Structure and asymmetric diels-alder reactions of optically active allene-1,3-dicarboxylates

Article abstract of DOI:10.1021/jo951762t

Optically active allene-1,3-dicarboxylates (1a and 2a), which contain the axial asymmetry of the allene moiety, were prepared. The Diels-Alder reaction of 1a and 2a with cyclopentadiene afforded the 1:1 (1a or 2a to cyclopentadiene) endo adducts 3a and 4a through the combination of the sterically favorable approach of the diene and the dienophile owing to the axial asymmetry of the allene moiety and the effective secondary orbital interaction. The absolute configurations of 3a and 4a were determined by chemical transformation and X-ray analysis. The absolute configuration of the axial asymmetry of 1a was also determined to be R by X-ray analysis.

Full text of DOI:10.1021/jo951762t

J . Org. Chem. 1996, 61, 2031-2037
2031
Str u ctu r e a n d Asym m etr ic Diels-Ald er Rea ction s of Op tica lly
Active Allen e-1,3-d ica r boxyla tes
Izumi Ikeda,† Kazuhiko Honda,‡ Eiji Osawa,‡ Motoo Shiro,§ Mariko Aso,† and
Ken Kanematsu*,†
Institute of Synthetic Organic Chemistry, Faculty of Pharmaceutical Sciences, Kyushu University 62,
Maidashi, Higashi-ku, Fukuoka 812-82, J apan, Department of Knowledge-Based Information
Engineering, Toyohashi University of Technology, Tenpaku-cho, Toyohashi 44, J apan, and Rigaku
Corporation, 3-9-12, Matsubara-cho, Akishima, Tokyo 196, J apan
Received September 26, 1995X
Optically active allene-1,3-dicarboxylates (1a and 2a ), which contain the axial asymmetry of the
allene moiety, were prepared. The Diels-Alder reaction of 1a and 2a with cyclopentadiene afforded
the 1:1 (1a or 2a to cyclopentadiene) endo adducts 3a and 4a through the combination of the
sterically favorable approach of the diene and the dienophile owing to the axial asymmetry of the
allene moiety and the effective secondary orbital interaction. The absolute configurations of 3a
and 4a were determined by chemical transformation and X-ray analysis. The absolute configuration
of the axial asymmetry of 1a was also determined to be R by X-ray analysis.
In tr od u ction
As early as in 1875, van’t Hoff predicted that unsym-
metrically substituted allenes should exist in two enan-
tiomeric forms.1 Since the synthesis of the enantiomeric
1,3-diphenyl-1,3-di-R-naphthylallenes after 60 years,2
several general methods have been developed for the
synthesis of optically active allenes,3,4 and an evergrowing
volume of publications is unfolding their interesting
properties.5
The cycloaddition reactions of optically active allenes
which involve the transfer of the axial chiral element of
allenes to products is a powerful tool for the enantiose-
lective synthesis. In recent years, enantioselective in-
tramolecular Diels-Alder reactions5a and intramolecular
F igu r e 1.
[2 + 2] photocycloadditions5b of optically active allenes
have been reported. On the other hand, the intermo-
lecular Diels-Alder reaction of allene-1,3-dicarboxylic
1,3-dicarboxylic acid.6 However, the definitive examples
of the Diels-Alder reactions of this type have not been
reported up to now.
derivative was reported by Agosta in 1964 to establish
the absolute configuration of partially resolved (-)-allene-
As a part of systematic studies on pericyclic reactions,
we have studied the asymmetric Diels-Alder reactions
of allene-1,3-dicarboxylates with the aim of π-face selec-
tive reactions owing to the axial asymmetry of the allene
moiety. The activating influence that a carboxylate
function exerts upon the allene framework makes these
compounds excellent dienophiles in Diels-Alder reac-
tions.7 It was predicted that the Diels-Alder reaction
of the optically active allene-1,3-dicarboxylate proceeds
with high stereoselectivity derived from the axial asym-
metry of the allene moiety. From this point of view, it is
expected that the endo adduct A would be preferentially
obtained through the combination of the sterically favor-
able approach of the diene and the dienophile (the re face
attack of the (R)-allene-1,3-dicarboxylate) owing to the
axial asymmetry of the allene moiety and the effective
secondary orbital interaction (Figure 1). While the
adduct B would be formed without secondary orbital
interaction of carboxylate moiety, the adduct C must be
* Address correspondence to this author.
† Kyushu University.
‡ Toyohashi University of Technology.
§ Rigaku Corporation.
X Abstract published in Advance ACS Abstracts, February 15, 1996.
(1) van’t Hoff, J . H. La Chimie dans l’Espace; Bazendijk: Rotterdam,
1875; p 29.
(2) (a) Maitland, P.; Mills, W. H. Nature 1935, 135, 994. (b) Maitland,
P.; Mills, W. H. J . Chem. Soc. 1936, 987.
(3) (a) Alexakis, A. Pure Appl. Chem. 1992, 64, 387. (b) Alexakis,
A.; Marek, I.; Mangeney, P.; Normant, J . F. J . Am. Chem. Soc. 1990,
112, 8042. (c) Gooding, O. W.; Beard, C. C.; J ackson, D. Y.; Wren, D.
L.; Cooper, G. F. J . Org. Chem. 1991, 56, 1083. (d) Kang, S.-K.; Kim,
S.-G.; Cho, D.-G. Tetrahedron: Asymmetry 1992, 3, 1509. (e) Mori, K.;
Nukada, T.; Ebata, T. Tetrahedron 1981, 37, 1343. (f) Mukaiyama, T.;
Furuta, M.; Ohtsubo, A.; Kobayashi, S. Chem. Lett. 1991, 989. (g)
Cooper, G. F.; Wren, D. L.; J ackson, D. Y.; Beard, C. C.; Galeazzi, E.;
Van Horn, A. R.; Li, T. T. J . Org. Chem. 1993, 58, 4280. (h) Evans, R.
J . D.; Landor, S. R.; Regan, J . Chem. Commun. 1965, 397. (i) Marshall,
J . A.; Wang, X.-J . J . Org. Chem. 1992, 57, 2747, and references cited
therein. (j) Idem. Ibid. 1992, 57, 1242. (k) Buynak, J . D.; Borate, H.
B.; Lamb, G. W.; Khasnis, D. D.; Husting, C.; Isom, H.; Siriwardane,
U. J . Org. Chem. 1993, 58, 1325.
(4) (a) Ramaswamy, S.; Hui, R. A. H. F.; J ones, J . B. J . Chem. Soc.,
Chem. Commun. 1986, 1545. (b) Nishibayashi, Y.; Singh, J . D.;
Uemura, S. Tetrahedron Lett. 1994, 35, 3115. (e) Naruse, Y.; Watanabe,
H.; Inagaki, S. Tetrahedron: Asymmetry 1992, 3, 603.
(5) (a) Gibbs, R. A.; Bartels, K.; Lee, R. W. K.; Okamura, W. H. J .
Am. Chem. Soc. 1989, 111, 3717. (b) Carreira, E. M.; Hastings, C. A.;
Shepard, M. S.; Yerkey, L. A.; Millward, D. B. J . Am. Chem. Soc. 1994,
116, 6622. (c) Lathbury, D.; Gallagher, T. J . Chem. Soc., Chem.
Commun. 1986, 114.
(6) Agosta, W. C. J . Am. Chem. Soc. 1964, 86, 2638.
(7) (a) Schuster, H. F.; Coppola, G. M. Allenes in Organic Synthesis;
J ohn Wiley & Sons, Inc.: New York, 1984, and references cited therein.
(b) Smadja, W. Chem. Rev. 1983, 83, 263.
0022-3263/96/1961-2031$12.00/0 © 1996 American Chemical Society

2032 J . Org. Chem., Vol. 61, No. 6, 1996
Ikeda et al.
F igu r e 3. The 1H NMR spectrum of 1a .
F igu r e 2.
Sch em e 1a
1
F igu r e 4. The H NMR spectrum of a mixture of 1a and 1b.
20% hydrochloric acid. Esterification of 8 with (-)-
menthol (concd sulfuric acid, benzene, reflux) proceeded
to give the chloro di-(-)-menthyl ester 9 as a mixture of
geometrical isomers in high yield. The ratio of isomers
1
9 was determined by H NMR spectrum inspection (E:Z
) 6:1). Dehydrochlorination of 9 with triethylamine (1.2
equiv) in dry tetrahydrofuran at 0 °C gave a mixture of
diastereomers, which was recrystallized from pentane to
afford one of the diastereomers, 1a , in optically pure
form; mp 83 °C, [R]20D -251.1° (c 1.00, CHCl3). Although
it was presumed that the other diastereomer 1b was
enriched in the mother liquor, attempts to isolate 1b were
not successful.
The IR spectrum of 1a suggested the existence of an
allenic central carbon atom (1960 cm-1) and a carbonyl
group (1700 cm-1). The 1H NMR spectrum indicated two
equivalent olefinic protons of the allene at δ 5.99 (s)
(Figure 3). The 13C NMR spectrum exhibited the signal
for the allenic central carbon atom at δ 219.56 (s). In
contrast, the 1H NMR spectrum of the mixture of dia-
stereomers 1a and 1b indicated two signals of olefinic
protons of the allene at δ 6.01 (s) and 5.99 (s) (Figure 4).
In addition, two signals of the allenic central carbon
atoms were observed at δ 219.52 (s) and 219.17 (s),
respectively, in the 13C NMR spectrum.
formed against the steric hindrance. The adduct D would
be scarcely formed because of two disadvantageous
factors.
Moreover, the major adducts obtained by the asym-
metric Diels-Alder reactions of (R)- and (S)-allene-1,3-
dicarboxylates are considered to be useful chiral synthons
for the synthesis of optically active natural products such
as (-)-cyclosarkomycin (5), a synthetic precursor of
antitumor antibiotic sarkomycin (6) (Figure 2).8
Resu lts
P r ep a r a tion of Op tica lly P u r e Allen e-1,3-d ica r -
boxyla te. Optically pure di-(-)-menthyl allene-1,3-
dicarboxylate (1a ) was prepared by the modification of
Smith’s procedure9 of allene-1,3-dicarboxylate (Scheme
1). Menthol was used as a chiral auxiliary of choice with
the aim of preparation of (R)- or (S)-allene-1,3-dicarboxy-
late, because both optically pure (-)- and (+)-menthols
are readily available and comparatively inexpensive.
3-Chloroglutaconic acid (8) was obtained from dimethyl
1,3-acetonedicarboxylate (7) by treatment with phospho-
rus pentachloride (1.05 equiv) followed by hydrolysis with
On the other hand, the optically active di-(+)-menthyl
allene-1,3-dicarboxylate (2a ) (mp 83 °C, [R]22 +262.7°
D
(c 0.99, CHCl3)) was isolated in a similar manner to the
preparation of 1a (Scheme 2). Spectral and physical data
of 2a were identical with those of 1a except for antipodal
optical rotation.
(8) Ikeda, I.; Kanematsu, K. J . Chem. Soc., Chem. Commun. 1995,
453.
(9) Dell, C. P.; Smith, E. H.; Warburton, D. J . Chem Soc., Perkin
Trans. 1 1985, 747.
Asym m etr ic Cycloa d d ition Rea ction s of 1a a n d
2a w ith Cyclop en ta d ien e. The Diels-Alder reaction
of 1a with cyclopentadiene in the presence of aluminum

Diels-Alder Reactions of Allene-1,3-dicarboxylates
J . Org. Chem., Vol. 61, No. 6, 1996 2033
Sch em e 2a
Sch em e 5a
Sch em e 3a
Palladium-catalyzed hydrogenation of 3a produced 11 in
quantitative yield. Ozonolysis of the double bond of 11
proceeded to give the â-keto ester 12 in quantitative yield.
Compound 12 was hydrolyzed and decarboxylated di-
rectly by heating with concentrated hydrochloric acid to
give volatile norcamphor 13, which was treated with 2,4-
dinitrophenylhydrazine without purification to give 14,
(+)-norcamphor dinitrophenylhydrazone [mp 132 °C,
Sch em e 4a
[R]25 +32.7° (c 0.46, CHCl3)]. Spectral data were identi-
D
cal in all respects with the Agosta’s data of (+)-norcam-
phor dinitrophenylhydrazone [mp 129-130 °C, [R]28
D
+30° (CHCl3)] derived from the authentic (1S,4R)-nor-
camphor. J udging from these results, the absolute
configuration of 3a was determined to be (1S,2R,4R)-
form. Similarly, 4a was converted into (-)-norcamphor
chloride (AlCl3) proceeded with high diastereoselectivity
to afford a mixture of two 1:1 adducts in high yield. No
evidence for other adducts besides two adducts was found
by TLC and 1H NMR inspection. The ratio of adducts
(major (3a )/minor (3b) ) 98:2) was determined by HPLC
analysis. The major adduct 3a was isolated in 96% yield
(Scheme 3).
dinitrophenylhydrazone 18 [mp 131 °C, [R]23 -28.0° (c
D
1.03, CHCl3)] (Scheme 6).
The bridgehead structure and the exo-olefin geometry
of the endo adduct 4a derived from (S)-allene-1,3-dicar-
boxylate 2a was completely confirmed by X-ray analysis
as depicted in Figure 5, and thus the exo-olefin geometry
of 4a was determined to be Z.
The relative configuration of adducts 3a and 3b was
1
established on the basis of H NMR and other spectral
data. First, each 1:1 adduct showed two olefinic protons
(H5 and H6) [3a : δ 6.18-6.11 (m, 2H); 3b δ 6.33 (dd, J )
5.3, 3.0 Hz, 1H) and 6.12 (dd, J ) 5.3, 3.0 Hz, 1H)] and
the exo-olefinic proton (Ha) [3a : δ 5.98 (d, J ) 2.0 Hz,
1H); 3b: δ 5.99 (d, J ) 2.0 Hz, 1H)]. The major isomer
3a showed a characteristic signal of an exo-H2 at δ 3.87
as a doublet of doublet with coupling constants 3.5 and
2.0 Hz, which indicated that 3a was the endo adduct.
Deter m in a tion of th e Absolu te Con figu r a tion s of
1a a n d 2a . The absolute configurations of the Diels-
Alder adducts 3a and 4a 19 were determined by chemical
transformation and X-ray analysis. The stereochemistry
of the endo adduct 3a can only be derived by the reaction
of 1a from the re face and that suggested the absolute
configuration of the axial asymmetry of 1a was R.
An unequivocal support for the structure of 1a was
obtained by single-crystal X-ray analysis,19 and the axial
asymmetry of the allene moiety of 1a was determined to
be R (Figure 6). Crystallographic data are listed in
Tables 1-3. Interestingly, the X-ray analysis of 1a
showed that the two allenic double bonds retain their
linear arrangements (178.4°) and that the bond length
(1.298 Å) is somewhat shorter than the standard allenic
bond length (1.31 Å).11 The structure and the frontier
molecular orbitals of the allene portion of 1a were studied
1
Detailed inspection of H NMR showed that the minor
isomer 3b was the exo adduct (Scheme 3).
On the other hand, the reaction of the (S)-allene-1,3-
dicarboxylate 2a with cyclopentadiene in the presence
of AlCl3 proceeded similarly to that of 1a to afford the
1:1 adduct 4a in 95% yield (Scheme 4). Physical and
spectral data of 4a were identical with those of 3a except
for antipodal optical rotation.
The absolute configuration of 3a was determined by
Agosta’s procedure,6 the chemical transformation into
(+)-norcamphor 2,4-dinitrophenylhydrazone (Scheme 5).10
(10) Aso, M.; Ikeda, I.; Kawabe, T.; Shiro, M.; Kanematsu, K.
Tetrahedron Lett. 1992, 33, 5787.
(11) Patai, S., Ed. The Chemistry of Ketenes, Allenes, and Related
Compounds; J ohn Wiley & Sons, Inc.: Chichester, 1980; Part 1 and 2.

2034 J . Org. Chem., Vol. 61, No. 6, 1996
Ikeda et al.
Sch em e 6a
F igu r e 6. Computer-generated perspective drawing of 1a as
determined by X-ray analysis. The atom numbering is arbi-
trary.
Ta ble 1. Atom ic Coor d in a tes a n d Biso/Beq of 1a
a
atom
x
y
z
Beq
O(1)
O(2)
C(1)
C(2)
C(3)
C(4)
C(5)
C(6)
C(7)
C(8)
C(9)
C(10)
C(11)
C(12)
C(13)
H(1)
0.0749(2)
-0.0597(2)
0.1118(2)
0.2178(2)
0.2565(4)
0.2310(3)
0.1240(3)
0.0843(3)
0.2491(3)
0.2107(4)
0.3542(4)
0.0983(4)
-0.0099(3)
-0.0391(3)
0.0000
0.0772
0.2436
0.3340
0.2247
0.2579
0.2543
0.0927
0.0039
0.1071
0.2242
0.2326
0.2357
0.1450
0.3843
0.3862
0.3770
0.0319
0.1263
0.1227
-0.1089
0.3468(1)
0.3642(2)
0.3002(2)
0.3114(2)
0.2600(3)
0.1787(3)
0.1669(2)
0.2204(2)
0.3929(2)
0.4325(3)
0.3998(3)
0.0875(3)
0.3756(2)
0.4235(2)
0.4245(3)
0.3260
0.2847
0.2606
0.2662
0.1432
0.1584
0.1843
0.2210
0.1976
0.0379(2)
-0.0739(3)
-0.0704(3)
-0.0736(4)
-0.1846(4)
-0.1591(5)
-0.1483(4)
-0.0425(4)
-0.0881(4)
-0.2086(5)
-0.0791(7)
-0.1164(6)
0.0209(4)
0.1325(4)
0.2500
5.15(6)
9.1(1)
4.64(8)
5.11(8)
6.2(1)
6.7(1)
6.3(1)
5.74(9)
6.1(1)
8.4(1)
9.8(2)
9.1(2)
5.45(9)
5.58(10)
5.0(1)
4.6000
5.2000
6.2000
6.2000
6.7000
6.7000
6.3000
5.8000
5.8000
6.1000
8.5000
8.5000
8.5000
9.9000
9.9000
9.9000
9.0000
9.0000
9.0000
5.5000
F igu r e 5. Computer-generated perspective drawing of 4a as
determined by X-ray analysis. The atom numbering is arbi-
trary.
-0.1657
0.0288
H(2)
H(3a)
H(3b)
H(4a)
H(4b)
H(5)
H(6a)
H(6b)
H(7)
H(8a)
H(8b)
H(8c)
H(9a)
H(9b)
H(9c)
H(10a)
H(10b)
H(10c)
H(12)
-0.1956
-0.2783
-0.2354
-0.0425
-0.2580
-0.0454
0.0610
-0.0102
-0.2169
-0.2904
-0.2154
-0.0023
-0.1573
-0.0892
-0.1144
-0.1781
-0.0280
0.1160
by ab initio calculations of model structures with Gauss-
ian 9212 employing the 6-31G basis set.13 The X-ray
structure of the central portion of 1a was almost super-
imposable with the optimized geometry of dimethyl
allenedicarboxylate (DMAD). In our previous study,14
AM1 revealed a remarkable decrease in the LUMO level
of allene upon the introduction of carboxylate groups at
1,3-positions (1.74 eV). This trend has been confirmed
and accentuated by ab initio calculations which produced
a larger decrease in the LUMO level (2.44 eV); LUMO:
allene 4.85 eV, DMAD 2.41 eV).
0.4200
0.4818
0.4057
0.4300
0.3812
0.3753
0.4527
0.0777
(12) Frisch, M. J .; Trucks, G. W.; Schlegel, H. B.; Gill, P. M. W.;
J ohnson, B. G.; Wong, M. W.; Foreman, J . B.; Robb, M. A.; Head-
Gordon, M.; Replogle, E. S.; Gomperts, R.; Andres, J . L.; Raghavachari,
K.; Binkley, J . S.; Gonzalez, C.; Martin, R. L.; Fox, D. J .; DeFrees, D.
J .; Baker, J .; Stewart, J . J . P.; Pople, J . A., Gaussian 92/DFT, obtained
from Gaussian Inc, Carnegue Office Park, Building 6, Pittsburgh, PA
15106.
(13) Allinger, N. L.; Zhou, X.; Bergsma, J . J . Mol. Struct. 1994, 312-
(118), 69.
(14) Yoshida, M.; Hidaka, Y.; Nawata, Y.; Rudsinski, J . M.; Osawa,
E.; Kanematsu, K. J . Am. Chem Soc. 1988, 110, 1232.
0.0522
0.0744
0.4470
a
Beq
)
8/3π2(U11(aa*)2 + U22(bb*)2 + U33(cc*)2 + 2U12aa*bb*
cos γ + 2U13aa*cc* cos â + 2U23bb*cc* cos R).
Discu ssion
Optically active dimenthyl allenedicarboxylates 1a and
2a were prepared, and the absolute configurations were

Diels-Alder Reactions of Allene-1,3-dicarboxylates
J . Org. Chem., Vol. 61, No. 6, 1996 2035
Ta ble 2. Bon d Len gth s of 1a in An gstr om s
activity. Lewis acid catalysis in the Diels-Alder reac-
tions of 1a and 2a with furan also effected the higher
endo/exo selectivity (the endo adduct analogous to A:the
exo adduct analogous to B ) 53:47 (uncatalyzed; 40 °C)
and 81:19 (2 equiv of TiCl4; -78 °C) although the
selectivity was not as high as that in the reaction with
cyclopentadiene.15,16
The adducts 3a and 3b both formed by the reaction of
1a from the re face, which suggests that the π-face
selectivity of the reaction is completely controlled. The
axial asymmetry of the allene moiety and the two (-)-
menthyl groups could contribute to the asymmetric
Diels-Alder reaction of 1a .
Yamamoto et al. reported that the diastereoselectivity
in the asymmetric Diels-Alder reaction of fumarate
using menthol as a chiral auxiliary was improved dra-
matically by switching catalyst from AlCl3 to homoge-
neous organoaluminum reagent such as diethylalumi-
num chloride.17 They described that the Lewis acid
coordinated fumarate was considered to exist in the
s-trans form predominantly and that the two (-)-menthyl
groups should cooperatively cover the re face of the double
bond. Consequently, a diene approached from the si face
of the double bond of the fumarate for cycloaddition.
In marked contrast to their result, the asymmetric
Diels-Alder reaction of optically pure di-(-)-menthyl (R)-
allene-1,3-dicarboxylate proceeded from the re face of the
double bond of 1a under Lewis acid-catalyzed conditions.
It is presumed that high π-facial selectivity of the
optically pure allene-1,3-dicarboxylate in the Diels-Alder
reaction is elicited from the axial asymmetry of the allene
moiety and not from the topological feature of the (-)-
menthyl group. It is assumed that the asymmetry of the
(-)-menthyl group of the carboxylate which was attached
to the reacting double bond of the allene may have rather
a disadvantageous effect in approach of diene under
Lewis acid-catalyzed conditions. The other (-)-menthyl
group which is attached to the unreacting double bond
of allene-1,3-dicarboxylate increases the influence of the
axial asymmetry of the allene moiety in the Diels-Alder
reaction.
O(1)-C(1)
O(2)-C(11)
C(1)-C(6)
C(2)-C(7)
C(4)-C(5)
C(5)-C(10)
C(7)-C(9)
C(12)-C(13)
1.464(4)
1.200(5)
1.509(5)
1.535(5)
1.537(6)
1.504(7)
1.498(7)
1.298(5)
O(1)-C(11)
C(1)-C(2)
C(2)-C(3)
C(3)-C(4)
C(5)-C(6)
C(7)-C(8)
C(11)-C(12)
1.320(4)
1.518(5)
1.542(5)
1.523(7)
1.535(6)
1.500(6)
1.466(6)
C(1)-H(1)
1.17
1.10
1.06
1.22
1.16
0.94
0.94
1.00
0.96
0.98
C(2)-H(2)
1.19
1.05
1.26
1.14
0.98
1.01
0.94
1.01
0.97
1.09
C(3)-H(3a)
C(4)-H(4a)
C(5)-H(5)
C(3)-H(3b)
C(4)-H(4b)
C(6)-H(6a)
C(7)-H(7)
C(6)-H(6b)
C(8)-H(8a)
C(8)-H(8c)
C(9)-H(9b)
C(10)-H(10a)
C(10)-H(10c)
C(8)-H(8b)
C(9)-H(9a)
C(9)-H(9c)
C(10)-H(10b)
C(12)-H(12)
Ta ble 3. Bon d An gles of 1a in Degr ees
C(1)-O(1)-C(11)
117.1(3) O(1)-C(1)-C(2)
108.2(3) C(2)-C(1)-C(6)
106.8(3) C(1)-C(2)-C(7)
113.5(3) C(2)-C(3)-C(4)
112.2(4) C(4)-C(5)-C(6)
112.6(4) C(6)-C(5)-C(10)
111.7(3) C(2)-C(7)-C(8)
111.2(4) C(8)-C(7)-C(9)
124.8(4) O(1)-C(11)-C(12)
107.2(3)
112.7(3)
114.5(3)
111.6(3)
109.0(4)
110.9(4)
115.0(4)
111.7(5)
112.9(4)
O(1)-C(1)-C(6)
C(1)-C(2)-C(3)
C(3)-C(2)-C(7)
C(3)-C(4)-C(5)
C(4)-C(5)-C(10)
C(1)-C(6)-C(5)
C(2)-C(7)-C(9)
O(1)-C(11)-O(2)
O(2)-C(11)-C(12)
122.2(4) C(11)-C(12)-C(13) 125.0(3)
C(12)-C(13)-C(12)* 178.4(6)
O(1)-C(1)-H(1)
C(6)-C(1)-H(1)
C(3)-C(2)-H(2)
C(2)-C(3)-H(3a)
C(4)-C(3)-H(3a)
H(3a)-C(3)-H(3b)
C(3)-C(4)-H(4b)
C(5)-C(4)-H(4b)
C(4)-C(5)-H(5)
C(10)-C(5)-H(5)
C(1)-C(6)-H(6b)
C(5)-C(6)-H(6b)
C(2)-C(7)-H(7)
C(9)-C(7)-H(7)
C(7)-C(8)-H(8b)
H(8a)-C(8)-H(8b)
H(8b)-C(8)-H(8c)
C(7)-C(9)-H(9b)
H(9a)-C(9)-H(9b)
H(9b)-C(9)-H(9c)
C(5)-C(10)-H(10b)
103.0 C(2)-C(1)-H(1)
110.3
103.5
112.1
115.2
98.6
114.7 C(1)-C(2)-H(2)
105.6 C(7)-C(2)-H(2)
114.8 C(2)-C(3)-H(3b)
105.2 C(4)-C(3)-H(3b)
109.8 C(3)-C(4)-H(4a)
111.6 C(5)-C(4)-H(4a)
98.8 H(4a)-C(4)-H(4b)
105.1 C(6)-C(5)-H(5)
110.1 C(1)-C(6)-H(6a)
115.3 C(5)-C(6)-H(6a)
106.9 H(6a)-C(6)-H(6b)
107.0 C(8)-C(7)-H(7)
105.6 C(7)-C(8)-H(8a)
107.1 C(7)-C(8)-H(8c)
105.2 H(8a)-C(8)-H(8c)
105.5 C(7)-C(9)-H(9a)
111.5 C(7)-C(9)-H(9c)
105.8 H(9a)-C(9)-H(9c)
101.0 C(5)-C(10)-H(10a)
112.7 C(5)-C(10)-H(10c)
111.6
108.8
113.2
108.9
104.2
110.8
107.8
105.6
113.4
113.4
111.5
118.2
113.1
105.6
114.6
109.5
Exp er im en ta l Section
Melting points are uncorrected. Optical rotations were
measured using a 5 cm path length cell. Analytical thin layer
chromatography (TLC) was carried out on precoated TLC
plates (Kieselgel 60 F254, 0.2 mm). Nuclear magnetic reso-
nance spectra (1H NMR and 13C NMR) were taken in CDCl3
unless otherwise noted. Chemical shifts are reported as δ
values with respect to tetramethylsilane (TMS) as an internal
standard. Signal multiplicities are represented by s (singlet),
d (doublet), t (triplet), q (quartet), br (broad), and m (multiplet).
Column chromatography was performed by using silica gel
(70-230 mesh) as the stationary phase. Flash column chro-
matography was performed by using silica gel (230-400 mesh)
as the stationary phase.
H(10a)-C(10)-H(10b) 107.2 H(10a)-C(10)-H(10c) 106.5
H(10b)-C(10)-H(10c) 105.8 C(11)-C(12)-H(12) 111.7
C(13)-C(12)-H(12) 121.3
determined by chemical transformation and X-ray analy-
sis. The Diels-Alder reactions of 1a and 2a proceeded
with ease under Lewis acid-catalyzed conditions. Opti-
cally pure 1a , the axial asymmetry of which was deter-
mined to be R, afforded the endo adduct 3a (96%),
accompanied by the exo adduct 3b (2%).
Lewis acid catalysis resulted in the high endo selectiv-
ity in this reaction. Agosta studied the Diels-Alder
reaction of allene-1,3-dicarboxylic acid.6 According to his
result, the Diels-Alder reaction of racemic allene-1,3-
dicarboxylic acid with cyclopentadiene (ether, room tem-
perature) afforded approximately equal amounts of iso-
meric adducts, the endo adduct A and the exo adduct B
(R ) H, Figure 1). It is also reported that the reaction
of partially resolved (-)-allene-1,3-dicarboxylic acid with
cyclopentadiene under similar conditions gave a mixture
from which the adduct B was separated, but the adduct
A could not be purified without total loss in optical
3-Ch lor o-2-p en ten ed ioic a cid (8) was prepared according
to the method of Smith et al.9,18 To well-stirred dimethyl
acetone-1,3-dicarboxylate (7) (25.0 g, 0.143 mol) was added
(15) Ikeda, I.; Gondo, A.; Shiro, M.; Kanematsu, K. Heterocycles
1993, 36, 2669.
(16) The Lewis acid-catalyzed Diels-Alder reaction of 1a with
diphenylfulvene only led to polymerization although the uncatalyzed
reaction (benzene, 60 °C) gave the exo adduct (68 %) and the endo
adduct (32%).
(17) (a) Furuta, K.; Iwanaga, K.; Yamamoto, H. Tetrahedron Lett.
1986, 27, 4507. (b) Maruoka, K.; Saito, S.; Yamamoto, H. J . Am. Chem.
Soc. 1992, 114, 1089.
(18) Malachowski, R.; Kalinski, T. Roczniki. Chem. 1926, 6, 768.

2036 J . Org. Chem., Vol. 61, No. 6, 1996
Ikeda et al.
phosphorus pentachloride (31.4 g, 0.151 mol) in ten portions
during 30 min when the mixture turned red. The mixture was
heated at 40 °C for 40 min and then cooled in an ice-bath,
carefully poured onto ice (100 g), and stirred for 30 min. The
reaction vessel was rinsed with dichloromethane/water. The
combined two-phase mixture was separated, and the aqueous
layer was extracted with dichloromethane. The organic layer
and the extract were combined, washed with brine, and
evaporated to give a red oil. This red oil was used in the
subsequent reaction without further purification. This oil was
suspended in 20% hydrochloric acid (100 mL), and the mixture
was boiled for 5 h. The mixture was cooled to room temper-
ature and was extracted with ether. The organic layer was
dried over Na2SO4 and evaporated to give an orange-brown
solid. Recrystallization from benzene afforded 8 (8.77 g, 37%
for two steps) as a colorless solid: mp 127.5-128.5 °C
(recrystallized from benzene) (lit.,28 mp 129 °C); IR (KBr) 3000
(m), 1720 (s), 1705 (s), 1640 (s) cm-1; 1H NMR (60 MHz, DMSO-
d6) δ 6.18 (s, 1H), 3.94 (s, 2H).
[2E(1R,2S,5R)]-Bis[5-m et h yl-2-(1-m et h ylet h yl)cyclo-
h exyl] 3-Ch lor o-2-p en t en ed ioa t e ((E)-9) a n d [2Z(1R,-
2S,5R)]-Bis[5-m eth yl-2-(1-m eth yleth yl)cycloh exyl] 3-Ch lo-
r o-2-p en ten ed ioa te ((Z)-9). (-)-Menthol used was deter-
mined to be optically pure from optical rotation. To a mixture
of (-)-menthol (4.75 g, 30.4 mmol) and 8 (1.00 g, 6.08 mmol)
in dry benzene (30 mL) was added concentrated sulfuric acid
(3 drops) and the solution was boiled at reflux with a Dean-
Stark separator for 12 h. After cooling, ether was added, the
solution was washed with saturated aqueous NaHCO3 solution
and brine, and the organic layer was dried over Na2SO4. After
evaporation, the residue was chromatographed on silica gel
eluting with ethyl acetate/hexane (1:80) to give a mixture of
(E)- and (Z)-9 (2.48 g, 93%) as a yellow oil. Analytical samples
of two isomers were prepared by flash column chromatogra-
phy: Ma jor : Rf 0.42 (ethyl acetate/hexane, 1:10); IR (neat)
1745 (s), 1710 (s), 1635 (m) cm-1; 1H NMR (60 MHz) δ 6.23 (s,
1H), 4.96-4.51 (m, 2H), 4.08 (s, 2H), 2.23-0.96 (m, 18H),
0.96-0.62 (m, 18H); LRMS (FD) m/ z (rel inten) 440 (M+, base).
Min or : Rf 0.31 (ethyl acetate/hexane, 1:10); IR (neat) 1745
(s), 1710 (s), 1635 (m) cm-1; 1H NMR (60 MHz) δ 6.17 (s, 1H),
4.96-4.51 (m, 2H), 3.42 (s, 2H), 2.23-0.96 (m, 18H), 0.96-
0.62 (m, 18H); LRMS (FD) m/ z (rel inten) 440 (M+, base).
[3R(1R,2S,5R)]-Bis[5-m et h yl-2-(1-m et h ylet h yl)cyclo-
h exyl] 2,3-P en ta d ien ed ioa te (1a ). To a stirred, ice-cooled
solution of 9 (4.00 g, 9.08 mmol) in dry tetrahydrofuran was
added dropwise dry triethylamine (1.5 mL, 10.8 mmol). The
resultant solution was stored at -5 °C until precipitates had
appeared. The solid was filtered off and washed with dry
ether. The combined filtrates and washings were washed with
0.2 N hydrochloric acid (×4), water (×1), and brine (×3) and
dried over Na2SO4. The solution was evaporated in vacuo, the
residue was chromatographed on silica gel eluting with ethyl
acetate/hexane (1:50) to give a mixture of 1a and 1b (3.60 g,
98%) as a pale yellow oil: Rf 0.33 (ethyl acetate/hexane, 1:10);
IR (CHCl3) 1945 (m), 1685 (s) cm-1; 1H NMR (270 MHz) δ 6.01
(s, 1.07H), 5.99 (s, 0.93H), 4.74 (ddd, J ) 10.9, 10.9, 4.3 Hz,
2H), 2.03 (dm, J ) 11.9 Hz, 2H), 1.87, 1.84 (qd, J ) 6.9, 2.6
Hz, total 2H), 1.77-1.63 (m, 4H), 1.63-1.34 (m, 6H), 1.18-
0.81 (m, 16H), 0.78, 0.77 (d, J ) 6.9 Hz, total 6H); 13C NMR
(67.8 MHz, CDCl3) δ 219.52 (s), 219.17 (s), 162.96 (s), 92.68
(d), 92.61 (d), 75.72 (d), 75.64 (d), 46.99 (d), 46.92 (d), 40.72
(t), 34.19 (t), 31.43 (d), 31.36 (d), 26.48 (d), 26.41 (d), 23.71 (t),
23.67 (t), 21.95 (q), 20.63 (q), 16.59 (q), 16.52 (q).
CDCl3) δ 219.56 (s), 163.07 (s), 92.66 (d), 75.68 (d), 47.01 (d),
40.74 (t), 34.21 (t), 31.39 (d), 26.47 (d), 23.70 (t), 22.01 (q), 20.66
(q), 16.60 (q); LRMS (EI, 30 eV) m/ z (rel inten) 404 (M+, 1),
403 (2), 390 (5), 389 (18), 267 (55), 266 (40), 251 (20), 249 (26),
248 (40), 223 (90), 222 (29), 200 (base). Anal. Calcd for
C25H40O4: C, 74.22; H, 9.97. Found: C, 74.08; H, 9.90.
Further attempts at isolation and purification of 1b from the
mother liquor was failed.
[2E(1S,2R,5S)]-Bis[5-m et h yl-2-(1-m et h ylet h yl)cyclo-
h exyl] 3-Ch lor o-2-p en t en ed ioa t e ((E)-10) a n d [2Z(1S,-
2R,5S)]-Bis[5-m eth yl-2-(1-m eth yleth yl)cycloh exyl] 3-Ch lo-
r o-2-p en ten ed ioa te ((Z)-10). In a similar manner to the
synthesis of 9, 10 (34.7 g, 94%) was obtained as a yellow oil
from 8 (13.9 g, 84.2 mmol) and (+)-menthol (30.6 g, 196
mmol): Ma jor : Rf 0.42 (ethyl acetate/hexane, 1:10); IR (neat)
1745 (s), 1710 (s), 1635 (m) cm-1; 1H NMR (60 MHz) δ 6.23 (s,
1H), 4.80-4.40 (m, 2H), 4.09 (s, 2H), 2.20-1.30 (m, 18H),
1.30-0.50 (m, 18H); LRMS (FD) m/ z (rel inten) 440 (M+, base).
Min or : Rf 0.31 (ethyl acetate/hexane, 1:10); IR (neat) 1745
(s), 1710 (s) cm-1; 1H NMR (60 MHz) δ 6.14 (s, 1H), 4.80-4.40
(m, 2H), 3.41 (s, 2H), 2.40-1.10 (m, 18H), 1.10-0.60 (m, 18H);
LRMS (FD) m/ z (rel inten) 440 (M+, base).
[3S(1S,2R,5S)]-Bis[5-m et h yl-2-(1-m et h ylet h yl)cyclo-
h exyl] 2,3-P en ta d ien ed ioa te (2a ). In a similar manner to
the synthesis of 1a , a mixture of 2a and 2b (1.03 g, 75%) was
obtained as a yellow oil from a mixture of (E)- and (Z)-10 (1.48
g, 3.36 mmol): Rf 0.33 (ethyl acetate/hexane, 1:10); IR (CHCl3)
1
1945 (m), 1685 (s) cm-1; H NMR (270 MHz) δ 6.01 (s, 1H),
5.99 (s, 1H), 4.74 (ddd, J ) 10.9, 10.9, 4.3 Hz, 2H), 2.03 (dm,
J ) 11.9, 2H), 1.87, 1.84 (qd, J ) 6.9, 2.6 Hz, total 2H), 1.77-
1.63 (m, 4H), 1.63-1.34 (m, 6H), 1.18-0.91 (m, 16H), 0.78,
0.77 (d, J ) 6.9 Hz, total 6H). This oil was crystallized and
repeatly recrystallized from pentane to give 2a (0.212 g, 25%)
as colorless needles: Rf 0.33 (ethyl acetate/hexane, 1:10); mp
83 °C; [R]22D +262.7° (c 0.99, CHCl3); IR (CHCl3) 1945 (m), 1685
(s) cm-1 1H NMR (270 MHz) δ 5.99 (s, 2H), 4.74 (ddd, J )
;
10.9, 10.9, 4.3 Hz, 2H), 2.03 (dm, J ) 11.9 Hz, 2H), 1.87, 1.84
(qd, J ) 6.9, 2.6 Hz, total 2H), 1.77-1.63 (m, 4H), 1.63-1.34
(m, 6H), 1.18-0.91 (m, 16H), 0.78, 0.77 (d, J ) 6.9 Hz, total
6H); 13C NMR (67.8 MHz, CDCl3) δ 219.56 (s), 163.07 (s), 92.66
(d), 75.68 (d), 47.01 (d), 40.74 (t), 34.21 (t), 31.40 (d), 26.47
(d), 23.70 (t), 22.01 (q), 20.66 (q), 16.60 (q); LRMS (EI, 30 eV)
m/ z (rel inten) 404 (M+, 1), 403 (2), 390 (5), 389 (18), 267 (55),
266 (40), 251 (20), 249 (26), 248 (40), 223 (90), 222 (29), 200
(base). Anal. Calcd for C25H40O4: C, 74.22; H, 9.97. Found:
C, 74.14; H, 9.95. In this case, further attempts at isolation
and purification of 2b from the mother liquior was failed.
[1S,2R(1R,2S,5R),3Z(1R,2S,5R),4R]-5-Meth yl-2-(1-m eth -
yleth yl)cycloh exyl 3-[2-[[5-Meth yl-2-(1-m eth yleth yl)cy-
cloh exyl]oxy]-2-oxoeth ylid en e]bicyclo [2.2.1]h ep t-5-en e-
2-car boxylate (3a) an d [1R,2R(1R,2S,5R),3Z(1R,2S,5R),4S]-
5-Meth yl-2-(1-m eth yleth yl)cycloh exyl 3-[2-[[5-Meth yl-2-
(1-m e t h y le t h y l)c y c lo h e x y l]o x y ]-2-o x o e t h y li d e n e ]-
bicyclo[2.2.1]h ep t-5-en e-2-ca r boxyla te (3b). To a suspen-
sion of aluminum chloride (AlCl3) (0.592 g, 4.44 mmol, 1.20
equiv) in 12 mL of dry dichloromethane at -78 °C under
nitrogen was added a solution of 1a (1.49 g, 3.69 mmol) in dry
dichloromethane. After 30 min, cyclopentadiene (3 mL, excess)
was added. The reaction mixture was stirred at -78 °C for 5
h, and the reaction was quenched with water. The resultant
slurry was diluted with dichloromethane, and the two-phase
mixture was separated. The aqueous layer was extracted with
dichloromethane, and the combined organic layers were dried
over Na2SO4 and concentrated in vacuo. The residue was
purified by flash chromatography on silica gel eluting with
ethyl acetate/hexane (0:1 f 1:80) to afford the adduct 3a (1.66
g, 96%) and 3b (0.03 g, 2%); 3a : Rf 0.33 (ethyl acetate/hexane,
This oil was crystallized and repeatedly recrystallized from
pentane to give 1a (0.84 g, 23%) as colorless needles: Rf 0.33
(ethyl acetate/hexane, 1:10); mp 83 °C; [R]20 -251.1° (c 1.00,
D
-1
CHCl3); IR (CHCl3) 1945 (m), 1685 (s) cm
;
1H NMR (270
1:10); mp 97 °C (recrystallized from ether); [R]23 -48.2° (c
MHz) δ 5.99 (s, 2H), 4.74 (ddd, J ) 10.9, 10.9, 4.3 Hz, 2H),
2.03 (dm, J ) 11.9, 2H), 1.87, 1.84 (qd, J ) 6.9, 2.6 Hz, total
2H), 1.77-1.63 (m, 4H), 1.63-1.34 (m, 6H), 1.18-0.91 (m,
16H), 0.78, 0.77 (d, J ) 6.9 Hz, total 6H); 13C NMR (67.8 MHz,
D
1.03, CHCl3); IR (CHCl3) 1710 (s), 1690 (s) cm-1; 1H NMR (270
MHz) δ 6.18-6.11 (m, 2H), 5.98 (d, J ) 2.0 Hz, 1H), 4.62 (ddd,
J ) 10.9, 10.9, 4.3 Hz, 1H), 4.55 (ddd, J ) 10.9, 10.9, 4.3 Hz,
1H), 3.87 (dd, J ) 3.5, 2.0 Hz, 1H), 3.41 (br s, 1H), 3.33 (br s,
1H), 2.15-1.81 (m, 4H), 1.77-1.57 (m, 5H), 1.57-1.20 (m, 6H),
1.17-0.62 (m, 23H); 13C NMR (67.8 MHz, CDCl3) δ 170.60 (s),
165.95 (s), 159.86 (s), 135.71 (d), 133.55 (d), 113.70 (d), 74.20
(d), 73.58 (d), 53.13 (d), 51.00 (d), 50.58 (t), 46.96 (d), 46.91
(19) The author has deposited atomic coordinates for this structure
with the Cambridge Crystallographic Data Centre. The coordinates
can be obtained, on request, from the Director, Cambridge Crystal-
lographic Data Centre, 12 Union Road, Cambridge, CB2 1EZ, UK.

Diels-Alder Reactions of Allene-1,3-dicarboxylates
J . Org. Chem., Vol. 61, No. 6, 1996 2037
(d), 46.33 (d), 41.05 (t), 40.59 (t), 34,34 (t), 31.42 (d), 31.34 (d),
26.13 (d), 25.53 (d), 23.6 (t), 23.05 (t), 22.02 (q), 20.92 (q), 20.70
(q), 16.53 (q), 15.99 (q); LRMS (FAB) m/ z (rel inten) 471 ([M
+ H]+, 43), 333 (20), 195 (85), 177 (base). Anal. Calcd for
C30H46O4: C, 76.55; H, 9.85. Found: C, 76.45; H, 9.80. 3b (a
aqueous NaOH solution, water, and brine and dried over Na2-
SO4. The solvent was removed under reduced pressure, and
the residue was used for the subsequent reaction without
further purification. A solution of the crude 13 (Rf 0.23 (ethyl
acetate/hexane, 1:10)), 2,4-dinitrophenylhydrazine (0.132 g,
0.665 mmol), and concd hydrochloric acid (0.7 mL) in dry
methanol was heated at 40 °C for 3 h. After cooling, the
solvent was concentrated under reduced pressure, and the
residue was diluted with diethyl ether. After addition of water,
the resulting mixture was extracted with diethyl ether. The
organic layer was washed with brine, dried over Na2SO4, and
evaporated in vacuo. After flash column chromatography on
silica gel eluting with ethyl acetate/hexane (1:20), recystalli-
zation of the crude hydrazone 14 from methanol gave 14 (46.8
mg, 52% for two steps) as yellow crystals: Rf 0.48 (ethyl
acetate/hexane, 1:1); mp 132 °C (recrystallized from methanol);
colorless syrup): Rf 0.43 (ethyl acetate/hexane, 1:10); [R]23
D
-341.7° (c 1.03, CHCl3); IR (CHCl3) 1710 (s) cm-1; H NMR
1
(270 MHz) δ 6.33 (dd, J ) 5.3, 3.0 Hz, 1H), 6.12 (dd, J ) 5.3,
3.0 Hz, 1H), 5.99 (d, J ) 2.0 Hz, 1H), 4.69 (ddd, J ) 10.9, 10.9,
4.3 Hz, 1H), 4.62 (ddd, J ) 10.6, 10.6, 4.3 Hz, 1H), 3.43-3.36
(m, 2H), 3.18 (br s, 1H), 2.14-1.83 (m, 5H), 1.74-1.57 (m, 5H),
1.55-1.31 (m, 4H), 1.15-0.79 (m, 16H), 0.76 (d, J ) 6.9 Hz,
3H), 0.72 (d, J ) 6.9 Hz, 3H); 13C NMR (67.8 MHz, CDCl3) δ
171.34 (s), 165.81 (s), 161.28 (s), 138.95 (d), 135.58 (d), 113.80
(d), 74.27 (d), 73.66 (d), 51.63 (d), 51.31 (d), 47.73 (d), 47.07
(t), 46.95 (d), 41.08 (t), 40.66 (t), 34.35 (t), 31.42 (d), 26.28 (d),
25.69 (d), 23.70 (t), 23.04 (t), 22.04 (q), 21.98 (q), 21.04 (q),
20.67 (q), 16.57 (q), 15.98 (q); LRMS (FAB) m/ z (rel inten) 471
([M + H]+, 29), 333 (21), 195 (90), 177 (base); HRMS (FAB)
m/ z calcd for C30H47O4 ([M + H]+) 471.3474, found 471.3484.
[1R,2S(1S,2R,5S),3Z(1S,2R,5S),4S]-5-Meth yl-2-(1-m eth -
yleth yl)cycloh exyl 3-[2-[[5-Meth yl-2-(1-m eth yleth yl)cy-
cloh exyl]oxy]-2-oxoeth ylid en e]bicyclo[2.2.1]h ep t-5-en e-
2-ca r boxyla te (4a ). In a similar manner to the synthesis of
3a , 4a (5.53 g, 95%) was obtained from 2a (5.00 g, 12.4 mmol),
cyclopentadiene (5.7 mL), and AlCl3 (1.89 g, 14.2 mmol).
Purification of 4a by recrystallization from ether to afford
colorless prisms: Rf 0.33 (ethyl acetate/hexane, 1:10); mp 104.5
[R]25 +32.7° (c 0.46, CHCl3); IR (CHCl3) 1615 (s) cm-1 1H
;
D
NMR (60 MHz) δ 10.73 (br s, 1H), 9.11 (d, J ) 2.4 Hz, 1H),
8.29 (dd, J ) 9.6, 2.4 Hz, 1H), 7.89 (d, J ) 9.6 Hz, 1H), 3.16-
2.92 (m, 1H), 2.92-2.50 (m, 2H), 1.82-0.82 (m, 7H).
[1S,2S(1S,2R,5S),3Z(1S,2R,5S),4R]-5-Meth yl-2-(1-m eth -
yleth yl)cycloh exyl 3-[2-[(5-Meth yl-2-(1-m eth yleth yl)cy-
cloh exyl)oxy]-2-oxoeth ylid en e]bicyclo[2.2.1]h ep ta n e-2-
ca r boxyla te (15). A similar manner to the synthesis of 11,
15 (0.297 g, 98%) was obtained as colorless crystals from 4a
(0.301 g, 0.641 mmol): Rf 0.35 (ethyl acetate/hexane, 1:10);
mp 142.5-143 °C (recrystallized from diethyl ether); IR
(CHCl3) 1730 (s), 1700 (s) cm-1;1H NMR (270 MHz) δ 5.81 (d,
J ) 2.6 Hz, 1H), 4.63 (ddd, J ) 10.7, 10.7, 4.6 Hz, 1H), 4.61
(ddd, J ) 10.8, 10.8, 4.3 Hz, 1H), 3.76-3.69 (m, 1H), 2.84 (d,
J ) 4.3 Hz, 1H), 2.72 (br s, 1H), 2.25-2.08 (m, 1H), 2.08-1.84
(m, 3H), 1.84-1.29 (m, 14H), 1.14-0.63 (m, 6H), 0.91, 0.88
(each d, J ) 6.9 Hz, 12H), 0.78 (d, J ) 6.9 Hz, 3H), 0.74 (d, J
) 6.9 Hz, 3H); LRMS (FAB) m/ z (rel inten) 473 (M+, 85), 179
(base). Anal. Calcd for C30H48O4: C, 76.23; H, 10.24. Found:
C, 76.34; H, 10.25.
°C (recrystallized from diethyl ether); [R]22 +47.1° (c 1.08,
D
CHCl3); IR (CHCl3) 1710 (s), 1690 (s) cm-1; 1H NMR (270 MHz)
δ 6.18-6.11 (m, 2H), 5.98 (d, J ) 2.0 Hz, 1H), 4.62 (ddd, J )
10.9, 10.9, 4.3 Hz, 1H), 4.55 (ddd, J ) 10.9, 10.9, 4.3 Hz, 1H),
3.87 (dd, J ) 3.5, 2.0 Hz, 1H), 3.41 (br s, 1H), 3.33 (br s, 1H),
2.11-1.28 (m, 20H), 1.10-0.70 (m, 18H); LRMS (EI, 30 eV)
m/ z (rel inten) 470 (M+, 10), 455 (11), 33 (base). Anal. Calcd
for C30H46O4: C, 76.55; H, 9.85. Found: C, 76.48; H, 9.85.
[1R,2R(1R,2S,5R),3Z(1R,2S,5R),4S]-5-Meth yl-2-(1-m eth -
yleth yl)cycloh exyl 3-[2-[(5-Meth yl-2-(1-m eth yleth yl)cy-
cloh exyl)oxy]-2-oxoeth ylid en e]bicyclo[2.2.1]h ep ta n e-2-
ca r boxyla te (11). A mixture of 3a (0.313 g, 0.665 mmol) and
a catalytic amount of 5% Pd/C in ethyl acetate was stirred at
room temperature under hydrogen atmosphere. The mixture
was filtered, and the filtrate was evaporated in vacuo. The
residue was subjected to column chromatography on silica gel
eluting with ethyl acetate/hexane (1:10) to afford 11 (0.314 g,
100%) as a colorless syrup: Rf 0.35 (ethyl acetate/hexane, 1:10);
IR (CHCl3) 1730 (s), 1700 (s) cm-1;1H NMR (60 MHz) δ 5.81
(d, J ) 2.4 Hz, 1H), 4.84-4.20 (m, 2H), 3.72 (dd, J ) 4.2, 2.4
Hz, 1H), 2.92-2.62 (m, 2H), 2.44-1.08 (m, 24H), 1.08-0.51
(m, 18H).
[1S,2S(1S,2R,5S),4R]-5-Meth yl-2-(1-m eth yleth yl)cyclo-
h exyl 3-Oxobicyclo[2.2.1]h ep ta n e-2-ca r boxyla te (16). A
similar manner to the synthesis of 12, 16 (0.209 g, 98%) was
obtained as a colorless syrup from 15 (0.346 g, 0.773 mmol):
Rf 0.23 (ethyl acetate/hexane, 1:10); IR (CHCl3) 1755 (s), 1720
1
(s) cm-1; H NMR (270 MHz) δ 4.72 (ddd, J ) 10.9, 10.9, 4.6
Hz, 0.21H), 4.70 (ddd, J ) 10.9, 10.9, 4.6, 0.79H), 3.03 (br d,
J ) 3.7 Hz, 0.21 H), 2.93-2.99 (m, 0.21H), 2.89 (t, J ) 1.7 Hz,
0.79H), 2.82 (d, J ) 3.3 Hz, 0.79H), 2.70 (br d, J ) 4.6 Hz,
0.21H), 2.65 (br d, J ) 3.3 Hz, 0.79H), 2.21 (dm, J ) 10.8 Hz,
0.79H), 2.06-1.33 (m, 10.21H), 1.16-0.64 (m, 4H), 0.90, 0.89
(each d, J ) 6.9 Hz, 6H), 0.75 (d, J ) 6.9 Hz, 3H); LRMS (FAB)
m/ z (rel inten) 293 ([M + H]+, 51), 155 (base); HRMS (FAB)
m/ z calcd for C18H29O3 ([M + H]+) 293.2118, found 293.2112.
(1R,4S)-Bicyclo[2.2.1]h ep ta n -2-on e [(1R,4S)-Nor ca m -
p h or ] (17) a n d (1R,4S)-Bicyclo[2.2.1]h ep ta n -2-on e 2,4-
Din itr op h en ylh yd r a zon e [(-)-Nor ca m p h or 2,4-Din itr o-
ph en ylh ydr azon e] (18). In a similar manner to the synthesis
of 14, 18 (76.1 mg, 39% for two steps) was obtained as colorless
crystals from 16 (0.195 g, 0.668 mmol) Rf 0.48 (ethyl acetate/
[1R,2R(1R,2S,5R),4S]-5-Meth yl-2-(1-m eth yleth yl)cyclo-
h exyl 3-Oxobicyclo[2.2.1]h eptan e-2-car boxylate (12). Com-
pound 11 (0.314 g, 0.665 mmol) in dichloromethane (15 mL)
was treated with ozone at -78 °C until the blue color persisted.
The excess ozone was removed by bubbling of dry nitrogen gas,
and then dimethyl sulfide (1 mL) was added dropwise at -78
°C. The reaction mixture was then allowed to warm up to
room temperature with stirring and was evaporated in vacuo.
The residue was purified by flash column chromatography on
silica gel eluting with ethyl acetate/hexane (1:25) to afford the
ketone 12 (0.195 g, 100%) as a colorless syrup: Rf 0.23 (ethyl
hexane, 1:1); mp 131 °C (recrystallized from methanol); [R]23
D
-28.0° (c 1.03, CHCl3); IR (CHCl3) 1615 (s) cm-1; 1H NMR (270
MHz) δ 10.73 (br s, 1H), 9.12 (d, J ) 2.6 Hz, 1H), 8.28 (ddd, J
) 9.6, 2.6, 0.7 Hz, 1H), 7.91 (d, J ) 9.6 Hz, 1H), 3.03 (d, J )
3.3 Hz, 1H), 2.74 (br s, 1H), 2.37 (ddd, J ) 16.7, 4.4, 2.3 Hz,
1H), 2.12 (dd, J ) 16.7, 3.3 Hz, 1H), 1.97-1.74 (m, 2H), 1.69-
1.49 (m, 3H), 1.46-1.33 (m, 1H); LRMS (EI, 30eV) m/ z (rel
inten) 290 (M+, 86), 67 (base).
1
acetate/hexane, 1:10); IR (CHCl3) 1760 (s), 1720 (s) cm-1; H
NMR (60 MHz) δ 5.08-4.40 (m, 2H), 3.05-2.86 (m, 1H), 2.61
(m, 1H), 2.28-1.06 (m, 15H), 1.06-0.56 (m, 9H).
(1S,4R)-Bicyclo[2.2.1]h ep ta n -2-on e [(1S,4R)-Nor ca m -
p h or ] (13) a n d (1S,4R)-Bicyclo[2.2.1]h ep ta n -2-on e 2,4-
Din itr op h en ylh yd r a zon e [(+)-Nor ca m p h or 2,4-Din itr o-
p h en ylh yd r a zon e] (14). A suspension of 12 (0.195 g, 0.665
mmol) in concd hydrochloric acid (5.6 mL) was refluxed for 5
h. After cooling to room temperature, the reaction mixture
was diluted with water. The resulting mixture was extracted
with diethyl ether. The organic layer was washed with 5%
Su p p or tin g In for m a tion Ava ila ble: 1H NMR spectra of
compounds (8 pages). This material is contained in libraries
on microfiche, immediately follows this article in the microfilm
version of the journal, and can be ordered from the ACS; see
any current masthead page for ordering information.
J O951762T