The Synthesis and Structure of Substituted Dimenthyl Malonate Derivatives

Article abstract of DOI:10.1080/10242430215697

A series of substituted dimenthyl malonate derivatives were efficiently synthesized from dimenthyl malonate using a deprotonation and alkylation strategy. The elucidation of the structure of these derivatives were determined by a combination of X-ray crystallography, NMR and IR spectroscopy.

Full text of DOI:10.1080/10242430215697

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Enantiomer: A Journal of Sterochemistry
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The Synthesis and Structure of Substituted Dimenthyl
Malonate Derivatives
Gregory S. Coumbarides a , Jason Eames a , Majid Motevalli a & Yonas Yohannes a
a Department of Chemistry, Queen Mary , University of London , London, E1 4NS, UK
Published online: 17 Sep 2010.
To cite this article: Gregory S. Coumbarides , Jason Eames , Majid Motevalli & Yonas Yohannes (2002) The Synthesis and
Structure of Substituted Dimenthyl Malonate Derivatives, Enantiomer: A Journal of Sterochemistry, 7:6, 317-328, DOI:
10.1080/10242430215697
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Enantiomer, Vol. 7, pp.317–328
c
Copyright 2002 Taylor & Francis
1024-2430/02 $12.00 + .00
DOI: 10.1080/10242430290015917
The Synthesis and Structure of Substituted
Dimenthyl Malonate Derivatives
Gregory S. Coumbarides,
Jason Eames, Majid Motevalli,
and Yonas Yohannes
Department of Chemistry,
Queen Mary, University
ABSTRACT A series of substituted dimenthyl malonate derivatives
were efficiently synthesized from dimenthyl malonate using a deproto-
nation and alkylation strategy. The elucidation of the structure of these
derivatives were determined by a combination of X-ray crystallography,
NMR and IR spectroscopy.
of London, London E1 4NS, UK
KEYWORDS alkylation, deprotonation, malonate, structure determination and
symmetry
he synthesis of substituted 1,3-dicarbonyl derivatives is very well
documented [1]. Reports into the structural nature of these deriva-
T
tives are less common [2]. The majority of these reports have dealt
with substituted malonic acid derivatives [3], whereas some attention
has been focused on related keto- [4] and aldehyde derivatives [5]. By
comparison, little is known about malonic ester derivatives [6]. However,
through single crystal x-ray structure determination, substituted malonic
acids [7] have been shown to exist in an intramolecular or intermolecu-
lar hydrogen bonded arrangement; where both carbonyl groups are posi-
tioned in an anti-relationship A, rather than a syn-relationship S (Figure 1).
This anti-conformer arrangement is also evident in their related malonate
salts [8]. However, in the absence of intramolecular hydrogen bonding
and internal metal co-ordination; keto- [9] and aldehyde [10] derivatives
have been shown to adopt a wide range of conformers (ranging from anti-
alignment through to perpendicular and syn-alignment of both carbonyl
groups) within the crystal phase, whereas related substituted malonate
esters have been shown to preferentially adopt a syn-alignment [11].
We previously investigated the use of 1,3-dicarbonyl containing
molecules as achiral proton donor in the enantio- [12] and regioselec-
tive protonation [13] of prostereogenic enolates. However, reports into
the preferred conformation of these chiral carbon-based acids are limited
[14]. In an attempt to increase this understanding, we chose to synthesize
a series of related dimenthyl malonate derivatives and examine their con-
formational preferences using single crystal x-ray crystallography.
We first synthesized the symmetrical dimenthyl malonate 2 and inves-
tigated its structural properties. We chose to use enantiomerically pure
Received June 15, 2002;
accepted September 29, 2002.
Telephone: +44-020-7882-5251;
Fax: +44-020-7882-7794; E-mail:
J.Eames@qmw.ac.uk
317

FIGURE 2 A view of molecule 2 with the atom-numbering
scheme. Displacement ellipsoids are drawn at the 50% proba-
bility level and H atoms are shown as small spheres of arbitrary
radii.
identical molecules of 2 as illustrated in Figure 2.
All the substituents on the cyclohexyl ring are in the
expected equatorial positions.
FIGURE 1 Assignment of the relative carbonyl group
arrangements.
We were next concerned whether this dimenthyl
malonate 2 existed as its related enol tautomer [15].
However, this was found not to be the case with
a C1 C2 C3 bond angle of 111.5 (5) , which is
clearly representative of an sp3 hybridised carbon
atom with similar C1 C2 and C2 C3 bond lengths
( )-menthol 1 as our ester scaffold as this would
lead directly to the dimenthyl ester 2 without con-
tamination resulting from the formation of other
stereoisomers (Scheme 1). Treatment of commer-
cially available malonyl dichloride to a stirred so-
lution of naturally occurring ( )-menthol and Et3N
in dichloromethane gave the required C2 symmet-
ric ( )-dimenthyl malonate 2 as a cream coloured
precipitate in 66% yield. After purification through
flash column chromatography (on silica gel) and va-
por re-crystallization (from hexane) gave a colorless
needle-like crystal of 2, the structure of which was de-
termined by single crystal x-ray diffraction (Figure 2).
The stereochemistry present in this derivative was de-
termined by reference to ( )-menthol. On closer in-
spection of the unit cell, it was evident that the struc-
ture of menthyl malonate 2 was not C2 symmetric
in its solid phase, due to the nonequivalence of the
carbonyl groups, C1 O4 and C3 O3. However, so-
˚
of 1.492 (7) and 1.497 (8) A respectively (Table 1).
This is consistent with the presence of a single car-
bonyl (C O) stretching peak in the IR spectrum at
1
1720 cm and the absence of an enolic hydrogen
around 3000–3500 cm 1. A striking feature of this
molecule is the relative orientation of both carbonyl
groups, C1 O4 and C3 O3; these are evidently
twisted away from each other, as shown by torsion an-
gles of 138.3 (6) for O4 C2 C2 O3 and 102.6 (6)
for C1 C2 C3 O3 (Table 1). This may presumably
be due to a combination of hyperconjugation effects
associated with the hydrogen atoms at the C2 posi-
tion with both carbonyl groups and a minimization
of their relative dipole moments. This orientation
can be seen further by a related twist involving the
other oxygen atom in the ester motif; the torsion
angles for O1 C1 C2 C3 and O1 C1 C2 C3
are 42.5 (6) and 73.4 (6) , respectively. In
contrast, both ester motifs (C O C O) exist in a
predictable s-cis conformation [16] around the cen-
tral single C O bond and clearly strive for pla-
narity [ 0.8 (8) for C14 O1 C1 O4 and 9.5 (7)
for C4 O2 C3 O3] through anomeric assistance.
This type of anti-parallel alignment of the C O
bonds has previously been reported in the structural
1
lution phase H and 13C NMR studies in CDCl3
at room temperature have been shown to be consis-
tent with C2 symmetry due to the equivalence of the
menthyloxycarbonyl motif. The overall unit cell was
shown to pseudo-C2 symmetric and contained two
SCHEME 1 Preparation of Di-( )-menthyl malonate 2.
318
G. S. COUMBARIDES ET AL.

˚
TABLE 1 Selected geometric parameters for dimenthyl malonate 2 (A, )
C2-C3
1.497 (8)
C1-C2
1.492 (7)
C14-O1-C1-O4
C14-O1-C1-C2
O4-C1-C2-C3
O1-C1-C2-C3
C12-C11-C5-C4
C13-C11-C5-C4
0.8 (8)
180.0 (4)
138.3 (6)
42.5 (6)
62.9 (6)
172.7 (4)
C4-O2-C3-O3
C4-O2-C3-C2
C1-C2-C3-O3
C1-C2-C3-O2
C21-C20-C19-C14
C22-C20-C19-C14
9.5 (7)
166.6 (4)
102.6 (6)
73.4 (6)
173.5 (4)
60.9 (6)
arrangement of malonic acids [17], diones [9a],
triketones [18], diamides [19], and related malonate
derivatives [20].
of an appropriate alkylating reagent, such as ben-
zyl bromide and allyl iodide, gave after stirring for
12 hours the required malonate 4a+b in low yield
(Scheme 3). However, repeating the same reaction
with methyl and ethyl iodide gave surprisingly the
di-substituted malonates 3c+d. It appears that un-
der these reversible conditions, the reaction is under
thermodynamic control favoring the formation of
the more substituted and more thermodynamically
stable enolate 6. Presumably, this is due to compet-
itive deprotonation as a result of slow C-alkylation
with a nonactivated electrophile (Scheme 4). How-
ever, if the reaction time was lowered to 3 hours and
a sub-stoichiometric quantity of alkylating agent and
base was used (0.5 equilvalent), the required kinetic
mono-substituted malonates 4c–d could exclusively
be formed (Scheme 5). However, for activated elec-
trophiles reagents, such as allyl bromide and benzyl
bromide, the yields were found to be slightly lower
than that for nonactivated electrophiles. This is not
that surprising since it has previously been docu-
mented [21] that activated electrophiles prefer O-
alkylation of enolates (derived from 1,3-dicarbonyl
derivatives) to give enol ethers rather than tradi-
tional C-alkylation [22]. We next turned our atten-
tion to the synthesis of unsymmetrical di-substituted
We next introduced some substitution at the car-
bon adjacent to both carbonyl groups to determine
if this would alter the relative orientation of the car-
bonyl groups by lowing the amount of C H hy-
perconjugation. We first synthesized the symmetri-
cally di-substituted malonates derivatives 3a–d since
there would be no further complication with stere-
ochemistry (Scheme 2). Treatment of a solution of
( )-dimenthyl malonate 2 in THF with an excess
of NaOEt (2 equivalents), and subsequent alkyla-
tion of the intermediate enolate(s) gave the sym-
metrically substituted malonates 3a–d as colorless
oils in good chemical yield. These derivatives were
shown to be C2 symmetric by the equivalence of
1
the menthyloxycarbonyl motifs—determined by H
and 13C NMR spectroscopy. The presence of a sin-
gle carbonyl stretching frequency at approximately
1
1718 cm in the IR spectra further illustrates the
carbonyl group (C O) equivalence.
We next focused our attention on synthesizing
a series of mono-substituted malonate derivatives
4a–d. Deprotonation of the parent dimenthyl mal-
onate 2 with NaOEt (1 equivalent) and addition
Starting
Entry
material
RX
Product
[ ]D
Yield
1
2
3
4
2
2
2
2
PhCH2Br
CH2CHCH2I
CH3CH2I
CH3I
3a
3b
3c
3d
44.2 (c = 9.7)
44.6 (c = 3.1)
56.8 (c = 8.1)
61.0 (c = 3.7)
42%
63%
70%
73%
SCHEME 2 Synthesis of symmetrically di-substituted di-( )-menthyl malonates 3a–d.
THE SYNTHESIS OF SUBSTITUTED DIMENTHYL MALONATE DERIVATIVES
319

Starting
material
Entry
RX
Product
[ ]D
Yield
1
2
3
4
2
2
2
2
PhCH2Br
CH2CHCH2I
CH3CH2I
CH3I
4a
4b
3c
3d
61.1 (c = 2.0)
67.9 (c = 2.6)
56.8 (c = 8.1)
61.0 (c = 3.7)
28%
37%
21%
30%
SCHEME 3 Attempted synthesis of mono-substituted di-( )-menthyl malonates 4a–d.
malonate derivatives 7 and 8 (Scheme 6). We chose
to alkylate our existing benzyl-substituted malonate
4a using nonactivated electrophiles (e.g., methyl and
ethyl iodide) to ensure efficient C-alkylation. Treat-
ment of 4a with NaOEt and addition of an excess of
CH3I and CH3CH2I (16–25 equivalents) gave the
corresponding methylbenzyl and ethylbenzyl mal-
onates derivatives 7 and 8 in good yield.
Introduction of a prostereogenic position adjacent
to both menthyl motifs by single alkylation (e.g., to
give 4a) or by sequential addition of two different
alkylating reagents (e.g., to give 7) causes both men-
thyloxycarbonyl groups to be nonequilivalent. This
effect can easily be seen in the 13C NMR spectra
due to the presence of two carbonyl (C O) signal (at
approximately 169 ppm), as well as up to 20 car-
bon atoms associated with both menthyl groups. It
is rather interesting to note that the carbonyl (C O)
stretching frequencies in the IR spectra fall into two
categories (Table 2): those for mono-substituted mal-
onates 4a–d give rise to two distinct sharp carbonyl
1
(C O) stretching frequencies at 1728 and 1745 cm
due to the nonequivalence of the C O groups,
whereas the unsymmetrically di-substituted deriva-
tives 7 and 8 gave a broad stretching frequency be-
tween 1716–1724 cm 1. All samples were purified
through flash column chromatography (on silica gel)
and vapor re-crystallized (from hexane). However,
only the benzyldimenthyl malonate 4a and the re-
lated methylbenzyldimenthyl malonate 7 gave suffi-
ciently good crystals for x-ray diffraction.
X-ray diffraction of benzyldimenthyl malonate 4a
revealed the structure illustrated in Figure 3. From
this structure determination it is clear that both car-
bonyl groups (C9 O9 and C20 O20) have a syn-
orientation (as illustrated by the torsion angles for
O9 C9 C1 C20 and O20 C20 C1 C9 of 56.9
(3) and 115.2 (3) , respectively) rather than being
oriented away from each other as in the case for
the parent dimenthyl malonate 2 (Table 3). This
molecule is not an enol derivative, with bond an-
gles of 109.11 (19) and 110.82 (19) for C2 C1 C9
SCHEME 4 Synthesis of disubstituted di-( )-menthyl
malonate 3d.
320
G. S. COUMBARIDES ET AL.

TABLE 2 Carbonyl infrared stretching frequencies for malonates 2, 3a–d, 4a–d, 7 and 8
1
Entry
Product
R1
R2
(C O)/cm
max
1
2
3
4
5
6
7
8
9
2
H
H
1720
1718
1716
1716
3a
3b
3c
3d
4a
4b
4c
4d
7
PhCH2
PhCH2
CH2CHCH2
CH3CH2
CH3
H
H
H
H
CH2CHCH2
CH3CH2
CH3
1720
PhCH2
1728, 1745
1728, 1745
1728, 1745
1728, 1745
1724
CH2CHCH2
CH3CH2
CH3
PhCH2
PhCH2
10
11
CH3
CH3CH2
8
1718
Starting
Entry
material
RX
Product
[ ]D
Yield
1
2
2
2
CH3CH2I
CH3I
4c
4d
64.8 (c = 1.6)
73.5 (c = 1.8)
61%
75%
SCHEME 5 Synthesis of mono-substituted di-( )-menthyl malonates 4c–d under kinetic control.
Starting
Entry
material
RI
Product
[ ]D
Yield
1
2
4a
4a
CH3I
CH3CH2I
7
8
49.2 (c = 1.8)
47.8 (c = 3.0)
66%
79%
SCHEME 6 Synthesis of unsymmetrically di-substituted di-( )-menthyl malonates 7 and 8.
THE SYNTHESIS OF SUBSTITUTED DIMENTHYL MALONATE DERIVATIVES
321

FIGURE 4 A view of molecule 7 with the atom-numbering
scheme. Displacement ellipsoids are drawn at the 50% proba-
bility level and H atoms are shown as small spheres of arbitrary
radii.
FIGURE 3 A view of molecule 4a with the atom-numbering
scheme. Displacement ellipsoids are drawn at the 50% proba-
bility level and H atoms are shown as small spheres of arbitrary
radii.
ented so the smaller C H bond is syn-planar with
the adjacent C O single bond to avoid steric repul-
sion. The ester motif [OC C O] is predictably in
its s-cis conformation, and the carbonyl group (C O)
was arranged parallel to the adjacent H CO bond
of the cyclohexyl ring. X-ray diffraction of these di-
menthyl malonate derivatives 2, 4a and 7 has re-
vealed that the menthyloxycarbonyl motif behaves
similarly and that the substitution at the central car-
bon (to which they are joined) is responsible for their
structural characteristics. These structural feature has
been found to be present in all cases so far examined
[23]. The relative orientation of the C O bonds has
been shown to be anti-planar for menthyl malonate
2 and syn-planar for the substituted cases, benzyl-
menthyl and benzylmethylmenthyl malonate 4a and
7, respectively. These types of alignment has previ-
ously been reported in the structural arrangement of
related malonate derivatives [4,9–11]. However, this
carbonyl alignment appears to be unimportant with
respect to the layered arrangement throughout the
crystal structure, which appear as an AB arrangement
and C2 C1 C20, respectively, and with similar
C1 C9 and C1 C20 bond lengths of 1.520 (3)
˚
and 1.511 (3)A, respectively. This particular syn-
arrangement of the carbonyl groups is also present in
the structure obtained from x-ray diffraction of ben-
zylmethyl malonate 7 (Figure 4); these are oriented
toward each other as shown by the torsion angles
of 140.92 (16) for O10 C10 C1 C21 and 68.25
(18) for O21 C21 C1 C10 (Table 4). It is inter-
esting to note, that enol formation cannot occur in
this case and the associated C1 C21 and C1 C10
˚
˚
bond lengths [1.529 (2)A and 1.529 (2)A, respec-
tively] were found to be similar to 2 and 4a in which
enol formation could have potentially occurred.
In all cases studied so far, we have found the men-
thyloxycarbonyl motif to be surprisingly uniform in
its structural conformation. All the substituents on
the cyclohexyl ring are in the expected equatorial
positions. The isopropyl group [–CH(CH3)2] is ori-
˚
TABLE 3 Selected geometric parameters for benzyl dimenthyl malonate 4a (A, )
C9-C1
C2-C1-C9
1.520 (3)
109.11 (19)
2.8 (3)
175.3 (18)
56.9 (3)
124.9 (2)
72.3 (2)
163.22 (19)
64.5 (3)
C1-C20
C2-C1-C20
1.511 (3)
110.82 (19)
9.2 (3)
170.15 (18)
115.2 (3)
64.1 (2)
176.6 (6)
57.3 (3)
5.2 (3)
C10-O10-C9-O9
C10-O10-C9-C11
O9-C9-C1-C20
O10-C9-C1-C20
C18-C17-C15-C10
C19-C17-C15-C10
C2-C1-C9-O9
C21-O21-C20-O20
C21-O21-C20-C1
O20-C20-C1-C9
O21-C20-C1-C9
C30-C28-C20-C21
C29-C28-C26-C21
C2-C1-C20-O20
322
G. S. COUMBARIDES ET AL.

˚
TABLE 4 Selected geometric parameters for benzylmethyl dimenthyl malonate 7 (A, )
C1-C21
C3-C1-C21
1.529 (2)
109.98 (12)
8.02 (2)
167.78 (12)
140.92 (17)
43.34 (16)
61.2 (2)
C1-C10
C3-C1-C10
1.531 (2)
109.49 (12)
4.8 (2)
165.07 (11)
68.25 (18)
111.64 (13)
169.00 (14)
65.53 (18)
50.65 (19)
C11-O11-C10-O10
C11-O11-C10-C1
O10-C10-C1-C21
O11-C10-C1-C21
C19-C18-C16-C11
C20-C18-C16-C11
C3-C1-C10-O10
C22-O22-C21-O21
C22-O22-C21-C1
O21-C21-C1-C10
O22-C21-C1-C10
C30-C29-C27-C22
C31-C29-C27-C22
C3-C1-C21-O21
173.82 (14)
21.7 (2)
due to the presence of a local pseudo-twofold axis
present within the unit cell. This layered sequence is
positioned in an ABAB arrangement with the layer
B positioned anti-parallel to layer A.
light petroleum (b.p. 40–60 C)-ether (19:1) to give
the malonate 2 [24] (9.0 g, 66%) as light cream solid.
This solid was recrystallized in hexane to give white
needle crystals; mp = 54–55 C; RF [light petroleum
1
(40–60 C):ether (19:1)] 0.75;
(film)/cm 1725
max
(CO); [ ]D 83.7 (c 2.7 in CHCl3);
(250 MHz,
H
EXPERIMENTAL
CDCl3) 4.8 (2H, td, J 10.8 and 4.4, CHO), 3.36 (2H,
s, CH2CO), 2.15–0.85 (18H, m, 6 CH2 and 6
CH), 1.1–0.95 (6H, m, 2 CH3) and 0.85 (3H, d,
All solvents were distilled before use. Tetrahydro-
furan (THF) and ether were freshly distilled from
sodium wire using benzophenone as the indica-
tor. Triphenylmethane was used as the indicator for
THF. All reactions were carried out under nitro-
gen using oven-dried glassware. Flash column chro-
matography was carried out using Merck Kieselgel 60
(230–400 mesh). Thin layer chromatography (TLC)
was carried out on commercially available precoated
plates (Merck Kieselgel 60F254 silica). Proton and car-
bon NMR spectra were recorded on a JEOL EX
270 and Bruker AM 250 fourier transform spec-
trometer (using an internal deuterium lock). Chem-
ical shifts are quoted in parts per million downfield
from tetramethylsilane. Carbon NMR spectra were
recorded with broad proton decoupling. Infrared
spectra were recorded on a Shimadzu 8300 FTIR ma-
chine, and mass spectra were recorded on a Kratos
50MSTC machine using a DS503 data system for
high-resolution analysis.
J 7.0, CHCH3);
(67 MHz, CDCl3) 166.2, 75.5,
C
46.9, 42.4, 40.7, 34.2, 31.4, 26.1, 23.4, 22.0, 20.8
and 16.3 (Found M+ 381.3017. C23H41O4 requires
M+, 381.3005); m/z 381 (80%, M) and 243 (100,
M C10H18).
Di-( )-menthyl Dibenzylmalonate
3a
Di-menthyl malonate 2 (0.5 g, 1.31 mmol) was
added slowly to a stirred solution of sodium ethox-
ide (0.17 g, 2.62 mmol) in THF (100 ml). The result-
ing solution was stirred for 1 hour. Benzyl bromide
(0.44 g, 2.62 mmol) was added and the reaction mix-
ture was stirred for a further 3 hours. The reaction
was quenched with water (30 ml) and the organic
layer was extracted with diethyl ether (3
50 ml),
dried (MgSO4) and evaporated under reduced pres-
sure. The residue was purified by flash column chro-
matography on silica gel eluting with light petroleum
(b.p. 40–60 C)-ether (19:1) to give the malonate 3a
Di-( )-menthyl Malonate 2
Malonyl dichloride (5.0 g, 3.45 ml, 35.5 mmol)
was slowly added to a stirred solution of triethy-
lamine (7.2 g, 9.90 ml, 70.9 mmol) and ( )-menthol 1
(11.1 g, 70.9 mmol) in dichloromethane (100 ml) and
the resulting solution was stirred for 1 h. The reac-
tion was quenched slowly with water (30 ml) and
the organic layer was extracted with diethyl ether
(3 50 ml), dried (MgSO4) and evaporated under
reduced pressure. The residue was purified by flash
column chromatography on silica gel eluting with
(0.31 g, 42%) as a colorless oil; RF [light petroleum
1
(40–60 C):ether (19:1)] 0.80;
(film)/cm 1718
max
(CO); [ ]D 44.2 (c 9.7 in CHCl3);
(250 MHz,
H
CDCl3) 7.26–7.10 (5H, m, Ph), 4.72 (1H, td, J 10.6
and 4.4, CHO), 3.25 (2H, AB quartet, CH2Ph), 2.04–
0.70 (18H, m, 6
d, J 7.5, CH3CH), 0.80 (3H, d, J 7.5, CH3CH) and
0.75 (3H, d, J 7.2, CH3CH); (67 MHz, CDCl3)
CH2 and 6
CH), 0.78 (3H,
C
171.0, 136.5, 130.5, 130.3, 128.8, 128.4, 128.1, 126.7,
75.7, 47.0, 46.7, 40.5, 40.4, 40.2, 38.6, 34.6, 34.2, 31.3,
THE SYNTHESIS OF SUBSTITUTED DIMENTHYL MALONATE DERIVATIVES
323

25.4, 22.9, 22.0, 21.0, 15.9 (Found MH+, 560.3963.
C37H53O4 requires 560.3944); m/z 561 (15%, MH)
and 423 (100, M C10H18).
chromatography on a silica gel the malonate 3d
(0.26 g, 73%) as a colourless oil; RF [light petroleum
1
(40–60 C):ether (19:1)] 0.60;
(film)/cm 1720
max
(CO); [ ]D 61.0 (c 3.7 in CHCl3);
(250 MHz,
H
CDCl3) 4.66 (1H, td, J 10.8 and 5.1, CHO), 2.05–
0.80 (18H, m, 6 CH2 and 6 CH), 1.60 (6H, s,
Di-( )-menthyl Diallylmalonate 3b
2
CH3), 0.93 (3H, d, J 7.1, CH3CH), 0.85 (3H, t,
In the same way as di-( )-menthyl dibenzyl-
malonate 3a, malonate 2 (1.50 g, 3.94 mmol),
sodium ethoxide (0.53 g, 7.88 mmol) and allyl
bromide (0.95 g, 7.88 mmol) gave, after column
chromatography on a silica gel the malonate 3b
J 7.4, CH3CH) and 0.75 (3H, d, J 7.3, CH3CH);
C
(67 MHz, CDCl3) 172.5, 75.0, 50.2, 47.0, 40.7, 34.3,
31.3, 25.9, 23.1, 22.8, 22.0, 20.8 and 16.0. (Found
MH+, 409.3300. C25H45O4 requires 409. 3318); m/z
409 (40%, MH) and 271 (100, M C10H18).
(1.14 g, 63%) as a colourless oil; RF [light petroleum
1
(40–60 C):ether (19:1)] 0.80;
(film)/cm 1716
max
(CO); [ ]D 44.6 (c 3.1 in CHCl3);
(250 MHz,
Di-( )-malonate
H
CDCl3) 5.60 (1H, m, CH CH2), 5.1 (2H, AB quar-
tet, CH CH2), 4.68 (1H, td, J 10.8 and 4.8, CHO),
2.65 (2H, AB quartet, CH2CH CH2), 2.05–0.80
Benzylmalonate 4a
Di-menthyl malonate 2 (18.5 g, 48.7 mmol) was
added slowly to a stirred solution of sodium ethox-
ide (3.15 g, 48.7 mmol) in THF (100 ml). The result-
ing solution was stirred for 1 hour. Benzyl bromide
(3.15 g, 48.7 mmol) was added and the reaction mix-
ture was stirred for a further 3 hours. The reaction
was quenched with water (30 ml) and the organic
(18H, m, 6
CH2 and 6
CH), 0.90–0.85 (6H,
m, 2 CH3), and J 7.5, CH3CH) and 0.73 (3H, d,
J 7.2, CH3CH) (Found MH+, 461.3639. C29H49O4
requires 461.3631); m/z 461 (40%, MH) and 323
(100, M C10H18).
layer was extracted with diethyl ether (3
50 ml),
dried (MgSO4) and evaporated under reduced pres-
sure. The residue was purified by flash column chro-
matography on silica gel eluting with light petroleum
(b.p. 40–60 C)-ether (19:1) to give benzyl malonate
4a (6.7 g, 29%) as a white powder, which was re-
crystallized from cold hexane to give white needles;
Di-( )-menthyl Diethylmalonate 3c
In the same way as di-( )-menthyl dibenzyl-
malonate 3a, malonate 2 (1.0 g, 2.63 mmol), sodium
ethoxide (0.34 g, 5.26 mmol) and ethyl iodide (0.82 g,
5.26 mmol) gave, after column chromatography on
a silica gel the malonate 4c (0.80 g, 70%) as a colour-
less oil; RF [light petroleum (40–60 C):ether (19:1)]
0.80; max (film)/cm 1 1716 (CO); [ ]D 56.8 (c 8.1
mp = 82–84 C; RF [light petroleum (40–60 C):ether
1
(19:1)] 0.75;
(film)/cm 1745 (CO) and 1728
max
(CO); [ ]D 61.1 (c. 2.0 in CHCl3);
(250 MHz,
H
in CHCl3);
(250 MHz, CDCl3) 4.66 (1H, td, J
H
CDCl3) 7.29–7.15 (5H, m, Ph), 4.75–4.61 (1H, m,
CHO), 3.60 (1H, t, J 7.2, CHCH2CO), 3.23 (2H, dd
AB quartet, J 7.8 and 3.5, CH2Ph), 2.07–0.70 (18H, m,
10.8 and 4.8, CHO), 2.05–0.80 (18H, m, 6 CH2
and 6
CH), 1.95 (4H, q, J 7.2, 2
CH2CH3),
0.90–0.85 (6H, m, 2
CH3), 0.80 (6H, t, J 7.2,
6
CH2 and 6 CH), 0.91 (3H, d, J 7.5, CH3CH),
2
CH2CH3), and 0.73 (3H, d, J 7.2, CH3CH);
C
0.89 (3H, d, J 7.5, CH3CH) and 0.62 (3H, d, J 7.0,
CH3CH); C (67 MHz, CDCl3) 168.6, 168.5, 138.0,
136.5, 130.3, 128.9, 128.4, 128.1, 126.8, 75.7, 75.4,
54.1, 47.0, 46.8, 40.6, 40.5, 40.3, 38.7, 34.6, 34.2,
31.3, 25.9, 25.7, 23.3, 23.1, 22.0, 21.9, 21.0, 20.9, 16.1
and 16.0 (Found MH+, 471.3487. C30H47O4 requires
471.3474); m/z 471 (10%, MH), 333 (60, M C10H16)
and 285 (100, M C11H21O2).
(67 MHz, CDCl3) 171.4, 74.9, 58.9, 46.9, 40.7, 34.3,
31.3, 25.7, 24.0, 22.9, 22.0, 20.9, 15.7 and 8.1 (Found
MH+, 437.3611. C27H49O4 requires 437.3631); m/z
437 (40%, MH) and 299 (100, M C10H18).
Di-( )-menthyl
Dimethylmalonate 3d
In the same way as di-( )-menthyl dibenzyl-
malonate 3a, malonate 2 (0.29 g, 0.76 mmol),
sodium ethoxide (52 mg, 0.76 mmol) and methyl
iodide (0.11 g, 0.76 mmol) gave, after column
Di-( )-menthyl Allylmalonate 4b
In the same way as di-( )-menthyl benzyl-
malonate 4a, malonate 2 (1.5 g, 3.9 mmol), sodium
324
G. S. COUMBARIDES ET AL.

CHO), 3.39 (1H, q, J 7.3, CHCH3CO), 2.14–0.78
(18H, m, 6 CH2 and 6 CH), 1.44 (3H, d, J 6.5,
CH3CH), 0.90 (3H, d, J 7.5, CH3CH), 0.88 (3H, d,
ethoxide (0.26 g, 3.9 mmol) and allyl bromide (0.47 g,
3.94 mmol) gave, after column chromatography on
a silica gel the allyl malonate 4b (0.62 g, 37%) as
J 7.4, CH3CH) and 0.78 (3H, d, J 6.9, CH3CH);
an oil; RF [light petroleum (40–60 C):ether (19:1)]
C
1
(67 MHz, CDCl3) 169.9, 169.7, 75.2, 75.1, 47.0, 46.9,
40.7, 40.6, 34.3, 31.4, 26.2, 25.9, 23.4, 23.3, 22.0, 20.8,
20.7, 16.3, 16.1 and 13.6 (Found MH+, 395.3163.
C24H43O4 requires 395.3161); m/z 395 (10%, MH),
379 (15, M CH3) and 257 (100, M C10H17).
0.75;
(film)/cm 1745 (CO) and 1728 (CO);
max
[ ]D 67.9 (c. 2.6 in CHCl3); H (250 MHz, CDCl3)
5.81 (1H, m, CH CH2), 5.10 (2H, m, CH CH2),
4.73 (2H, td, J 10.8 and 4.4, CHO), 3.39 (1H, t, J 7.6,
COCHCH2), 2.71–2.58 (2H, m, CH2CH CH2),
2.05–0.70 (18H, m, 6 CH2 and 6 CH), 0.90 (3H,
d, J 7.5, CH3CH), 0.88 (3H, d, J 7.5, CH3CH) and
Di-( )-menthyl
Methylbenzylmalonate 7
0.61 (3H, d, J 7.0, CH3CH);
(67 MHz, CDCl3)
C
168.7, 168.5, 134.2, 117.3, 65.4, 52.1, 47.0, 46.9, 40.8,
40.6, 34.2, 32.8, 31.4, 26.1, 25.8, 23.3, 23.1, 22.0,
20.9, 20.8, 16.2, and 16.0 (Found MH+, 421.3325.
C26H45O4 requires 421.3318); m/z 421 (25%, MH)
and 283 (100, M C12H18).
In the same way as di-( )-menthyl benzyl-
malonate 4a, malonate 4a (0.51 g, 1.07 mmol),
sodium ethoxide (73 mg, 1.07 mmol) and methyl
iodide (3.77 g, 26.6 mmol) gave, after column
chromatography on a silica gel the malonate 7
(0.34 g, 66%) as a solid, which was recrystallized
(in hexane) to give white needles; m.p. 83–85 C;
Di-( )-menthyl Ethylmalonate 4c
RF [light petroleum (40–60 C):ether (19:1)] 0.86;
1
In the same way as di-( )-menthyl benzyl-
malonate 4a, malonate 2 (0.5 g, 1.31 mmol), sodium
ethoxide (44.7 mg, 0.65 mmol) and ethyl iodide
(0.1 g, 0.65 mmol) gave the malonate 4d (0.16 g,
61%) as a white powder, which was recrystallized
from cold hexane to give white needles; mp = 74–
(film)/cm 1724 (CO); [ ]D 49.2 (c 1.8 in
max
CHCl3);
(250 MHz, CDCl3) 7.29–7.13 (5H, m,
H
Ph), 4.77–4.65 (2H, m, CHO), 3.13 (2H, br s, AB
quartet, CH2Ph), 2.00–0.60 (18H, m, 6 CH2 and
6
CH), 1.25 (3H, s, CH3), 0.89 (3H, d, J 7.5,
CH3CH), 0.87 (3H, d, J 7.5, CH3CH) and 0.62 (3H,
d, J 7.1, CH3CH); C (67 MHz, CDCl3) 171.7, 171.1,
136.4, 130.4, 130.3, 128.0, 126.7, 75.7, 55.3, 47.0,
46.9, 41.1, 40.5, 34.2, 31.3, 25.6, 23.1, 23.0, 22.0,
20.9, 20.8, 19.6 and 15.3 (Found MH+, 485.3647.
C31H49O4 requires 485.3631); m/z 485 (25%, MH),
393 (M CH2Ph), 346 (100, M C12H18) and 285
(100 C12H24O2).
75 C; RF [light petroleum (40–60 C):ether (19:1)]
1
0.75;
(film)/cm 1745 (CO) and 1728 (CO);
max
[ ]D 64.8 (c 1.6 in CHCl3); H (250 MHz, CDCl3)
4.72 (2H, td, J 10.8 and 4.4, CHO), 3.32 (1H, t, J 7.5,
CHCH2CO), 2.10–0.78 (18H, m, 6 CH2 and 6
CH), 0.92 (3H, t, J 7.2, CH3CH2), 0.91 (3H, d, J 7.5,
CH3CH), 0.89 (3H, d, J 7.5, CH3CH) and 0.75 (3H,
d, J 7.0, CH3CH); C (67 MHz, CDCl3) 169.2, 169.0,
75.2, 54.2, 47.0, 46.9, 40.8, 40.6, 34.3, 31.4, 26.2, 25.9,
23.4, 23.2, 22.2, 22.0, 16.2, 16.1 and 11.8 (Found
MH+, 409.3330. C25H45O4 requires 409.3318); m/z
409 (55%, MH) and 271 (100, M C10H17).
Di-( )-menthyl
Ethylbenzylmalonate 8
In the same way as di-( )-menthylbenzylmalonate
4a, malonate 4a (0.40 g, 869 mol), sodium ethox-
ide (65 mg, 86.9 mmol) and ethyl iodide (1.94 g,
14.6 mmol) gave, after column chromatography on
a silica gel the malonate 8 (0.34 g, 80%) as a colour-
Di-Menthyl Methylmalonate 4d
In the same way as di-( )-menthyl benzyl-
malonate 4a, malonate 2 (0.5 g, 1.31 mmol), sodium
ethoxide (44.7 mg, 0.65 mmol) and methyl iodide
(93.2 mg 0.65 mmol) gave the malonate 4d (0.18 g,
72%) as a colorless oil; RF [light petroleum (40–
60 C):ether (19:1)] 0.75; max (film)/cm 1 1745 (CO)
less oil; RF [light petroleum (40–60 C):ether (19:1)]
1
0.86;
(film)/cm 1718 (CO); [ ]D 47.8 (c 3.0
max
in CHCl3);
(250 MHz, CDCl3) 7.26–7.10 (5H,
H
m, Ph), 4.72 (1H, td, J 9.6 and 3.4, CHO), 4.70 (1H,
td, J 9.6 and 3.4, CHO), 3.25 (2H, br s, AB quar-
tet, CH2), 2.05–0.65 (18H, m, 6
CH2 and 6
and 1738 (CO); [ ]D 73.5 (c 1.8 in CHCl3);
(250 MHz, CDCl3) 4.72 (2H, td, J 10.8 and 1.6,
CH), 0.93 (3H, d, J 7.5, CH3CH), 0.89 (3H, d, J 7.5,
CH3CH), 0.75 (3H, d, J 7.1, CH3CH) and 0.69 (3H,
H
THE SYNTHESIS OF SUBSTITUTED DIMENTHYL MALONATE DERIVATIVES
325

t, J 7.3, CH3CH2); 171.5, 171.3, 136.5, 130.2, 128.2,
126.7, 75.5, 66.0, 60.0, 57.1, 46.9, 40.5, 34.3, 34.2,
31.4, 25.5, 22.1, 21.1, 21.0, 15.9, 15.4 and 8.7. (Found
MH+, 499.3768. C32H51O4 requires 499.3787); m/z
499 (50%, MH) and 361 (100, M C10H18).
F
2 using the SHELXL-97 program [27]. The H atoms
were calculated geometrically and refined with rid-
ing model. The program ORTEP-3 [31] was used
for drawing the molecules and WINGX [32] was
used to prepare material for publication. All data
relating to these single crystal X-ray structures have
been deposited at the Cambridge Crystallographic
Database: reference number CCDC 188449 (for 4a)
and 188488 (for 7).
X-Ray Crystallography
of Di-( )-menthyl Malonate 2
The intensity data were collected at 180 k on
a CAD-4 diffractometer using MoK radiation
ACKNOWLEDGEMENTS
˚
(
0.71069 A) with ω-2 scans. All data were cor-
rected for absorption by empirical methods ( scan)
[25] and for Lorentz-polarization effects by XCAD4
[26]. The structures were solved by the heavy-atom
method using the programs SHELXS-97 [27], and
DIRDIF-99 [28] and refined anisotropically (non-
hydrogen atoms) by full-matrix least-squares on F2
using SHELXL-97 [28]. The H atom positions were
calculated geometrically and refined with a riding
model. In the final stage of refinement, data were cor-
rect for absorption by DIFABS [29]. The programs
ORTEP-3 [30], PLATON [31] were used for drawing
the molecules and WINGX [32] was used to pre-
pare material for publication. All data relating to this
single crystal X-ray structure have been deposited at
the Cambridge Crystallographic Database: reference
number CCDC 182024 [14].
We thank the London University Central Research
Fund, The Nuffield Foundation (NUF-NAF 99), The
Royal Society, and GOSS Scientific Instruments Ltd
for their generous financial assistance. We are grateful
to Dr. Simon Coles from EPSRC National Crystal-
lography service and Dr. Mark Thornton-Pett from
University of Leeds, Department of Chemistry, for
data collection.
REFERENCES
[1] Reactions involving dimenthyl malonate; a) T. P. Hilditch,
J. Chem. Soc. 1909, 95, 1580; b) H. H. Fox, M. O. Wolf, R.
O’Dell, B. L. Lin, R. R. Schrock, and M. S. Wrighton, J. Am.
Chem. Soc. 1994, 116, 2827; c) N. Katagiri, T. Haneda, N.
Watanabe, E. Hayasaka, and C. Kaneko, Chem. Pharm.
Bull. 1988, 36, 3867; d) A. Saba, Tetrahedron Asymmetry
1992, 3, 371; e) N. Katagiri, H. Akatsuka, C. Kaneko, and
A. Sera, Tetrahedron Lett. 1988, 29, 5397–5400; e) G.
Quinkert, U. Schwartz, H. Stark, W. D. Weber, F. Adams,
H. Baier, G. Frank, G. Durner, Liebigs Ann. Chem. 1982,
11, 1999; f) G. Chelucci and A. Saba, Tetrahedron Lett.
1995, 36, 4673; g) X. Camps and A. Hirsch, J. Chem.
Soc. Perkin Trans 1, 1997, 1595; h) W. T. Hoeve and H.
Wynberg, J. Org. Chem. 1980, 45, 2754.
X-Ray Crystallography of
Benzyldi-( )-menthyl Malonate 4a
and Methylbenzyldi-( )-menthyl
Malonate 7
[2] a) G. Roelofsen, J. A. Kanters, J. Kroon, H. M. Doesburg,
and T. Koops, Acta Crystallogr. Sect B 1978, 34, 2565;
b) L. El-Masdouri, A. Aubry, E. Gomez, B. Vitoux, and
M. Marraud, Acta Crystallogr., Sect. C (Cr. Str. Comm.)
1992, 48, 178; c) M. Soriano-Garcia and S. N. Rao, Acta
Crystallogr., Sect. C. (Cr. Str. Comm.) 1983, 39, 850;
d) H. Stoecki-Evans, T. Kallimopoulos, P. de Angelis, and
A. Jacot-Guillarmod, Acta Crystallogr., Sect. C. (Cr. Str.
Comm.) 1987, 43, 2155; e) Y. Kubozono, I. Kohno,
K. Ooishi, S. Namazue, M. Haisa, and S. Kashino, Bull.
Chem. Soc. Jpn. 1992, 65, 3234.
[3] G. Chapuis, A. Zalkin, and D. H. Templeton, J. Chem.
Phys. 1975, 62, 4919.
[4] R. Destro, U. Cosentino, G. Moro, E. Ortoleva, and
T. Pilatit, J. Mol. Struct. 1989, 212, 97.
[5] G. Lundgren and B. Aurivillius, Acta Chem. Scand. 1964,
18, 1642.
[6] A. Saba, V. Adovasio, and M. Nardelli, Tetrahedron:
Asymmetry 1992, 3, 1573.
Data for benzyldi-( )-menthyl malonate 4a and
methylbenzyldi-( )-menthyl malonate 7 were col-
lected at 120 and 150 k using a Nonius Kappa CCD
area detector diffractometer mounted at the window
of a molybdenum rotating anode generator (50 KV,
˚
90 mA, = 0.71069 A). The crystal to detector dis-
tance was 45 mm and and scans (0.7 increments,
84 s exposure time) were carried out to fill the Ewald
sphere. Data collection and processing were carried
out using the programs COLLECT [33], DENZO
[34] and maXus [35] and empirical absorption
correction was applied using SORTAV [36]. The
structure was solved by direct methods using
SHELXS-97 [27] and refined anisotropically-
(nonhydrogen atoms) by full-matrix least-squares on
326
G. S. COUMBARIDES ET AL.

[7] M. A. M. Meester, H. Schenk, and C. H. MacGillavry, Acta
Crystallogr., Sect. B (Str. Sci.) 1971, 27, 630.
[8] P. Brehin, J. Kozelka, and C. Bois, Acta Crystallogr., Sect.C
(Cr. Str. Comm.) 1992, 48, 2094.
N. P. Schepp, J. Chem. Soc., Chem. Commun. 1989,
1548; H. E. Zimmerman, Acc. Chem. Res. 1987, 20, 263;
A. J. Kesge, Chem. Soc. Rev. 1996, 25, 275.
[16] U. Rychlewska and B. Warzajtis, Acta Crystallogr., Sect. B
2000, 56, 833.
[9] For anti-carbonyl alignment see a) J. A. Jarvis and P. J.
Taylor, J. Chem. Soc., Perkin Trans 2 1979, 972; R. M.
Wilson, A. C. Hengge, A. Ataei, and D. M. Ho, J. Am.
Chem. Soc. 1991, 113, 7240; for syn-carbonyl align-
ment see b) D. Adhikesavalu and K. Venkatesan, Acta
Crystallogr., Sect. C (Cr. Str. Comm.) 1983, 39, 1044;
M. Moreno-Manas, J. F. Piniella, A. Alvarez-Larena,
N. Galvez, M. E. Lloris, J. Marquet, A. C. Siani, and
G. Germain, Tetrahedron 1992, 48, 3611; J. Kopf, C.
Bretzke, I. N. Domnin, and V. N. Plotkin, Acta Crystal-
logr., Sect. C (Cr. Str. Comm.) 1996, 52, 722; for perpen-
dicular carbonyl alignment see c) C. F. Bemasconi and
A. Kanavariotti, J. Am. Chem. Soc. 1986, 108, 7744;
D. F. Mullica, J. W. Karban, and D. A. Grossie, Acta
Crystallogr., Sect. C. (Cr. Str. Comm.) 1987, 43, 601; J.
Emsley, N. J. Freeman, M. B. Hursthouse, and P. A. Bates,
J. Mol. Struct. 1987, 161, 181; N. Judas, B. Kaitner, and
E. Mestrovic, Acta Crystallogr., Sect. C (Cr. Str. Comm.)
1995, 51, 2123.
[17] B. D. Santarsiero, J. Chem. Phys. 1990, 92, 3794; R. T.
Kops and H. Schenk, Cryst. Struct. Commun. 1974, 3,
665; A. Dubourg, J. Rambaud, J. L. Delarbre, J. Maury,
and J.-P. Declercq, Acta Crystallogr., Sect. C (Cr. Str.
Comm.) 1988, 44, 1987; J. G. Garcia, J. D. Enas, and
F. R. Fronczek, Acta Crystallogr., Sect. C (Cr. Str. Comm.)
1994, 50, 1141; N. van der Putten, R. T. Kops, J. Bode,
and H. Schenk, Acta Crystallogr., Sect. B 1978, 34, 322.
[18] R. L. Beddoes, J. R. Cannon, M. Heller, O. S. Mills, V. A.
Patrick, M. B. Rubin, and A. H. White, Aust. J. Chem.
1982, 35, 543.
[19] J. A. Lerbscher, K. V. Krishna Rao, and J. Trotter, Curr. Sci.
1970, 39, 560.
[20] T. E. Haran, A. Nudelman, and Z. Shakked, Acta Crys-
tallogr., Sect. B (Str. Sci.) 1983, 39, 438; D. S. Brown,
M. C. Elliott, C. J. Moody, T. J. Mowlem, J. P. Marino
Junior, and A. Padwa, J. Org. Chem. 1994, 59, 2447.
[21] J. C. J. Barna and M. J. T. Robinson, Tetrahedron Lett.
1979, 20, 1455; G. Roberge and P. Brassard, J. Chem.
Soc., Perkin Trans 1 1978, 1041–1046; J. Marquet, M.
Moreno-Manas, P. Pacheco, M. Pratt, A. R. Katritzky, and
B. Brycki, Tetrahedron 1990, 46, 5333.
[22] P. S. Clezy, B. N. Ravi, and L. V Thuc, Aust. J. Chem.
1986, 39, 419–432; T. Itoh, J.-I. Chika, Y. Takagi, and S.
Nishiyama, J. Org. Chem. 1993, 58, 5717; G. T. Szabo,
K. Aranyosi, M. Csiba, and L. Toke, Synthesis 1987, 565;
B. C. Ranu and S. Bhar, J. Chem. Soc., Perkin Trans 1
1992, 365–368; B. C. Bernd, V. Sernau, G. Huttner, A.
Asam, O. Walter, Chem. Ber. 1995, 128, 63; H. H. Fox,
M. O. Wolf, R. O’Dell, B. L. Lin, R. R. Schrock, and M. S.
Wrighton, J. Am. Chem. Soc. 1994, 116, 2827.
[23] S. V. Evans, J. Trotter, and V. C. Yee, Acta Crystallogr.,
Sect. C (Cr. Str. Comm.) 1988, 44, 878; M. Moreno-
Manas, R. M. Sebastian, A. Valirbera, E. Molins, and E.
Esphinosa, Tetrahedron: Asymmetry 1997, 8, 1525; M.
Egli and M. Dobler, Hel. Chim. Acta 1989, 72, 1136; P. D.
Robinson, Y. Hou, C. Y. Meyers, S. Adler, W. J. Banz, and
T. A. Winter, Acta Crystallogr., Sect.C (Cr. Str. Comm.)
1999, C55, IUC9900020; J. P. Gilday, J. C. Gallucci, and
L. A. Paquette, J. Org. Chem. 1989, 54, 1399; D. Yang,
X.-Y. Ye, and M. Xu, J. Org. Chem. 2000, 65, 2208; R. W.
Baker, T. W. Hambley, P. Turner, and B. J. Wallace, Chem.
Commun. 1996, 2571; T. Salto, H. Fujii, S. Hayashibe,
T. Matsushita, H. Kato, and K. Kobayashi, J. Chem.
Soc., Perkin Trans 1 1996, 1897; J. Mulzer, F. Meyer, J.
Buschmann, and P. Luger, Tetrahedron Lett. 1995, 36,
3503; T. Kolev, H. Preut, L. Koniczek, P. Bleckmann, I.
Juchnovski, and M. Miladenova, Acta Crystallogr., Sect.
C (Cr. Str. Comm.) 1995, 51, 1634; L. M. Sweeting, A. L.
Rheingold, J. M. Gingerich, A. W. Rutler, R. A. Spence,
C. D. Cox, and T. J. Kim, Chem. Mater. 1997, 9, 1103.
[24] H. H. Fox, M. O. Wolf, R. O’Dell, B. L. Lin, R. R. Schrock,
M. S. Wrighton, J. Am. Chem. Soc. 1994, 116, 2827.
[25] A. C. T. North, D. C. Phillips, and F. S. Mathews, Acta
Crystallogr., Sect. A 1968, 24, 351.
[10] For syn-carbonyl alignment see R. Allmann, A. Kutoglu,
Acta Crystallogr., Sect. B 1975, 31, 2734.
[11] For anti-carbonyl alignment see a) G. Mloston, M.
Celeda, A. Swiatek, M. Kagi, and H. Heimgartner, Pol.
J. Chem. 1998, 72, 1907; N. Katagiri, N. Watanabe,
J. Sakaki, T. Kawai, and C. Kaneko, Tetrahedron Lett.
1990, 31, 4633; for syn-carbonyl alignment see b) M. A.
Abbady, D. Craig, A. L. Ternay, G. E. Martin, J. Galloy,
and W. H. Watson, J. Org. Chem. 1981, 46, 1793; M. R.
Caira, W. H. Watson, A. L. Ternay, and R. McKellar, Acta
Crystallogr., Sect. C (Cr. Str. Comm.) 1984, 40, 1710;
D. Kanagapushpam, K. Venkatesan, and T. S. Cameron,
Acta Crystallogr., Sect. C (Cr. Str. Comm.) 1988, 44,
337; L. Sebo, J. Alfoldi, G. Rihs, and S. Toma, Col-
lect Czech. Chem. Commun. 1996, 61, 1805; A. Saba,
V. Adovasio, and M. Nardelli, Tetrahedron: Asymmetry
1992, 3, 1573; for perpendicular carbonyl alignment
c) T. N. Guru Row, H. Ramachandra Swamy, K. Ravi
Acharya, V. Ramamurthy, K. Venkatesan, and C. N. R.
Rao, Tetrahedron Lett. 1983, 24, 3263; Z. Rappoport, A.
Gazit, J. Org. Chem. 1986, 51, 4107; B. Ya. Antosyak,
V. N. Biyushikin, T. I. Malinovskii, A. V. Moskvin, B. A.
Ivin, Zh. Strukt. Khim. 1991, 32, 127.
[12] J. Eames and N. Weerasooriya, Tetrahedron Lett. 2000,
41, 521; Review: J. Eames and N. Weerasooriya, Tetrahe-
dron: Asymmetry 2001, 12, 1; and references therein.
[13] J. Eames and N. Weerasooriya, J. Chem. Res. (S) 2001, 2;
and references therein.
[14] Preliminary communication: J. Eames, G. S.
Coumbarides, M. Motevalli, and Y. Yohannes, Acta
Cryst. 2002, C58, o84–85; For additional examples see
M. Moreno-Manas, R. M. Sebastian, A. Vallribera, E.
Molins, and E. Espinosa, Tetrahedron: Asymmetry 1997,
8, 1525; D. Yang, X.-Y. Ye, and M. Xu, J. Org. Chem.
2000, 65, 2208; L. Sebo, J. Alfoldi, G. Rihs, and S. Toma,
Collect. Czech. Chem. Commun. 1996, 61, 1805; D.
Kanagapushpam, K. Venkatesan, and T. S. Cameron,
Acta Crystallogr., Sect.C (Cr. Str. Comm.) 1988, 44, 337.
[15] Y. Chiang, A. J. Kresge, P. A. Walsh, and Y. Yin, J. Chem.
Soc., Chem. Commun. 1989, 869; A. J. Kresge and
[26] XCAD4-CAD4 Data Reduction, K. Harms, and S.
Wocadlo, University of Marburg, Marburg, Germany,
1995.
THE SYNTHESIS OF SUBSTITUTED DIMENTHYL MALONATE DERIVATIVES
327

[27] G. M. Sheldrick, SHELX-97. Program for solution and Re-
finement of Crystal Structures. University of Go¨ ttingen,
Germany, 1997.
[28] N. Walker and D. Stuart, Acta Crystallogr., Sect. A 1983,
39, 158.
[32] L. J. Farrugia, WinGX-A Windows Program for Crys-
tal Structure Analysis, University of Glasgow, Glasgow,
1998; L. J. Farrugia, J. Appl. Crystallogr. 1999, 32, 837.
[33] R. Hooft, Collect, Data Collection Software, Nonius B.V.,
Delft, The Netherlands, 1998.
[29] DIRDIF-99 program system. P. T. Beurskens, G. Beurskens,
W. P. Bosman, R. de Gelder, S. Garcia-Granda, R. O.
Gould, R. Israel, and J. M. M. Smits, Crystallography Lab-
oratory, University of Nijmegen, The Netherlands, 1999.
[30] L. J. Farrugia, ORTEP-3 for Windows, J. Appl. Crystallogr.
1997, 30, 565.
[31] PLATON/PLUTON (a) A. L. Spek, Acta Crystallogr.,
Sect. A 1990, 46, 34; (b) PLATON, A Multipurpose
Crystallographic Tool, Utrecht University, Utrecht, The
Netherlands, A.L. Spek, 1998.
[34] Z. Otwinowski and W. Minor, Methods Enzymol. 1997,
276, 307.
[35] S. Macay, C. J. Gilmore, C. Edwards, M. Tremayne,
N. Stuart, and K. Shankland, maXus, Computer Pro-
gram for the Solution and Refinement of Crystal Struc-
tures from Diffraction Data, University of Glasgow,
Nonius B.V., Delft, and MacScience Co. Ltd., Yokohama,
1998.
[36] R. H. Blessing, Acta Crystallogr., Sect. A 1995, 51, 33;
R. H. Blessing, J. Appl. Crystallogr. 1997, 30, 421.
328
G. S. COUMBARIDES ET AL.