Cyclopropanespiro-β-lactones derived from 4-[(Z)-ethylidene]-3- methyloxetan-2-one: Diastereoselective formation and rearrangement reactions

Article abstract of DOI:10.1016/j.tet.2011.03.013

The metal catalysed reaction of monosubstituted diazo esters and ketones with 4-[(Z)-ethylidene]-3-methyloxetan-2-one results in the formation of cyclopropanespiro-β-lactones. In contrast to most alkene cyclopropanations, including those involving diketene, the reaction occurs diastereoselectively. A computational model of the reaction has been developed that accounts for the observed stereochemistry. The metal promoted thermal rearrangement of these spiro compounds is also unusual in that it affords pyranones, rather than the decarboxylation products characteristic of β-lactones in general, or the furanones formed from diketene derived cyclopropanespiro-β-lactones.

Full text of DOI:10.1016/j.tet.2011.03.013

Tetrahedron 67 (2011) 3546e3552
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Cyclopropanespiro-
b-lactones derived from 4-[(Z)-ethylidene]-3-methyloxetan-
2-one: diastereoselective formation and rearrangement reactions
*
Niall W.A. Geraghty , Patrick McArdle, Laverne M.A. Mullen
School of Chemistry, National University of Ireland, Galway, Ireland
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 5 August 2010
Received in revised form 24 February 2011
Accepted 7 March 2011
Available online 15 March 2011
The metal catalysed reaction of monosubstituted diazo esters and ketones with 4-[(Z)-ethylidene]-3-
methyloxetan-2-one results in the formation of cyclopropanespiro-b-lactones. In contrast to most alkene
cyclopropanations, including those involving diketene, the reaction occurs diastereoselectively. A com-
putational model of the reaction has been developed that accounts for the observed stereochemistry. The
metal promoted thermal rearrangement of these spiro compounds is also unusual in that it affords
pyranones, rather than the decarboxylation products characteristic of
anones formed from diketene derived cyclopropanespiro- -lactones.
b-lactones in general, or the fur-
b
Ó 2011 Elsevier Ltd. All rights reserved.
1. Introduction
R R
N2
R R
Rh2(OAc)4
O
The cyclopropanation of diketene 1 using
a-diazo esters or
+
O
O
O
ketones,1 diazoalkanes,1c -diazoalkyl)phosphonates2 or phenyl-
(a
O
O
(tribromomethyl)mercury3 leads to the formation of cyclo-
propanespiro- -lactones (Scheme 1). These methods afford access
to a wide range of structurally diverse cyclopropanespiro- -lac-
1
b
R = H, 72%
R = Me, 46%
b
tones, with, for example, diazocycloalkanes producing doubly spiro
systems (Scheme 1).
Scheme 2. Reaction of 2-diazo-1.3-dicarbonyl compounds with diketene 1.
As cyclopropanespiro-b-lactones are highly strained and,
C(O)Ph
Cl Cl
although relatively small, contain a significant amount of function-
ality, these compounds are potentially valuable synthetic in-
termediates. As would be expected from their structure, they react
readily with a variety of nucleophiles, including amines,1b,2 giving
acyclic products and with carbanions2 from acetoacetate giving
cyclopentenones. BF3 promoted ring opening also results in the for-
mation of acyclic products. Surprisingly however, unlike larger
N2CHC(O)Ph
Rh2(OAc)4
PhHgCBr3
O
O
O
O
O
O
O
Δ
1
55%
O
75%
O
Rh2(OAc)4
O
O
cycloalkanespiro-
carboxylation, the classic reaction of
dergo a metal-promoted rearrangement to furanones (Scheme 3).1c,5
Although all cyclopropanespiro- -lactones reported to date have
been derived from diketene, the related 4-[(Z)-ethylidene]-3-meth-
yloxetan-2-one
is also readily available6 through the
b-lactones, they do not undergo thermal de-
O
b-lactones. Instead they un-
N2
1
40%
b
Scheme 1. Synthesis of cyclopropanespiro-b-lactones from diketene 1.
2
diastereoselective base promoted dimerization of methylketene
generated from propionyl chloride. If the base used in the di-
Only 2-diazo-1,3-dicarbonyl compounds fail to produce cyclo-
propanespiro- -lactones, affording instead benzofurans through
b
merization reaction is chiral, the
b-lactone is formed enantiose-
a formal 1,3-dipolar cycloaddition of a carbenoid to the exocyclic
lectively.7 The range of reactivity previously observed for 1 and the
fact that 2 is readily available in both racemic and enantioenriched
forms, provided the justification for a consideration of the synthesis
double bond of diketene4 (Scheme 2).
and reactions of cyclopropanespiro-
The successful synthesis of a number of these compounds is reported
b-lactones based on the latter.
* Corresponding author. Tel.: þ353 91 492474; fax: þ353 91 525700; e-mail
address: niall.geraghty@nuigalway.ie (N.W.A. Geraghty).
0040-4020/$ e see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2011.03.013

N.W.A. Geraghty et al. / Tetrahedron 67 (2011) 3546e3552
3547
The gross structure of 3 was assigned on the basis of its IR, 1H
and 13C NMR spectra. A coupling constant of 6.0 Hz is indicative of
a trans relationship between the cyclopropyl protons.9 The only
significant correlation in the NOE difference spectrum of 3 involved
2-H and 6-CH3. This established the stereochemical relationship of
these protons as a HartreeeFock (3-21G) generated structure10 for
3 indicated a separation of only 3.00 Ǻ between 2-H and the carbon
atom of 6-CH3, whereas the other three diastereomeric possibilities
EtO2C
EtO2C
+
Cu(acac)2
O
EtO2C
O
O
O
O
O
refluxing
toluene
90%, 1:2
O
O
Cu(acac)2
for a cyclopropanespiro-b-lactone with trans cyclopropyl protons
refluxing
toluene
O
O
O
ꢀ
involved significantly larger separations: 3.98, 4.09 and 4.69 A.
The reaction of 2 with a range of other monosubstituted diazo
compounds was carried out using CuOTf, in general, as catalyst
(Table 2). The reactions of diazoacetophenone and diazo-
heptanone also proceeded diastereoselectively to give a single
O
85%
Scheme 3. Metal promoted rearrangement of cyclopropanespiro-b-lactones.
here. Surprisingly, unlike most cyclopropanation reactions with diazo
compounds, including those involving diketene 1, the reaction of 2
with a range of monosubstituted diazo compounds resulted in the
cyclopropanespiro-b-lactone, in low to modest isolated yield, ac-
companied by small amounts of a product derived from the pro-
pionic anhydride present as an impurity in 2. The stereochemistry
of the cyclopropanation product was assigned on the basis of 1H
NMR coupling constant and NOE data, and in the case of the
diastereoselective formation of a cyclopropanespiro-b-lactone, albeit
in at best modest yield (Scheme 4). The chemistry of these molecules
was also surprising in that metal promoted thermal rearrangement
led to the formation of a pyranone ring system, rather than the fur-
anones obtained from the diketene derived analogues.
cyclopropanespiro-b-lactone 5 derived from diazoacetophenone,
it was confirmed by X-ray crystallography11 (Fig. 1).
Table 2
,b,
The reaction of 2a c with diazo compounds
O
CO2Et
O
+
N2CHCO2Et EtO2C
O
CO2Et
O
3
metal
O
catalyst
+
EtO2C
O
2
4
Scheme 4. Reaction 4-[(Z)-ethylidene]-3-methyloxetan-2-one 2 with ethyl diazoacetate.
2. Results and discussion
2.1. Reaction of diazo compounds with 4-[(Z)-ethylidene]-3-
methyloxetan-2-one 2
The b-lactone 2 was prepared by the reaction of triethylamine
with propionyl chloride6 and was obtained as a mixture with
propionic anhydride. The removal of the last traces of the latter
proved difficult and so the 4-[(Z)-ethylidene]-3-methyloxetan-2-
one 2 used in the experiments described here contained w20% of
the anhydride. The reaction between 2 and ethyl diazoacetate was
carried using a fivefold excess of the lactone and a variety of
standard cyclopropanation catalysts (Table 1). Although copper(I)
triflate proved to be the most efficient catalyst, the outcome of the
reaction was in all cases the same: the diastereoselective formation
of ethyl (1R
*
,2R
*
,3S
*
,6R )-2,6-dimethyl-5-oxo-4-oxaspiro[2,3]hex-
*
ane-1-carboxylate 3 (Scheme 4) in, at best, modest yield. 1H NMR
and GC analysis confirmed the diastereoselectivity of the process,
indicating that the only low molecular mass compounds present in
the crude product were 3, diethyl maleate and fumarate and 2-
ethoxy-2-oxoethyl propionate 4,8 which resulted from the reaction
of the diazo compound with the propionic anhydride present as an
impurity in the lactone 2.
a
Containing ~20% propionic anhydride.
Addition time/stirring to complete reaction of diazo compound (IR).
Time for complete reaction (IR) with diazo compound added in a single amount.
b
c
The outcome of the reaction of 2 with a disubstituted diazo
compounddepended on the nature of the latter. The photochemical12
reaction of diethyl diazomalonate with 2 was not stereoselective and
resulted in the formation of a partially separable mixture of di-
Table 1
The reaction of 2 with ethyl diazoacetate
astereomeric cyclopropanespiro-b-lactones (9e12, Table 2). The rel-
Metal catalyst
Solvent/
temperatute
Timea
h
Fumarate/
maleateb
3b
4b
ative stereochemistry at C-2 and C-3 is assigned on the basis that the
system iselectronicallysimilartoavinyl acetate.13 Thecis relationship
between2-Hand theoxetanoneringO-atomin9 and10 isreflected in
Cu powder
Rh2(OAc)4
CuOTf
CuOTf (syringe pump)
Cu(acac)2
Neat 2, 80ꢀ
Neat 2, rt
2/DCM, reflux
2/DCM, reflux
Neat 2, rt
2/1
2/17
2/1
12/1
2/1
13
11
20
6
10
3
20
29
1
11
1
6
4
the downfield shift observed for 2-H with these compounds,
and 2.54, respectively, relative to those observed for 11 ( 2.23) and 12
2.00) in which the relationship is trans. The relative stereochem-
istry at 6-C in 9 and 10 can be assigned on the basis of the chemical
shift of 6-H: the downfield shift of this proton in 9 ( 4.42), compared
to that of the corresponding proton in 10 ( 3.88), is accounted for by
d 2.75
d
(
d
8
Trace
a
Diazoacetate addition time/additional stirring time needed for complete
reaction of diazoacetate (IR).
d
b
d
Isolated yield based on diazoacetate (%)

3548
N.W.A. Geraghty et al. / Tetrahedron 67 (2011) 3546e3552
A molecular mechanics search procedure15 was used to explore the
conformational space of this intermediate. A five-membered ring,
involving stabilization of the developing electrophilic carbon by the
ester carbonyl, was a feature of all the low energy conformers located.
Such an arrangement is compatible with the stereoselectivities ob-
served with other systems14 and is a feature of most of the mecha-
nismssuggestedforthesecyclopropanationreactions;16 thefactthatit
arisesnaturallyfromtheconformationalsearchprovidesvalidationfor
the appropriateness of this computational approach. The low energy
conformers divided into two groups on the basis of the stereochemical
relationshipbetweenthe ringoxygen of the oxetanoneand the methyl
substituent of what was the alkene. The lowest energy conformer in
each set was refined using a DFT calculation (B3LYP 6-31G
):10 the
*
structure in which the oxygen and the methyl have a cis relationship
(Fig. 2), as they have in the product 3, was found to be 2.04 kJ molꢁ1
lower in energy than that in which the relationship is trans (Fig. 3).
Fig. 1. (1R
*
,2R*,3R
*
,6R )-1-Benzoyl-2,6-dimethyl-4-oxaspiro[2.3]-hexan-5-one 5.
*
the close spatial relationship between 6-H and one of the estergroups
in the 1-position in the former. The difference between the chemical
shift of H-6 in 11 and 12 is only 0.03 ppm, and so the stereochemical
assignment at 6-C is more tentative in this case. However the relative
chemical shifts of 6-CH3 in 11 (
keeping with the proposed assignment.
Although the reaction of diazofluorene with diketene 1 results in
the formation of a cyclopropanespiro-
-lactone,1c this is not the case
d 1.27) and 12 (d 1.35) are also in
b
for its CuOTf catalysed reaction with 2. Instead other carbenoid de-
rived products, such as 9,90-bifluorenylidene are formed, suggesting
that cyclopropanation of 2 is not competitive with processes such as
dimerization, presumably for steric reasons. Reaction in the presence
of Rh2(OAc)4 also gave 9,90-bifluorenylidene and in addition another
dimerization product, difluoren-9-ylidene hydrazine. Photochemical
reaction, which would involve free carbenes, also failed to produce
any cyclopropanation products, giving 9,90-bifluorenylidene and
9H-fluoren-9-yl propionate, a propionic anhydride derived product.
In a similar fashion, the disubstituted ethyl 2-diazopropionate gave
only propionic anhydride derived products (Scheme 5).
,
2 containing
20%
EtO2C
O
EtO2C CO2Et
O
CO2Et
N2
(EtC(O))2O
O
Rh2(OAc)4
Fig. 2. B3LYP 6-31G optimized geometry of the product forming intermediate.
*
13 5%
14 15%
Scheme 5. The metal catalysed reaction of ethyl 2-diazopropionate in the presence of
2 containing approx. 20% propionic anhydride.
The CeC bond formation, which completes the cyclopropane is
accompanied by a lengthening of the metaleC bond, a process,
which reduces the steric influence of the catalyst framework. It also
involves the rotation of the ester group into its final position: in the
case of diketene 1 there is no difference between the two possible
rotation directions and a mixture of diastereomers results. In the
case of 2 rotation of the ester group occurs under the influence of
what was the ethylidene methyl group, resulting in the stereo-
selectivity observed for the reaction of this molecule with diazo
esters and ketones. The success of the molecular modelling
approach used here in providing an insight into the factors
determining the stereochemical outcome of the cyclopropanation
reaction under consideration, suggests that it could be used to
explore the behaviour of other related reaction systems as well.
A computational approach was used to obtain an understanding of
the stereoselectivity observed in the cyclopropanation of the alkene
bond in 2 with monosubstituted diazo compounds. The generally
accepted mechanism for such reactions is based on a transition state
involvingthemetalcarbenoidandthealkene,inwhichthemetalatom
has a partial negative charge and one of the alkene carbons a partial
positive charge.14 The computational approach adopted considered
the reaction as a two-step process involving a dipolar intermediate
corresponding to this transition state. A starting geometry for
a Rh2(OAc4) derived intermediate of this type was generated on the
basis that the formation of the first CeC bond involved an approach of
the alkene to the carbenoid, which avoided steric interactions be-
tween the ester group and the olefinic and oxetanone methyl groups,
and between the oxetanone and the catalyst ligands (Scheme 6).
2.2. Rearrangement reactions of cyclopropanespiro-b-
lactones derived from 4-[(Z)-ethylidene]-3-methyloxetan-2-
one 2
H
_
LnM
H
δ
CO2Et
LnM CO2Et
O
+
O
δ
As their strained nature might lead one to expect, the cyclo-
propanespiro-b-lactones derived from diketene 1 undergo a range of
LnM = Rh2(OAc)4
O
O
H
rearrangement reactions, the most unexpected of which is their
H
H
metal-catalysedconversiontofuranones(Scheme3).1c,5 Interestingly,
and in contrast tothe behaviour of cyclobutanespiro-b
-lactones17 and
Scheme 6. Transition state for cyclopropanation of 2.

N.W.A. Geraghty et al. / Tetrahedron 67 (2011) 3546e3552
3549
Surprisingly, although the cyclopropanespiro-b-lactones derived
from 2 do undergo a metal-catalysed rearrangement, the product is,
in general, a pyranone (Scheme 7, Table 3). The rearrangement of the
diketene derived cyclopropanespiro-b-lactones has been rational-
ized in terms of a mechanism involving the formation of a metal-
locycle (Scheme 8, R1¼H).1c,5 Cleavage of the metallocycle generates
a carboxylate anion, nucleophilic attack of which on the now elec-
tron-deficient cyclopropane generates the furanones. The rear-
rangement reactions of the cyclopropanespiro-b-lactones derived
from 2 (Scheme 8, R1¼Me) involves a new reaction pathway:
a methyl migration accompanied by a cyclopropane to cyclobutane
ring expansion, which occurs to the exclusion of the pathway ob-
served when R1¼H. The addition of a small amount of ethyl diazo-
acetate did not have the same accelerating effect on these reactions
as had been observed for the diketene derived cyclopropanespiro-
lactones.5b The formation of the 1,4-diketone 19 from cyclo-
propanespiro- -lactone 7 under these conditions is atypical. The
b-
b
structure of 19 is analogous to that of the minor product 16 obtained
in the boron trifluoride catalysed reaction of 3 and in both cases the
products may be the result of a reaction between the cyclo-
propanespiro-b-lactone and adventitious water.
Ln
Ln
R1
R1
R1
MLn
M
Δ
O
M
O
O
O
R1
R
R
R
R1
R1
R1 = H
O2C
R1 = Me
Fig. 3. B3LYP 6-31G optimized geometry of the non-product forming intermediate.
*
larger ring analogues,18 simple thermal reaction does not result in the
elimination of carbon dioxide. Instead, a range of different products
MLn
R
R
+
results depending on the structure of the spiro-b-lactone involved,
O
R
O
O
O
O
with the formation of a dimeric pyranone from the spiro-
b-lactone
O
produced by the reaction of ethyl diazoacetate with diketene being
- MLn
R
the most remarkable.1c The boron trifluoride catalysed rearrange-
ment of diketene derived cyclopropanespiro-
formation of -keto acids. The availability of methyl substituted
cyclopropanespiro- -lactones through the cyclopropanation of 4-
b-lactones leads to the
R
b
b
O
O
O
O
[(Z)-ethylidene]-3-methyloxetan-2-one 2 facilitated an exploration
of the effect of substitution on these rearrangement pathways.
Scheme 8. Rearrangement of cyclopropanespiro-b-lactones derived from 4.
The major, or sole, reaction pathway in the boron trifluoride
promoted rearrangement of the cyclopropanespiro- -lactones de-
Cu(acac)2
O
R
b
O
refluxing
toluene
R
rived from 2, parallels that observed for their diketene derived
O
O
analogues.1c Although the products formed (Table 3) are formally
the result of a reaction between the cyclopropanespiro-b-lactone
Scheme 7. Rearrangement of cyclopropanespiro-b-lactones derived from 2.
Table 3
The rearrangement of cyclopropanespiro-
b
-lactones derived from 2
Cyclopropanespiro-
-lactone
Product of metal-
catalysed rearrangement
Isolated
Yield (%)
Product of BF3 catalysed
rearrangement
Isolated
Yield (%)
b
O
O
O
16, 5
17, 33
EtO
CO2Et
17
O
EtO
68
EtO2C
3
O
15
O
16
1:1
O
Ph
O
O
52
30
Complex mixture of products
d
O
5
Ph
18
O
O
O
O
O
O
CO2Et
19%
20
H11C5
7
O
O
19
O

3550
N.W.A. Geraghty et al. / Tetrahedron 67 (2011) 3546e3552
and ethanol, the source of the latter or its synthetic equivalent
remains unclear.1c
J¼7.1 Hz), 1.18 (3H, t, J¼7.6 Hz). 13C NMR (100 MHz):
d 173.9, 168.0,
61.4, 60.7, 27.2, 14.2, 11.4.
4.2.2. Reaction with diazoacetophenone. A solution of diazo-
acetophenone (1.73 g, 12.0 mmol) in ether (20 mL) was added
dropwise over 3 h at 40 ꢀC to a solution of copper(I) triflate benzene
complex (0.05 g, 0.099 mmol) and 4-[(Z)-ethylidene]-3-methylox-
etan-2-one 2 (containing w19% propionic anhydride) (6.64 g,
0.059 mol) in ether (20 mL). After the addition was completed, the
mixture was stirred for a further hour to ensure complete reaction
of the diazo compound (IR) and was then eluted through a short
column of silica with ether. Following removal of solvent and excess
lactone, chromatography (silica; ether (2e20%)/pet. ether) gave
3. Conclusion
Parallelling the behaviour of diketene 1, the reaction of the
unsaturated
b-lactone 2 with monosubstituted diazo compounds
leads to the formation of cyclopropanespiro-
b
-lactones in poor to
modest yield. These reactions, unusually and in contrast to those of
diketene and most alkenes, are diastereoselective. A computational
model has been developed to account for the observed stereo-
chemistry and may be of value in exploring the mechanisms of
related cyclopropanations. Surprisingly the metal-catalysed rear-
rangement of the cyclopropanespiro-
produces pyranones, rather than the furanones formed from the
cyclopropanespiro- -lactones derived from diketene 1. Overall
these cyclopropanespiro- -lactones continue to surprise in terms
(1R
,2R ,3R
* * *
,6R )-1-benzoyl-2,6-dimethyl-4-oxaspiro[2.3]hexan-5-
*
b-lactones derived from 2
one 5 (0.65 g, 24%), a yellow solid, 2-oxo-2-phenylethyl propionate
619 (0.30 g, 13%) and propionic acid (0.25 g) (1H NMR)ꢁ. 1
.
1H NMR
b
Compound 5: mp 76e78 ꢀC; IR: 1838, 1663 cm
b
(400 MHz):
d
8.09e7.42 (5H, m), 3.77 (1H, q, J¼7.8 Hz), 3.05 (1H, d,
of their formation and their reactions; their chemistry warrants
further study.
J¼6.0 Hz,), 2.09e2.02 (1H, m), 1.48 (3H, d, J¼7.8 Hz), 1.40 (3H, d,
J¼6.4 Hz).13C NMR (100 MHz):
d197.1,170.8,137.2,133.0,128.9,128.3,
76.9, 48.4, 33.0, 23.5, 11.9, 11.5. Found: C, 72.82; H, 6.50; C14H14O3
requires: C, 73.03; H, 6.13. A crystal suitable for X-ray diffraction was
obtained by crystallisation from deuterochloroform/cyclohexane.11
4. Experimental
4.1. General
Compound 6:19 IR: 1744,1702 cmꢁ1.1H NMR (400 MHz):
d7.93e7.46
(5H, m), 5.35 (2H, s), 2.53 (2H, q, J¼7.4 Hz), 1.22 (3H, t, J¼7.4 Hz). 13C
1H NMR and 13C NMR spectra were measured in CDCl3 using
a Joel JNM-LA400 or ECX400 spectrometer. All GC analyses were
carried out on a Varian 3900 chromatograph, using an Agilent
HP-5 (95% dimethylpolysiloxane-5% diphenylpolysiloxane) column
NMR (100 MHz): d 192.3,173.9,134.2,133.8,128.8,127.7, 65.8, 27.2, 9.0.
4.2.3. Reaction with 1-diazo-2-heptanone. 1-Diazo-2-heptanone
(1.66 g, 0.012 mol) was dissolved in ether (30 mL) and was added
via syringe pump over 9½ h to a refluxing solution of copper(I)
triflate benzene complex (0.05 g, 0.099 mmol) and 4-[(Z)-ethyl-
idene]-3-methyloxetan-2-one 2 (which contained w19% propionic
anhydride) (6.64 g, 0.059 mol) in ether (20 mL). The solution was
refluxed for a further hour to ensure complete reaction of the diazo
compound (IR). Removal of solvent and excess lactone, and chro-
(30 mꢂ0.32 mmꢂ0.25
mm). IR spectra were measured on a Per-
kineElmer Spectrum 1 FT-IR equipped with a diamond ATR attach-
ment. The photochemical reactions were carried out in cylindrical
quartz tubes in a Rayonet reactor, RPR-100, fitted with sixteen
254 nm mercury lamps. Flash column chromatography was carried
out using Merck silica gel 60, 234e400 mesh, with gradient elution
using ether/petroleum ether (40e60 ꢀC) or DCM. Melting points
were determined using a Stuart Scientific SMP3 apparatus and are
uncorrected. A Waters GCT spectrometer was used for GCeMS.
Elemental analyses were carried out using a PerkineElmer 2400
analyser. All solvents were dried and distilled according to literature
procedures.
matography (SiO2, ether (2e15%)/pet. ether), gave (1R
*
,2R ,
*
3R ,6R )-1-hexanoyl-2,6-dimethyl-4-oxaspiro[2.3]hexan-5-one
*
*
(0.44 g, 17%) 7 and some analytically impure 2-oxoheptyl pro-
pionate 8 (0.40 g, 18%), both as pale yellow liquids.
Compound 7: IR: 1840, 1693 cmꢁ1 1H NMR (400 MHz):
. d 3.67
(1H, q, J¼7.4 Hz), 2.59 (2H, t, J¼7.6 Hz), 2.31 (1H, d, J¼6.0 Hz),
1.83e1.76 (1H, m), 1.63e1.55 (2H, m), 1.41 (3H, d, J¼7.4 Hz),
1.37e1.24 (4H, m), 1.30 (3H, d, J¼6.4 Hz), 0.90 (3H, t, J¼6.9 Hz). 13C
4.2. Reaction of 4-[(Z)-ethylidene]-3-methyloxetan-2-one 2
with diazo compounds
NMR (100 MHz):
d 207.8, 170.8, 76.5, 48.3, 44.8, 35.8, 31.3, 23.3,
23.0, 22.4, 13.8, 11.7, 11.3. (m/z) (CI, CH4) 225 (100), 169 (42), 99 (50).
HRMS (CI, CH4) (m/z): [MþH]þ calcd for C13H20O3 225.1491; found
225.1487.
4.2.1. Reaction with ethyl diazoacetate. A solution of ethyl diazo-
acetate (2.70 g, 24.0 mmol) in DCM (20 mL) was added dropwise via
a syringe pump over 12 h to a refluxing solution of copper(I) triflate
benzene complex (0.10 g, 0.198 mmol) and 4-[(Z)-ethylidene]-3-
methyloxetan-2-one 2 (containing w15% propionic anhydride)
(13.27 g, 0.118 mol) in DCM (20 mL). The solution was refluxed until
complete reaction of the diazo compound had occurred (IR, 1 h).
Removal of solvent and excess lactone, and chromatography (SiO2,
ether (2e8%)/pet. ether), gave diethyl fumarate (0.16 g, 4%),
Compound 8: IR: 1747, 1731 cmꢁ1. 1H NMR (400 MHz):
d 4.44 (2H,
s), 2.46 (2H, q, J¼7.3 Hz), 2.41 (2H, t, J¼7.3 Hz), 1.64e1.59 (2H, m),
1.35e1.25(4H, m),1.19(3H, t, J¼7.3 Hz), 0.89(3H, t, J¼7.1 Hz). 13CNMR
(100 MHz): d 204.3, 173.8, 67.8, 38.7, 31.3, 27.1, 23.0, 22.4, 13.8, 9.0.
4.2.4. Reaction with dimethyl diazomalonate. A solution of dimethyl
diazomalonate (1.26 g, 8.07 mmol), 4-[(Z)-ethylidene]-3-methylox-
etan-2-one
2 (containing w24% propionic anhydride) (6.72 g,
0.060 mol) and benzophenone (1.46 g, 8.01 mmol) in acetonitrile
(60 mL) in a quartz tube was degassed for 15 min using N2, and was
irradiated at 254 nm until the diazo compound had completely reacted
(IR, 3 h). Removal of solvent and excess lactone gave a yellow oil con-
taining four products (1:1.4:1:1, GC), chromatography (silica, ether
(2e24%)/pet. ether) of which gave two fractions. The first fraction was
(1R
*
,2R
*
,3S
*
,6R )-2,6-dimethyl-5-oxo-4-oxaspiro[2,3]hexane-1-
*
carboxylate 3 (1.36 g, 29%), a colourless liquid, 2-ethoxy-2-oxoethyl
propionate 48 (0.17 g, 4%) and diethyl maleate (0.08 g, 2%).
Compound 3: IR: 1841, 1732 cmꢁ1 1H NMR (400 MHz):
.
d
4.15e4.09 (2H, m), 3.79 (1H, q, J¼7.6 Hz), 1.95 (1H, d, J¼6.0 Hz),
1.73e1.67 (1H, m), 1.37 (3H, d, J¼7.6 Hz), 1.27 (3H, d, J¼6.2 Hz), 1.25
(3H, t, J¼7.1 Hz). 13C NMR (100 MHz):
d
171.0, 170.8, 74.2, 61.2, 48.6,
an inseparable mixture of dimethyl (2R
*
,3S
*
,6R
*
)-2,6-dimethyl-5-oxo-
,3S ,6S )-
4-oxaspiro[2.3]hexane-1,1-dicarboxylate 9 and dimethyl (2R
*
*
*
28.7, 20.7,14.3,11.7, 11.4. (m/z) (CI, CH4) 199 (100), 171 (80),153 (86),
125 (6), 69 (3). HRMS (CI, CH4) (m/z): [MþH]þ calcd for C10H15O4
199.0970; found: 199.0966.
2,6-dimethyl-5-oxo-4-oxaspiro[2.3]-hexane-1,1-dicarboxylate (1:1.5,
0.45 g, 23%) 10. The second fraction was an inseparable mixture of
Compound 4:8 IR: 1744, 1167 cmꢁ1
.
1H NMR (400 MHz):
d
4.60
dimethyl (2R
*
,3R
*
,6S
*
)-2,6-dimethyl-5-oxo-4-oxaspiro[2.3]hexane-
1,1-dicarboxylate 11 and dimethyl (2R
*
,3R ,6R )-2,6-dimethyl-5-
*
*
(2H, s), 4.21 (2H, q, J¼7.1 Hz), 2.44 (2H, q, J¼7.6 Hz), 1.28 (3H, t,

N.W.A. Geraghty et al. / Tetrahedron 67 (2011) 3546e3552
3551
oxo-4-oxaspiro[2.3]hexane-1,1-di-carboxylate 12 (1.1:1, 0.24 g,
13%). Both fractions were obtained as pale yellow liquids.
4.2.6. Reaction with ethyl 2-diazopropionate. Ethyl 2-diazo-
propionate (1.37 g, 0.011 mol) (containing some residual p-tosyl
azide) was dissolved in dichloromethane (20 mL) and was added by
syringe pump over 13 h to a refluxing solution of Rh2(OAc)4 (4.1 mg,
Compounds 9/10: IR: 1845, 1728 cmꢁ1. 1H NMR (400 MHz) (from
the mixture): 9:
d
4.42 (1H, q, J¼7.6 Hz), 3.74 (3H, s), 3.73 (3H, s),
2.75 (1H, q, J¼6.9 Hz), 1.46 (3H, d, J¼7.6 Hz), 1.19 (3H, d, J¼6.9 Hz);
10.0
mmol) and 4-[(Z)-ethylidene]-3-methyloxetan-2-one 2 (con-
10:
d
3.88 (1H, q, J¼7.8 Hz), 3.74 (3H, s), 3.71 (3H, s), 2.54 (1H, q,
taining w20% propionic anhydride) (5.99 g, 0.053 mol) in ether
(20 mL). The solution was refluxed for a further hour to ensure
complete reaction of the ethyl 2-diazopropionate (IR). Following
removal of solvent and excess lactone, chromatography (silica, ether
(10%)/pet. ether) gave p-tosyl azide (0.3 g), ethyl 2-(propionyloxy)
propanoate23 13 (0.09 g, 5%) and diethyl 2,20-oxydipropanoate24 14
(0.18 g, 15%).
J¼6.9 Hz), 1.51 (3H, d, J¼7.8 Hz), 1.21 (3H, d, J¼6.9 Hz). 13C NMR
(100 MHz) (mixture of 9 and 10):
d 169.9, 169.8, 166.4, 165.7, 165.6,
165.5, 74.3, 73.1, 53.4, 53.3, 52.8, 52.6, 49.2, 47.9, 39.44, 39.4, 26.4,
25.7, 12.9, 11.2, 8.3, 8.1. Found: C, 54.32; H, 6.10; C11H14O6 requires:
C, 54.54; H, 5.83.
Compounds 11/12: IR: 1849, 1730 cmꢁ1 1H NMR (400 MHz)
.
(from the mixture): 11:
d
3.86 (1H, q, J¼7.8 Hz), 3.78 (3H, s), 3.75
Ethyl 2-(propionyloxy)propanoate 13:23 IR: 1745 cmꢁ1
(400 MHz):
5.05 (1H, q, J¼7.1 Hz), 4.18 (2H, q, J¼7.1 Hz), 2.41e2.36
(2H, m),1.46 (3H, d, J¼7.1 Hz), 1.26 (3H, t, J¼7.1 Hz), 1.15 (3H, t, J¼7.4 Hz).
13C NMR (100 MHz):
171.5, 168.5, 66.0, 58.9, 24.8, 14.4, 11.6, 6.4.
Diethyl 2,20-oxydipropanoate 14:24 IR: 1747, 1735 cmꢁ1. 1H NMR
.
1H NMR
(3H, s), 2.23 (1H, q, J¼6.6 Hz), 1.27 (3H, d, J¼7.8 Hz), 1.22 (3H, d,
d
J¼6.6 Hz); 12: 3.83 (1H, q, J¼7.6 Hz), 3.78 (3H, s), 3.75 (3H, s), 2.00
d
(1H, q, J¼6.6 Hz), 1.35 (3H, d, J¼7.6 Hz), 1.26 (3H, d, J¼6.6 Hz). 13C
d
NMR (100 MHz) (mixture of 11 and 12):
d 169.7, 169.6, 168.6, 167.7,
164.2, 164.1, 74.0, 73.9, 53.1, 53.06, 52.8, 52.77, 49.8, 49.3, 37.6, 36.6,
26.0, 24.5, 11.2, 11.1, 8.8, 8.6. Found: C, 54.61; H, 6.05; C11H14O6 re-
quires: C, 54.54; H, 5.83.
(400 MHz):
d
4.14 (4H, q, J¼7.3 Hz), 4.07 (2H, q, J¼6.7 Hz), 1.38 (6H,
d, J¼6.7 Hz),1.23 (6H, t, J¼7.3 Hz). 13C NMR (100 MHz):
d 172.6, 74.3,
61.0, 18.4, 14.2.
4.2.5. Reaction with diazofluorene. (i) Using Rh2(OAc)4 as catalyst. A
solution of diazofluorene (2.00 g, 0.010 mol) in ether (60 mL) was
added dropwise (2 h) to a stirred solution of Rh2(OAc)4 (3.0 mg,
4.3. Rearrangement reactions of cyclopropanespiro-b-
lactones derived from 4-[(Z)-ethylidene]-3-methyloxetan-2-
one 2
7.0
mmol) in 4-[(Z)-ethylidene]-3-methyloxetan-2-one 2 (which
contained w21% propionic anhydride) (5.60 g, 0.050 mol). On
complete reaction of the diazo compound (IR, 3 h), the reaction
mixture was cooled in ice for 1 h and filtered. The red solid obtained
was washed with pet. ether (50 mL) and was shown spectroscopi-
cally to be 9,90-bifluorenylidene (0.62 g, 38%). The mother liquor and
washings were combined and concentrated. The solid, which pre-
cipitated was filtered and washed with pet. ether (50 mL) to give
difluoren-9-ylidene hydrazine as a bright red solid (0.42 g, 24%).
9,90-Bifluorenylidene: mp 184e186 ꢀC (lit. 186e188 ꢀC).20 IR:
4.3.1. (1R
1-carboxylate 3. (i) Cu(acac)2 catalysed. A solution of the spiro-
-lactone 3 (0.22 g, 1.11 mmol) and Cu(acac)2 (0.025 g, 0.096 mmol)
in toluene (5 mL) was refluxed until none of the spiro- -lactone
*
,2R
*
,3S
*
,6R
*
)-2,6-Dimethyl-5-oxo-4-oxaspiro[2,3]hexane-
b
b
remained (45 h, GC). Removal of the solvent and chromatography
(silica, ether (1e35%)/pet. ether) gave ethyl 2,4-dimethyl-6-oxo-5,6-
dihydro-2H-pyran-3-carboxylate 15 (0.15 g, 68%) as a white solid.
Ethyl 2,4-dimethyl-6-oxo-5,6-dihydro-2H-pyran-3-carboxylate
15: mp 72e73 ꢀC. IR: 1754, 1734, 1648 cmꢁ1 1H NMR (400 MHz):
.
1598 cmꢁ1. 1H NMR (400 MHz):
d
8.38 (4H, d, J¼7.6 Hz), 7.70 (4H, d,
d
5.06 (1H, br q, J¼6.9 Hz), 4.17 (2H, q, J¼7.1 Hz), 3.46 (1H, d,
J¼7.6 Hz), 7.32 (4H, dt, J¼7.6, 0.7 Hz), 7.20 (4H, dt, J¼7.6, 0.7 Hz). 13C
J¼16.0 Hz), 3.27 (1H, d, J¼16.0 Hz), 1.84 (3H, br s), 1.39 (3H, d,
NMR (100 MHz):
d
141.4, 141.1, 138.3, 129.3, 127.0, 126.8, 120.0.
J¼6.9 Hz), 1.27 (3H, t, J¼7.1 Hz). 13C NMR (100 MHz):
d 173.8, 168.2,
Difluoren-9-ylidene hydrazine: mp 267e268 ꢀC (lit. 269 ꢀC).21
155.6, 126.2, 78.9, 61.8, 32.5, 18.1, 16.5, 8.9. (m/z) (CI, CH4) 199 (55),
127 (25), 114 (100), 57 (22). HRMS (CI, CH4) (m/z): [MþH]þ calcd for
C10H14O4 199.0970; found 199.0968.
IR: 1624, 1600 cmꢁ1 1H NMR (400 MHz):
.
d
8.13 (2H, d, J¼7.6 Hz),
8.05 (2H, d, J¼7.4 Hz), 7.65 (2H, d, J¼7.3 Hz), 7.64 (2H, d, J¼7.6 Hz),
7.49e7.45 (2H, m), 7.43e7.37 (4H, m), 7.26e7.24 (2H, m). 13C NMR
(ii) BF3 catalysed. The spiro-b-lactone 3 (0.13 g, 0.630 mmol) was
(100 MHz):
d
154.9, 142.4, 141.4, 136.6, 131.5, 131.4, 131.1, 129.9,
dissolved in DCM (12.5 mL) and freshly distilled BF3 etherate
128.3, 129.4, 123.0, 120.2, 120.1.
(1.25 mL) was added. The solution was refluxed for 13½ h at which
(ii) Using copper(I) triflate benzene complex as catalyst. Repeating
the reaction between 2 (containing w25% propionic anhydride)
(6.64 g, 0.059 mol) and diazofluorene (4.30 g, 0.022 mol) using
copper(I) triflate benzene complex (0.10 g, 0.198 mmol) as catalyst
gave, after chromatography (silica; ether (2e3%)/pet.22 ether),
9,90-bifluorenylidene20 (0.37 g, 10%) and fluorenone21 (1.21 g, 31%).
point all of the spiro-b-lactone had reacted (GC). The reaction
mixture was washed with 10% NaHCO3 (2ꢂ20 mL) and water
(2ꢂ20 mL) and the organic layer was dried over magnesium sulfate.
Filtration, removal of the solvent and chromatography (silica, ether
(2e6%)/pet. ether) gave ethyl 3-methyl-4-oxohexanoate 1625
(0.006 g, 5%) and, as an inseparable mixture of diastereomers
(1:1, 1H NMR), diethyl 2,4-dimethyl-3-oxohexanedioate 17 (0.05 g,
33%). Both materials were obtained as colourless liquids.
Fluorenone: IR: 1713 cmꢁ1 1H NMR (400 MHz):
. d 7.49 (2H, d,
J¼7.3 Hz), 7.30e7.26 (4H, m), 7.14 (2H, d, J¼7.1 Hz). 13C NMR
(100 MHz):
d
194.0, 144.5, 134.8, 134.2, 129.2, 124.4, 120.4.
Ethyl 3-methyl-4-oxohexanoate 16:25 IR: 1735, 1712 cmꢁ1
.
1H
(iii) Photochemical reaction. A solution of diazofluorene (0.50 g,
2.60 mmol) in 4-[(Z)-ethylidene]-3-methyloxetan-2-one 2 (con-
taining w21% propionic anhydride) (1.40 g, 0.013 mol), in a quartz
tube, was degassed (15 min) using N2 and was irradiated at 254 nm.
When no diazo compound remained (5 h, IR), solvent and excess
lactone were removed to give an orange liquid. Chromatography
(silica, ether (2e3%)/pet. ether) gave 9,90-bifluorenylidene (0.15 g,
35%) and, as a colourless liquid, some analytically impure 9H-flu-
oren-9-yl propionate (0.13 g, 21%).
NMR (400 MHz):
d
4.09(2H, q, J¼7.1 Hz), 3.04e2.96(1H, m), 2.77 (1H,
dd, J¼7.8, 16.7 Hz), 2.57e2.52 (2H, m), 2.28 (1H, dd, J¼5.2, 16.7 Hz),
1.23 (3H, t, J¼7.1 Hz), 1.11 (3H, d, J¼7.3 Hz), 1.06 (3H, t, J¼7.1 Hz). 13C
NMR (100 MHz): d 213.6, 172.5, 60.6, 41.8, 37.2, 34.4, 16.9, 14.2, 7.8.
Diethyl 2,4-dimethyl-3-oxohexanedioate 17: IR: 1735,
1716 cmꢁ1 1H NMR (400 MHz) (from mixture containing pre-
dominantly one diastereomer): 4.21e4.14 (2H, m), 4.12e4.05 (2H,
.
d
m), 3.79 (1H, q, J¼7.1 Hz), 3.24e3.16 (1H, m), 2.77 (1H, dd, J¼9.2,
16.9 Hz), 2.33 (1H, dd, J¼5.1, 16.9 Hz), 1.35 (3H, d, J¼7.1 Hz), 1.25
(3H, t, J¼7.1 Hz), 1.22 (3H, t, J¼7.1 Hz), 1.14 (3H, d, J¼7.1 Hz). 1H NMR
(400 MHz) (from mixture containing predominantly other di-
9H-Fluoren-9-yl propionate: IR: 1730 cmꢁ1. 1H NMR (400 MHz):
d
7.66 (2H, d, J¼7.6 Hz), 7.54 (2H, d, J¼7.6 Hz), 7.40 (2H, t, J¼7.6 Hz),
7.32e7.28 (2H, m), 6.81 (1H, s), 2.45 (2H, q, J¼7.6 Hz), 1.22 (3H, t,
astereomer):
d
3.74 (1H, q, J¼7.1 Hz), 3.30e3.22 (1H, m), 2.75 (1H,
J¼7.6 Hz). 13C NMR (100 MHz):
d
175.6, 142.2, 141.1, 129.5, 127.9,
dd, J¼7.6, 16.6 Hz), 2.32 (1H, dd, J¼6.6, 16.6 Hz), 1.33 (3H, d,
J¼7.1 Hz), 1.26 (3H, t, J¼7.1 Hz), 1.24e1.20 (3H, m), 1.16 (3H, d,
125.9, 120.1, 74.8, 27.9, 9.4.

3552
N.W.A. Geraghty et al. / Tetrahedron 67 (2011) 3546e3552
J¼7.1 Hz). 13C NMR (100 MHz) (mixture):
d
208.7, 207.8, 172.1, 171.9,
d, J¼6.8 Hz), 1.26 (3H, t, J¼6.9), 1.29e1.20 (4H, m), 1.12 (3H, d,
170.5, 170.2, 61.5, 61.3, 60.8, 60.4, 52.0, 51.2, 41.6, 41.4, 37.8, 37.0,
16.9, 16.8, 14.2, 14.2, 14.1, 14.1, 13.1, 12.9. Found: C, 59.31; H, 8.19;
C12H20O5 requires: C, 59.00; H, 8.25.
J¼6.9 Hz), 0.88 (3H, t, J¼6.9 Hz). 1H NMR (400 MHz) (from mixture
containing predominantly the other diastereomer):
d 4.23e4.16
(2H, m), 3.77 (1H, q, J¼6.8 Hz), 3.36e3.28 (1H, m), 2.93 (1H, dd,
J¼8.2, 15.6 Hz), 2.44 (1H, dd, J¼6.8, 15.6 Hz), 2.38e2.33 (2H, m),
1.58e1.51 (2H, m), 1.34 (3H, d, J¼6.8 Hz), 1.26 (3H, t, J¼6.9),
1.30e1.21 (4H, m), 1.13 (3H, d, J¼6.9 Hz), 0.88 (3H, t, J¼6.9 Hz).
Found: C, 66.29; H, 9.45; C15H26O4 requires: C, 66.64; H, 9.69.
4.3.2. (1R
hexan-5-one 5. (i) Cu(acac)2 catalysed. A solution of the spiro-
-lactone 5 (0.09 g, 0.391 mmol) and Cu(acac)2 (0.02 g, 0.076 mmol)
in toluene (5 mL) was refluxed (69 h) until none of the spiro- -lac-
*
,2R
*
,3R
*
,6R
*
)-1-Benzoyl-2,6-dimethyl-4-oxaspiro[2.3]
b
b
tone remained (IR, 69 h). Removal of the solvent and chromatogra-
phy (silica, DCM) gave 5-benzoyl-4,6-dimethyl-3,6-dihydro-2H-
pyran-2-one 18 (0.052 g, 52%) as an off-white solid.
Acknowledgements
The Embark Fellowship awarded to LMAM by the Irish Research
Council for Science, Engineering and Technology (IRCSET) is
gratefully acknowledged.
5-Benzoyl-4,6-dimethyl-3,6-dihydro-2H-pyran-2-one 18: mp
61e63 ꢀC. IR: 1751, 1690, 1599 cmꢁ1. 1H NMR (400 MHz):
d 7.99 (2H,
d, J¼7.3 Hz), 7.65 (1H, t, J¼7.3 Hz), 7.53 (2H, t, J¼7.3 Hz), 5.14 (1H, 6-
H, J¼6.4 Hz), 4.24 (1H, d, J¼17.4 Hz), 3.88 (1H, d, J¼17.4 Hz), 1.86
References and notes
(3H, br s), 1.39 (3H, d, J¼6.4 Hz). 13C NMR (100 MHz):
d 193.9, 173.8,
1. (a) Kato, T.; Katagiri, N.; Sato, R. Chem. Pharm. Bull. 1979, 27, 1176e1180; (b) Kato,
T.; Katagiri, N.; Sato, R. J. Chem. Soc., Perkin Trans. 1 1979, 525e528; (c) Murphy,
P. V.; O’Sullivan, T. J.; Geraghty, N. W. A. J. Chem. Soc., Perkin Trans. 1 2000,
2109e2119.
156.7, 135.8, 134.0, 128.9, 128.2, 126.2, 78.9, 36.2, 18.0, 8.9. Found: C,
72.89; H, 6.01; C14H14O3 requires: C, 73.03; H, 6.13.
(ii) BF3 catalysed. Freshly distilled BF3 etherate (0.63 mL) was
added to a solution of the spiro-
b
-lactone 5 (0.073 g, 0.317 mmol) in
2. Kato, T.; Katagiri, N.; Sato, R. J. Org. Chem. 1980, 45, 2587e2592.
3. Kato, T.; Chiba, T.; Sato, R.; Yashima, T. J. Org. Chem. 1980, 45, 2020e2022.
4. (a) Cunningham, P. D.; Geraghty, N. W. A.; Kennedy, B. D.; McArdle, P. J.;
Murphy, P. V.; O’Sullivan, T. J. J. Chem. Soc., Perkin Trans. 1 1997, 1, 1e4; (b)
Murphy, P. V.; O’Sullivan, T. J.; Kennedy, B. D.; Geraghty, N. W. A. J. Chem. Soc.,
Perkin Trans. 1 2000, 13, 2121e2126.
5. (a) Kato, T.; Katagiri, N.; Sato, R. Chem. Pharm. Bull. 1981, 29, 2361e2366; (b)
Geraghty, N. W. A.; Murphy, P. V. Tetrahedron Lett. 1994, 35, 6737e6740.
6. Hintermann, L.; Togni, A. Helv. Chim. Acta 2000, 83, 2425e2435.
7. Calter, M. A.; Liao, W. J. J. Am. Chem. Soc. 2002, 124, 13127e13129.
8. Burton, T. M.; Fife, W. B. J. Am. Chem. Soc. 1954, 74, 3935e3936.
9. Hoberg, J. O.; Claffey, D. J. Tetrahedron Lett. 1996, 37, 2533e2536.
10. Spartan ’06; Wavefunction: Inc.: Irvine, 2006.
DCM (6 mL). The solution was refluxed for 10 h and the reaction
mixture was monitored by TLC. Spectroscopic analysis (1H NMR) of
the material resulting from the usual workup indicated it was
a complex mixture. Chromatography failed to provide any identi-
fiable products.
4.3.3. (1R
*
,2R
*
,3R
*
,6R
*
)-1-Hexanoyl-2,6-dimethyl-4-oxaspiro[2.3]
-lactone
hexan-5-one 7. (i) Cu(acac)2 catalysed. The spiro-
b
7
(0.098 g, 0.437 mmol) and Cu(acac)2 (0.020 g, 0.076 mmol) were
11. Crystallographic data (excluding structure factors) for 5 have been deposited
with the Cambridge Crystallographic Data Centre as supplementary publication
no. CCDC 760958. Copies of the data can be obtained, free of charge, on ap-
plication to CCDC, 12 Union Road, Cambridge CB2 1EZ, UK, (fax: þ44 (0)1223
336033 or e-mail: deposit@ccdc.cam.ac.uk).
12. This reaction was carried out photochemically as the metal catalysed reaction
of diethyl diazomalonate with diketene 2 led to the formation of a complex
mixture of products: Geraghty, N. W. A.; Murphy, P. V., unpublished results.
13. House, H. O.; Kramar, V. J. Org. Chem. 1963, 28, 3362e3379.
14. (a) Doyle, M. P. Acc. Chem. Res. 1986, 19, 991e1001; (b) Doyle, M. P.; McKervey,
M. A.; Ye, T. Modern Catalytic Methods for Organic Synthesis with Diazo Com-
pounds; John Wiley: New York, NY, 1998, pp 178e183.
15. Monte Carlo; MMFF. Spartan ’06; Wavefunction: Inc.: Irvine, 2006.
16. (a) Doyle, M. P.; Dorow, R. L.; Buhro, W. E.; Griffin, J. H.; Tamblyn, W. H. Or-
ganometallics 1984, 3, 44e52; (b) O’Bannon, P. E.; Dailey, W. P. Tetrahedron 1990,
46, 7341e7358; (c) Davies, H. M. L.; Clark, T. J.; Church, L. A. Tetrahedron Lett.
1989, 30, 5057e5060.
dissolved in toluene (5 mL) and the solution was then refluxed until
all the spiro-b-lactone had reacted (7½ h, GC). Removal of the
solvent and chromatography (silica, DCM) gave 4-methylundecane-
3,6-dione 19 (0.03 g, 30%) as a colourless liquid.
4-Methylundecane-3,6-dione 19: IR: 1711 cmꢁ1
.
1H NMR
(400 MHz):
d
3.08e3.00 (1H, m), 2.94 (1H, dd, J¼8.2, 17.6 Hz), 2.56
(2H, q, J¼7.1 Hz), 2.41e2.33 (3H, m), 1.56e1.49 (2H, m), 1.30e1.21
(4H, m), 1.06 (3H, d, J¼6.6 Hz), 1.03 (3H, t, J¼7.1 Hz), 0.87 (3H, t,
J¼7.1 Hz). 13C NMR (100 MHz):
d 214.4, 210.0, 45.8, 42.9, 40.7, 34.5,
32.0, 23.5, 22.5, 17.0, 14.0, 7.8. (m/z) (CI, CH4) 199 (55), 181 (6), 127
(4). HRMS (CI, CH4) (m/z): [MþH]þ calcd for C12H22O2 199.1698;
found 199.1705.
(ii) BF3 catalysed. The spiro-b-lactone 7 (0.075 g, 0.334 mmol)
17. Domelsmith, L. N.; Houk, K. N.; Dagenhardt, C. R.; Paquette, L. A. J. Am. Chem.
was dissolved in DCM (6 mL) and freshly distilled BF3 etherate
(0.63 mL) was added. The usual workup and chromatography (sil-
ica, DCM) gave ethyl 2,4-dimethyl-3,6-dioxoundecanoate 20
(0.017 g, 19%), a light yellow solid, as an inseparable mixture of
diastereomers (1:0.94, 1H NMR).
Soc. 1978, 100, 100e105.
18. Mulzer, J.; Speck, T.; Buschmann, J.; Luger, P. Tetrahedron Lett. 1995, 36,
7643e7646.
19. Manzocchi, A.; Fiecchi, A.; Santaniello, E. J. Org. Chem. 1988, 53, 4405e4407.
20. Nishida, S.; Komiya, Z.; Mizuno, T.; Mikuni, A.; Fukui, T.; Tsuji, T.; Murakami, M.;
Shimizu, N. J. Org. Chem. 1984, 49, 495e502.
21. Pinck, L. A.; Hilbert, G. E. J. Am. Chem. Soc. 1946, 68, 867e868.
22. Jackman, L. M.; Trewella, J. C. J. Am. Chem. Soc. 1976, 98, 5712e5714.
23. Seebach, D.; Hungerbuehler, E.; Naef, R.; Schnurrenberger, P.; Weidmann, B.;
Zueger, M. Synthesis 1982, 138e141.
Ethyl 2,4-dimethyl-3,6-dioxoundecanoate 20: mp 90e92 ꢀC. IR:
1742, 1712 cmꢁ1 1H NMR (400 MHz) (from mixture containing
.
predominantly one diastereomer): d 4.22e4.15 (2H, m), 3.87 (1H, q,
J¼6.9 Hz), 3.27e3.20 (1H, m), 2.98 (1H, dd, J¼8.3, 15.1 Hz), 2.44 (1H,
24. Parsons, D. G. J. Chem. Soc., Perkin Trans. 1 1975, 245e250.
25. Ahlbrecht, H.; Kompter, H.-M. Synthesis 1983, 645e647.
dd, J¼6.8, 15.1 Hz), 2.39e2.35 (2H, m), 1.59e1.52 (2H, m), 1.37 (3H,