Reactivity of 2-methylene-1,3-dicarbonyl compounds. stereoselective and asymmetric Diels-Alder reactions

Article abstract of DOI:10.1021/jo9518819

The Diels-Alder reaction of 1,1-dicarbonylethenes 1 with dienes was investigated. The adduct of the reaction of 1, whose two carbonyl groups were different, with cyclopentadiene showed moderate stereoselectivity and this was explained by FMO theory. However, in the Lewis acid-catalyzed addition, the reaction proceeded with high stereoselectivity to give the exo adduct 3x. This might be due to steric hindrance because the benzene ring cannot orient in the plane of the conjugated system in the metal-chelated enedione 6. Applying this principle to (1′R,2′S,5′R)-5-methyl-2-(1-methyl-1-phenylethyl)cyclohexyl 2-benzoylacrylate (1d), we achieved a diastereomeric Diels-Alder reaction to afford 3x-R, whose structure was confirmed by the X-ray crystal analysis.

Full text of DOI:10.1021/jo9518819

J . Org. Chem. 1996, 61, 2719-2725
2719
Rea ctivity of 2-Meth ylen e-1,3-d ica r bon yl Com p ou n d s.
Ster eoselective a n d Asym m etr ic Diels-Ald er Rea ction s
Masashige Yamauchi,*,† Yuko Honda,† Nobuhiko Matsuki,† Toshio Watanabe,†
Kimimasa Date,‡ and Hajime Hiramatsu‡
Faculty of Pharmaceutical Sciences, J osai University, Keyakidai, Sakado, Saitama 350-02, J apan, and
Organic Chemistry Research Laboratory, Tanabe Seiyaku Co Ltd., Kawaguchi, Toda,
Saitama 335, J apan
Received October 20, 1995X
The Diels-Alder reaction of 1,1-dicarbonylethenes 1 with dienes was investigated. The adduct of
the reaction of 1, whose two carbonyl groups were different, with cyclopentadiene showed moderate
stereoselectivity and this was explained by FMO theory. However, in the Lewis acid-catalyzed
addition, the reaction proceeded with high stereoselectivity to give the exo adduct 3x. This might
be due to steric hindrance because the benzene ring cannot orient in the plane of the conjugated
system in the metal-chelated enedione 6. Applying this principle to (1′R,2′S,5′R)-5-methyl-2-(1-
methyl-1-phenylethyl)cyclohexyl 2-benzoylacrylate (1d ), we achieved a diastereomeric Diels-Alder
reaction to afford 3x-R, whose structure was confirmed by the X-ray crystal analysis.
Sch em e 1
In the Diels-Alder reaction, the effect of a functional
group attached directly to the diene or dienophile has
been extensively studied.1 The introduction of an electron-
withdrawing group into the dienophile lowers the LUMO
energy level and increases its reactivity toward a diene
having an electron-rich substituent.2 R,â-Unsaturated
carbonyl compounds,3 as reactive dienophiles, have been
employed widely, and endo adducts are produced under
kinetically-controlled reaction conditions. The remark-
able stereoselectivity and regioselectivity of the reaction
are well explained by frontier molecular orbital (FMO)
theory.4 Lewis acid catalysis influences the rate of
reaction as well as regioselectivity and stereoselectivity.4
Based on these principles, asymmetric Diels-Alder reac-
tions have been investigated widely in both diastereo-
metric5 and enantiomeric6 versions. Still lacking among
the excellent studies reported so far is a study of a
dienophile having two electron-withdrawing groups at
the same olefinic carbon. Because of the instability of
1,1-dicarbonylethenes,7 they can be used as reaction
intermediates in a normal electron-demand Diels-Alder
reaction.8 We reported the synthesis of the 1,1-dicar-
bonylethenes 1,9 in which at least one of the carbonyls
was a benzoyl group, and their use in regioselective
hetero-Diels-Alder reactions.10 When the two carbonyl
groups on the ethene are of different types, an interesting
problem arises; namely, which substituent would orient
endo in the normal electron-demand Diels-Alder reac-
tion. If endo/exo stereoselectivity is achieved, an asym-
metric reaction might be expected when one carbonyl
group is an ester of a chiral alcohol. In the present paper
we report a study of the reactions of 1 with 1,3-butadiene
and cyclopentadiene and the diastereomeric Diels-Alder
reaction of (1′R,2′S,5′R)-5-methyl-2-(1-methyl-1-phenyl-
ethyl)cyclohexyl 2-benzoylacrylate 1d with cyclopenta-
diene.11
Diels-Ald er Rea ction of 2-Meth ylen e-1,3-d ica r -
bon yl Com p ou n d s 1a -c. First, the reaction with
butadiene was examined by using 1,1-dibenzoylethene
(1a ) (Scheme 1). Whereas the Diels-Alder adduct was
not formed at ambient temperature after 10 h, the adduct
was obtained after 10 h at 70 °C in a sealed tube. Thus
the reaction of 2-methylene-1,3-dicarbonyl compounds 1
with butadiene was carried out in a sealed tube at 100
°C for 15 h. The low yield of this reaction might be due
to polymerization of 1 under the reaction conditions. On
the other hand the reaction with cyclopentadiene pro-
ceeded smoothly even at ambient temperature to yield
† J osai University.
‡ Tanabe Seiyaku Co Ltd.
X Abstract published in Advance ACS Abstracts, March 15, 1996.
(1) For reviews, see (a) Sauer, J . Angew Chem., Int. Ed. Engl. 1980,
19, 779. (b) Petrgilka, M.; Grayson, J . I. Synthesis 1981, 753.
(2) For theoretical studies, see (a) Herndon, W. C. Chem. Rev. 1972,
72, 157. (b) Houk, K. N. Acc. Chem. Res. 1975, 8, 361. (c) Kan, S. D.;
Dau. C. F; Overman, L. E.; Hehre, W. J . J . Am. Chem. Soc. 1986, 108,
7381.
(3) Ramezanian, M.; Aldelkader, M.; Oadias, A. B., Hall, H. K., J r.;
Brois, S. J . J . Org. Chem. 1989, 54, 282 and references cited therein.
(4) Fleming, I. In Frontier Orbitals and Organic Chemical Reactions;
Wiley: New York, 1975; Chapter 4.
(5) For reviews, see (a) Opplzer, W. In Comprehensive Organic
Synthesis; Trost, B. M., Fleming, I., Eds.; Pergamon Press: Tokyo,
1991; Vol. 5, p 352. (b) Paquette, L. A. In Asymmetric Synthesis;
Morrison, J . D., Ed.; Academic Press: Tokyo, 1984; Vol. 3, p 455. For
theoretical studies, see (c) Tucker, J . A.; Houk, K. N.; Trost, B. M. J .
Am. Chem. Soc. 1990, 112, 5465. (d) Pascual-Teresa, B.; Gonzalez, J .;
Asensio, A.; Houk, K. N. J . Am. Chem. Soc. 1995, 117, 4347.
(6) For reviews, see (a) Narasaka, K. Synthesis 1991, 1. (b) Kagan,
B. H.; Riant, O. Chem. Rev. 1992, 92, 1007.
(7) Snider, B. B.; Patricia, J . J .; Kates, S. A. J . Org. Chem. 1988,
53, 2137.
(8) Hoye, T. R.; Caruso, A. J .; Magee, A. S. J . Org. Chem. 1982, 47,
4152.
(10) Yamauchi, M.; Katayama, S.; Baba, O.; Watanabe, T. J . Chem.
Soc., Chem. Commun. 1983, 281. Yamauchi, M.; Katayama, S.; Baba,
O.; Watanabe, T. J . Chem. Soc., Perkin Trans. 1 1990, 3041.
(11) A part of this work was reported as a preliminary communica-
tion: J . Chem. Soc., Chem. Commun. 1988, 27.
(9) Yamauchi, M.; Katayama, S.; Watanabe, T. Synthesis 1982, 935.
0022-3263/96/1961-2719$12.00/0 © 1996 American Chemical Society

2720 J . Org. Chem., Vol. 61, No. 8, 1996
Yamauchi et al.
Ta ble 2. Com p u ted Da ta for 1b
Ta ble 1. Rea ction s of 1 w ith Cyclop en ta d ien e
reaction conditions
LUMO coefficients
total
product ratioa
total
energy (eV)
LUMO
energy (eV)
entry reactant catalyst T, °C t, h yield (%)
3n :3x
1
Cbza
Cesb or Cacc
1
2
3
4
5
6
7
8
9
10
11
12
13
1a
1b
1b
1b
1b
1b
1b
1b
1c
1c
1c
1c
1c
none
none
rtb
rt
0
5
5
1
3
7
0.2
3
7
0.5
1
70
67
30
54
50
47
75
73
80
80
80
80
81
1b-A
1b-B
1b-C
1b-D
1c-A
1c-B
1c-C
1c-D
-2669.33280
-2669.33605
-2669.32602
-2669.23242
-2190.45442
-2190.47647
-2190.46117
-2190.29849
-0.581
-0.591
-0.573
-0.605
-0.611
-0.576
-0.577
-0.524
0.283
0.288
0.286
0.289
0.257
0.316
0.265
0.292
0.260
0.232
0.236
0.248
0.316
0.267
0.284
0.299
79:21
25:75
17:83
9:91
12:88
5:95
c
BF3‚OEt2
BF3‚OEt2 -40
BF3‚OEt2 -78
d
ZnCl2
ZnCl2
ZnCl2
none
ZnCl2
ZnCl2
ZnCl2
ZnCl2
rt
-40
-78
rt
4:96
32:68
15:85
14:86
11:89
6:94
a
b
Cbz ) benzoyl carbonyl carbon. Ces ) ester carbonyl carbon.
c Cac ) acetyl carbonyl carbon.
0
-15 1.5
-40
-78
3
7
Ch a r t 1
a
b
Ratios were determined by 1H NMR (olefinic protons). rt )
room temperature. c 1 equiv of BF3‚OEt2 was used with respect
to 1. 1.5 equiv of ZnCl2 was used with respect to 1.
d
Sch em e 2
by the olefinic proton signals (5-Hs) in the 1H NMR
spectra. The stereochemistry of the adduct was also
confirmed by the Paterno-Bu¨chi reaction. Thus irradia-
tion of the product, prepared in the absence of Lewis acid,
at 300 nm through Pyrex gave the oxetane derived from
[2 + 2] cyclization between the C-C double bond and the
benzoyl carbonyl group. Under these conditions the
acetyl carbonyl group did not react with the double bond
and the endo isomer was recovered.
the corresponding adduct (Table 1).12 1-Benzoyl-1-
(ethoxycarbonyl)ethene (1b) gave an inseparable mixture
of exo/endo adducts13 in which the endo product was
predominant (entry 2). In the 1H NMR spectrum two
olefinic protons of the adduct appear as a pair of double
doublets at δ 6.00 and δ 6.15 for the endo isomer and at
δ 5.96 and δ 6.39 for the exo isomer. Compared with the
higher field signals of the 6-Hs, the lower field signals of
the 5-Hs are sufficiently separated to determine the endo/
exo ratio. The exo or endo relationship of the benzoyl to
the bicyclo[2.2.1] system was determined through a
Paterno-Bu¨chi reaction14 of the product (Scheme 2).
Irradiation of the product at 300 nm through Pyrex gave
the isomer 4b formed from the endo product 3bn and
unreacted exo isomer 3bx. Interestingly, the stereo-
chemistry of the product was reversed when the reaction
was carried out in the presence of a Lewis acid. The
reaction was performed by the initial addition of the
Lewis acid to the dienophile followed by addition of
cyclopentadiene at various temperatures as shown in
Table 1. When boron trifluoride etherate was added to
the dienophile in CH2Cl2, the temperature of the reaction
mixture increased and the solution turned dark. The
yield of adducts was lower than that obtained in the
presence of ZnCl2.
Generally, the endo isomer is kinetically preferred in
the Diels-Alder reaction of electron-poor dienophiles,
such as R,â-unsaturated carbonyl compounds or maleic
anhydride. In the case of 2-methylene-1,3-dicarbonyl
compounds 1, it is interesting to speculate as to which
carbonyl group would facilitate an endo approach to the
diene. FMO theory which employs secondary attractive
interactions4,15 clarifys the problem. MNDO16 calcula-
tions were carried out for four possible conformers A-D
(Chart 1). Brief calculations show that the most stable
form is one in which the plane of the benzene ring of the
benzoyl group is situated perpendicular to the conjugated
enedione system in each conformer (A-D). This is
presumably due to the steric hindrance between the ortho
hydrogen of benzoyl benzene and the carbonyl oxygen (in
A), the cis-oriented vinyl hydrogen (in B and C), or the
R group (in D). The optimized total energies and LUMO
energies and coefficients for the most stable conformers
(A-D) were listed in Table 2. The total energies of
conformers A-C are almost the same (energy differences
<0.5 kcal/mol in 1b and <0.3 kcal/mol in 1c). Since the
total energies of both D conformers are ca. 2.5 kcal/mol
and ca. 4 kcal/mol higher than that of the others in 1b
and 1c, respectively, the contribution of the conformer
D to the reaction might be neglected.
In the case of 1-acetyl-1-benzoylethene (1c), the ste-
reoselectivity was somewhat lower than that of 1b in the
absence of a Lewis acid, and the exo isomer was pre-
dominant. In the presence of a Lewis acid, however, exo
selectivity was observed, similar to the reaction of 1b.
In this case the ratios of endo to exo were also determined
In the case of 1-(ethoxycarbonyl)-1-benzoylethene (1b)
the coefficients of the benzoyl carbonyl carbons are larger
than that of the ester carbonyl carbons in the A-C
conformers. In the transition state the orientation (see
5) giving the endo-benzoyl adduct has a larger secondary
interaction than that leading to the endo-ester adduct.
(12) The rection times have been reported as 5-7 h in ref 11. We
reexamined the reaction throughout and found the reactions were
completed within the times shown.
(13) Since all of the ethenes have at least one benzoyl group, exo
and endo are defined by the relationship of the benzoyl group and the
bicyclo[2.2.1]heptene to unify and easily understand the reaction series.
(14) (a) J ones, G., II. In Organic Photochemistry; Padwa, A., Ed.;
Dekker: New York, 1981; Vol. 5, ch. 1. (b) Sauers, R. R.; Henderson,
T. R. J . Org. Chem. 1974, 39, 1850. (c) Sauers, R. R.; Rousseau, A. D.;
Byrne, B. J . Am. Chem. Soc. 1975, 97, 4947. (d) Smith, A. B., III, ;
Dieter, R. K. Tetrahedron Lett. 1976, 327.
(15) (a) Woodward, R. B.; Hoffmann, R. The Conservation of Orbital
Symmetry; Verlag Chemie: Weinheim, 1970. (b) Sauer, J .; Sustmann,
R. Angew. Chem., Int. Ed. Engl. 1980, 19, 779.
(16) QCPE 353, modified by Osawa and Buda, which converted to
PC version by Tokiwa.

Reactivity of 2-Methylene-1,3-dicarbonyl Compounds
J . Org. Chem., Vol. 61, No. 8, 1996 2721
Ch a r t 2
Sch em e 3
Taking the conformation of the benzoyl benzene ring into
consideration with the approaching diene, the conformer
A might be preferable to the others.
In the case of 1-acetyl-1-benzoylethene (1c), the situ-
ation is more complex. As shown in Table 2 the coef-
ficients of the acetyl carbonyl carbons are not always
larger than that of benzoyl carbonyl carbons. The
conformer (B or C), in which the benzoyl carbonyl and
the methylene group are in an s-trans relationship, is less
important because the benzene ring, situated perpen-
dicular to the conjugated enedione system, causes a large
steric hindrance to the approaching diene in the transi-
tion state. Furthermore the energy level in the LUMO
of 1c-A is lower than that of the others. Thus the most
important conformer is A, and the coefficient of the acetyl
carbonyl carbon is larger than that of the benzoyl
carbonyl carbon in A. As a result, the exo-adduct is
formed preferentially over the endo-adduct.
Sch em e 4
In order to obtain a better understanding of the
preponderance of the exo-isomer in the Lewis acid-
catalyzed reaction, we carried out molecular mechanics
calculations17 of the metal-chelated enedione. Although
the tetrahedral zinc-complex 6 is more stable than the
planar one, the conformation of the enedione is almost
identical in both complexes. In conformer 6 the benzene
ring is situated nearly perpendicular to the ene. Hence
cyclopentadiene approaches from the side leading to the
exo-isomer because of the steric hindrance of the benzene
ring in the fixed metal-chelated enedione. The reason
that the same stereoselectivity is observed with monova-
lent boron trifluoride is not obvious but the similarity
between boron and divalent metals has been noted.18
From these results it was expected that the Diels-
Alder reaction of (1′R,2′S,5′R)-5-methyl-2-(1-methyl-1-
phenylethyl)cyclohexyl 2-benzoylacrylate (1d ) in the
presence of a Lewis acid would proceed via transition
state 7 stereoselectively. The π-stacking19 of the chelated
conjugated system and the benzene ring of the phenyl-
menthyl group restricts the attack of diene from the back
side, and the steric hindrance of benzoyl benzene blocks
the approach of the diene from the benzoyl group.
Diels-Ald er Rea ction of 1d w ith Cyclop en ta d i-
en e in th e Absen ce of Lew is Acid . (1′R,2′S,5′R)-5-
Methyl-2-(1-methyl-1-phenylethyl)cyclohexyl 2-benzoyl-
acrylate (1d ) was synthesized as follows (Scheme 3). The
acid chloride, obtained by treatment of 2-phenyl-1,3-
dioxolan-2-ylacetic acid (8) with oxalyl chloride, was
treated with (-)-8-phenylmenthol20 to yield chiral ester
9. Selective hydrolysis was achieved by treatment of 10
with 10% HCl(aq)-MeOH (1:6) at ambient temperature.
The resulting dione 10 was converted into 1d by the
method previously developed in our laboratory.9 The
reaction of 1d with cyclopentadiene in the absence of a
Lewis acid gave all four possible stereoisomers (Scheme
4), which showed one spot on TLC but partially separated
on HPLC. Repeated preparative HPLC separated the
adducts into four fractions. Fractions 1, 2, and 4 con-
tained almost pure isomers but not fraction 3. The
signals of the olefinic protons (5-Hs and 6-Hs) and the
proton (1′-H) attached to the carbon bearing the oxycar-
bonyl group of the mixture and each isomer and the
(17) Molecular mechanics calculations were carried out with IBM
PC/2 using MMX program (v. 3.3, Serena Software).
(18) Smith, A. B., III; Leahy, J . W.; Node, I.; Remiszewski, S. W.;
Liverton, N. J .; Zibuck, R. J . Am. Chem. Soc. 1992, 114, 2995.
(19) For review, see: J ones, G. B.; Chapman, B. J . Synthesis 1995,
475.
(20) (a) Corey, E. J .; Ensley, H. E. J . Am. Chem. Soc. 1975, 97, 6908.
(b) Ort, O. Organic Synthesis; Wiley: Tokyo, 1993; Coll. Vol. VIII, p
522.

2722 J . Org. Chem., Vol. 61, No. 8, 1996
Yamauchi et al.
Ch a r t 3
Ta ble 3. Rea ction s of 1d w ith Cyclop en ta d ien e
reaction conditions
total
product ratioa
entry
catalyst
T, °C
t, h
yield (%)
3n -R:3x-R
b
1
2
3
4
5
6
7
8
9
BF3‚OEt2
BF3‚OEt2
-40
-78
rtd
-40
-78
rt
-40
rt
0
3
7
0.5
3
7
0.5
3
0.5
1
3
7
57
49
46
91
88
86
86
81
80
80
78
13:87
8:92
14:86
10:90
4:96
29:71
24:76
<1:>99
<1:>99
0:100
0:100
c
ZnCl2
ZnCl2
ZnCl2
FeCl2
FeCl2
FeCl2Ib
FeCl2I
FeCl2I
FeCl2I
10
11
-40
-78
a
b
Ratios were determined by 1H NMR (olefinic protons).
1
equiv of Lewis acid was used with respect to 1d . c 1.5 equiv of
ZnCl2 was used with respect to 1d . rt ) room temperature.
d
the unusual upfield shift of 2′-Hax (-0.09 ppm) is because
this proton is over the plane of the benzene ring of the
benzoyl group of the most stable conformer 12.
Diels-Ald er Rea ction of 1d w ith Cyclop en ta d i-
en e in th e P r esen ce of Lew is Acid . The reactions in
the presence of Lewis acid are shown in Table 3.12 In
the presence of BF3‚OEt2 or ZnCl2, a detectable amount
of a minor isomer was obtained. Each endo or exo
product was a single isomer and corresponded to fraction
1 or fraction 4, which implied that the reaction proceeded
with perfect diasteroselectivity. The signals of the ole-
finic protons and 1′-H of the product obtained under
FeCl2 catalysis are shown in Figure 1f. Provided π-stack-
ing occurs in the metal-chelated transition state, cyclo-
pentadiene attacks only from the front side to afford 3x-R
from 7, and 3n -R from 13 (Chart 4). As the reaction
temperature is lowered, the plane of the benzene ring of
the benzoyl group is fixed perpendiculer to the conjugated
system, which increases the exo/endo selectivity. A single
recrystallization (entry 5) from ethanol gave pure 3x-R
F igu r e 1. 1H NMR spectra (270 MHz) of (a) the adduct of no
catalyst, (b) fraction 1, (c) fraction 2, (d) fraction 3, (e) fraction
4, and (f) the adduct under FeCl2 at ambient temperature.
upper field signals of each isomer are shown in Figure
1. Considering the reaction of 1b with cyclopentadiene,
we should assign a pair of double triplets (ca. 4.8 ppm in
a) to a pair of endo isomers, 3n -S and 3n -R, since these
should be predominant in the absence of Lewis acid as
well as in the case of 1b. Therefore fractions 1 and 2
should be the endo isomers, and fractions 3 and 4 the
exo isomers. Olefinic protons (5-H and 6-H) of fraction
1 appeared as a broad singlet (b), and that of fraction 2
were split as two double doublets (c). No significant
differences were observed in the signals of the secondary
and tertiary dimethyl groups. At this point we could not
determine which fraction was 3n -R or 3n -S. However,
we could determine that fractions 1 and 2 were 3n -R and
3n -S, respectively, from the results of the reaction
catalyzed by Lewis acid (vide infra.). The signals of
tertiary dimethyl group of fractions 3 appeared at
considerable upfield shift compared with the other. This
is because the dimethyl groups are situated over the
plane of the benzene ring of the benzoyl group, consistent
with the most stable conformer 11 of 3x-S calculated by
MMX (Chart 3). Therefore fraction 4 should be 3x-R and
[mp 135-136 °C; [R]30 +135° (c, 0.38, CHCl3)] whose
D
X-ray crystal structure21 confirmed the assignment of
stereochemistry. The conformation, as shown by the
X-ray data is very similar to the most stable conformation
(21) An X-ray crystal structure analysis indicated the space group
P212121, a ) 12.404(25) Å, b ) 28.961(18) Å, c ) 7.193(18) Å, U )
2583.9(R 77) Å3, Z ) 4, r ) 1.174 g/mL, m(Cu KR) ) 0.586 mm-1. Final
R and RW were 0.0498 and 0.1488 for 2539 reflections. The atomic
coordinates of 3x-R have been deposited with the Cambridge Crystal-
lographic Data Centre. They can be obtained, on request, from the
Director, Cambridge Crystallographic Data Centre, 12 Union Road,
Cambridge, CB2 1EZ, UK.

Reactivity of 2-Methylene-1,3-dicarbonyl Compounds
J . Org. Chem., Vol. 61, No. 8, 1996 2723
pressure. The residue was subjected to column chromatogra-
phy to give the corresponding adducts.
Ch a r t 4
1,1-Dibenzoylethene (1a ) gave (2-benzoylbicyclo[2.2.1]hept-
5-en-2-yl)phenylmethanone (3a ): mp 109-110 °C (from hex-
1
ane); IR (KBr) 1660, 1600, 1585, 1575 cm-1, H NMR δ 1.59
(br d, J ) 8.8 Hz, 1H), 1.73 (br d, J ) 8.8 Hz, 1H), 2.18 (dd, J
) 12.5, 3.6 Hz, 1H), 2.82 (dd, J ) 12.5, 2.9 Hz, 1H), 2.98 (br s,
1H), 3.91 (br s, 1H), 5.74 (dd, J ) 5.1, 2.9 Hz, 1H), 6.28 (dd, J
) 5.1, 2.9 Hz, 1H), 7.33 (t, J ) 7.3 Hz, 4H), 7.43 (t, J ) 7.3
Hz, 2H), 7.90 (d, J ) 7.3 Hz, 2H), 7.94 (d, J ) 7.3 Hz, 2H); 13
C
NMR δ 36.8, 42.9, 49.2, 51.6, 71.8, 128.4, 128.5, 129.1, 129.8,
132.6, 132.8, 133.0, 136.5, 137.4, 140.0, 196.9, 200.0. Anal.
Calcd for C12H18O2: C, 83.42; H, 6.00. Found: C, 83.41; H,
6.00.
1-Benzoyl-1-(ethoxycarbonyl)ethene (1b) gave endo/exo ethyl
2-benzoylbicyclo[2.2.1]hept-5-ene-2-carboxylate 3bn /3bx (3.8:
1) mixture. HRMS Calcd for C17H18O3: 270.1256. Found:
270.1229. Major component 3bn : 1H NMR δ 1.06 (t, J )
7.3Hz, 3H), 1.50 (br d J ) 8.8 Hz, 1H), 1.79 (br d, J ) 8.8 Hz,
1H), 2.03 (dd, J ) 12.5, 2.9 Hz, 1H), 2.49 (dd, J ) 12.5, 3.7
Hz, 1H), 2.94 (br s, 1H), 3.54 (br s, 1H), 4.12 (q, J ) 7.3 Hz,
2H), 6.00 (dd, J ) 5.1, 2.9 Hz, 1H), 6.12 (dd, J ) 5.1, 2.9 Hz,
1H), 7.41 (t, J ) 7.3 Hz, 2H), 7.51 (t, J ) 7.3 Hz, 1H), 7.87 (d,
J ) 7.3 Hz, 2H); 13C NMR δ 13.8, 36.6, 42.1, 47.7, 51.0, 61.7,
65.6, 128.3, 128.5, 132.7, 134.7, 136.2, 138.4, 174.0, 195.5. The
minor component 3bx was obtained in pure form after irradia-
tion of the mixture or from the reaction in the presence of
Lewis acid, and its spectral data are described below.
1-Acetyl-1-benzoylethene (1c) gave endo/exo 1-(2-benzoyl-
bicyclo[2.2.1]hept-5-en-2-yl)ethanone 3cn /3cx (1:2.1) mixture.
HRMS Calcd for C16H16O2: 240.1149. Found: 240.1146. The
major component 3cx was obtained in pure form after irradia-
tion of the mixture, and the spectral data are listed below.
Minor component 3cn : 1H NMR δ 1.46 (m, 2H), 1.98 (dd, J )
12.5, 3.5 Hz, 1H), 2.15 (s, 3H), 2.49 (dd, J ) 12.5, 3.6 Hz, 1H),
2.90 (br s, 1H), 3.57 (br s, 1H), 5.98 (dd, J ) 5.9, 2.2 Hz, 1H),
6.12 (dd, J ) 5.9, 2.9 Hz, 1H), 7.41 (t, J ) 7.3 Hz, 2H), 7.52 (t,
J ) 7.3 Hz, 1H), 7.81 (d, J ) 7.3 Hz, 2H).
12 of 3x-R calculated by MMX. In order to obtain higher
exo/endo selectivity, we carried out the reaction under
FeCl2I catalysis.22 The addition product obtained was
almost single isomer 3x-R even at ambient temperature
(entry 8).
Exp er im en ta l Section
Gen er a l. Melting points are uncorrected. MgSO4 was used
to dry organic layers after extraction. Column chromatogra-
phy was performed with silica gel (Micro Bead 4B, Fuji-
Davison Chemical Ltd.). HPLC was carried out with a column,
Megapak SIL (10 µm), 1.0 × 25 cm. NMR spectra were
recorded in chloroform-d at 270 MHz for 1H and 67.89 MHz
for 13C using tetramethylsilane (TMS) as the internal refer-
ence. IR spectra were determined either neat or in KBr
pellets. Mass spectra were recorded at 70 eV.
Rea ction of 2-Meth ylen e-1,3-d ica r bon yl Com p ou n d 1
w ith Bu ta d ien e. A solution of 2-methylene-1,3-dicarbonyl
compound 1 (1 mmol) and butadiene (ca. 5 mmol) in benzene
(5 mL) was heated at 100 °C in a sealed tube for 15 h. The
reaction mixture was evaporated off at reduced pressure, and
the residue was subjected to column chromatography to yield
the corresponding adduct.
Rea ction of 2-Meth ylen e-1,3-d ica r bon yl Com p ou n d 1
w ith Cyclop en ta d ien e in th e P r esen ce of Lew is Acid .
The following procedure was carried out at the temperature
listed in Table 1. Boron trifluoride etherate (1.0 mmol) or zinc
chloride (1.5 mmol) was added to a solution of 2-methylene-
1,3-dicarbonyl compound 1 (1.0 mmol) in CH2Cl2 (5 mL). The
reaction mixture was stirred for 30 min. A 1.0 M solution of
cyclopentadiene in CH2Cl2 (3 mL) was added dropwise, and
the mixture was stirred for 7 h. The reaction mixture was
washed with water, NaHCO3 solution, brine, and dried.
Evaporation of the mixture gave an oily residue which was
subjected to column chromatography to yield the corresponding
adducts in the ratio listed in Table 1. A single recrystallization
of the product (entry 8) gave pure 3bx: mp 60-62 °C (from
1,1-Dibenzoylethene (1a ) gave (1-benzoylcyclohex-3-enyl)-
phenylmethanone (2a ): mp 107-108 °C (from MeOH); IR
1
(KBr) 1660, 1600, 1580 cm-1; H NMR δ 1.94 (br s, 2H), 2.45
(t, J ) 6.5 Hz, 2H), 2.71 (br s, 2H), 5.72 (m, 2H), 7.34 (t, J )
7.3 Hz, 4H), 7.45 (t, J ) 7.3 Hz, 2H), 7.88 (d, J ) 7.3 Hz, 4H);
13C NMR δ 21.7, 29.6, 33.1, 62.8, 124.3, 125.4, 128.7, 129.1,
133.0, 136.0, 199.0. Anal. Calcd for C20H18O2: C, 82.73; H,
6.25. Found: C, 82.49; H, 6.35.
1
benzene-hexane); IR 1735, 1680, 1595, 1580 cm-1; H NMR
1-Benzoyl-1-(ethoxycarbonyl)ethene (1b) gave ethyl 1-ben-
zoylcyclohex-3-enecarboxylate (2b): viscous oil; IR (neat) 1735,
δ 0.98 (t, J ) 7.3 Hz, 3H), 1.53 (m, 2H), 2.01 (dd, J ) 11.7, 3.6
Hz, 1H), 2.43 (dd, J ) 11.7, 2.2 Hz, 1H), 2.97 (br s, 1H), 3.67
(br s, 1H), 3.96 (dq J ) 7.3, 2.2 Hz, 2H), 5.96 (dd, J ) 5.9, 2.9
Hz, 1H), 6.39 (dd, J ) 5.9, 2.9 Hz, 1H), 7.41 (t, J ) 7.3 Hz,
2H), 7.52 (t, J ) 7.3 Hz,1H), 7.93 (d, J ) 7.3 Hz, 2H); 13C NMR
δ 13.8, 36.2, 43.1, 49.7, 50.2, 61.3, 64.0, 128.4, 129.1, 132.6,
132.9, 135.8, 140.5, 172.3, 197.1. Anal. Calcd for C17H18O3:
C, 75.53; H, 6.71. Found: C, 75.28; H, 6.61. HRMS Calcd for
C17H18O3: 270.1255. Found: 270.1257.
1685, 1600, 1580 cm-1 1H NMR δ 1.10 (t, J ) 7.3 Hz, 3H),
;
2.03 (m, 2H), 2.28 (m, 2H), 2.63 (br s, 2H), 4.15 (q, J ) 7.3 Hz,
2H), 5.69 (br s, 2H), 7.3-7.5 (m, 3H), 7.84 (d, J ) 6.6 Hz, 2H).
Anal. Calcd for C16H18O3: C, 74.39; H, 7.02. Found: C, 74.16;
H, 7.31.
1-Acetyl-1-benzoylethene (1c) gave 1-(benzoylcyclohex-3-
enyl)ethanone (2c): viscous oil; IR (neat) 1715, 1670, 780, 700
1
cm-1; H NMR δ 1.96 (m, 2H), 2.15 (s, 3H), 2.27 (tABq, J )
17.0, 7.0 Hz, 2H), 2.57 (ABq, J ) 17.0 Hz, 2H), 5.67 (br s, 2H),
7.41 (t, J ) 7.3 Hz, 2H), 7.53 (t, J ) 7.3 Hz, 1H), 7.77 (d, J )
7.3 Hz, 2H). Anal. Calcd for C15H16O2: C, 78.92; H, 7.06.
Found: C, 78.41; H, 7.14. HRMS Calcd for C15H16O2: 228.1150.
Found: 228.1145.
Rea ction of 2-Meth ylen e-1,3-d ica r bon yl Com p ou n d 1
w ith Cyclop en ta d ien e in th e Absen ce of Lew is Acid . A
1.0 M solution of cyclopentadiene in CH2Cl2 (3 mL) was added
to a solution of 2-methylene-1,3-dicarbonyl compound 1 (1.0
mmol) in CH2Cl2 (3 mL) at ambient temperature. The reaction
mixture was stirred for 5 h and evaporated off at reduced
Ir r a d ia tion of th e Ad d u cts. A Diels-Alder adduct was
dissolved in benzene in a Pyrex tube, which was then flushed
with nitrogen and irradiated for 10 h. The reaction mixture
was evaporated off, and the residue was subjected to column
chromatography to remove a more polar unidentified product.
The less polar mixture of products was further subjected to
preparative centrifugal TLC.
(a) (2-Benzoylbicyclo[2.2.1]hept-5-en-2-yl)phenylmethanone
(3a ) (90 mg) gave (1-phenyl-9-oxapentacyclo[5.2.1.0.2,604,8]-
nonyl)phenylmethanone (4a ) (82 mg, 91%): mp 118 °C (from
benzene-hexane); IR (KBr): 1650, 1595, 1575 cm-1; 1H NMR
δ 1.84 (br s, 2H), 1.95 (d, J ) 11.0 Hz, 1H), 2.21 (br s, 1H),
2.54 (br d, J ) 11.0 Hz, 1H), 3.44 (br s, 1H), 3.65 (m, 1H), 5.01
(m, 1H), 7.1-7.6 (m, 8H), 8.05 (d, J ) 7.0 Hz, 2H); 13C NMR
(22) Corey, E. J .; Imai, N.; Zhang, H.-Y. J . Am. Chem. Soc. 1991,
113, 728.

2724 J . Org. Chem., Vol. 61, No. 8, 1996
Yamauchi et al.
δ 33.8, 42.4, 46.4, 50.9, 62.7, 67.5, 86.3, 104.1, 126.4, 128.1,
128.2, 128.5, 129.5, 132.0, 135.9, 138.3, 202.1. Anal. Calcd
for C21H18O2: C, 83.42; H, 6.00. Found: C, 83.21; H, 5.87.
(b) A mixture of the adducts 3bn and 3bx (150 mg ratio
3.8:1) gave the less polar, recovered 3bx (25 mg, 17%) and
ethyl 1-phenyl-9-oxapentacyclo[5.2.1.0.2,604,8]nonane-2-carboxy-
late (4b) (106 mg 71% (89% from 3bn )): bp0.1 140 °C; IR (neat)
added to the residue. The organic layer separated was washed
with water (50 mL × 2) and brine (50 mL), dried, and
evaporated. The residue was subjected to column chromatog-
raphy to give (1′R,2′S,5′R)-5-methyl-2-(1-methyl-1-phenyleth-
yl)cyclohexyl 2-[(methylthio)methyl]-3-oxo-3-phenylpropionate
(2.20 g, 96%): IR (neat) 1735, 1685, 1600, 1580 cm-1; 1H NMR
δ 0.78 (d, J ) 6.6 Hz, 3H), 1.16 (s, 3H), 1.29 (s, 3H), 2.08 (s,
3H), 2.95 (d, J ) 7.0 Hz, 2H), 3.76 (t, J ) 7.0 Hz, 1H), 4.81
(dt, J ) 10.5, 4.4 Hz, 1H), 7.25-7.97 (m, 5H). Anal. Calcd
for C27H34O3S: C, 73.93; H, 7.81. Found: C, 73.68; H, 8.11.
HRMS Calcd for C27H34O3S: 438.2227. Found: 438.2224.
(1′R,2′S,5′R)-5-Meth yl-2-(1-m eth yl-1-p h en yleth yl)cyclo-
h exyl 2-[(Meth ylsu lfin yl)m eth yl]-3-oxo-3-p h en ylp r op i-
on a te. A solution of NaIO4 (8.7 g, 40.7 mmol) in water (100
mL) was slowly added to a solution of (1′R,2′S,5′R)-5-methyl-
2-(1-methyl-1-phenylethyl)cyclohexyl 2-[(methylthio)methyl]-
3-oxo-3-phenylpropionate (2.22 g, 5.07 mmol) in MeOH (300
mL) at 0 °C. The reaction mixture was stirred for 12 h at
ambient temperature and evaporated to 1/5 of its original
volume. The residue was diluted with water (100 mL) and
extracted with AcOEt (100 mL × 3). The organic layer was
washed with water (100 mL × 3) and brine (80 mL), dried,
and evaporated. The residue was subjected to column chro-
matography to yield (1′R,2′S,5′R)-5-methyl-2-(1-methyl-1-
phenylethyl)cyclohexyl 2-[(methylsulfinyl)methyl]-3-oxo-3-
phenylpropionate (2.01 g, 92%): IR (neat) 1730, 1680, 1600,
1
1720, 760, 700 cm-1; H NMR δ 1.22 (t, J ) 7.0 H, 3H), 1.82
(br s, 2H), 1.84 (d, J ) 11.0 Hz, 1H), 2.18 (br s, 1H), 2.27 (br
d, J ) 11.0 Hz, 1H), 3.22 (br s, 1H), 3.47 (dd, J ) 3.6, 2.2 Hz,
1H), 4.09 (q, J ) 7.0 Hz, 2H), 4.86 (dd, J ) 3.6, 2.2 Hz, 1H),
7.2-7.4 (m, 5H); 13C NMR δ 14.2, 34.7, 42.0, 44.0, 50.4, 60.3,
60.5, 61.4, 86.0, 102.4, 126.0, 128.0, 128.4, 136.2, 172.6. HRMS
Calcd for C17H18O3: 270.1256. Found: 270.1258.
(c) A mixture of the adducts 3cn and 3cx (130 mg ratio
1:2.1) gave the less polar, unreacted 3cx (63 mg, 48%): IR
(neat) 1715, 1670, 1600, 1580 cm-1; 1H NMR δ 1.45 (br d, J )
8.8 Hz, 1H), 1.57 (br d, J ) 8.8 Hz, 1H), 1.89 (dd, J ) 11.7, 3.7
Hz, 1H), 2.03 (s, 3H), 2.59 (dd, J ) 11.7, 2.9 Hz, 1H), 2.93 (br
s, 1H), 3.82 (br s, 1H), 5.88 (dd, J ) 5.9, 2.9 Hz, 1H), 6.34 (dd,
J ) 5.9, 2.9 Hz, 1H), 7.41 (t, J ) 7.3 Hz, 2H), 7.52 (t, J ) 7.3
Hz, 1H), 7.87 (d, J ) 7.3 Hz, 2H); 13C NMR δ 27.7, 34.3, 43.2,
49.7, 49.9, 73.8, 128.5, 129.6, 131.3, 133.2, 136.0, 140.8, 198.8,
204.3. Also formed was 1-(1-phenyl-9-oxapentacyclo[5.2.1.-
0.2,604,8]nonyl)ethanone (4c) {38 mg, 29% (91% from 3cn )}: IR
(neat) 1700, 1600, 750, 700 cm-1; 1H NMR δ 1.80 (m, 2H), 1.89
(d, J ) 11.0 Hz, 1H), 2.06 (s, 3H), 2.18 (br s, 1H), 2.29 (br d,
J ) 11.0 Hz,1H), 3.17 (br s, 1H), 3.50 (m, 1H), 4.89 (m, 1H),
7.2-7.4 (m, 5H). HRMS Calcd for C16H16O2: 240.1150.
Found: 240.1161.
(1′R,2′S,5′R)-5-Meth yl-2-(1-m eth yl-1-p h en yleth yl)cyclo-
h exyl (2-P h en yl-1,3-d ioxola n -2-yl)a ceta te (9). Oxalyl chlo-
ride (3.0 mL, 34.4 mmol) was added dropwise to a solution of
2-phenyl-1,3-dioxolan-2-ylacetic acid (8) (3.0 g, 14.4 mmol) in
benzene (40 mL), and the reaction mixture was stirred for 3 h
at ambient temperature. The solvent was evaporated off. The
resulting residue was dissolved in CH2Cl2 (5 mL) and added
to a solution of (-)-8-phenylmenthol (2.32 g, 10.0 mmol), Et3N
(1.5 g, 14.9 mmol), and DMAP (10 mg, 0.082 mmol) in CH2Cl2
(40 mL) at 0 °C. After addition was completed, the reaction
mixture was stirred for 10 h at ambient temperature. The
reaction mixture was washed with water (30 mL × 3) and
brine (20 mL), dried, and evaporated. The residue was
subjected to column chromatography (8% AcOEt in hexane as
eluent) to give (1′R,2′S,5′R)-5-methyl-2-(1-methyl-1-phenyl-
ethyl)cyclohexyl (2-phenyl-1,3-dioxolan-2-yl)acetate (3.50 g,
1580 cm-1
.
(1′R,2′S,5′R)-5-Meth yl-2-(1-m eth yl-1-p h en yleth yl)cyclo-
h exyl 2-Ben zoyla cr yla te 1d . A solution of (1′R,2′S,5′R)-5-
methyl-2-(1-methyl-1-phenylethyl)cyclohexyl 2-[(methylsulfinyl)-
methyl]-3-oxo-3-phenylpropionate (2.01 g, 4.43 mmol) in toluene
(2 mL) was refluxed for 12 h. The reaction mixture was diluted
with benzene (30 mL), washed with water (20 mL × 3) and
brine (15 mL), dried, and evaporated. The residue was
subjected to column chromatography to yield (1′R,2′S,5′R)-5-
methyl-2-(1-methyl-1-phenylethyl)cyclohexyl 2-benzoylacrylate
(1d ) (1.67 g, 97%): IR (neat) 1715, 1680, 1600, 1580 cm-1; 1H
NMR δ 0.70-2.10 (m, 8H), 0.85 (d, J ) 6.4 Hz, 3H), 1.20 (s,
3H), 1.26 (s, 3H), 4.91 (dt, J ) 10.5, 4.5 Hz, 1H), 5.83 (s, 1H),
6.04 (s, 1H), 7.1-7.6 (m, 8H), 7.78 (dd, J ) 8.5, 1.2 Hz, 2H);
13C NMR δ 21.7, 26.4, 26.8, 26.9, 31.3, 34.4, 39.8, 41.3, 50.2,
76.0, 125.2, 125.5, 128.1, 128.4, 129.4, 131.3, 133.4, 136.5,
141.2, 151.2, 163.5, 193.2; [R]23D ) -19.0° (c, 3.0, CHCl3). Anal.
Calcd for C26H30O3: C, 79.97; H, 7.74. Found: C, 79.77; H,
7.97. HRMS Calcd for C26H30O3: 390.2193. Found: 390.2211.
Diels-Ald er Rea ction of (1′R,2′S,5′R)-5-Meth yl-2-(1-
m eth yl-1-p h en yleth yl)cycloh exyl 2-Ben zoyla cr yla te (1d ).
(a ) In th e Absen ce of Lew is Acid . A solution of cyclopen-
tadiene in CH2Cl2 (2.1 M solution, 1.0 mL) was added to a
solution of 1d (100 mg, 0.256 mmol) in CH2Cl2 (5 mL). The
reaction mixture was stirred for 6 h at ambient temperature.
The mixture was diluted with CH2Cl2 (20 mL), washed with
water (10 mL × 2) and brine (5 mL), dried, and evaporated.
The residue was subjected to column chromatography to yield
a mixture of four stereoisomers. The preparative HPLC of the
mixture gave endo-(1′R,2′S,5′R)-5-methyl-2-(1-methyl-1-phen-
ylethyl)cyclohexyl (1S,2R,4S)-2-benzoylbicylo[2.2.1]hept-5-ene-
2-carboxylate (3n -R) (as first fraction): 1H NMR δ 0.47 (q, J
) 11.3 Hz, 1H), 0.57 (dq, J ) 11.7, 3.0 Hz, 1H), 0.64 (d, J )
6.6 Hz, 3H), 0.80 (dq, J ) 13.2, 2.5 Hz, 1H), 1.13 (s, 3H), 1.16
(s, 3H), 1.19-1.53 (m, 5H), 1.68-1.83 (m, 2H), 1.89 (dd, J )
12.1, 2.5 Hz, 1H), 2.66 (dd, J ) 12.1, 3.7 Hz, 1H), 2.93 (br s,
1H), 3.46 (br s, 1H), 4.82 (dt, J ) 10.6, 4.7 Hz, 1H), 6.12 (m,
2H), 7.08-7.53 (m, 8H), 7.90 (dd, J ) 7.3, 1.5 Hz, 2H), endo-
(1′R,2′S,5′R)-5-methyl-2-(1-methyl-1-phenylethyl)cyclohexyl
(1R,2S,4R)-2-benzoylbicylo[2.2.1]hept-5-ene-2-carboxylate (3n -
S) (as second fraction): 1H NMR δ 0.64 (q, J ) 10.0 Hz, 1H),
0.73 (d, J ) 6.2 Hz, 3H), 0.78-0.92 (m, 2H), 1.06 (s, 3H), 1.08
(s, 3H), 1.11-1.54 (m, 5H), 1.70-1.79 (m, 3H), 2.09 (dd, J )
12.1, 2.9 Hz, 1H), 2.39 (dd, J ) 12.1, 3.7 1H), 2.93 (br s, 1H),
3.57 (br s, 1H), 4.80 (dt, J ) 10.5, 4.4 Hz, 1H), 5.93 (dd, J )
15.5, 2.9 Hz, 1H), 6.14 (dd, J ) 15.5, 2.9 Hz, 1H), 7.09-7.54
(m, 8H), 7.92 (dd, J ) 7.0, 1.5 Hz, 2H), exo-(1′R,2′S,5′R)-5-
methyl-2-(1-methyl-1-phenylethyl)cyclohexyl (1S,2S,4S)-2-
benzoylbicylo[2.2.1]hept-5-ene-2-carboxylate (3x-S) (as major
component of third fraction): 1H NMR δ 0.65 (q, J ) 10.5 Hz,
83% from the alcohol): IR (neat) 1735, 1500, 760, 700 cm-1
;
1H NMR δ 0.81 (d, J ) 6.6 Hz, 3H), 1.16 (s, 3H), 1.24 (s, 3H,),
2.38 (ABq, J ) 14.7 Hz, 2H), 3.75 (m, 2H), 4.01 (m, 2H), 4.72
26
(dt, J ) 10.5, 4.4 Hz, 1H), 7.10-7.43 (m, 5H); [R]
) +2.1°
D
(c, 2.4, CHCl3). Anal. Calcd for C27H34O4: C, 76.75; H, 8.11.
Found: C, 76.99; H, 8.18.
(1′R,2′S,5′R)-5-Meth yl-2-(1-m eth yl-1-p h en yleth yl)cyclo-
h exyl 3-Oxo-3-p h en ylp r op ion a te (10). To a solution of
(1′R,2′S,5′R)-5-methyl-2-(1-methyl-1-phenylethyl)cyclohexyl (2-
phenyl-1,3-dioxolan-2-yl)acetate (9) (3.35 g, 7.94 mmol) in
MeOH (120 mL) was added dropwise 10% HCl (18 mL), and
the reaction mixture was stirred for 12 h at ambient temper-
ature. A large part of MeOH was evaporated off under reduced
pressure at ambient temperature, and water (50 mL) and ether
(50 mL) were added to the residue. The organic layer was
separated, and the aqueous layer was extracted with ether (40
mL × 2). The combined organic layer was washed with brine
(50 mL × 2), dried, and evaporated. The residue was subjected
to column chromatography to give 10 (2.90 g, 97%): IR (neat)
1
1735, 1685, 1600, 1580 cm-1; H NMR δ 0.86 (d, J ) 6.6 Hz,
3H), 1.20 (s, 3H), 1.32 (s, 3H), 3.27 (ABq, J ) 15.7 Hz, 2H),
4.86 (dt, J ) 10.6, 4.4 Hz, 1H), 7.24-7.79 (m, 5H); [R]23
)
D
+49.5° (c, 2.0, CHCl3). Anal. Calcd for C25H30O3: C,79.33;
H, 7.99. Found: C, 79.05; H, 8.24.
(1′R,2′S,5′R)-5-Meth yl-2-(1-m eth yl-1-p h en yleth yl)cyclo-
h exyl 2-[(Meth ylth io)m eth yl]-3-oxo-3-p h en ylp r op ion a te.
A mixture of 10 (2.00 g, 5.29 mmol) and N-[(methylthio)-
methyl]piperidine hydrochloride (1.43 g, 7.88 mmol) in dioxane
(110 mL) was stirred for 17 h at 90 °C. The solvent was
evaporated off, and AcOEt (100 mL) and water (50 mL) were

Reactivity of 2-Methylene-1,3-dicarbonyl Compounds
J . Org. Chem., Vol. 61, No. 8, 1996 2725
1H), 0.71 (s, 3H), 0.81 (d, J ) 6.2 Hz, 3H), 0.88 (s, 3H), 0.91-
1.97 (m, 10H), 2.10 (dd, J ) 12.1, 3.7 Hz, 1H), 2.53 (dd, J )
12.1, 2.6 Hz, 1H), 2.96 (br s, 1H), 3.78 (br s, 1H), 4.61 (dt, J )
10.6, 4.0 Hz, 1H), 6.06 (dd, J ) 15.5, 2.9 Hz, 1H), 6.42 (dd, J
) 15.5, 2.9 Hz, 1H), 7.02-7.54 (m, 8H), 8.02 (dd, J ) 7.3, 1.5
Hz, 2H), and 3x-R (as fourth fraction), whose spectral data
are shown below.
(b) In th e P r esen ce of Lew is Acid . A equimolar amount
of Lewis acids (BF3‚OEt2, FeCl2, FeCl2I) and 1.5 equiv of ZnCl2
were used. A solution of 1d (100 mg, 0.256 mmol) in CH2Cl2
(5 mL) was added to a solution or suspension of Lewis acids
in CH2Cl2 (5 mL) and stirred for 30 min at the temperatures
shown in Table 3. Then a solution of cyclopentadiene in CH2-
Cl2 (2.1 M solution, 1.0 mL) was added to the above mixture
and stirred under the reaction conditions shown in Table 3.
After the reaction was completed, water (5 mL) was added to
the mixture and the resulting solution was stirred for 5 min
at ambient temperature, washed with water (15 mL × 2) and
brine (5 mL), dried, and evaporated. The residue was sub-
jected to column chromatography to yield the adduct (yields
and exo/endo ratios were shown in Table 3). A single recrys-
tallization of the product under ZnCl2 catalyst at -78 °C gave
pure exo-(1′R,2′S,5′R)-5-methyl-2-(1-methyl-1-phenylethyl)cy-
clohexyl (1R,2R,4R)-2-benzoylbicylo[2.2.1]hept-5-ene-2-carbox-
ylate (3x-R): mp 135-136 °C (from EtOH); IR (KBr) 1730,
1680 cm-1; 1H NMR δ -0.09 (q, J ) 11.5 Hz, 1H), 0.45 (dq, J
) 12.5, 3.5 Hz, 1H), 0.49 (d, J ) 6.8 Hz, 3H), 0.72 (dq, J )
13.2, 3.3 Hz, 1H), 1.04 (dq, J ) 12.6, 3.3 Hz, 1H), 1.14 (dq, J
) 11.5, 4.0 Hz, 1H), 1.21 (s, 3H), 1.26 (m, 1H), 1.30 (m, 1H),
1.40 (s, 3H), 1.56 (m, 2H), 1.69 (dt, J ) 12.0, 3.3 Hz, 1H), 2.05
(dd, J ) 12.0, 3.6 Hz, 1H), 2.43 (dd, J ) 12.0, 1.8 Hz, 1H),
2.98 (br s, 1H), 3.57 (br s, 1H), 4.66 (dt, J ) 10.6, 4.0 Hz, 1H),
5.99 (dd, J ) 5.5, 2.9 Hz, 1H), 6.43 (dd, J ) 5.5, 2.9 Hz, 1H),
7.10-7.60 (m, 8H), 7.91 (dd, J ) 7.0, 1.8 Hz, 2H); 13C NMR δ
21.4, 27.4, 30.87, 30.91, 34.1, 36.6, 39.9, 40.3, 43.2, 49.3, 49.8,
50.1, 63.4, 77.1, 125.4, 125.7, 128.0, 128.3, 129.2, 132.3, 132.8,
136.0, 140.5, 150.4, 171.8, 197.2; [R]30 ) +135° (c, 0.35,
D
CHCl3). Anal. Calcd for C31H36O3: C, 81.54; H, 7.95. Found:
C, 81.54; H, 8.13. HRMS Calcd for C31H36O3: 456.2663.
Found: 456.2653.
Ack n ow led gm en t. We thank Dr. Tokiwa of Uni-
versity of Shizuoka for providing the program of MNDO
converted to PC version.
J O9518819