heating in diethyl ether. Both series of
diazoketones were obtained in good yields.
The C–H insertion reaction was effected by dirhodium
tetraacetate catalysis in dichloromethane (Scheme 3). The
yields of the diketospiranes 12 and 13 were all in the range 40–
45% irrespective of the presence or absence of the carboxylic
ester group. Any stereoselectivity during the spiroannulation
remains unknown since the the ester products 13 were partly
enolized as judged by NMR. In the two-step process from
the acyclic bis(diazo)-substrate 2 in the formation of the
Experimental
1
The H NMR spectra were recorded at 200 or 300 MHz, and
the 13C NMR spectra at 50 or 75 MHz unless otherwise
specified. The mass spectra were recorded at 70 eV under
electron impact conditions (EI) and are presented as m/z (% rel.
int.). Dry THF was distilled from sodium and benzophenone.
Dry dichloromethane was distilled from calcium hydride.
Ethereal diazomethane solution was prepared from Diazald.16
1892
J. Chem. Soc., Perkin Trans. 1, 2000, 1891–1896

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1,9-Bisdiazononane-2,8-dione 2a
General procedure for the preparation of spiro[4.4]nonane-2,7-
diones 4
Compound 2a was synthesized according to the procedure
described in ref. 17.
The 1,9-bisdiazononane-2,8-dione 2 (6.0 mmol) was dissolved
in dry dichloromethane (600 ml) under nitrogen and a solution
of Rh2(OAc)4 (0.13 g, 5 mol%) in dichloromethane (10 ml)
added. The mixture was stirred at ambient temperature for 12 h.
Nitrogen gas was evolved and the color of the mixture
changed from yellow to a bright emerald green. The mixture
was filtered, the solvent distilled off and the residue subjected to
flash chromatography.
1,9-Bisdiazo-3,7-dimethylnonane-2,8-dione 2b
DMF (5 drops) was added to 2,6-dimethylpimelic acid18 (9.0 g,
47 mmol) in thionyl chloride (30 ml) and the mixture heated
under reflux for 6 h. Excess thionyl chloride was distilled off.
Distillation of the residual material furnished 2,6-dimethyl-
pimeloyl chloride (10.33 g, 96%) as a colorless liquid, bp
90–93 ЊC/0.5 mmHg (HRMS: M 224.0349. C9H14Cl2O2 requires
Spiro[4.4]nonane-2,7-dione 4a. The product 4a, obtained
after flash chromatography using EtOAc–CH2Cl2 1:3 (Rf 0.44),
was further purified by sublimation at 65 ЊC/0.1 mmHg and was
isolated as a white crystalline solid (27%) with mp 84–85 ЊC
(CH2Cl2) (HRMS: M 152.0832. C9H12O2 requires 152.0837);
224.0348); νmax(film)/cmϪ1 1780 (C᎐O); δ (CDCl ) 1.25–1.28
᎐
H
3
(6 H, d, 2 × CH3), 1.37–1.6 (4 H, m, 2 × CH2), 1.71–1.91 (2 H,
m, CH2), 2.76–2.92 (2 H, m, 2 × CH); δC(CDCl3) 16.89 (CH3),
23.80 (CH2), 23.90 (CH2), 32.85 (CH2), 32.92 (CH2), 51.07
(CH), 177.2 (C᎐O); m/z (EI) 224 (Mϩ, 24%), 171 (5), 161 (22),
νmax(KBr)/cmϪ1 1730 (C᎐O); δ (CDCl ) 1.98 (4 H, t, 2 × CH ),
᎐
᎐
H
3
2
149 (25), 133 (16), 126 (36), 105 (11), 97 (100), 69 (64).
2.25 (4 H, s, 2 × CH2), 2.29–2.39 (4 H, m, 2 × CH2); δC(CDCl3)
The acid chloride 1b (1.32 g, 0.58 mmol) in dry diethyl ether
(100 ml) was added dropwise with stirring to a solution of
diazomethane (1.0 g, 2.4 mmol) in diethyl ether (100 ml) at
0 ЊC. The reaction was allowed to proceed at 0 ЊC for 4 h before
the solvent and excess reagent were removed by evaporation at
reduced pressure. The residual material was subjected to flash
chromatography using hexane–EtOAc 1:2. The product (1.09
g, 80%) was a yellowish, partly crystalline, oily material
35.3 (CH ), 38.1, (CH ), 44.6 (C), 51.1 (CH ), 216.92 (C᎐O); m/z
᎐
2
2
2
(EI) 152 (Mϩ, 100%), 123 (21), 109 (27), 96 (51), 81 (42), 67 (64).
3,8-Dimethylspiro[4.4]nonane-2,7-dione 4b. The crude prod-
uct was subjected to flash chromatography using EtOAc–
CH2Cl2–hexane 4:4:5 (Rf 0.5) and further purified by
sublimation at 74 ЊC/0.1 mmHg. The product 4b was obtained
as a white solid (35%), mp 90–92 ЊC (Found: C, 73.44; H, 8.73.
C11H16O2 requires C, 73.33; H, 8.88%) (HRMS: M 180.1155.
(HRMS:
M
236.1302. C11H16N4O2 requires 236.1313);
νmax(film)/cmϪ1 2100 (C᎐N ), 1621 (C᎐O); δ (CDCl ) 0.85–0.97
C11H16O2 requires 180.1150); νmax(KBr)/cmϪ1 1720 (C᎐O);
᎐
᎐
᎐
2
H
3
(6 H, d, 2 × CH3), 1.0–1.3 (4 H, m, 2 × CH2), 1.4–1.55 (2 H, m,
2 × CH ), 2.0–2.3 (2 H, m, 2 × CH); 5.2 (2 H, s, 2 × CH᎐N );
δH(CDCl3) 1.03–1.12 (6 H, d, 2 × CH3), 1.3–2.5 (10 H, m,
5 × CH2); δC(CDCl3) 14.0 (CH3), 14.35 (CH3), 39.4 (C), 39.7
(C), 42.7 (CH), 43.2 (CH), 43.8 (CH2), 44.2 (CH2), 44.7 (CH2),
᎐
2
2
δC(CDCl3) 17.3 (CH3), 17.5 (CH3), 24.9 (CH2), 25.2 (CH2), 33.5
(CH2), 33.6 (CH2), 44.5 (CHN2), 53.5 (COCHCH3), 53.55 (2 ×
50.1 (CH ), 50.4 (CH ), 218.0 (C᎐O), 219.0 (C᎐O); m/z (EI) 180
᎐
᎐
2
2
CH), 198 (C᎐O); m/z (EI) 236 (Mϩ, 0.8%), 109 (10), 98 (19), 81
(Mϩ, 96%), 152 (26), 137 (65), 123 (17), 110 (56), 95 (33), 82
(100), 67 (98).
᎐
(14), 69 (100), 55 (50), 41 (80).
3-Methylspiro[4.4]nonane-2,7-dione 4c. The product 4c,
obtained after flash chromatography using EtOAc–CH2Cl2 6:1
(Rf 0.52) and sublimation at 69 ЊC/0.2 mmHg, was a white solid
(35%) with mp 70–72 ЊC (Found: C, 72.13; H, 8.48. C10H14O2
requires C, 72.28; H, 8.43%) (HRMS: M 166.1002. C10H14O2
1,9-Bisdiazo-3-methylnonane-2,8-dione 2c
2-Methylpimelic acid was prepared from diethyl methyl-
malonate and ethyl 5-bromovalerate,18 and then converted
into its acid chloride,19 which was subsequently reacted with
diazomethane to yield the diazoketone 2c as above. The prod-
uct (1.11 g, 70%) was obtained as a yellowish oily material after
flash chromatography using hexane–EtOAc 1:2. The product
could be kept for a few days in the dark in the refrigerator
requires 166.1001); νmax(KBr)/cmϪ1 1720 (C᎐O); δ (CDCl )
᎐
H
3
1.07–1.11 (3 H, d, CH3), 1.59–1.71 (1 H, m, CH), 1.88–2.05
(2 H, m, CH2), 2.21–2.38 (8 H, m, 4 × CH2); δC(CDCl3) 14.3
(CH3), 14.5 (CH3), 34.5 (CH2), 35.6 (CH2), 37.1 (C), 42.9 (CH),
43.0 (CH), 43.5 (CH2), 43.6 (CH2), 49.55 (CH2), 49.8 (CH2),
50.9 (CH ), 51.0 (CH ), 217.4 (C᎐O), 218.7 (C᎐O); m/z (EI)
(HRMS:
M
222.1119. C10H14N4O2 requires 222.1117);
νmax(film)/cmϪ1 2080 (C᎐N ), 1650 (C᎐O); δ (CDCl ) 1.00–1.04
᎐
᎐
2
H
3
᎐
᎐
2
2
166 (Mϩ, 100%), 146 (5), 138 (12), 123 (33), 109 (20), 96 (36),
82 (44), 67 (57).
(3 H, d, CH3), 1.17–1.59 (6 H, m, 3 × CH2), 2.10–2.37 (3 H, m,
CHCH and CH CO), 5.20 (1 H, s, CH᎐N ); δ (CDCl ) 17.2
᎐
3
2
2
C
3
(CH3), 24.9 (CH2), 26.7 (CH2), 33.3 (CH2), 40.5 (CHN2), 44.7
(CHN2), 53.6 (CH), 54.25 (CH), 195.5 (COCHN2), 199.4
(COCHN2); m/z (EI) 222 (Mϩ, 0.92%), 137 (6), 123 (5), 109
(11), 98 (21), 81 (20), 64 (84), 55 (100).
1,6-Dimethylspiro[4.4]nonane-2,7-dione 4d. When the reac-
tion with 2,10-bisdiazoundecane-3,9-dione (2d) was run under
the above conditions polymeric products were obtained from
which no identified product was isolated.
2,10-Bisdiazoundecane-3,9-dione 2d
Methyl 3-(3-oxocyclopentyl)acrylate 6a14
Pimeloyl chloride (1.32 g, 5.8 mmol) in dry diethyl ether (100
ml) was added dropwise with stirring to a solution of
diazoethane20 (1.5 g, 2.6 mmol) in diethyl ether (100 ml) at 0 ЊC.
The reaction was allowed to proceed at 0 ЊC for 3 h before the
solvent and excess reagent were removed by evaporation at
reduced pressure. The residual material was subjected to flash
chromatography using hexane–EtOAc 1:1 (Rf 0.3) which gave
a yellow oily material (0.8 g, 60%) (HRMS: M 236.1288.
C11H16N4O2 requires 236.1278); νmax(film)/cmϪ1 2060 (C᎐N ),
A 1.2 M solution of potassium tert-butoxide in THF (8 ml,
10 mmol) was added dropwise to a solution of methyl
3-nitropropionate15 (1.3 g, 10 mmol) in dry THF (20 ml) at
Ϫ20 ЊC. The mixture was stirred at this temperature for 15 min,
cooled to Ϫ20 ЊC and cyclopent-2-enone (9.96 g, 10 mmol)
added slowly. The mixture was stirred for 30 min and allowed to
reach ambient temperature during 3 h. Methanol (1.76 ml) was
then added and the mixture stirred at ambient temperature
for 4 days. The reaction was stopped by addition of 2 M HCl
(70 ml) and the product extracted into diethyl ether for further
purification as described in the reference given.
᎐
2
1630 (C᎐O); δ (CDCl ) 1.21–1.35 (2 H, m, CH ), 1.48–1.65
᎐
H
3
2
(4 H, m, 2 × CH2), 1.85 (6 H, s, 2 × CH3), 2.33–2.40 (4 H, t,
2 × CH2); δC(CDCl3) 7.9 (CH3), 24.2 (CH2), 28.6 (CH2), 37.1
(CH ), 61.95 (C᎐N ), 194.25 (C᎐O); m/z (EI) 181 (29), 165
(14), 137 (13), 123 (5), 109 (20), 95 (38), 81 (25), 69 (45), 55
(100).
᎐
᎐
2
2
Methyl 3-(3-oxocyclohexyl)acrylate 6b
The product 6b, obtained after flash chromatography using
J. Chem. Soc., Perkin Trans. 1, 2000, 1891–1896
1893

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hexane–Et2O 1:1, was a colorless oil (50%) (HRMS: M
182.0944. C10H14O3 requires 182.0943); νmax(film)/cmϪ1 2980
3-(3-Oxocycloheptyl)propionic acid 8c
Compound 8c was prepared in 98% yield by following the
procedure described in ref. 22.
(C–H), 1710, 1650 (C᎐O); δ (CDCl ) 1.38–1.79 (2 H, m, CH ),
᎐
H
3
2
1.87–2.47 (6 H, m, 3 × CH2), 2.56–2.73 (1 H, m, CH), 3.67 (3 H,
s, OCH ), 5.71–5.80 (1 H, dd, J 1.5, J 16, CH᎐CHCO Me),
᎐
3
1
2
2
3-(3-Oxocyclopentyl)propionyl chloride 9a
6.78–6.88 (1 H, dd, J 6.6, J 16, CH᎐CHCO Me); δ (CDCl )
᎐
1
2
2
C
3
24.9 (CH2), 30.2 (CH2), 40.7 (CH2), 45.7 (CH), 45.8 (CH2),
A solution of oxalyl chloride (11.4 mmol) in benzene (5 ml)
was added to a solution of 3-(3-oxocyclopentyl)propionic acid
(8a) (7.6 mmol) in dry benzene (20 ml) with ice-cooling. The
resultant solution was stirred at ambient temperature for 1 h,
and at 50 ЊC for 1 h, before the solution was evaporated
to dryness. The acid chloride was isolated after distillation,
bp 88 ЊC/0.3 mmHg, yield 81–82% (HRMS: M 170.0447.
C8H11ClO2 requires 174.0448); νmax(film)/cmϪ1 2960 (C–H),
51.4 (CO CH ), 119.7 (CH᎐CHCO Me), 149.9 (CH᎐CHCO -
᎐
᎐
2
3
2
2
Me), 166.1 (CO Me), 208.5 (C᎐O, ketone); m/z (EI) 182 (Mϩ,
᎐
2
74%), 167 (47), 150 (42), 139 (9), 123 (100), 111 (44), 95 (62),
81 (46).
Methyl 3-(3-oxocycloheptyl)acrylate 6c
Product 6c, obtained after flash chromatography using hexane–
Et2O 1:1, was a colorless oil (45%) (HMRS: M 196.1098.
C11H16O3 requires 196.1099); νmax(film)/cmϪ1 2910, 2850 (C–H),
1780, 1720 (C᎐O); δ (CDCl ) 1.3–1.92 (5 H, m, 2 × CH , CH),
᎐
H
3
2
2–2.45 (4 H, m, 2 × CH2), 2.84–2.97 (2 H, m, CH2COCl);
δC(CDCl3) 29.1 (CH2), 30.5 (CH2), 35.9 (CH2), 38.3 (CH), 44.5
1710, 1640 (C᎐O); δ (CDCl ) 1.37–1.98 (6 H, m, 3 × CH ),
᎐
H
3
2
(CH ), 45.4 (CH ), 173.4 (COCl), 218.1 (C᎐O, ketone); m/z (EI)
᎐
2
2
2.43–2.6 (5 H, m, CH2COCH2 and CH), 3.67 (3 H, s, OCH3),
5.71–5.79 (1 H, dd, J 7.0, J 16.0, CH᎐CHCO Me), 6.78–6.90
174.8 (Mϩ, 3%), 174 (22), 145 (6), 139 (44), 111 (8), 96 (24),
83 (14), 55 (100).
᎐
1
2
2
(1 H, dd, J1 1.0, J2 16.0, CH᎐CHCO Me); δ (CDCl ) 23.9
᎐
2
C
3
(CH2), 28.3 (CH2), 35.90 (CH2), 38.6 (CH2), 43.95 (CH), 47.9
(CH ), 51.6 (OCH ), 119.4 (CH᎐CHCO Me), 151.6 (CH᎐
3-(3-Oxocyclohexyl)propionyl chloride 9b
᎐
᎐
2
3
2
CHCO Me), 166.7 (CO Me), 212.0 (C᎐O, ketone); m/z (EI) 196
Compound 9c was obtained as above from oxalyl chloride in
85–89% yield, bp 89–92 ЊC/0.3 mmHg (HRMS: M 188.0587.
C9H13ClO2 requires 188.0582); νmax(film)/cmϪ1 2950 (C–H),
᎐
2
2
(Mϩ, 9%), 164 (44), 136 (100), 122 (7), 107 (26), 94 (23), 87 (9),
81 (24).
1780, 1700 (C᎐O); δ (CDCl ) 1.18–2.13 (8 H, m, 4 × CH ),
᎐
H
3
2
Methyl 3-(3-oxocyclopentyl)propionate 7a
2.16–2.33 (3 H, m, CH2, CH), 2.78–2.85 (2 H, t, CH2COCl);
δC(CDCl3) 24.4 (CH2), 30.2 (CH2), 30.8 (CH2), 37.2 (CH2), 40.6
Compound 7a was prepared according to the procedure
described in ref. 14.
(CH), 43.9 (CH ), 46.8 (CH ), 172.4 (COCl), 209.2 (C᎐O,
᎐
2
2
ketone); m/z (EI) 188 (Mϩ, 25%), 153 (38), 145 (41), 124 (16),
116 (5), 110 (100), 97 (78), 89 (20), 82 (50), 69 (35), 55 (96).
Methyl 3-(3-oxocyclohexyl)propionate 7b
A solution of methyl 3-(3-oxocyclohexyl)acrylate (6b) (1.5 g,
8.2 mmol) in acetic acid (15 ml) was hydrogenated over 10%
palladium-on-charcoal (0.5 g) at atmospheric pressure for 6 h.
The catalyst was removed by filtration through a plug of Celite,
the filtrate evaporated at reduced pressure and the residual
material subjected to flash chromatography using hexane–Et2O
1:1. The product (1.42 g, 94%) was a colorless oil (HRMS:
M 184.1086. C11H16O3 requires 184.1091); νmax(film)/cmϪ1 2910
3-(3-Oxocycloheptyl)propionyl chloride 9c
Compound 9c was obtained as above from oxalyl chloride in
81–83% yield, bp 90–92 ЊC/0.3 mmHg (HRMS: M 202.0758.
C10H15ClO2 requires 202.0760); νmax(film)/cmϪ1 2910, 2860
(C–H), 1770, 1680 (C᎐O); δ (CDCl ) 1.25–1.91 (9 H, m,
᎐
H
3
4 × CH2, CH), 2.39–2.48 (4 H, m, 2 × CH2), 2.88–2.95 (2 H, t,
CH2COCl); δC(CDCl3) 24.1 (CH2), 27.95 (CH2), 31.7 (CH2),
34.8 (CH2), 36.3 (CH2), 43.8 (CH), 44.7 (CH2), 49.0 (CH2),
(C–H), 1720, 1690 (C᎐O); δ (CDCl ) 1.18–1.38 (2 H, m, CH ),
᎐
173.6 (COCl), 213.3 (C᎐O, ketone); m/z (EI) 202 (Mϩ, 0.6%),
H
3
2
᎐
1.44–2.0 (6 H, m, 3 × CH2), 2.11–2.39 (5 H, m, 2 × CH2, CH),
3.62 (3 H, s, OCH3); δC(CDCl3) 21.2 (CH2), 25.4 (CH2), 31.2
(CH2), 31.6 (CH2), 38.6 (CH), 41.4 (CH2), 47.75 (CH2), 51.8
184 (18), 166 (10), 138 (27), 124 (44), 111 (100), 96 (23), 83 (30),
55 (95).
(OCH ), 172.85 (CO CH ), 210.0 (C᎐O, ketone); m/z (EI)
᎐
3
2
3
1-Diazo-4-(3-oxocyclopentyl)butan-2-one 10a
184 (Mϩ, 10%), 153 (21), 124 (7), 110 (100), 97 (98), 82 (13),
74 (18).
A solution of 3-(3-oxocyclopentyl)propionyl chloride (9a)
(6 mmol) in anhydrous diethyl ether (10 ml) was added drop-
wise over 30 min to a solution of diazomethane (12 mmol) in
anhydrous diethyl ether (50 ml) with stirring at 0 ЊC. The solu-
tion was stirred at this temperature for 3 h before the solvent
was evaporated. The residual oil was subjected to flash chrom-
atography using hexane–EtOAc 1:3; the product was a yellow
oily material (0.864 g, 80%) (HRMS (M Ϫ N2) 152.0829.
C9H12O2 (M Ϫ N2) requires 152.0838); νmax(film)/cmϪ1 3030,
Methyl 3-(3-oxocycloheptyl)propionate 7c
Compound 7c was prepared from methyl 3-(3-oxocycloheptyl)-
acrylate (6c) (2.02 g, 10 mmol) as above. Flash chromatography
using hexane–Et2O 1:1 gave the product 7c (1.85 g, 90%)
as a colorless oil (HRMS: M 198.1265. C11H18O3 requires
198.1256); νmax(film)/cmϪ1 2900, 2870 (C–H), 1750, 1680 (C᎐O);
᎐
δH(CDCl3) 1.15–1.60 (4 H, m, 2 × CH2), 1.78–1.84 (3 H, m,
CH2, CH), 2.23–2.43 (6 H, m, 3 × CH2), 3.6 (3 H, s, OCH3);
δC(CDCl3) 24.2 (CH2), 28.2 (CH2), 31.5 (CH2), 31.9 (CH2), 35.3
(CH2), 36.4 (CH2), 43.75 (CH2), 49.3 (CH2), 51.5 (OCH3), 173.0
2900 (C–H), 2094 (C᎐N ), 1720, 1630 (C᎐O); δ (CDCl ) 1.20–
᎐
᎐
2
H
3
1.80 (4 H, m, CH2CH2COCHN2 and CH2CH2CO), 2.07–2.35
(7 H, m, CH2COCHN2, CH2COCH2 and CH), 5.25 (1 H, s,
CHN2); δC(CDCl3) 29.2 (CH2), 30.4 (CH2), 36.5 (CH2), 38.4
(CH), 38.9 (CH2), 44.8 (CH2), 54.5 (CHN2), 194.0 (COCHN2),
218.7 (C᎐O, ring); m/z (EI) 152 (Mϩ Ϫ N , 17%), 123 (51), 109
(CO CH ), 213.7 (C᎐O, ketone); m/z (EI) 198 (Mϩ, 11%), 167
᎐
2
3
(25), 155 (6), 138 (29), 124 (68), 111 (100), 96 (26), 83 (25).
᎐
2
(14), 95 (27), 84 (65), 67 (26), 55 (100).
3-(3-Oxocyclopentyl)propionic acid 8a
Compound 8a was prepared in 96% yield by following the
1-Diazo-4-(3-oxocyclohexyl)butan-2-one 10b
procedure described in ref. 20.
Compound 10b was obtained as above from 3-(3-oxocyclo-
hexyl)propionyl chloride (9b) as a yellow oil (88%) (HRMS
(M Ϫ N2) 166.0986. C9H12O2 (M Ϫ N2) requires 166.0994);
νmax(film)/cmϪ1 3010, 2910, 2880 (C–H), 2100 (C᎐N ), 1700,
3-(3-Oxocyclohexyl)propionic acid 8b
Compound 8b was prepared in 98% yield by following the
᎐
2
procedure described in ref. 21.
1630 (C᎐O); δ (CDCl ) 1.15–1.40 (2 H, m, CH ), 1.51–2.06
᎐
H 3 2
1894
J. Chem. Soc., Perkin Trans. 1, 2000, 1891–1896

View Article Online
(8 H, m, 4 × CH2), 2.18–2.42 (5 H, m, 2 × CH2, CH), 5.23 (1 H,
s, CHN2); δC(CDCl3) 25.1 (CH2), 31.2 (CH2), 31.4 (CH2), 38.0
(CH2), 38.6 (CH), 41.3 (CH2), 47.8 (CH2), 54.5 (CHN2), 194.15
Spiro[4.4]nonane-2,7-dione 12a (4a)
A solution of 1-diazo-4-(3-oxocyclopentyl)butan-2-one (10a)
(0.63 g, 3.5 mmol) in dry dichloromethane (100 ml) was added
dropwise over 1 h to a stirred suspension of Rh2(OAc)4 (0.074 g,
0.17 mmol) in dry methylene chloride (60 ml) under nitrogen at
ambient temperature. The mixture was stirred at this temper-
ature for 14 h. Filtration, evaporation of the filtrate and flash
chromatography of the residual material using EtOAc–CH2Cl2
1:3 gave the product as a white crystalline solid (0.234 g, 44%)
with mp 84–85 ЊC (sublimed at 65 ЊC/0.1 mmHg) (HRMS: M
152.0832. C9H12O2 requires 152.0837); νmax(KBr)/cmϪ1 2980
(COCHN ), 211.1 (C᎐O, ring); m/z (EI) 166 (Mϩ Ϫ N , 2%),
᎐
2
2
138 (35), 123 (48), 109 (23), 95 (19), 84 (99), 55 (100).
1-Diazo-4-(3-oxocycloheptyl)butan-2-one 10c
Compound 10c was obtained as above from 3-(3-oxocyclo-
heptyl)propionyl chloride (9c) as a yellow oil (78%) (HRMS
(M Ϫ N2) 180.1141. C10H14O2 (M Ϫ N2) requires 180.1148);
νmax(film)/cmϪ1 3060, 2910, 2860 (C–H), 2080 (C᎐N ), 1680,
᎐
2
1620 (C᎐O); δ (CDCl ) 1.18–1.7 (6 H, m, 3 × CH ), 1.76–1.91
(C–H), 1730 (C᎐O); δ (CDCl ) 1.98 (4 H, t, 2 × CH ), 2.25
᎐
H 3 2
᎐
H
3
2
(3 H, m, CH2, CH), 2.27–2.43 (6 H, m, 3 × CH2), 5.22 (1 H, s,
CHN2); δC(CDCl3) 24.1 (CH2), 28.0 (CH2), 31.8 (CH2), 35.3
(CH2), 36.6 (CH2), 38.1 (CH), 43.7 (CH2), 49.1 (CH2), 54.4
(4 H, s, CH2), 2.29–2.39 (4 H, m, 2 × CH2); δC(CDCl3) 35.3
(CH ), 38.1 (CH ), 44.6 (C), 51.1 (CH ), 216.9 (C᎐O); m/z (EI)
᎐
2
2
2
152 (Mϩ, 100%), 123 (21), 109 (27), 96 (51), 81 (42), 67 (64).
(CHN ), 194.3 (COCHN ), 213.8 (C᎐O, ring); m/z (EI) 180
᎐
2
2
(Mϩ Ϫ N2, 4%), 151 (21), 137 (3), 123 (27), 109 (19), 95 (21),
Spiro[4.5]decane-2,7-dione 12b
84 (83), 55 (100).
Compound 12b was obtained as above from 1-diazo-4-(3-oxo-
cyclohexyl)butan-2-one (10b). After flash chromatography using
CH2Cl2–EtOAc 12:1 the product 12b was obtained as an
oily material (44%) (Found: C, 72.06; H, 8.44. C10H14O2
requires C, 72.28; H, 8.43%) (HRMS: M 166.1000. C10H14O2
requires 166.0994); νmax(KBr)/cmϪ1 2980 (C–H), 1730, 1700
Ethyl 2-diazo-3-oxo-5-(3-oxocyclopentyl)pentanoate 11a
3-(3-Oxocyclopentanyl)propionyl chloride (9a) (6 mmol)
and ethyl diazoacetate (13 mmol) were mixed. The mixture was
stirred at ambient temperature for 30 min; the stirring was
continued at 40 ЊC for 1 h and at 60 ЊC for 6 h. Excess ethyl
diazoacetate and the ethyl chloroacetate, which was formed
in the reaction, were removed by distillation under reduced
pressure. The residual oily material was purified by flash
chromatography using hexane–EtOAc 2:1. The product (1.05
g, 70%) was a yellow oil (HRMS (M Ϫ N2) 224.1103. C12H16O4
(M Ϫ N2) requires 224.1111); νmax(film)/cmϪ1 2899 (C–H), 2120
(C᎐O); δ (CDCl ) 1.73–2.04 (6 H, m, 3 × CH ), 2.10–2.17 (2 H,
᎐
H
3
2
m, CH2), 2.25–2.42 (6 H, m, 3 × CH2); δC(CDCl3) 23.4 (CH2),
34.4 (CH2), 36.15 (CH2), 36.7 (CH2), 41.3 (CH2), 44.8 (C), 50.7
(CH ), 52.45 (CH ), 208.35 (7-C᎐O), 215.7 (2-C᎐O); m/z (EI)
᎐
᎐
2
2
167 (Mϩ, 100%), 148 (7), 138 (38), 123 (42), 110 (50), 95 (33),
82 (43), 67 (80), 55 (91).
(C᎐N ), 1740, 1700, 1640 (C᎐O); δ (CDCl ) 1.20–1.27 (3 H, t,
Spiro[4.6]undecane-2,7-dione 12c
᎐
᎐
2
H
3
CH3CH2O), 1.39–1.80 (4 H, m, CH2CH2COCN2CO, CH2-
CH2CO), 2.0–2.4 (5 H, m, CH2COCH2, CH), 2.78–2.86 (2 H,
m, CH2COCN2), 4.15–4.26 (2 H, q, CH3CH2O); δC(CDCl3)
14.8 (CH3), 29.8 (CH2), 30.3 (CH2), 37.6 (CH2), 39.3 (CH),
Compound 12c was obtained as above from 1-diazo-4-(3-
oxocycloheptyl)butan-2-one (10c). Flash chromatography
using CH2Cl2–EtOAc 6:1 gave a colourless oil (43%) (HRMS:
M 180.1157. C11H16O2 requires 180.1150); νmax(KBr)/cmϪ1
39.4 (CH ), 45.9 (CH ), 54.1 (C᎐N), 62.1 (CH CH O), 160.7
᎐
2
2
3
2
2910–2900 (C–H), 1730, 1680 (C᎐O); δ (CDCl ) 1.58–1.90
᎐
H
3
(CO Et), 191.4 (CN CO), 217.8 (C᎐O, ring); m/z (EI) 224
᎐
2
2
(8 H, m, 4 × CH2), 2.06–2.08 (2 H, d, CH2), 2.21–2.32 (2 H, d,
CH2), 2.36–2.44 (2 H, m, CH2), 2.58–2.61 (2 H, d, CH2);
δC(CDCl3) 23.9 (CH2), 25.4 (CH2), 34.5 (CH2), 36.3 (CH2), 41.3
(C), 42.2 (CH2), 44.1 (CH2), 51.6 (CH2), 53.8 (CH2), 212.4
(7-C᎐O), 217.9 (2-C᎐O); m/z (EI) 180 (Mϩ, 59%), 162 (51),
(Mϩ Ϫ N2, 0.63%), 178 (33), 156 (44), 150 (16), 139 (15), 122
(24), 109 (11), 99 (42), 83 (20), 55 (100).
Ethyl 2-diazo-3-oxo-5-(3-oxocyclohexyl)pentanoate 11b
᎐
᎐
Compound 11b was obtained as above from 3-(3-oxocyclo-
hexyl)propionyl chloride (9b) as a yellow oil (73%) (HRMS
(M Ϫ N2) 238.1196. C13H18O4 (M Ϫ N2) requires 238.1205);
νmax(film)/cmϪ1 2910, 2890 (C–H), 2110 (C᎐N ), 1700, 1650
152 (18), 137 (16), 122 (93), 109 (72), 96 (100), 81 (53), 67 (53).
Ethyl 2,7-dioxospiro[4.4]nonane-1-carboxylate 13a
᎐
2
A solution of ethyl 2-diazo-3-oxo-5-(3-oxocyclopentyl)pentan-
oate (0.882 g, 3.5 mmol) in dry dichloromethane (100 ml) was
added dropwise over 1 h to a stirred suspension of Rh2(OAc)4
(0.074 g, 0.17 mmol) in dry dichloromethane (60 ml) under
nitrogen at ambient temperature. The mixture was stirred at this
temperature for 14 h. Filtration, evaporation of the filtrate and
flash chromatography of the residual material using CH2Cl2–
EtOAc 6:1 gave the product (0.31 g, 43%) as a colorless oil
(Found: C, 64.22; H, 7.48. C12H16O4 requires C, 64.28; H,
7.14%) (HRMS: M 224.1044. C12H16O4 requires 224.1048);
(C᎐O); δ (CDCl ) 1.25–1.32 (3 H, t, OCH CH ), 1.47–2.42
᎐
H
3
2
3
(11 H, m, 5 × CH2, CH), 2.77–2.86 (2 H, m, CH2COCN2),
4.18–4.28 (2 H, q, CH3CH2O); δC(CDCl3) 14.9 (CH3), 25.6
(CH2), 31.2 (CH2), 31.5 (CH2), 37.8 (CH2), 39.0 (CH), 41.8
(CH ), 48.3 (CH ), 53.2 (C᎐N ), 61.8 (CH CH O), 161.2
᎐
2
2
2
3
2
(CO Et), 192.2 (COCN ), 211.1 (C᎐O, ring); m/z (EI) 238
᎐
2
2
(Mϩ Ϫ N2, 3%), 210 (11), 192 (25), 164 (44), 156 (87), 135 (18),
123 (21), 110 (28), 99 (55), 55 (100).
Ethyl 2-diazo-3-oxo-5-(3-oxocycloheptyl)pentanoate 11c
νmax(film)/cmϪ1 2910 (C–H), 1740, 1700, 1635, 1600 (C᎐O);
᎐
Compound 11c was obtained as above from 3-(3-oxocyclo-
heptyl)propionyl chloride (9c) as a yellow oil (72%) (HRMS
(M Ϫ N2) 252.1350. C14H20O4 (M Ϫ N2) requires 252.1361);
νmax(film)/cmϪ1 2900 (C–H), 2120 (C᎐N ), 1700–1640 (C᎐O);
δH(CDCl3) 1.19–1.39 (5 H, m, OCH2CH3, CH2), 1.40–1.68 (4 H,
m, 2 × CH2), 1.79–1.88 (3 H, m, CH2, CH), 2.37–2.50 (4 H, m,
2 × CH2), 2.80–2.87 (2 H, t, CH2COCN2), 4.20–4.31 (2 H, q,
CH3CH2O); δC(CDCl3) 14.4 (CH3), 24.4 (CH2), 28.5 (CH2), 31.5
(CH2), 35.6 (CH2), 36.5 (CH2), 37.7 (CH), 43.9 (CH2), 49.6
δH(500 MHz; CDCl3) 1.22–1.36 (3 H, m, OCH3CH2), 1.61–2.64
(10 H, m, 5 × CH2), 2.76, 2.79, 3.08, 3.11 (1 H, 4 × s), 4.13–4.36
(2 H, m, OCH2CH3) 10.87 (1 H, s, OH enol); δC(125 MHz;
CDCl3) 14.1, 14.25 (OCH2CH3), 29.55, 29.6, 29.8, 30.4, 30.5
(5 × CH2), 33.3, 33.5, 33.5, 34.0, 34.3, 34.45, 34.7, 34.9
(8 × CH2), 36.1, 36.4, 36.5, 36.6, 36.6, 36.8, 37.0, 37.3
(8 × CH2), 44.5, 44.8, 46.3, (3 × CH2), 48.2, 48.2, 49.2 (3 × C),
50.2, 50.3, 50.5, 50.9, 51.1 (6 × CH2), 60.2, 61.6, 61.6
(OCH2CH3), 63.0, 63.1, 63.2, 63.75 (CHCO2), 84.6, 104.6
(C–OH, enol), 167.95, 168.1, 169.4, 169.85, 169.95, 175.9, 177.5
(CO Et), 210.6, 212.1, 216.1–216.3, 217.35, 219.4 (C᎐O); m/z
᎐
᎐
2
(CH ), 54.6 (C᎐N ), 61.4 (CH CH O), 160.95 (CO Et), 192.1
᎐
2
2
3
2
2
(CN CO), 213.5 (C᎐O, ring); m/z (EI) 252 (Mϩ Ϫ N , 8%), 206
᎐
᎐
2
2
2
(17), 195 (5), 188 (13), 178 (19), 167 (21), 156 (100), 149 (18),
135 (15), 99 (47).
(EI) 224 (Mϩ, 61%), 206 (19), 195 (20), 178 (61), 168 (24), 160
(15), 149 (41), 136 (25), 122 (100).
J. Chem. Soc., Perkin Trans. 1, 2000, 1891–1896
1895

View Article Online
Ethyl 2,7-dioxospiro[4.5]decane-1-carboxylate 13b
214.7, 214.8, 215.9, 216.0 (4 × C᎐O); m/z (EI) 238 (Mϩ, 92%),
210 (44), 193 (30), 155 (33), 137 (80), 123 (41), 109 (100), 95
(50), 81 (47), 67 (43), 55 (78), 41 (56), 29 (84).
᎐
Compound 13b was prepared as above from ethyl 2-diazo-3-
oxo-5-(3-oxocyclohexyl)pentanoate (11b). The product (45%)
was a colorless oily material (Found: C, 65.27; H, 7.48.
C13H18O4 requires C, 65.54; H, 7.56%) (HRMS: M 238.1213.
C13H18O4 requires 238.1205); νmax(film)/cmϪ1 2190 (C–H), 1740,
1-Methylspiro[4.4]nonane-2,7-dione 16
A
solution of ethyl 1-methyl-2,7-dioxospiro[4.4]nonane-1-
1700, 1635, 1600 (C᎐O); δ (500 MHz; CDCl ) 1.22–1.25, 1.28–
carboxylate (15) (0.110 g, 0.46 mmol) in acetic acid (2 ml) and
HCl (6 ml; 20%) was heated under reflux for 14 h. The cold
reaction mixture was extracted with diethyl ether (3 × 10 ml),
the combined ethereal solutions washed with water and aq.
20% NaHCO3, dried (MgSO4), the ether distilled off and the
residual material subjected to flash chromatography using
CH2Cl2–EtOAc 6:1. The product (0.046 g, 60%) was a white
solid with mp 71–72.5 ЊC (sublimed at 60–62 ЊC/0.1 mmHg)
(Found: C, 72.18; H, 8.46. C10H14O2 requires C, 72.28; H, 8.44%)
(HRMS: M 166.1003. C10H14O2 requires 166.1001); νmax(KBr)/
᎐
H
3
1.31 (3 H, t, CH3CH2O), 1.5–1.79 (4 H, m, 2 × CH2), 1.8–2.1
(4 H, m, 2 × CH2), 2.26–2.32 (2 H, m, CH2), 2.4–2.5 (2 H, m,
CH2), 2.82, 2.87, 2.99 (1 H, 3 × s), 4.13–4.17, 4.23–4.35 (2 H, q,
CH3CH2O), 10.84 (1 H, s, OH enol); δC(125 MHz; CDCl3) 14.0,
14.1, 14.1, 14.25 (CH3CH2O), 21.6, 22.1, 22.2 (3 × CH2), 24.95,
25.0, 25.9, 30.2, 30.8, 30.85, 31.2, 31.3, 31.45, 31.5 (10 × CH2),
34.9, 35.5, 35.7, 35.7 (4 × CH2), 40.5, 40.7, 40.75, 40.8, 40.85,
41.2, 41.25 (7 × CH2), 47.6, 47.65, 47.8 (3 × C), 48.1, 49.55,
51.4, 51.9, 52.1 (5 × CH2), 60.0, 61.3, 61.3, 61.35 (CH3CH2O),
64.2, 64.84, 65.8 (CHCO2Et), 106.45 (C–OH, enol), 167.7, 167.8,
169.2, 169.6, 177.25 (CO2Et), 208.85, 209.2, 210.8, 211.15,
cmϪ1 1726 (C᎐O); δ (CDCl ) 1.01–1.07 (3 H, t, CH ), 1.19–1.27
᎐
H
3
3
(1 H, m, CHCH3), 1.96–2.43 (10 H, m, CH2); δC(CDCl3)
8.7, 8.9 (2 × CH3), 27.3, 32.7, 33.9, 35.2, 35.4, 36.85, 37.0
(7 × CH2), 47.9, 49.8 (2 × C), 52.15, 52.3 (2 × CHCH3), 217.4,
211.3, 211.4 (C᎐O); m/z (EI) 238 (Mϩ, 61%), 220 (11), 192 (100),
᎐
181 (59), 164 (43), 149 (77), 135 (92), 122 (77), 108 (37).
218.2 (2 × C᎐O); m/z (EI) 166 (Mϩ, 100%), 155 (13), 137 (46),
᎐
Ethyl 2,7-dioxospiro[4.6]undecane-1-carboxylate 13c
123 (45), 109 (92), 95 (45), 67 (77).
Compound 13c was prepared as above from ethyl 2-diazo-3-
oxo-5-(3-oxocycloheptyl)pentanoate (11c). The product (41%)
was a colorless oily material (HRMS: M 252.1368. C14H20O4
requires 252.1362); νmax(film)/cmϪ1 2900, 2850 (C–H), 1750,
References
1 M. L. Falck-Pedersen and K. Undheim, Tetrahedron, 1999, 55, 8525.
2 D. Sirbu, M. L. Falck-Pedersen, C. Rømming and K. Undheim,
Tetrahedron, 1999, 55, 6703.
1720, 1680, 1640, 1600 (C᎐O); δ (500 MHz; CDCl ) 1.20–1.25,
᎐
H
3
3 J. A. Nieman, M. Parvez and B. A. Keay, Tetrahedron: Asymmetry,
1993, 4, 1973.
4 M. F. Semmelhack, J. S. Foos and S. Katz, J. Am. Chem. Soc., 1973,
95, 7325.
5 S. Danishefsky, S. Chackalamannil and B. J. Uang, J. Org. Chem.,
1982, 47, 2231.
6 P. S. Aburel and K. Undheim, Tetrahedron Lett., 1998, 39, 3813.
7 G. A. Molander and C. Alonso-Alija, Tetrahedron, 1997, 53, 8067.
8 S. Yamada, S. Karasawa, Y. Takahashi, M. Aso and H. Suemune,
Tetrahedron, 1998, 54, 15555.
9 (a) M. P. Doyle, M. A. McKervey and T. Ye, Modern Catalytic
Methods for Organic Synthesis with Diazo Compounds. From
Cyclopropanes to Ylides, Wiley-Interscience, New York, 1998,
p. 112; (b) M. P. Doyle, in Comprehensive Organometallic Chemistry
II, ed. L. S. Hegedus, Pergamon Press, New York, 1995, Vol. 12,
Chapter 5.2.
1.28–1.31 (3 H, m, CH3CH2O), 1.49–1.9 (8 H, m, 4 × CH2),
2.0–2.52 (6 H, m, 3 × CH2), 2.84, 2.86, 2.89, 2.91, 2.98 (1 H,
5 × s), 4.11–4.18, 4.21–4.24 (2 H, m, CH3CH2O), 10.74 (1 H, s,
OH); δC(125 MHz; CDCl3) 14.0, 14.1, 14.25 (3 × CH3CH2O),
23.3–23.5, 24.5, 24.6, 28.9, 30.4, 30.8, 31.7, 35.35, 35.6, 37.6,
40.0, 42.2, 43.8, 43.9, 44.2, 44.8, 45.0 (18 × CH2), 46.35, 48.7
(2 × C), 51.95, 53.2, 53.8, 59.9 (4 × CH2), 61.1, 61.2, 61.3
(4 × CH3CH2O), 65.4, 65.9 (2 × CHCO2Et), 109.0 (C–OH,
enol), 167.2, 167.9, 169.2, 169.5, 176.35 (5 × CO2Et), 211.0,
211.2, 211.3, 211.9, 213.4, 213.9 (6 × C᎐O); m/z (EI) 252 (Mϩ,
᎐
56%), 206 (89), 194 (68), 188 (28), 178 (35), 164 (54), 135 (36),
122 (100), 109 (25), 95 (36).
Ethyl 1-methyl-2,7-dioxospiro[4.4]nonane-1-carboxylate 15
10 A. Padwa and K. E. Krumpe, Tetrahedron, 1992, 48, 5385.
11 J. Adams and D. M. Spero, Tetrahedron, 1991, 47, 1765.
12 (a) D. F. Taber, in Comprehensive Organic Synthesis: Selectivity,
Strategy, and Efficiency in Modern Organic Chemistry, eds. B. M.
Trost and I. Fleming, Pergamon Press, New York, 1991, Vol. 3,
Chapter 4.2; (b) D. F. Taber and R. E. Ruckle, J. Am. Chem. Soc.,
1986, 108, 7686; (c) D. F. Taber, J. C. Amedio and R. G. Sherill,
J. Org. Chem., 1986, 51, 3382; (d) D. F. Taber and E. H. Petty, J. Org.
Chem., 1982, 47, 4808.
13 S.-i. Hashimoto, N. Watanabe and S. Ikegami, Tetrahedron Lett.,
1992, 33, 2709.
14 R. O. Duthaler and P. Maienfisch, Helv. Chim. Acta, 1984, 67, 856.
15 D. Seebach, R. Henning and T. Mukhapadhyay, Chem. Ber., 1982,
1705.
A solution of ethyl 2,7-dioxospiro[4.4]nonane-1-carboxylate
(13a) (0.140 g, 0.66 mmol) in dry THF (3 ml) was added drop-
wise over 10 min to a stirred suspension of NaH (30 mg, 0.75
mmol) in dry THF (5 ml) under nitrogen at 0 ЊC. The mixture
was allowed to reach ambient temperature before a solution of
methyl iodide (0.093 g, 0.66 mmol) in THF (2 ml) was added.
The mixture was stirred at ambient temperature for 10 h when
the reaction was acidified with HCl. The mixture was extracted
with diethyl ether, the ethereal solution dried (MgSO4), evap-
orated and the residual material subjected to flash chrom-
atography using CH2Cl2–EtOAc 6:1. The product (0.110 g,
80%) was a colorless oil (HRMS: M 238.1214. C13H18O4
requires 238.1205); νmax(film)/cmϪ1 2915 (C–H), 1735, 1688,
16 L. F. Fieser and M. Fieser, Reagents for Organic Synthesis, 1967,
p. 191.
17 E. Fahr, Liebigs Ann. Chem., 1960, 638, 1.
18 P. Karrer, F. Benz, R. Morf, H. Raudnitz, M. Stoll and T.
Takahashi, Helv. Chim. Acta, 1932, 15, 1399.
1630, 1605 (C᎐O); δ (CDCl ) 1.17 (3 H, s, CH ), 1.20–1.25
᎐
H
3
3
(3 H, m, CH3CH2O), 1.71–2.45 (10 H, m, 5 × CH2), 4.05–4.19
(2 H, m, CH3CH2O); δC(CDCl3) 14.45, 14.5 (2 × CH3), 15.0,
15.5 (CH3CH2O), 29.3, 31.35, 31.5, 36.0, 36.1, 36.55, 36.6,
46.9, 48.3 (9 × CH2), 51.0, 51.4 (2 × C) 61.3, 61.35 (2 × EtO2-
CCCH3), 61.8, 61.9 (2 × CH3CH2O), 171.2, 171.5 (2 × EtO2C ),
19 M. Mousseron and J. Jullien, Bull. Soc. Chim. Fr., 1947, 605.
20 F. Foubelo, F. Lioret and M. Yus, Tetrahedron, 1992, 48, 9531.
21 H. Gerlach, Helv. Chim. Acta, 1978, 61, 2773.
22 W. L. Mock and M. E. Hartman, J. Org. Chem., 1977, 42, 459.
1896
J. Chem. Soc., Perkin Trans. 1, 2000, 1891–1896