Stereoselective intramolecular coupling of diaroylacetates of (1R,1′R)-exo,exo′-3,3′-biisoborneol by oxidation with Br 2

Article abstract of DOI:10.1016/S0957-4166(03)00572-X

The oxidative coupling of diaroylacetate derivatives prepared from (1R,1′R)-exo,exo′-3,3′-biisoborneol with NaH-Br₂ gave the corresponding intramolecularly coupled products stereoselectively. The major (R,R)-isomers thus obtained were transformed to (-)-Sesamin and (-)-Eudesmin.

Full text of DOI:10.1016/S0957-4166(03)00572-X

TETRAHEDRON:
ASYMMETRY
Pergamon
Tetrahedron: Asymmetry 14 (2003) 2495–2497
Stereoselective intramolecular coupling of diaroylacetates of
(1R,1%R)-exo,exo%-3,3%-biisoborneol by oxidation with Br2
Naoki Kise,* Azumi Fujimoto, Noriaki Moriyama and Nasuo Ueda
Department of Biotechnology, Faculty of Engineering, Tottori University, Koyama, Tottori 680-8552, Japan
Received 31 May 2003; accepted 30 June 2003
Abstract—The oxidative coupling of diaroylacetate derivatives prepared from (1R,1%R)-exo,exo%-3,3%-biisoborneol with NaH–Br2
gave the corresponding intramolecularly coupled products stereoselectively. The major (R,R)-isomers thus obtained were
transformed to (−)-Sesamin and (−)-Eudesmin.
© 2003 Elsevier Ltd. All rights reserved.
Oxidative homocoupling of aroylacetates provides use-
ful precursors for the synthesis of furofuran lignans,1
such as Sesamin2 and Eudesmin.3 Recently, we have
reported the first stereoselective homocoupling of chiral
aroylacetate derivatives using (4R,5S)-3,4-dimethyl-5-
phenyl-2-imidazolidinone as a chiral auxiliary.4 The
stereoselectivities of the mainly formed (R,R)-dimers
were, however, moderate (70–72% de). Therefore, a
more efficient chiral auxiliary is desired. Herein, we
report that the oxidative intramolecular coupling of
diaroylacetates derived from (1R,1%R)-exo,exo%-3,3%-
biisoborneol5 as a difunctional chiral auxiliary takes
place more stereoselectively.
ucts. The starting diaroylacetates of 1 were synthesized
in three steps as depicted in Scheme 2: diacetylation of
1, condensation of the diacetates 2 with aromatic alde-
hydes, and Jones oxidation of the resulting b-hydroxy
esters 3 afforded diaroylacetates 4.
In preliminary experiments, we found that the inter-
molecular coupling of chiral aroylacetates prepared
from (−)-menthol, (−)-endo-borneol, and (−)-exo-bor-
neol resulted in non-stereoselective formation of the
three isomeric dimers [approximately (R,R):(R,S):
(S,S)=1:2:1]. Next, we attempted this type of oxidative
coupling in the intramolecular mode. For this purpose,
we selected (1R,1%R)-exo,exo%-3,3%-biisoborneol 1 as a
difunctional chiral auxiliary. Since 1 was obtained in
poor yields (<20%) according to the reported method5
for oxidative coupling of (+)-camphor with CuCl2, we
modified the preparation of 1 as shown in Scheme 1.
The oxidation of the Li-enolate of the (+)-camphor
with PhI(OAc)2 in THF and subsequent LAH reduc-
tion of the resulting mixture gave 1 in 54% overall yield
after recrystallization (three times) from the crude prod-
Scheme 1.
* Corresponding author. Fax: +81-857-31-5636; e-mail: kise@
bio.tottori-u.ac.jp
Scheme 2.
0957-4166/$ - see front matter © 2003 Elsevier Ltd. All rights reserved.
doi:10.1016/S0957-4166(03)00572-X

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N. Kise et al. / Tetrahedron: Asymmetry 14 (2003) 2495–2497
Table 1. Oxidative intramolecular coupling of 4 to 5 with NaH–Br2
Run
4
Solvent
NaH (equiv.)
Time (h)
Yielda (%) of 5
(R,R):(R,S):(S,S)b
Yielda (%) of 6
1
2
3
4
5
6
7
4a DMF
4a THF
2.5
2.5
2.5
2
2.5
2.5
2.5
6
6
6
6
5a 95
Trace
5a 47
5a 59
5a 83
5b 92
5b 78
29:51:20
–
6a 80
6a 45
6a 34
–
–
–
4a DMF/THF (1:1)
4a DMF/THF (1:1)
4a DMF/THF (1:1)c
4b DMF
93:5:2
22:53:25
96:3:1
32:43:25
97:2:1
1+12
6
1+12
4b DMF/THF (1:1)c
a Isolated yields.
b Determined by 1H NMR spectra (see Ref. 6).
c THF was added after 1 h (see text).
with high stereoselectivity [(R,R):(R,S):(S,S)=96:3:1].
Another diaroylacetate 4b (Ar=3,4-dimethoxyphenyl)
was also transformed to (R,R)-5b stereoselectively
according to the method of run 5 (run 7).
The results of the oxidative coupling of 4a (Ar=3,4-
methylenedioxyphenyl) by the successive treatment with
NaH and Br2 (1 equiv.) at 25°C are summarized in
Table 1. The reaction with 2.5 equiv. of NaH in DMF
gave the intramolecularly coupled product 5a in excel-
lent yield (95%), but the ratio of the three diastereomers
of 5a was essentially statistical (run 1). When the
reaction was performed in THF, monobromide 6a was
obtained as the predominant product (run 2). The
formation of 6a was probably due to rapid proton
abstraction from the brominated methyne group in 6a.
On the other hand, the stereoselective formation of
(R,R)-5a [(R,R):(R,S):(S,S)=93:5:2] resulted from the
reaction in a mixed solvent of DMF/THF (1:1),
although accompanied with a considerable amount of
6a (run 3). Treatment with 2 equiv. of NaH in the same
solvent, however, brought about a statistical ratio of 5a
(run 4). These results suggest the following three points:
(1) The kinetic formation of 5a is non-stereoselective;
(2) the isomers of 5a are equilibrated in the presence of
an excess of NaH in DMF/THF (1:1); (3) (R,R)-5a is
much more thermodynamically stable than the other
two isomers. Indeed, isomerization from an
(R,R):(R,S):(S,S)=29:51:20 mixture of 5a to an
(R,R):(R,S):(S,S)=95:4:1 mixture was observed by
treatment with 1 equiv. of NaH in the same solvent
(25°C, 6 h). On the other hand, the isomerization of 5a
could barely be detected within 6 h in DMF at 25°C
and in DMF/THF (1:1) at 0°C. The reaction of 5a with
NaH in DMF at 60°C led to a complex mixture. In the
previously reported intermolecular coupling of chiral
1-aroylacetyl-2-imidazolidinones,4 such isomerizations
of the coupled products were not observed. To obtain
the intramolecularly coupled products in high yield and
selectivity in one-pot, the reaction was initially carried
out in DMF as run 1 (25°C, 1 h) and then the same
amount of THF was added to the reaction mixture to
attain equilibrium (25°C, 12 h, run 5). By using this
procedure, (R,R)-5a was obtained in good yield (83%)
Fortunately, the major isomers of 5a and 5b could be
isolated from the other isomers by column chromatog-
raphy on silica gel. Their absolute stereochemistry was
confirmed to be (R,R)- by a two-step conversion to
(−)-Sesamin 77 and (−)-Eudesmin 8:8 LAH reduction in
THF (reflux, 6 h) and subsequent treatment with PPTS
in benzene (reflux, 12 h, Scheme 3). In addition, the
chiral auxiliary 1 was recovered in more than 90%
yield.
Scheme 3.
The equilibriation of the three isomers of 5 was
observed as described previously. Semiempirical and
DFT calculations9 were, therefore, carried out on the
three isomers of dibenzoylacetate 9 (Ar=phenyl in 5)
as a model compound to evaluate the energies of their
optimized structures (Fig. 1). As exhibited in Table 2,

N. Kise et al. / Tetrahedron: Asymmetry 14 (2003) 2495–2497
2497
Figure 1.
Table 2. Relative energies between isomers of 9 (kcal/mol)
Jack, I. R. J. Chem. Soc., Perkin
1
1982, 183–
190.
Method
(R,R)-9
(R,S)-9
(S,S)-9
2. (a) Takano, S.; Ohkawa, T.; Tamori, S.; Satoh, S.;
Ogasawara, K. J. Chem. Soc., Chem. Commun. 1988,
189–191; (b) Samizu, K.; Ogasawara, K. Chem. Lett. 1995,
543–544.
3. (a) van Oeveren, A.; Jansen, J. F. G. A.; Feringa, B. L. J.
Org. Chem. 1994, 59, 5999–6007; (b) Latip, J.; Hartley,
T. G.; Waterman, P. G. Phytochemistry 1999, 51, 107–
110.
RHF/AM1
RHF/PM3
RB3LYP 3-21G*
RB3LYP 6-31G*
0
0
0
0
5.13
3.58
4.20
1.32
3.84
3.65
2.84
4.16
all the methods show that (R,R)-9 is the most thermo-
dynamically stable isomer. These computational results
are consistent with the experimental results.
4. Kise, N.; Fujimoto, A.; Ueda, N. Tetrahedron: Asymmetry
2002, 13, 1845–1847.
5. McNulty, J.; Millar, M. J. J. Org. Chem. 1999, 64, 5312–
5314.
In conclusion, the oxidative intramolecular coupling of
the diaroylacetates of (1R,1%R)-exo,exo%-3,3%-biisobor-
neol with NaH–Br2 gave the corresponding (R,R)-iso-
mers in high stereoselectivity (92–94% de). The
stereoselectivity was considerably improved by this
intramolecular methodology, when compared with the
intermolecular coupling previously reported by us.4
6. The chemical shifts (l) of newly formed methyne protons
in 5 were as follows: (R,R)-5a 5.03 (s); (R,S)-5a 4.75 and
4.79 (d, J=3.2 Hz); (S,S)-5a 5.60 (s); (R,R)-5b 5.13 (s);
(R,S)-5b 4.85 and 4.89 (d, J=3.2 Hz); (S,S)-5b 5.66 (s).
7. (−)-Sesamin 7: [h]2D5=−64.0 (c 1.0, CHCl3), lit.2a [h]2D2=−
64.5 (c 1.05, CHCl3).
8. (−)-Eudesmin 8: [h]2D5=−64.7 (c 1.0, CHCl3), lit.3b [h]2D3=−
64.2 (c 1.1, CHCl3).
The typical procedure for the oxidative coupling of 4
with NaH-Br2 is as follows (run 5 in Table 1): To a
suspension of NaH (2.5 mmol) in DMF (2.5 mL) was
added a solution of 4 (1.0 mmol) in DMF (2.5 mL) at
25°C under N2. After the mixture was stirred for 30
min, Br2 (160 mg, 1.0 mmol) was added. After the
mixture was stirred for an additional hour, THF (5 mL)
was added. The mixture was stirred for a further 12 h,
diluted with 1 M HCl (20 mL), and then extracted with
Et2O. The major isomer of 5 was isolated by column
chromatography on silica gel (hexane/ethyl acetate),
and gave satisfactory spectroscopic data and elemental
analysis. (R,R)-5a: [h]2D5=+110 (c 0.97, CHCl3). (R,R)-
5b: mp 123–125°C; [h]2D5=+100 (c 0.99, CHCl3).
9. The calculations were carried out using the Gaussian 98W
program: Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.;
Scuseria, G. E.; Robb, M. A.; Cheeseman, J. R.;
Zakrzewski, V. G.; Montgomery, J. A., Jr.; Stratmann, R.
E.; Burant, J. C.; Dapprich, S.; Millam, J. M.; Daniels, A.
D.; Kudin, K. N.; Strain, M. C.; Farkas, O.; Tomasi, J.;
Barone, V.; Cossi, M.; Cammi, R.; Mennucci, B.; Pomelli,
C.; Adamo, C.; Clifford, S.; Ochterski, J.; Petersson, G.
A.; Ayala, P. Y.; Cui, Q.; Morokuma, K.; Malick, D. K.;
Rabuck, A. D.; Raghavachari, K.; Foresman, J. B.;
Cioslowski, J.; Ortiz, J. V.; Baboul, A. G.; Stefanov, B. B.;
Liu, G.; Liashenko, A.; Piskorz, P.; Komaromi, I.; Gom-
perts, R.; Martin, R. L.; Fox, D. J. Keith, T.; Al-Laham,
M. A.; Peng, C. Y.; Nanayakkara, A.; Challacombe, M.;
Gill, P. M. W.; Johnson, B.; Chen, W.; Wong, M. W.;
Andres, J. L.; Gonzalez, C.; Head-Gordon, M.; Replogle,
E. S.; Pople, J. A. Gaussian 98W, Revision A.9; Gaussian,
Inc.: Pittsburgh, PA, 1998.
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