Stereoselective Hydrocoupling of Optically Active 3-fraws-Cinnamoyloxazolidinones by Electroreduction

Article abstract of DOI:10.1021/jo981231f

Reductive hydrocoupling of chiral 3-trans-cinnamoyloxazolidinones was studied by an electrochemical method. The electroreduction was performed conveniently at a constant current using an undivided cell. The stereoselectivity of the hydrodimers was strongly affected by the electrolyte employed. Electroreduction of (S)-4-isobutyl-3-trais-cinnamoyloxazolidinone la in 0.3 M Et₄NOTs/ AN gave a mixture of two diastereomers of all-trans cyclized hydrodimer 2a, and the selectivity was R,S,R/S,R,S = 85:15. On the other hand, the reduction of la in 1.7 M LiClO₄/THF afforded a diastereomeric mixture of hydrodimers in a selectivity of R,R/S,S/R,S = 5:52:43. The stereoselectivities were explained by considering stable conformations of intermediate anion radicals, that is, syn-Z type for naked anion radicals and anti-Z type for lithiated anion radicals. Semiempirical calculations also supported this hypothesis. Electroreductions of (S)-4-isobutyl-3-c/s-cinnamoyloxazolidinone and (S)-4-isobutyl-3-phenylpropioloyloxazolidinone gave 2a in the same stereoselectivity as electroreduction of la did. The electroreductive hydrocoupling was not inhibited by para and meta substitution on the aryl group of 3-Zrans-cinnamoyloxazolidinones. An ortho substitution, however, hindered the hydrocoupling and lowered the stereoselectivity of the hydrodimers. Electroreduction of 3-trans-cinnamoyloxazolidinethione and thiazolidinethione gave trarcs-3,4-diphenylcyclopentanone as a product, and the stereoselectivities were similar to that obtained from the corresponding oxazolidinone.

Full text of DOI:10.1021/jo981231f

J . Org. Chem. 1998, 63, 7931-7938
7931
Ster eoselective Hyd r ocou p lin g of Op tica lly Active
3-tr a n s-Cin n a m oyloxa zolid in on es by Electr or ed u ction
Naoki Kise,* Syun-ichiro Mashiba, and Nasuo Ueda
Department of Biotechnology, Faculty of Engineering, Tottori University, Tottori 680, J apan
Received J une 25, 1998
Reductive hydrocoupling of chiral 3-trans-cinnamoyloxazolidinones was studied by an electrochemi-
cal method. The electroreduction was performed conveniently at a constant current using an
undivided cell. The stereoselectivity of the hydrodimers was strongly affected by the electrolyte
employed. Electroreduction of (S)-4-isobutyl-3-trans-cinnamoyloxazolidinone 1a in 0.3 M Et4NOTs/
AN gave a mixture of two diastereomers of all-trans cyclized hydrodimer 2a , and the selectivity
was R,S,R/S,R,S ) 85:15. On the other hand, the reduction of 1a in 1.7 M LiClO4/THF afforded a
diastereomeric mixture of hydrodimers in a selectivity of R,R/S,S/R,S ) 5:52:43. The stereoselec-
tivities were explained by considering stable conformations of intermediate anion radicals, that is,
syn-Z type for naked anion radicals and anti-Z type for lithiated anion radicals. Semiempirical
calculations also supported this hypothesis. Electroreductions of (S)-4-isobutyl-3-cis-cinnamoylox-
azolidinone and (S)-4-isobutyl-3-phenylpropioloyloxazolidinone gave 2a in the same stereoselectivity
as electroreduction of 1a did. The electroreductive hydrocoupling was not inhibited by para and
meta substitution on the aryl group of 3-trans-cinnamoyloxazolidinones. An ortho substitution,
however, hindered the hydrocoupling and lowered the stereoselectivity of the hydrodimers.
Electroreduction of 3-trans-cinnamoyloxazolidinethione and thiazolidinethione gave trans-3,4-
diphenylcyclopentanone as a product, and the stereoselectivities were similar to that obtained from
the corresponding oxazolidinone.
Sch em e 1
Electroreductive hydrocoupling of R,â-unsaturated com-
pounds in aqueous solution is well-known as a practical
method for the synthesis of adipic acid derivatives.1 The
electroreductive hydrocoupling of â-substituted R,â-
unsaturated compounds is, however, usually nondiaste-
reoselective. On the other hand, it has been reported that
the electroreduction of cinnamic acid esters in an aprotic
solvent gave cyclized products of hydrodimers2 and they
were obtained as all-trans isomers stereospecifically (eq
1).2a-c These results prompt us to investigate enantiose-
lective hydrocoupling of cinnamic acid derivatives, be-
cause the obtained hydrodimers are able to be converted
into a variety of C2-symmetric compounds (Scheme 1).
We have started the study using easily available chiral
auxiliaries (X) such as optically active alcohols, oxazo-
lines,3 and oxazolidinones.3b,4 Among them, we have
found that optically active oxazolidinones were most
effective as the chiral auxiliary for the stereoselective
hydrocoupling (eq 2).5,6 In this paper, we report the
results of further study on the stereoselective hydrocou-
pling of optically active 3-trans-cinnamoyloxazolidinones
1 by electroreduction. We found that the electroreductive
hydrocoupling of 1 was achieved under constant current
conditions more conveniently than under constant po-
tential conditions. We also found that the stereoselec-
tivity was strongly influenced by the supporting electro-
lyte. Use of a tetraalkylammonium salt as an electrolyte
was essential for high stereoselectivity. The observed
stereoselectivities were interpreted by regarding the
reaction mechanism as homocoupling of stable conforma-
(1) (a) Baizer, M. M. J . Electrochem. Soc. 1964, 111, 215-222. (b)
Baizer, M. M.; Anderson, J . D. J . Electrochem. Soc. 1964, 111, 223-
226. (c) Rifi, M. R. In Technique of Electroorganic Synthesis, Part II;
Weinberg, N. L., Ed.; Wiley: New York, 1975; pp 192-215.
(2) (a) Klemm, L. H.; Olson, D. R. J . Org. Chem. 1973, 58, 3390-
3394. (b) Kanetsuna, H.; Nonaka, T. Denki Kagakuoyobi Kogyo Butsuri
Kagaku 1981, 49, 526-531. (c) Smith, C. Z.; Utley, H. P. J . Chem.
Soc., Chem. Commun. 1981, 492-494. (d) Nishiguchi, I.; Hirashima,
T. Angew. Chem., Int. Ed. Engl. 1983, 22, 52-53.
(3) (a) Lutomski, K. A.; Meyers, A. I. In Asymmetric Synthesis;
Morrison, J . D., Ed.; Academic Press: New York, 1984; Vol. III, pp
213-274. (b) Ager, D. J .; Prakash, I.; Schaad, D. R. Chem. Rev. 1996,
96, 835-875.
(5) Kise, N.; Echigo, M.; Shono, T. Tetrahedron Lett. 1994, 35, 1897-
1900.
(6) Electroreduction of trans-cinnamates derived from optically
active alcohols such as (-)-menthol, (-)-8-phenylmenthol, and (-)-
endo-borneol gave the corresponding dl-hydrodimers in modest selec-
tivities (10-20% ee). Oxazolines derived from trans-cinnamic acid
yielded only simply reduced products. After our report,5 electroreduc-
tive hydrodimerization of chiral cinnamates was presented by Utley
et al.7 They reported >95% dl-selectivity using (-)-endo-bornyl trans-
cinnamate on the basis of 1H NMR and HPLC analyses of the cyclized
hydrodimer. We therefore re-examined the reduction of (-)-endo-bornyl
ester under their and our conditions. However, we could not reproduce
such high selectivity. In all the cases, only modest selectivities (10-
20% ee) were obtained by 1H NMR with Eu(hfc)3 and chiral HPLC
analyses of 3,4-diphenyl adipate and 3,4-diphenylcyclopentanone
derived from the hydrodimers.
(4) (a) Evans, D. A. In Asymmetric Synthesis; Morrison, J . D., Ed.;
Academic Press: New York, 1984; Vol. III, pp 87-90. (b) Heathcock,
C. H. In Asymmetric Synthesis; Morrison, J . D., Ed.; Academic Press:
New York, 1984; Vol. III, pp 184-188.
10.1021/jo981231f CCC: $15.00 © 1998 American Chemical Society
Published on Web 10/08/1998

7932 J . Org. Chem., Vol. 63, No. 22, 1998
Kise et al.
Ta ble 1. Electr or ed u ction of 1 a t a Con sta n t Cu r r en t of
0.1 A
% yield of 2a
1
R1
R2
(2R,3S,4R/2S,3R,4S)b
1a
1b
1c
1d
1e
i-Bu (S)
i-Pr (S)
Bn (S)
Ph (R)
Me (S)
H
H
H
H
75 (85:15)
76 (83:17)
68 (70:30)
70 (30:70)
72 (75:25)
Ph (R)
a
Isolated yields. b Diastereomeric ratios determined by 1H NMR
spectra.
F igu r e 1. Correlation between yields of the products and
currents in the electrolysis of 1a in 0.3 M Et4NOTs/AN.
Sch em e 2
tions of anion radical intermediates. A semiempirical
calculation of anion radicals also supported this mecha-
nism. The result obtained from the cis isomer of 1 was
identical to that from 1. Aryl-substituted 1 gave the
similar results under the same conditions, except for
ortho-substituted 1. Electroreduction of 3-trans-cin-
namoyloxazolidinethione and thiazolidinethione resulted
in similar stereoselectivities, although the hydrocoupling
product was obtained as trans-3,4-diphenylcyclopen-
tanone. Furthermore, other reductive methods employ-
ing metal reducing agents were investigated. However,
electroreduction was most effective for the reductive
hydrocoupling of 1.
Deter m in a tion of Ster eoselectivity. The diaste-
1
reoselectivites of 2a -e were measured by their H NMR
spectra. The absolute configurations of 2a -e were
assigned by their conversion to dimethyl 3,4-diphenyla-
dipate 4a and comparison with authentic sample of (S,S)-
4a prepared from (2S,3S)-2,3-diphenylsuccinic acid8 (eq
1
3). The enantioselectivity of 4a was determined by H
NMR with Eu(hfc)3 and chiral HPLC analysis. Cyclized
hydrodimer 2a was also transformed to 3,4-diphenylcy-
clopentanone 5 by acid hydrolysis. The selectivity of 5
was measured by its optical rotation7 and further con-
firmed by transformation to 3,4-diphenylcyclopenntanol
6 and its chiral HPLC analysis. As shown in Scheme 2,
all the measurements of stereoselectivity gave similar
values.
Resu lts a n d Discu ssion
Con sta n t Cu r r en t Electr olysis. In our preliminary
study,5 the electroreduction of 3-trans-cinnamoyloxazo-
lidinones 1 was carried out at a constant potential of -1.8
V versus SCE in acetonitrile (AN) containing Et4NOTs
as a supporting electrolyte. From a standpoint of syn-
thetic chemistry, a constant current electorolysis is much
more convenient than constant potential one. Therefore,
we employed constant current electorolysis for the elec-
troreduction of (S)-4-isobutyl-3-trans-cinnamoyloxazoli-
dinone 1a in 0.3 M Et4NOTs/AN using an undivided cell
and a Pb cathode. Figure 1 shows the correlation
between yields of cyclized hydrodimer 2a and simply
reduced product 3a and currents. At 0.1 A of current,
the best yield of 2a (75%) was obtained and the stereo-
selectivity was the same as that in constant potential
electorolysis (R,S,R/S,R,S ) 85:15 by 1H NMR). This
result shows that constant current electorolysis is also
effective for the hydrocoupling of 1. Table 1 summarizes
the results of constant current (0.1 A) electrolysis of
several 3-trans-cinnamoyloxazolidinones 1a -e.
Effects of Su p p or tin g Electr olyte. The effect of the
supporting electolyte on the hydrocoupling of 1a was
(7) Utley, J . H. P.; Gu¨llu¨, M.; Motevalli, M. J . Chem. Soc., Perkin
Trans. 1 1995, 1961-1970.
(8) (a) Wren, H.; Still, C. J . J . Chem. Soc. 1915, 444-451. (b)
Buchan, R.; Watson, M. B. J . Chem. Soc. C 1968, 2465-2467. (c) Kise,
N.; Kumada, K.; Terao, Y.; Ueda, N. Tetrahedron 1998, 54, 2697-2708.

Hydrocoupling of 3-trans-Cinnamoyloxazolidinones
J . Org. Chem., Vol. 63, No. 22, 1998 7933
Ta ble 2. Electr or ed u ction of 1a w ith LiClO4 a s a n
Electr olyte in THF
Sch em e 3
concn of LiClO4
(M)
yield of 4a
dl/meso of
3R,4R/3S,4S of
(%)a
4a b
dl-4a c
0.3
1.1
1.7
63
45
44
50:50
50:50
48:52
46:54
24:76
11:89
a
b
Isolated yields. Determined by isolation. c Determined by 1H
NMR spectra using Eu(hfc)3.
investigated. Use of tetrabutylammonium perchlolate
(0.3 M in AN) gave 2a in 50% yield, and the stereoselec-
tivity (R,S,R/S,R,S ) 87:13) was similar to that obtained
with Et4NOTs. Use of LiClO4 in AN caused deposition
of Li metal on the cathode surface, and the starting 1a
was recovered, whereas electroreduction in THF with
LiClO4 gave hydrodimer 7a in place of cyclized dimer 2a .
The diastereomeric mixture of 7a was transformed to
dimethyl 3,4-diphenyladipate 4a , and its stereoselectivity
3-acyloxazolidinones are much more unstable than Z-
enolates owing to steric repulsion. The intermediate is
therefore either of two conformers of the Z-enolate-type
anion radicals A and B (Scheme 3). The results from
electroreduction using a tetraalkylammonium salt as a
supporting electrolyte suggest that the reaction occurs
from conformation A by coupling at the less hindered Si
face (â-side) to give R,R-dimer selectively. In the elec-
troreduction with LiClO4 as a supporting electrolyte, on
the contrary, conformation B couples each other at the
less hindered Re face (R-side) to afford the S,S-dimer
preferentially. According to our knowledge about enolate
anions of 3-acyloxazolidinones, conformation A seems less
stable than B for the naked anion radical due to
electronic repulsion between two oxygen atoms, while the
Li-chelated anion radical (lithiated A) seems more favor-
able than the nonchelated one (lithiated B). Therefore,
we carried out semiempirical calculations of the anion
radicals to evaluate their stable conformations. The
geometrry optimizations using the PM3 and AM1 meth-
ods10 gave two conformations C and D for naked anion
radicals of 3-trans-cinnamoyloxazolidinones (Scheme 4,
Table 3). In the gas phase, conformation D is more stable
than C, whereas calculations with the COSMO method11
revealed conformation C is more stable than D in AN or
THF. These results show conformation C is more likely
in a polar solvent. On the other hand, PM3 calculations
of lithiated anion radicals indicated conformation E is
more stable than F in the gas phase, but conformation
F is more stable than E in a polar solvent (Scheme 4,
Table 3). These results from semiempirical calculations
are consistent with the above-mentioned mechanism for
the electroreduction of 1a (Scheme 3); that is, the naked
anion radical of 1a favors conformation A and the
lithiated one prefers conformation B.
1
was confirmed by H NMR (Table 2). It is noted that
S,S-selectivity increased with an increase in the concen-
tration of LiClO4. However, significant amounts of meso-
isomer were also formed. These results show that the
stereoselectivities in the electroreductive hydrocoupling
of chiral 3-trans-cinnamoyloxazolidinones are strongly
influenced by the supporting electrolyte. On the other
hand, stereoselectivities in the hydrocoupling of chiral
cinnamic acid esters were little affected by the supporting
electrolyte. For example, similar selectivities were ob-
tained in the electroreduction of (-)-endo-bornyl trans-
cinnamate using Et4NOTs (R,S,R/S,R,S ) 55:45) and
LiClO4 (R,S,R/S,R,S ) 60:40) as a supporting electrolyte.
The large effect of the supporting electrolyte on the
stereoselectivity is characteristic of the hydrocoupling of
3-cinnamoyloxazolidinones.
Rea ction Mech a n ism . The reaction mechanism of
the hydrocoupling of 1 can be speculated to be similar to
that reported previously for cinnamic acid esters.2a,b,9
Namely, the cyclized hydrodimers 2 are formed by
coupling of two anion radicals produced by one-electron
transfer to 1 and a subsequent Dieckmann condensation.
Complete diastereoselectivity (dl/meso ) ∼100:0) in the
cyclized hydrodimer obtained by electroreduction of cin-
namic acid esters has been interpreted by interaction
between anion radicals and the cathode surface2a,b or by
templating between two anion radicals and water.9
Stereoselectivity in the formation of 2 can be explained
by steric interaction between the substituents on oxazo-
lidinone rings. In our previous report,5 we have supposed
an E-enolate type anion radical (A′ in Scheme 3) as the
most plausible intermediate for the electroreductive
hydrocoupling of 1 to elucidate the observed stereoselec-
tivity. However, it is well-known that E-enolates of
(10) All calculations were made by MOPAC 93 incorporated in CS
MOPAC Pro v.3.5 (KembrigeSoft Corporation, 1996). The optimizations
were carried on until GNORM < 0.1 (in gas phase) or 0.3 (in solution,
EPS ) 36.0 for AN and 7.58 for THF) using EF.
(11) Klamt, A.; Schu¨u¨rman, G. J . Chem. Soc., Perkin Trans. 2 1993,
799-805.
(9) Fussing, I.; Gu¨llu¨, M.; Hammerich, O.; Hussain, A.; Nielsen, M.
F.; Utley, J . H. P. J . Chem. Soc., Perkin Trans. 2 1996, 649-658.

7934 J . Org. Chem., Vol. 63, No. 22, 1998
Kise et al.
Sch em e 4
Ta ble 3. Sem iem p ir ica l Ca lcu la tion s of An ion Ra d ica ls
heats of formation (kcal/mol)a
method
PM3
phase
gas
in ANb
C
D
E
F
Electr or ed u ctive Hyd r ocou p lin g of Ar -Su bstitu t-
ed 1. Several aryl-substituted 3-trans-cinnamoyloxazo-
lidinones 1 were electrochemically reduced under the
constant current conditions described above. As shown
in Table 4, para and metasubstitution did not inhibit the
hydrocoupling, whereas orthosubstitution hindered it
considerably. In addition, orthosubstitution lowered the
stereoselectivity, especially in the case of the R-naphthyl
derivative 1j. Although the absolute stereoconfigurations
of 4f-j could not be confirmed, their major isomers were
assumed to be R,R from 1H NMR correlation of 2f-j
with 2a .
-112.31 -113.37
-182.67 -181.46
-79.03
-94.44
-69.24
-96.78
in THFb -171.17 -170.01 -100.57 -103.50
AM1
gas
-92.49
-164.50 -163.92
-93.93
in ANb
a
b
Boldfaced values show more stable conformations. Using the
COSMO method (EPS ) 36.0 for AN and 7.58 for THF).
Sch em e 5
Electr or ed u ctive Hyd r ocou p lin g of 3-tr a n s-Cin -
n am oyloxazolidin eth ion es an d Th iazolidin eth ion es.
Electroreduction of 3-trans-cinnamoyloxazolidinethione
11a and thiazolidinethione 11b gave trans-3,4-diphenyl-
cyclopentanone 5 as the sole product (eq 6). In these
cases, cyclized hydrodimers such as 2a are hydrolyzed
and then decarboxylated under the conditions of elec-
troreduction. The stereoselectivitiy of 5 was determined
by conversion to alcohol 6 and its chiral HPLC analysis.
The stereoselectivities were similar to that observed in
the hydrocoupling of the corresponding oxazolidinone 1b.
Sch em e 6
E lect r or ed u ct ive H yd r ocou p lin g of 3-cis-Cin -
n a m oyl- a n d 3-P h en ylp r op ioloyloxa zolid in on es.
Electroreduction of the cis analogue of 1a (8) was
examined, since inversion of the stereoselectivity was
expected (eq 4). The stereoselectivity was however the
same as that obtained from 1a . This result shows that
the sterically hindered s-cis anion radical isomerized
quickly to the s-trans one (A),12 which couples to give the
R,R-dimer preferentially (Scheme 5). Electroreduction
of 3-phenylpropioloyloxazolidinone 9 also gave cyclized
dimer 2a in the same stereoselectivity as above (eq 5).
In this case, noncyclized dimer 10 was yielded together
with 2a . These results show that the cyclized dimer 2a
was formed from 1a , which was produced in situ by
electroreduction of 9 (Scheme 6).
Red u ction of 1a w ith Meta l Red u cin g Agen ts.
Since reductive hydrocoupling of R,â-unsaturated carbo-
nyl compounds has been reported with Na,13 SmI2,14 and
(12) The isomerization of a cis-radical anion to a trans one has been
reported: Bowers, K. W.; Giese, R. W.; Grimshaw, J .; House, H. O.;
Kolodny, N. H.; Kronberger, K.; Roe, D. K. J . Am. Chem. Soc. 1970,
92, 2783-2799.
(13) (a) Totton, E. L.; Freeman, R, C.; Powell, H.; Yarboro, T. L. J .
Org. Chem. 1961, 26, 343-346. (b) House, H. O.; Giese, R, W.;
Kronberger, K.; Kaplan, J . P.; Simeone, J . F. J . Am. Chem. Soc. 1970,
92, 2800-2810.

Hydrocoupling of 3-trans-Cinnamoyloxazolidinones
J . Org. Chem., Vol. 63, No. 22, 1998 7935
Ta ble 4. Electr or ed u ctive Cou p lin g of Ar yl Su bstitu ted
1
4.62 (m, 1 H), 7.32-7.48 (m, 3 H), 7.56-7.69 (m, 2 H), 7.85 (d,
1 H, J ) 15.8 Hz), 7.96 (d, 1 H, J ) 15.8 Hz).
(S)-4-Ben zyl-3-tr a n s-cin n a m oyl-2-oxa zolid in on e (1c).
mp 122-123 °C. [R]20 +56.3 (c 1.82, CHCl3). 1H NMR
D
(CDCl3) δ 2.86 (dd, 1 H, J ) 9.5, 13.4 Hz), 3.39 (dd, 1 H, J )
3.3, 13.4 Hz), 4.16-4.37 (m, 2 H), 4.73-4.90 (m, 1 H), 7.20-
7.52 (m, 8 H), 7.59-7.75 (m, 2 H), 7.94 (s, 2 H).
(R)-3-tr a n s-Cin n a m oyl-4-p h en yl-2-oxa zolid in on e (1d ).
mp 172-173 °C. [R]20 -5.2 (c 2.1, CHCl3). 1H NMR (CDCl3)
D
δ 4.33 (dd, 1 H, J ) 3.7, 8.8 Hz), 4.75 (t, 1 H, J ) 8.8 Hz), 5.57
(dd, 1 H, J ) 3.7, 8.8 Hz), 7.30-7.50 (m, 3 H), 7.54-7.68 (m,
2 H), 7.79 (d, 1 H, J ) 15.8 Hz), 7.95 (d, 1 H, J ) 15.8 Hz).
(4S,5R)-3-tr a n s-Cin n a m oyl-4-m eth yl-5-p h en yl-2-oxa zo-
lid in on e (1e). mp 118 °C. [R]20 -85.0 (c 1.55, CHCl3). 1H
D
NMR (CDCl3) δ 0.98 (d, 3 H, J ) 6.6 Hz), 4.80-4.98 (m, 1 H),
5.73 (d, 1 H, J ) 7.3 Hz), 7.29-7.52 (m, 8 H), 7.58-7.71 (m,
2H), 7.87 (d, 1 H, J ) 15.8 Hz), 7.96 (d, 1 H, J ) 15.8 Hz).
(S)-3-(tr a n s-4-F lu or ocin n a m oyl)-4-isobu tyl-2-oxa zoli-
d in on e (1f). Rf ) 0.8 (hexane-ethyl acetate, 2:1). mp 77-
78 °C. [R]20D +90.9 (c 1.39, CHCl3). IR (KBr) 1736, 1605, 1510,
%yielda
Ar
2 (dr)b
4
3R,4R/3S,4S of 4c
837, 756 cm-1 1H NMR (CDCl3) δ 0.99 (d, 3 H, J ) 6.5 Hz),
.
Ph
1a
1f
1g
1h
1i
75 (85:15)
78 (75:25)
31 (65:35)
64 (70:30)
73 (80:20)
50 (60:40)
80
63
65
80
78
60
85:15
77:23
69:31
72:28
83:17
56:44
1.00 (d, 3 H, J ) 6.5 Hz), 1.49-1.68 (m, 2 H), 1.79-1.90 (m, 1
H), 4.15 (dd, 1 H, J ) 2.7, 8.4 Hz), 4.43 (t, 1 H, J ) 8.4 Hz),
4.57-4.64 (m, 1 H), 7.04-7.11 (m, 2 H), 7.57-7.62 (m, 2 H),
7.77 (d, 1 H, J ) 15.9 Hz), 7.83 (d, 1 H, J ) 16.2 Hz). 13C
NMR (CDCl3) δ 21.48 (q), 23.19 (q), 24.61 (d), 41.36 (t), 53.01
(d), 67.55 (t), 115.78 (d, J CCF ) 19.8 Hz), 116.76 (d), 130.27 (d,
J CCCF ) 6.6 Hz), 130.66 (s), 144.32 (d), 153.53 (s), 163.83 (s,
J CF ) 247.9 Hz), 164.64 (s). Anal. Calcd for C16H18NO3F: C,
65.97; H, 6.23; N, 4.81. Found: C, 65.96; H, 6.27; N, 4.74.
(S)-3-(tr a n s-2-Meth oxycin n a m oyl)-4-isobu tyl-2-oxa zo-
lid in on e (1g). Rf ) 0.3 (hexane-ethyl acetate, 5:1). mp 82-
83 °C. [R]20D +92.9 (c 1.58, CHCl3). IR (KBr) 1760, 1670, 1590,
p-FC6H4
o-MeOC6H4
m-MeOC6H4
p-MeOC6H4
1-Naphthyl
1j
Isolated yields. b Diastereomeric ratios determined by 1H NMR
a
spectra. c Determined by 1H NMR spectra with Eu(hfc)3.
TiCl4-Zn15 as a reducing agent, these nonelectrochemical
methods were employed for the reduction of 1a . How-
ever, the reactions of 1a with Na in Et2O or THF and
with SmI2 in THF-HMPA under the reported conditions
gave complex mixtures, and no hydrodimer was detected.
Only when the reaction was carried out with TiCl4-Zn
in THF according to the reported method was the cyclized
hydrodimer 2a obtained in 35% yield and R,S,R/S,R,S )
70:30 selectivity.
750 cm-1 1H NMR (CDCl3) δ 0.98 (d, 3 H, J ) 6.5 Hz), 1.00
.
(d, 3 H, J ) 6.5 Hz), 1.48-1.68 (m, 2 H), 1.83-1.92 (m, 1 H),
3.89 (s, 3 H), 4.13 (dd, 1 H, J ) 2.8, 8.6 Hz), 4.41 (t, 1 H, J )
8.6 Hz), 4.45-4.65 (m, 1 H), 6.90-6.99 (m, 2 H), 7.27-7.39
(m, 1 H), 7.62 (dd, 1 H, J ) 1.8, 7.7 Hz), 7.95 (d, 1 H, J ) 15.9
Hz), 8.20 (d, 1 H, J ) 15.9 Hz). 13C NMR (CDCl3) δ 21.58 (q),
23.34 (q), 24.81 (d), 41.55 (t), 53.20 (d), 55.41 (q), 67.60 (t),
111.08 (d), 117.35 (d), 120.63 (d), 123.56 (s), 129.15 (d), 131.79
(d), 141.29 (d), 153.68 (s), 158.57 (s), 165.43 (s). Anal. Calcd
for C17H21NO4: C, 67.31; H, 6.98; N, 4.62. Found: C, 67.25;
H, 6.99; N, 4.58.
Exp er im en ta l Section
Sta r tin g Ma ter ia ls. Optically active 3-acyl-2-oxazolidino-
nes 1 were prepared by treatment of optically active 2-oxazo-
lidinones with n-BuLi/hexane and acyl chlorides successively
in THF at -30 °C according to the reported method.16 In a
similar manner, 3-trans-cinnamoyl-2-oxazolidinethione 11a
and 2-thiazolidinethione 11b were synthesized from (S)-4-
isopropyl-2-oxazolidinethione and (S)-4-isopropyl-2-thiazolidi-
nethione,17 respectively. All the starting materials were
purified by column chromatography on silica gel or recrystal-
lization from hexane-ethyl acetate.
(S)-3-(tr a n s-3-Meth oxycin n a m oyl)-4-isobu tyl-2-oxa zo-
lid in on e (1h ). Rf ) 0.3 (hexane-ethyl acetate, 5:1). [R]20
D
+80.9 (c 3.54, CHCl3). IR (neat) 1774, 1678, 1620, 1580, 704,
679 cm-1 1H NMR (CDCl3) δ 0.99 (d, 3 H, J ) 6.5 Hz), 1.00
.
(d, 3 H, J ) 6.5 Hz), 1.48-1.71 (m, 2 H), 1.83-1.92 (m, 1 H),
3.83 (s, 3 H), 4.10-4.16 (m, 1 H), 4.42 (t, 1 H, J ) 8.1 Hz),
4.56-4.65 (m, 1 H), 6.93-6.96 (m, 1 H), 7.11-7.33 (m, 3 H),
7.76-7.90 (m, 2 H). 13C NMR (CDCl3) δ 21.58 (q), 23.29 (q),
24.81 (d), 41.55 (t), 53.20 (d), 55.21 (q), 67.65 (t), 113.33 (d),
116.46 (d), 117.49 (d), 121.16 (d), 129.73 (d), 135.90 (s), 145.84
(S)-3-tr a n s-Cin n a m oyl-4-isobu tyl-2-oxa zolid in on e (1a ).
Rf ) 0.45 (hexane-ethyl acetate, 5:1). mp 65-66 °C. [R]20
D
(d), 153.63 (s), 159.84 (s), 164.89 (s). Anal. Calcd for C17H21
-
+87.1 (c 1.54, CHCl3). 1H NMR (CDCl3) δ 0.99 (d, 3 H, J )
6.4 Hz), 1.01 (d, 3 H, J ) 6.4 Hz), 1.40-1.78 (m, 2 H), 1.78-
1.98 (m, 1 H), 4.16 (dd, 1 H, J ) 2.8, 8.6 Hz), 4.43 (t, 1 H, J )
8.6 Hz), 4.54-4.70 (m, 1 H), 7.36-7.49 (m, 3 H), 7.57-7.70
(m, 2 H), 7.83 (d, 1 H, J ) 15.7 Hz), 7.90 (d, 1 H, J ) 15.7 Hz).
(S)-3-tr a n s-Cin n am oyl-4-isopr opyl-2-oxazolidin on e (1b).
NO4: C, 67.31; H, 6.98; N, 4.62. Found: C, 67.18; H, 7.11; N,
4.53.
(S)-3-(tr a n s-4-Meth oxycin n a m oyl)-4-isobu tyl-2-oxa zo-
lid in on e (1i). Rf ) 0.65 (hexane-ethyl acetate, 2:1). mp
84-85 °C. [R]20D +82.2 (c 1.28, CHCl3). IR (KBr) 1765, 1667,
1590, 1510, 995, 830 cm-1 1H NMR (CDCl3) δ 0.98 (d, 3 H, J
.
Rf ) 0.3 (hexane-ethyl acetate, 5:1). [R]20 +89.9 (c 2.07,
D
) 6.5 Hz), 1.00 (d, 3 H, J ) 6.5 Hz) 1.48-1.70 (m, 2 H), 1.82-
1.90 (m, 1 H), 3.83 (s, 3 H), 4.13 (dd, 1 H, J ) 2.8, 8.6 Hz),
4.41 (t, 1 H, J ) 8.6 Hz), 4.55-4.63 (m, 1 H), 6.88-6.92 (m, 2
H), 7.54-7.57 (m, 2 H), 7.78 (d, 2 H, J ) 4.3 Hz). 13C NMR
(CDCl3) δ 21.53 (q), 23.29 (q), 24.76 (d), 41.50 (t), 53.11 (d),
55.21 (q), 67.55 (t), 114.16 (d), 114.51 (d), 127.28 (s), 130.22
(d), 145.65 (d), 153.68 (s), 161.56 (s), 165.68 (s). Anal. Calcd
for C17H21NO4: C, 67.31; H, 6.98; N, 4.62. Found: C, 67.26;
H, 7.01; N, 4.54.
CHCl3). 1H NMR (CDCl3) δ 0.92 (d, 3 H, J ) 7.0 Hz), 0.95 (d,
3 H, J ) 7.0 Hz), 2.33-2.59 (m, 1 H), 4.19-4.40 (m, 2 H), 4.50-
(14) (a) Inanaga, J .; Handa, Y.; Tabuchi, T.; Otsubo, K.; Yamaguchi,
M.; Hanamoto, T. Tetrahedron Lett. 1991, 32, 6557-6558. (b) Fleming,
I.; Ghosh, S. K. J . Chem. Soc., Chem. Commun. 1992, 1775-1777. (c)
Kanemasa, S.; Yamamoto, H.; Kobayashi, S. Tetrahedron Lett. 1996,
47, 8505-8506.
(15) Zhou, L.; Shi, D.; Gao, Y.; Shen, W.; Dai, G.; Chen, W.
Tetrahedron Lett. 1997, 38, 2729-2732.
(S)-3-[tr a n s-3-(1-Na p h th yl)p r op en oyl]-4-isobu tyl-2-ox-
a zolid in on e (1j). Rf ) 0.35 (hexane-ethyl acetate, 5:1). mp
65-66 °C. [R]20D +95.9 (c 1.09, CHCl3). IR (KBr) 1770, 1660,
(16) (a) Evans, D. A.; Bartroli, J .; Shih, T. L. J . Am. Chem. Soc.
1981, 103, 2127-2129. (b) Gage, J . G.; Evans, D. A. Organic Synthesis;
Wiley: New York, 1993; Vol. VIII, pp 339-343.
1605, 760 cm-1 1H NMR (CDCl3) δ 1.00 (d, 3 H, J ) 6.2 Hz),
.
(17) Delaunay, D.; Toupet, L.; Le Corre, M. J . Org. Chem. 1995, 60,
6604-6607.
1.02 (d, 3 H, J ) 6.5 Hz), 1.51-1.75 (m, 2 H), 1.87-1.96 (m, 1

7936 J . Org. Chem., Vol. 63, No. 22, 1998
Kise et al.
H), 4.15 (dd, 1 H, J ) 3.1, 8.3 Hz), 4.43 (t, 1 H, J ) 8.3 Hz),
4.60-4.67 (m, 1 H), 7.46-7.59 (m, 3 H), 7.85-8.01 (m, 4 H),
8.23 (d, 1 H, J ) 8.4 Hz), 8.70 (d, 1 H, J ) 15.4 Hz). 13C NMR
(CDCl3) δ 21.58 (q), 23.34 (q), 24.86 (d), 41.60 (t), 53.25 (d),
67.75 (t), 119.60 (d), 123.22 (d), 125.42 (d), 125.57 (d), 126.06
(d), 126.84 (d), 128.66 (d), 130.81 (d), 131.54 (s), 131.69 (s),
133.65 (s), 142.66 (d), 153.68 (s), 164.99 (s). Anal. Calcd for
C20H21NO3: C, 74.28; H, 6.55; N, 4.33. Found: C, 74.24; H,
6.57; N, 4.28.
H). Anal. Calcd for C25H27NO4: C, 71.24; H, 6.45; N, 3.32.
Found: C, 71.16; H, 6.52; N, 3.14.
(R,S,R)-2b (Ma jor ). Rf ) 0.55 (hexane-ethyl acetate, 2:1).
mp 159-161 °C. [R]20D -59.0 (c 0.50, CHCl3). IR (KBr) 1770,
1750, 1680, 750, 700 cm-1 1H NMR (CDCl3) δ 0.91 (d, 3 H, J
.
) 7.0 Hz), 1.01 (d, 3 H, J ) 6.7 Hz), 2.25-2.48 (m, 1 H), 2.68
(dd, 1 H, J ) 11.7, 19.7 Hz), 3.04 (dd, 1 H, J ) 7.7, 19.7 Hz),
3.47-3.68 (m, 1 H), 4.06 (t, 1 H, J ) 11.9 Hz), 4.21 (d, 2 H, J
) 5.2 Hz), 4.34-4.48 (m, 1 H), 5.52 (d, 1 H, J ) 11.9 Hz), 7.10-
7.32 (m, 10 H). 13C NMR (CDCl3) δ 13.99 (q), 17.46 (q), 27.78
(d), 46.22 (t), 47.28 (d), 51.83 (d), 58.26 (d), 62.33 (d), 62.93
(t), 126.95 (d), 127.12 (d), 127.41 (d), 127.67 (d), 128.51 (d),
138.96 (s), 139.96 (s), 153.85 (s), 167.47 (s), 207.75 (s). Anal.
Calcd for C24H25NO4: C, 73.64; H, 6.44; N, 3.58. Found: C,
73.60; H, 6.45; N, 3.53.
(S)-3-cis-Cin n a m oyl-4-isobu tyl-2-oxa zolid in on e (8). Rf
) 0.35 (hexane-ethyl acetate, 5:1). mp 68-69 °C. [R]20
D
+124 (c 1.10, CHCl3). IR (KBr) 1745, 1685, 1608, 980, 795,
755 cm-1 1H NMR (CDCl3) δ 0.96 (d, 6 H, J ) 6.8 Hz), 1.45-
.
1.66 (m, 2 H), 1.81-1.89 (m, 1 H), 4.12 (dd, 1 H, J ) 3.0, 8.5
Hz), 4.38 (t, 1 H, J ) 8.5 Hz), 4.50-4.59 (m, 1 H), 6.83 (d, 1 H,
J ) 12.7 Hz), 7.00 (d, 1 H, J ) 12.7 Hz), 7.30-7.40 (m, 3 H),
7.50-7.55 (m, 2 H). 13C NMR (CDCl3) δ 21.48 (q), 23.29 (q),
24.66 (d), 41.11 (t), 52.81 (d), 67.50 (t), 120.19 (d), 128.02 (d),
128.95 (d), 129.34 (d), 134.87 (s), 142.32 (d), 153.33 (s), 164.69
(s). Anal. Calcd for C16H19NO3: C, 70.31; H, 7.01; N, 5.12.
Found: C, 70.32; H, 7.05; N, 5.08.
(S,R,S)-2b (Min or ). Rf ) 0.50 (hexane-ethyl acetate, 2:1).
mp 188-190 °C. [R]20 +194 (c 0.50, CHCl3). IR (KBr) 1770,
D
1750, 1680, 770, 750, 700 cm-1
.
1H NMR (CDCl3) δ 0.53 (d, 3
H, J ) 6.2 Hz), 0.79 (d, 3 H, J ) 7.1 Hz), 2.02-2.25 (m, 1 H),
2.69 (dd, 1 H, J ) 10.2, 20.2 Hz), 3.03 (dd, 1 H, J ) 8.1, 20.2
Hz), 3.48-3.70 (m, 1 H), 4.04 (t, 1 H, J ) 12.0 Hz), 4.17 (dd,
1 H, J ) 2.5, 8.2 Hz), 4.32 (t, 1 H, J ) 8.2 Hz), 4.39-4.50 (m,
1 H), 5.57 (d, 1 H, J ) 12.0 Hz), 7.04-7.48 (m, 10 H). 13C
NMR (CDCl3) δ 13.96 (q), 17.37 (q), 28.16 (d), 46.24 (t), 47.45
(d), 53.13 (d), 58.69 (d), 62.12 (d), 63.27 (t), 127.05 (d), 127.22
(d), 127.44 (d), 128.50 (d), 128.57 (d), 138.36 (s), 139.88 (s),
154.08 (s), 167.92 (s), 208.32 (s). Anal. Calcd for C24H25NO4:
C, 73.64; H, 6.44; N, 3.58. Found: C, 73.58; H, 6.42; N, 3.54.
2c (70:30 Mixtu r e of Tw o Dia ster eom er s). Rf ) 0.46,
0.59 (hexane-ethyl acetate, 2:1). IR (KBr) 1780, 1740, 1680,
(S)-3-P h en ylp r op ioloyl-4-isobu tyl-2-oxa zolid in on e (9).
Rf ) 0.35 (hexane-ethyl acetate, 5:1). [R]20 +54.4 (c 2.15,
D
CHCl3). IR (neat) 1780, 1650, 990, 750, 725, 685 cm-1
.
1H
NMR (CDCl3) δ 0.99 (d, 6 H, J ) 6.2 Hz), 1.49-1.71 (m, 2 H),
1.83-1.93 (m, 1 H), 4.15 (dd, 1 H, J ) 2.7, 8.2 Hz), 4.42 (t, 1
H, J ) 8.2 Hz), 4.51-4.60 (m, 1 H), 7.35-7.50 (m, 3 H), 7.64-
7.70 (m, 2 H). 13C NMR (CDCl3) δ 21.58 (q), 23.19 (q), 24.66
(d), 41.21 (t), 52.96 (d), 67.50 (t), 81.16 (s), 93.99 (s), 119.70
(s), 128.46 (d), 130.81 (d), 133.11 (d), 150.49 (s), 152.06 (s).
Anal. Calcd for C16H17NO3: C, 70.83; H, 6.36; N, 5.16.
Found: C, 70.64; H, 6.46; N, 5.00.
750, 700 cm-1 1H NMR (CDCl3) δ 2.60-3.17 (m, 3 H), 3.25-
.
3.43 (m, 1 H), 3.46-3.70 (m, 1 H), 4.00-4.20 (m, 2.7 H), 4.30
(t, 0.3 H, J ) 8.1 Hz), 4.53-4.80 (m, 1 H), 5.52 (d, 1 H, J )
11.0 Hz), 6.78-6.92 (m, 0.6 H), 6.95-7.40 (m, 14.4 H).
(S,R,S)-2d (Ma jor ). Rf ) 0.53 (hexane-ethyl acetate, 2:1).
mp 186-188 °C. [R]20D -37.0 (c 1.00, CHCl3). IR (KBr) 1770,
(S )-3-t r a n s-Cin n a m oyl-4-isob u t yl-2-oxa zolid in e t h -
ion e (11a ). Rf ) 0.35 (hexane-ethyl acetate, 2:1). mp 53-
54 °C. [R]20 +166 (c 2.24, CHCl3). IR (KBr) 1677, 1612, 750
D
cm-1
.
1H NMR (CDCl3) δ 0.92 (d, 3 H, J ) 6.8 Hz), 0.96 (d, 3
H, J ) 7.0 Hz), 2.44-2.50 (m, 1 H), 4.43-4.50 (m, 2 H), 4.76-
4.82 (m, 1 H), 7.39-7.42 (m, 3 H), 7.59-7.63 (m, 2 H), 7.75 (d,
1 H, J ) 15.7 Hz), 8.44 (d, 1 H, J ) 15.7 Hz). 13C NMR (CDCl3)
δ 14.82 (q), 18.10 (q), 28.82 (d), 63.34 (d), 67.89 (t), 118.81 (d),
128.41 (d), 128.75 (d), 130.47 (d), 134.53 (s), 145.01 (d), 166.26
(s), 186.33 (s). Anal. Calcd for C15H17NO2S: C, 65.43; H, 6.22;
N, 5.09. Found: C, 65.50; H, 6.29; N, 5.01.
1740, 1690, 760, 745, 710, 695 cm-1 1H NMR (CDCl3) δ 2.60
.
(dd, 1 H, J ) 12.1, 18.8 Hz), 3.01 (dd, 1 H, J ) 8.0, 18.8 Hz),
3.45-3.67 (m, 1 H), 4.00 (t, 1 H, J ) 12.1 Hz), 4.21 (dd, 1 H,
J ) 5.2, 8.8 Hz), 4.63 (t, 1 H, J ) 8.8 Hz), 5.33 (dd, 1 H, J )
5.2, 8.8 Hz), 5.50 (d, 1 H, J ) 12.1 Hz), 7.02-7.50 (m, 15 H).
13C NMR (CDCl3) δ 46.39 (t), 47.47 (d), 51.54 (d), 57.90 (d),
62.49 (d), 69.81 (t), 125.95 (d), 127.08 (d), 127.26 (d), 127.46
(d), 127.78 (d), 128.63 (d), 129.23 (d), 138.,40 (s), 139.02 (s),
139.87 (s), 153.78 (s), 166.90 (s), 207.24 (s). Anal. Calcd for
(S )-3-t r a n s-Cin n a m oyl-4-isob u t yl-2-t h ia zolid in e t h -
ion e (11b). Rf ) 0.5 (hexane-ethyl acetate, 5:1). [R]20D +222
(c 3.37 CHCl3). IR (neat) 1674, 1614, 758 cm-1
.
1H NMR
C27H23NO4: C, 76.22; H, 5.45; N, 3.29. Found: C, 76.16; H,
(CDCl3) δ 1.03 (d, 3 H, J ) 6.5 Hz), 1.07 (d, 3 H, J ) 7.0 Hz),
2.47-2.55 (m, 1 H), 3.13 (dd, 1 H, J ) 2.7, 11.3 Hz), 3.56 (dd,
1 H, J ) 8.2, 11.3 Hz), 5.06-5.12 (m, 1 H), 7.37-7.39 (m, 4
H), 7.53-7.56 (m, 1 H), 7.66 (d, 1 H, J ) 15.6 Hz), 7.93 (d, 1
H, J ) 15.6 Hz). 13C NMR (CDCl3) δ 16.92 (q), 18.69 (q), 30.37
(d), 30.55 (t), 71.68 (d), 119.91 (d), 128.04 (d), 128.65 (d), 129.99
(d), 134.39 (s), 143.19 (d), 166.36 (s), 202.23 (s). Anal. Calcd
for C15H17NOS2: C, 61.82; H, 5.88; N, 4.81. Found: C, 61.96;
H, 5.93; N, 4.65.
5.48; N, 3.24.
(R,S,R)-2d (Min or ). Rf ) 0.44 (hexane-ethyl acetate,
2:1). mp 168-170 °C. [R]20 -184 (c 1.00, CHCl3). IR (KBr)
D
1750, 1690, 1660, 760, 700 cm-1
.
1H NMR (CDCl3) δ 2.61 (dd,
1 H, J ) 12.1, 19.1 Hz), 2.95 (dd, 1 H, J ) 8.1, 19.1 Hz), 3.42-
3.64 (m, 1 H), 3.88 (t, 1 H, J ) 11.8 Hz), 4.07 (dd, 1 H, J )
3.4, 8.8 Hz), 4.62 (t, 1 H, J ) 8.8 Hz), 5.38 (dd, 1 H, J ) 3.4,
8.8 Hz), 5.60-5.30 (m, 1 H), 6.67-7.23 (m, 15 H). 13C NMR
(CDCl3) δ 46.59 (t), 47.50 (d), 53.52 (d), 57.64 (d), 62.38 (d),
69.87 (t), 125.37 (d), 127.19 (d), 127.34 (d), 127.55 (d), 127.66
(d), 128.53 (d), 128.70 (d), 129.19 (d), 138.33 (s), 138.43 (s),
139.93 (s), 153.84 (s), 168.07 (s), 208.68 (s). Anal. Calcd for
Gen er a l P r oced u r e for Con sta n t Cu r r en t Electr olysis.
A solution of 1 (1 mmol) and Et4NOTs (1.5 g, 5 mmol) in dry
acetonitrile (16.5 mL) was put into a 40 mL beaker (3 cm
diameter, 6 cm height) equipped with a lead cathode (5 × 5
cm2) and a platinum anode (2 × 2 cm2). Electricity was passed
at a constant current of 0.1 A at room temperature until almost
all of 1 was consumed (ca. 250 c). The mixture was poured
into water (50 mL) and extracted with ether. The cyclized
hydrodimers 2 were isolated as diastereomeric mixtures by
column chromatography on silica gel. Diastereomers of 2b and
2d could be separated by column chromatography and further
purified by recrystallization from hexane-ethyl acetate.
2a (85:15 mixture of two diastereomers). Rf ) 0.22 (hex-
ane-ethyl acetate, 5:1). IR (neat) 1778, 1747, 1693,764, 733,
C
27H23NO4: C, 76.22; H, 5.45; N, 3.29. Found: C, 76.10; H,
5.38; N, 3.19.
2e (75:25 Mixtu r e of Tw o Dia ster eom er s). Rf ) 0.54,
0.59 (hexane-ethyl acetate, 2:1). IR (KBr) 1760, 1680, 760,
700 cm-1
.
1H NMR (CDCl3) δ 0.77 (d, 0.75 H, J ) 6.6 Hz),
0.93 (d, 2.25 H, J ) 6.5 Hz), 2.60-2.80 (m, 1 H), 3.05 (dd, 1 H,
J ) 8.0, 19.0 Hz), 3.50-3.69 (m, 1 H), 4.00-4.17 (m, 1 H),
4.67-4.83 (m, 1 H), 5.50 (d, 1 H, J ) 12.8 Hz), 5.57 (d, 0.75 H,
J ) 7.7 Hz), 5.77 (d, 0.25 H, J ) 7.2 Hz), 7.10-7.50 (m, 15 H).
2f (75:25 Mixtu r e of Tw o Dia ster eom er s). Rf ) 0.20,
0.28 (hexane-ethyl acetate, 5:1). IR (KBr) 1770, 1750, 1685,
700 cm-1
.
1H NMR (CDCl3) δ 0.84 (d, 0.45 H, J ) 6.5 Hz),
830 cm-1 1H NMR (CDCl3) δ 0.86 (d, 0.75 H, J ) 6.5 Hz),
.
0.87 (d, 0.45 H, J ) 6.2 Hz), 0.94 (d, 2.55 H, J ) 5.9 Hz), 0.96
(d, 2.55 H, J ) 5.9 Hz), 1.48-1.67 (m, 2 H), 1.72-1.88 (m, 1
H), 2.60-2.77 (m, 1 H), 2.93-3.07 (m, 1 H), 3.46-3.62 (m, 1
H), 4.00-4.12 (m, 2 H), 4.27 (t, 0.85 H, J ) 8.3 Hz), 4.35-
4.53 (m, 1.15 H), 5.50 (d, 1 H, J ) 10.9 Hz), 7.10-7.32 (m, 10
0.88 (d, 0.75 H, J ) 6.5 Hz), 0.94 (d, 2.25 H, J ) 6.2 Hz), 0.96
(d, 2.25 H, J ) 5.1 Hz), 1.30-1.90 (m, 3 H), 2.54-2.78 (m 1
H), 2.86-3.06 (m, 1 H,), 3.37-3.58 (m, 1 H), 3.90-4.03 (m, 1
H), 4.05-4.17 (m, 1 H), 4.27-4.51 (m, 2 H), 5.32-5.55 (m, 1
H), 6.86-6.98 (m, 4 H), 7.04-7.17 (m, 4 H).

Hydrocoupling of 3-trans-Cinnamoyloxazolidinones
J . Org. Chem., Vol. 63, No. 22, 1998 7937
2g (65:35 Mixtu r e of Tw o Dia ster eom er s). Rf ) 0.60
(hexane-ethyl acetate, 2:1). IR (neat) 1770, 1740, 1685, 745
4g (38% ee). Rf ) 0.57 (hexane-ethyl acetate, 2:1); [R]20
D
+13.4 (c 1.78, CHCl3). IR (neat) 1739, 1732, 754 cm-1
.
1H
cm-1
.
1H NMR (CDCl3) δ 0.84 (d, 1.05 H, J ) 6.5 Hz), 0.88 (d,
NMR (CDCl3) δ 2.61-2.77 (m, 4 H), 3.51 (s, 6 H), 3.75 (s, 6
H), 4.01-4.13 (m, 2 H), 6.65-6.75 (m, 6 H), 7.03-7.10 (m, 2
H). 13C NMR (CDCl3) δ 37.05 (t), 39.01 (d), 51.25 (q), 55.11
(q), 110.15 (d), 119.60 (d), 127.28 (d), 129.39 (s), 129.59 (d),
157.35 (s), 173.02 (s). Anal. Calcd for C22H26O6: C, 68.38; H,
6.78. Found: C, 68.55; H, 6.90.
1.05 H, J ) 6.2 Hz), 0.93 (d, 1.95 H, J ) 5.9 Hz), 0.95 (d, 1.95
H, J ) 6.5 Hz), 1.25-1.85 (m, 3 H), 2.58-2.73 (m, 1 H), 2.87-
3.01 (m, 1 H), 3.66 (s, 1.95 H), 3.67 (s, 1.05 H), 3.75 (s, 3 H),
3.57-3.87 (m, 1 H), 4.00-4.30 (m, 2 H), 4.34-4.53 (m, 2 H),
5.56-6.00 (m, 1 H), 6.72-6.88 (m, 4 H), 7.07-7.28 (m, 4 H).
2h (70:30 Mixtu r e of Tw o Dia ster eom er s). Rf ) 0.60
(hexane-ethyl acetate, 2:1). IR (neat) 1780, 1747, 1693, 735,
4h (44% ee). Rf ) 0.58 (hexane-ethyl acetate, 2:1). [R]20
D
-9.7 (c 5.4, CHCl3). IR (neat) 1750, 1732, 785, 702 cm-1 1H
.
700 cm-1 1H NMR (CDCl3) δ 0.86 (d, 0.9 H, J ) 6.2 Hz), 0.88
.
NMR (CDCl3) δ 2.55-2.78 (m, 4 H), 3.42-3.53 (m, 2 H), 3.57
(s, 6 H), 3.68 (s, 6 H), 6.41 (t, 2 H, J ) 1.9 Hz), 6.53 (d, 2 H, J
) 7.8 Hz), 6.67-6.74 (m, 2 H), 7.10 (t, 2 H, J ) 7.8 Hz). 13C
NMR (CDCl3) δ 37.34 (t), 46.01 (d), 51.44 (q), 54.87 (q), 112.30
(d), 114.31 (d), 121.07 (d), 128.66 (d), 141.58 (s), 158.96 (s),
172.28 (s). Anal. Calcd for C22H26O6: C, 68.38; H, 6.78.
Found: C, 68.49; H, 6.83.
(d, 0.9 H, J ) 6.5 Hz), 0.94 (d, 2.1 H, J ) 6.2 Hz), 0.96 (d, 2.1
H, J ) 5.9 Hz), 1.25-1.80 (m, 3 H), 2.57-2.75 (m, 1 H), 2.92-
3.06 (m, 1 H), 3.42-3.60 (m, 1 H), 3.69 (s, 3 H), 3.71 (s, 3 H),
3.95-4.13 (m, 2 H), 4.30 (t, 0.7 H, J ) 8.2 Hz), 4.37-4.55 (m,
1.3 H), 5.30-5.56 (m, 1 H), 6.62-6.81 (m, 6 H), 7.06-7.20 (m,
2 H).
4i (67% ee). Rf ) 0.53 (hexane-ethyl acetate, 2:1). [R]20
D
2i (80:20 Mixtu r e of Tw o Dia ster eom er s). Rf ) 0.56
(hexane-ethyl acetate, 2:1). IR (neat) 1770, 1740, 1680, 1605,
+33.5 (c 1.60, CHCl3). IR (neat) 1750, 1732, 1717, 814 cm-1
.
1H NMR (CDCl3) δ 2.48-2.60 (m, 2 H), 2.63-2.75 (m, 2 H),
3.35-3.47 (m, 2 H), 3.55 (s, 6 H), 3.75 (s, 6 H), 6.69-6.80 (m,
8 H). 13C NMR (CDCl3) δ 37.93 (t), 45.42 (d), 51.39 (q), 54.97
(q), 113.13 (d), 129.73 (d), 131.89 (s), 158.23 (s), 172.48(s). Anal.
Calcd for C22H26O6: C, 68.38; H, 6.78. Found: C, 68.44; H,
6.80.
825, 745 cm-1 1H NMR (CDCl3) δ 0.86 (d, 0.6 H, J ) 6.5 Hz),
.
0.88 (d, 0.6 H, J ) 6.2 Hz), 0.93 (d, 2.4 H, J ) 5.9 Hz), 0.95 (d,
2.4 H, J ) 5.9 Hz), 1.40-1.87 (m, 3 H), 2.52-2.71 (m, 1 H),
2.87-3.03 (m, 1 H), 3.37-3.52 (m, 1 H), 3.71 (s, 2.4 H), 3.72
(s, 0.6 H), 3.73 (s, 3 H), 3.87-4.16 (m, 2 H), 4.28 (t, 0.8 H, J )
8.2 Hz), 4.36-4.51 (m, 1.2 H), 5.30-5.53 (m, 1 H), 6.70-6.81
(m, 4 H), 7.00-7.12 (m, 4 H).
4j (12% ee). Rf ) 0.61 (hexane-ethyl acetate, 2:1). mp
123-124 °C. [R]20 -9.5 (c 2.1, CHCl3). IR (KBr) 1730, 780
D
2j (60:40 Mixtu r e of Tw o Dia ster eom er s). Rf ) 0.60
cm-1
.
1H NMR (CDCl3) δ 2.75-3.00 (m, 4 H), 3.35 (s, 6 H),
(hexane-ethyl acetate, 2:1). IR (KBr) 1770, 1740, 1680, 790,
4.52-4.76 (m, 2 H), 7.18-7.76 (m, 12 H), 8.31 (d, 2 H, J ) 8.4
Hz). 13C NMR (CDCl3) δ 37.68 (t), 39.69 (d), 51.39 (q), 123.27
(d), 124.74 (d), 125.33 (d), 125.86 (d), 127.28 (d), 128.80 (d),
131.84 (s), 133.89 (s), 137.91 (s), 172.43 (s). Anal. Calcd for
770 cm-1 1H NMR (CDCl3) δ 0.65 (d, 1.2 H, J ) 5.7 Hz), 0.73
.
(d, 1.2 H, J ) 6.2 Hz), 0.80-1.05 (m, 3.6 H), 1.35-1.85 (m, 3
H), 2.55-2.98 (m, 1 H), 3.10-3.47 (m, 1 H), 3.70-4.83 (m, 4
H), 5.53-5.84 (m, 1 H), 7.22-8.30 (m, 14 H).
C
28H26O4: C, 78.85; H, 6.14. Found: C, 78.67; H, 6.21.
Syn th esis of Au th en tic Sa m p le of (S,S)-4a . To an ice-
10. Rf ) 0.33 (hexane-ethyl acetate, 2:1). mp 185-186
°C. [R]20 +33.8 (c 0.37, CHCl3). IR (KBr) 1763, 1697, 755,
D
cooled solution of (2S,3S)-diphenylsuccinic acid (1.0 g, 3.7
mmol), prepared by our method (>98% ee),8c in THF (15 mL)
was added LAH (0.42 g, 11 mmol) and the suspension was
stirred at room temperature for 24 h. After the usual workup,
the crude diol (0.75 g) was treated with TsCl (1.7 g, 8.9 mmol)
in pyridine (10 mL) at 5 °C for 3 h. The mixture was diluted
with 1 M HCl (50 mL) and extracted with ether. The crude
ditosylate (1.3 g) was stirred with NaCN (0.49 g, 10 mmol) in
dry DMF (20 mL) at room temperature for 24 h. The mixtures
were diluted with sat. NaCl(aq)(60 mL) and extracted with
ether. The crude dinitrile (0.31 g) was refluxed with Ba(OH)2
(1.0 g) in water (20 mL) for 12 h. After filtration, the aqueous
solution was acidfied with concentrated HCl and extracted
with CH2Cl2. The crude diacid (0.25 g) was dissolved in sat.
HCl-MeOH, and the solution was stirred for 12 h at room
temperature. After removal of the solvent, (S,S)-4a was
isolated by column chromatography on silica gel (0.16 g, 13%
697 cm-1
.
1H NMR (CDCl3) δ 0.90 (d, 6 H, J ) 6.2 Hz), 0.91
(d, 6 H, J ) 6.5 Hz), 1.20-1.32 (m, 2 H), 1.35-1.63 (m, 4 H),
3.82-4.00 (m, 6 H), 4.16 (t, 2 H, J ) 8.4 Hz), 4.28-4.33 (m, 2
H), 7.22-7.40 (m, 10 H). 13C NMR (CDCl3) δ 21.72 (q), 23.29
(q), 24.61 (d), 41.16 (t), 42.29 (t), 52.91 (d), 67.35 (t), 127.24
(d), 127.63 (d), 128.61 (d), 134.97 (s), 141.24 (s), 170.42 (s).
Anal. Calcd for C32H38N2O6: C, 70.31; H, 7.01; N, 5.12.
Found: C, 70.16; H, 7.10; N, 4.98.
Gen er a l P r oced u r e for Meth a n olysis of Cyclized Hy-
d r od im er s 2. To a solution of sodium methoxide (2.2 mmol)
in MeOH (20 mL) was added a solution of 2 (1 mmol) in MeOH
(5 mL) at 0 °C, and the temperature was allowed to equilibrate
to room temperature. After being stirred for 8 h, the mixture
was neutralized with 1 N HCl, diluted with sat. NaCl (aq),
and then extracted with ether. Dimethyl esters 4 were isolated
by column chromatography on silica gel (hexane-ethyl
1
acetate). Enantioselectivity in 4 was determined by H NMR
total yield): [R]20 -17.1 (c 1.05, CHCl3).
D
analysis with Eu(hfc)3. The enantiomeric excess of 4a was
alternatively measured by chiral HPLC analysis: column,
Chiralpak OT (Daicel Chemical Ind., Ltd); eluent, methanol;
flow rate, 0.50 L/min; column temperature, 0 °C; detection,
284 nm; retention times, 15.3 min for (S,S)-4a and 18.2 min
for (R,R)-4a . Optically pure enantiomers of 4a were obtained
from the separated diastereomers of 2b and 2d .
Hyd r olysis of 2a . A 85:15 diastereomeric mixture of 2a
(406 mg, 1 mmol) was refluxed in 48% HBr (4 mL) and EtOH
(5 mL) for 6 h. After cooling, the mixture was diluted with
NaCl(aq)(30 mL) and extracted with ether. A 199 mg amount
of trans-3,4-diphenylcyclopentanone 5 was isolated by column
chromatography on silica gel (84% yield). The enantiomeric
excess of 5 was determined on the basis of the reported value
of the optical rotation for the enantiomer of 5 (lit.7 219).
(R,R)-5 (72% ee). Rf ) 0.45 (hexane-ethyl acetate, 5:1).
(R,R)-4a (>98% ee). Rf ) 0.30 (hexane-ethyl acetate,
5:1). [R]20 +17.4 (c 2.10, CHCl3). IR (neat) 1725, 700 cm-1
.
D
1H NMR (CDCl3) δ 2.54-2.81 (m, 4 H), 3.42-3.58 (m, 2 H),
3.55 (s, 6 H), 6.82-6.96 (m, 4 H), 7.10-7.24 (m, 6 H). 13C NMR
(CDCl3) δ 37.47 (t), 46.14 (d), 51.52 (q), 126.86 (d), 127.98 (d),
128.90 (d), 140.19 (s), 172.76 (s). Anal. Calcd for C20H22O4:
C, 73.60; H, 6.79. Found: C, 73.55; H, 7.78.
mp 162-165 °C. [R]20 -156 (c 2.06, CHCl3). IR (KBr) 1735,
D
760, 695 cm-1
.
1H NMR (CDCl3) δ 2.48-2.67 (m, 2 H), 2.79-
2.96 (m, 2 H), 3.40-3.56 (m, 2 H), 7.08-7.28 (m, 10 H). 13C
NMR (CDCl3) δ 47.17 (t), 50.11 (d), 126.84 (d), 127.19 (d),
128.56 (d), 140.85 (s), 215.74 (s). Anal. Calcd for C17H16O:
C, 86.41; H, 6.82. Found: C, 86.32; H, 6.85.
(S,S)-4a (>98% ee). [R]20 -17.3 (c 1.00, CHCl3).
D
4f (54% ee). Rf ) 0.62 (hexane-ethyl acetate, 2:1). [R]20
Red u ction of 5. To a solution of 5 (118 mg, 0.5 mmol) in
EtOH (5 mL) was added NaBH4 (57 mg, 1.5 mmol) at room
temperature. After being stirred for 30 min, the mixture was
diluted with NaCl(aq)(30 mL) and extracted with ether. A 113
mg amount of 3,4-diphenylcyclopentanol 6 was isolated by
column chromatography on silica gel (95% yield). The enan-
tiomeric excess of 6 was measured by chiral HPLC analysis:
column, Chiralpak OT (Daicel Chemical Ind., Ltd); eluent,
D
+7.1 (c 2.0, CHCl3). IR (neat) 1750, 1732, 837 cm-1
.
1H NMR
(CDCl3) δ 2.52-2.63 (m, 2 H), 2.68-2.79 (m, 2 H), 3.38-3.49
(m, 2 H), 3.56 (s, 6 H), 6.76-7.12 (m, 8 H). 13C NMR (CDCl3)
δ 38.12 (t), 45.62 (d), 51.59 (q), 114.70 (d, J CCF ) 19.8 Hz),
130.03 (d, J CCCF ) 6.6 Hz), 135.56 (s), 161.56 (s, J CF ) 244.6
Hz), 172.09 (s). Anal. Calcd for C20H20O4F2: C, 66.29; H, 5.56.
Found: C, 66.36; H, 5.59.

7938 J . Org. Chem., Vol. 63, No. 22, 1998
Kise et al.
methanol; flow rate, 0.50 L/min; column temperature, 0 °C;
detection, 284 nm; retention times, 9.3 min for (S,S)-6 and 10.6
min for (R,R)-6.
water (3 mL) was added LiOH‚H2O (0.21 g, 5 mmol) and 30%
H2O2 (1 mL) successively. The mixture was stirred for 24 h
at room temperature and then quenched with 1.5 M Na2SO3
(4 mL) at 0 °C. After the addition of 1 M HCl (10 mL), the
mixture was extracted with CH2Cl2. The crude diacid was
dissolved in sat. HCl-MeOH, and the solution was stirred for
12 h at room temperature. After removal of the solvent, dl-
and meso-4a were isolated by column chromatography on silica
gel (38 and 34 mg, respectively, 44% total yield from 1a ). The
enantiomeric excess of dl-4a was measured by 1H NMR
analysis with Eu(hfc)3.
(R,R)-6 (74% ee). Rf ) 0.50 (hexane-ethyl acetate, 2:1).
mp 65-66 °C. [R]20 -112 (c 5.07, CHCl3). IR (KBr) 3250,
D
750, 690 cm-1
.
1H NMR (CDCl3) δ 1.72 (brs, 1 H), 1.84-1.96
(m, 1 H), 2.06-2.27 (m, 2 H), 2.62-2.76 (m, 1 H), 3.11 (dd, 1
H, J ) 9.2, 19.7 Hz), 3.40-3.55 (m, 1 H), 4.55-4.63 (m, 1 H),
7.06-7.25 (m, 10 H). 13C NMR (CDCl3) δ 44.78 (t), 51.34 (d),
52.52 (d), 71.81 (d), 125.96 (d), 127.24 (d), 127.53 (d), 128.22
(d), 143.00 (s), 143.59 (s). Anal. Calcd for C17H18O: C, 85.67;
H, 7.61. Found: C, 85.64; H, 7.61.
Electr or ed u ction of 1a in LiClO4-THF . A solution of
1a (272 mg, 1 mmol) and LiClO4 (3.0 g, 28 mmol) in dry THF
(16.5 mL) was put into a 40 mL beaker (3 cm diameter, 6 cm
height) equipped with a lead cathode (5 × 5 cm2) and a
platinum anode (2 × 2 cm2). Electricity was passed at a
constant current of 0.1 A at room temperature until almost
all of 1 was consumed (ca. 300 c). The mixture was poured
into water (50 mL) and extracted with ether. The product 7a
was isolated as a diastereomeric mixture by column chroma-
tography on silica gel (145 mg). Rf ) 0.40-0.65 (hexane-
ethyl acetate, 2:1). 1H NMR (CDCl3) δ 0.7-1.2 (m, 12 H), 1.2-
2.1 (m, 6 H), 2.6-4.7 (m, 12 H), 6.6-7.8 (m, 10 H). Although
the isolated 7a was contaminated by small amounts of impuri-
ties, it was subjected to hydrolysis without further purification.
Hyd r olysis of 7a . To an ice-cooled solution of a diastere-
omeric mixture of 7a (145 mg) in THF (4 mL) and distilled
m eso-4a . Rf ) 0.40 (hexane-ethyl acetate, 5:1). mp 174-
177 °C (lit.12b 175-177 °C). IR (KBr) 1725, 705 cm-1 1H NMR
.
(CDCl3) δ 2.30-2.54 (m, 4 H), 3.22-3.40 (m, 2 H), 3.36 (s, 6
H), 7.02-7.46 (m, 10 H). 13C NMR (CDCl3) δ 39.60 (t), 47.59
(d), 51.20 (q), 127.23 (d), 128.25 (d), 128.80 (d), 141.86 (s),
172.65 (s).
Su p p or tin g In for m a tion Ava ila ble: Optimized confor-
mations of anion radicals C-F obtained by semiempirical
calculations (2 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 O981231F