Diastereoselective dl-Hydrocoupling of Benzalacetones by Electroreduction

Article abstract of DOI:10.1021/jo035280q

Electroreduction of benzalacetones with an undivided cell in Et ₄NOTs/acetonitrile gave cyclized dl-hydrodimers as mixtures of two diastereomers. The hydrodimerization proceeded stereoselectively to afford linear dl-hydrodimers, and the following cyclization led to two thermodynamically stable diasteromers of cyclopentanols.

Full text of DOI:10.1021/jo035280q

Dia ster eoselective d l-Hyd r ocou p lin g of Ben za la ceton es by
Electr or ed u ction
Naoki Kise,* Yasuo Kitagishi, and Nasuo Ueda
Department of Biotechnology, Faculty of Engineering, Tottori University,
Koyama, Tottori 680-8552, J apan
kise@bio.tottori-u.ac.jp
Received September 2, 2003
Electroreduction of benzalacetones with an undivided cell in Et4NOTs/acetonitrile gave cyclized
dl-hydrodimers as mixtures of two diastereomers. The hydrodimerization proceeded stereoselectively
to afford linear dl-hydrodimers, and the following cyclization led to two thermodynamically stable
diasteromers of cyclopentanols.
SCHEME 1
In tr od u ction
The electroreduction of cinnamic acid esters in aprotic
media is well-known to give all-trans cyclized hydro-
dimers stereoselectively.1 In addition, it has been re-
ported that the reductive coupling of chalcones by chemi-
cal2 and electrochemical methods3 also produced cyclic
dl-hydrodimers, cyclopentanols, stereoselectively (Scheme
1). On the other hand, the reductive dimerization of
benzalacetones with Yb metal did not give cyclopentanols
but cyclohexanones,2a and that with TiCl4-Zn led to linear
hydrodimers and pinacols.2c The reduction of aliphatic
R,â-unsaturated ketones with Yb-TMSBr afforded linear
hydrodimers albeit nonstereoselectively.4 To the best of
our knowledge, the reductive hydrodimerization of ben-
zalacetones to furnish cyclopentanols stereoselectively
has not so far been realized. We report herein that the
electroreduction of benzalacetones using an undivided
cell gave cyclic hydrodimers with extremely high dl-
stereoselectivity (Scheme 2). We calculated the transition
states for the hydrocoupling of benzalacetones with
semiempirical methods to elucidate the high dl-selectiv-
ity. The product cyclopentanols were formed as mixtures
of two diastereomers. Their stereostructures were con-
firmed by X-ray crystallographic analysis. We further-
more disclosed that the cyclization step from the linear
dl-hydrodimers to cyclopentanols is governed by ther-
modynamic control.
SCHEME 2
Resu lts a n d Discu ssion
The reaction conditions for the constant current elec-
trolysis of benzalacetone 1 at 125 mA were surveyed and
the results are summarized in Table 1. The electrore-
duction of 1 was carried out under the conditions by
which the best result was obtained in the hydrocoupling
of methyl cinnamate,1g that is, in 0.3 M Et4NOTs/
acetonitrile with a Pb cathode and an undivided cell (run
1). In this case also, the best yield of the cyclic hy-
drodimer 2 (80%) was attained under the same condi-
tions. Of eight possible diastereomers, 2 was obtained as
a mixture of two stereoisomers 2a (major) and 2b (minor).
In addition to 2, small amounts of saturated ketone
(<10%) and linear hydrodimer (<3%) were detected. The
electroreductive hydrodimerization of 1 was little affected
by currents in the range of 50 to 150 mA (at 50 mA,: 72%
yield of 2; at 75 mA, 75%; at 100mA, 78%; at 150 mA,
70%). As a cathode material, Au, Ag, and Cu afforded
comparative results to Pb (runs 2-4). Other cathode
materials Zn, Sn, and Pt except for Al produced 2,
although the yields somewhat decreased (runs 5-8).
Acetonitrile and Et4NOTs were the best choice of a
solvent and a supporting electrolyte, respectively (com-
pare run 1 with runs 9-16). By employing LiClO4 as a
supporting electrolyte, a complex mixture was formed
and the hydrodimers were scarcely produced (run 17). It
should be noted that the use of an undivided cell was
required for the reductive hydrocoupling of 1. When the
(1) (a) Klemm, L. H.; Olson, D. R. J . Org. Chem. 1973, 58, 3390-
3394. (b) Kanetsuna, H.; Nonaka, T. Denki Kagaku 1981, 49, 526-
531. (c) Smith, C. Z.; Utley, H. P. Chem. Commun. 1981, 492-494. (d)
Nishiguchi, I.; Hirashima, T. Angew. Chem., Int. Ed. Engl. 1983, 22,
52-53. (e) Utley, J . H. P.; Gu¨llu¨, M.; Motevalli, M. J . Chem. Soc.,
Perkin Trans. 1 1995, 1961-1970. (f) Kise, N.; Mashiba, S.; Ueda, N.
J . Org. Chem. 1998, 63, 7931-7938. (g) Kise, N.; Iitaka, S.; Iwasaki,
K.; Ueda, N. J . Org. Chem. 2002, 67, 8305-8315.
(2) (a) Takaki, K.; Beppu, F.; Tanaka, S.; Tsubaki, Y.; J intoku, T.;
Fujiwara, Y. Chem. Commun. 1990, 516-517. (b) Takaki, K.; Nagase,
K.; Beppu, F.; Fujiwara, Y. Chem. Lett. 1991, 1665-1668. (c) Zhou,
L.; Shi, D.; Gao, Y.; Shen, W.; Dai, G.; Chen, W. Tetrahedron Lett. 1997,
38, 2729-2732.
(3) Utley, J . H. P.; Smith, C. Z.; Motevalli, M. J . Chem. Soc., Perkin
Trans. 2 2000, 1053-1057.
(4) Taniguchi, Y.; Nakahashi, M.; Kuno, T.; Tsuno, M.; Makioka,
Y.; Takaki, K.; Fujiwara, Y. Tetrahedron Lett. 1994, 35, 4111-4114.
10.1021/jo035280q CCC: $27.50 © 2004 American Chemical Society
Published on Web 01/14/2004
J . Org. Chem. 2004, 69, 959-963
959

Kise et al.
CH3CO
TABLE 1. Electr or ed u ction of Ben za la ceton e (1)
TABLE 3. 1H NMR Ch em ica l Sh iftsa of 2-8
a
1-CH3
CH3CO
b
1-CH3
2a
3a
4a
5a
6a
7a
8a
1.51
1.57
1.50
1.50
1.62
1.58
1.47
1.85
1.76
1.88
1.89
1.71
1.83
2.02
2b
3b
4b
5b
6b
7b
8b
1.42
1.39
1.41
1.41
1.47
1.49
1.34
2.15
2.14
2.16
2.17
2.12
2.17
2.24
% yield of 2b
(2a + 2b)
run
cathode
solventa
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18c
19d
20e
Pb
Au
Ag
Cu
Zn
Sn
Pt
Et4NOTs/CH 3CN
Et4NOTs/CH 3CN
Et4NOTs/CH 3CN
Et4NOTs/CH 3CN
Et4NOTs/CH3CN
Et4NOTs/CH 3CN
Et4NOTs/CH3CN
Et4NOTs/CH 3CN
Et4NOTs/DMF
80 (46 + 34)
72 (42 + 30)
73 (42 + 31)
74 (40 + 34)
58 (34 + 24)
51 (30 + 21)
45 (26 + 19)
trace
39 (20 + 19)
30 (17 + 13)
36 (24 + 12)
53 (31 + 22)
47 (26 + 21)
43 (28 + 15)
42 (25 + 17)
45 (28 + 17)
trace
a
The chemical shifts (δ) of methyl protons (singlet).
SCHEME 3
Al
Pb
Pb
Pb
Pb
Pb
Pb
Pb
Pb
Pb
Pb
Pb
Pb
Bu4NClO4/DMF
Bu4NClO4/THF
Et4NBF4/CH3 CN
Et4NClO4/CH3CN
Bu4NBF4/CH 3CN
Bu4NClO4/CH 3CN
Bu4NPF6/CH 3CN
LiClO4/CH3CN
Et4NOTs/CH 3CN
Et4NOTs/CH 3CN
Et4NOTs/CH 3CN
trace
45 (27 + 18)
trace
a
b
0.3 M electrolyte in solvent. Isolated yields. c With a divided
cell. With a Zn anode. e With a Mg anode.
d
TABLE 2. Electr or ed u ction of Ben za la ceton es
SCHEME 4
% yielda
run
Ar
compd no.
(a + b)
1
2
3
4
5
6
p-MeOC6H4
p-FC6H4
3,4-(MeO)2C6H3
R-naphthyl
â-naphthyl
1-furyl
3
4
5
6
7
8
74 (44 + 30)
80 (48 + 32)
47 (27 + 20)
64 (38 + 26)
70 (40 + 30)
74 (41 + 33)
a
Isolated yields.
reduction of 1 was carried out with a divided cell, a
complex mixture was given probably due to the conden-
sation of the starting 1 (run 18). In addition, the use of
Zn or Mg as an anode significantly lowered the yield of
2 (runs 19 and 20). In particular, only complex mixture
was obtained with a Mg anode.
The hydrodimerization of other benzalacetones was
effected by electroreduction under the same conditions
as run 1 in Table 1, and the results are depicted in Table
2. In all cases, the corresponding cyclic hydrodimers were
obtained in moderate to good yields as mixtures of two
diastereomers.
The stereostructure of 2a (major) was determined to
be 1R*,2S*,3R*,4S* by X-ray crystallography, but 2b
(minor) did not form an analyzable single crystal. Thus,
we tried an X-ray crystallographic analysis of the other
cyclic hydrodimers shown in Table 2. Fortunately, R-naph-
thyl derivatives 6a and 6b afforded single crystals and
their structures were undoubtedly confirmed to be
1R*,2S*,3R*,4S* and 1S*,2S*,3R*,4S*, respectively. The
same stereostructures for the other cyclic hydrodimers
1
were assumed by H NMR correlation with 6 (Table 3).
These results disclose that both isomers of the cyclic
hydrodimers come from linear dl-hydrodimers, namely,
the dl-hydrodimers were formed predominantly.
Interestingly, each isomer of 2 isomerized slowly by
treatment with t-BuOK in THF at room temperature to
give a mixture of 2a and 2b together with dehydrated
product 9 after 3 days (Scheme 3). Moreover, treatment
of trimethylsilyl ether of each isomer of 2 (2a ′ and 2b′)
with Bu4NF in THF at room temperature reached equi-
librium within 1 h (Scheme 4). These observations imply
that the cyclization from linear dl-hydrodimer to the
cyclic hydrodimers is subject to thermodynamic control.
960 J . Org. Chem., Vol. 69, No. 3, 2004

dl-Hydrocoupling of Benzalacetones by Electroreduction
SCHEME 5
Rea ction Mech a n ism . The reaction mechanism of the
electroreductive hydrocoupling of 1 can be presumed to
be as illustrated in Scheme 5. Anion radicals 10 gener-
ated from 1 by one-electron transfer couple each other
to give a dianion of linear dl-hydrodimer (11). Since it
is likely that the high dl-selectivity is determined
kinetically,1e,g,3 we calculated the transition states for the
homocoupling of 10 by semiempirical methods (Figure
1).5,6 The results of calculations suggest that the transi-
tion states leading to dl-hydrodimer are more stable than
those to meso-hydrodimer and, therefore, well explain the
high dl-selectivity despite low-level methods.7 Next, the
dienolate anion 11 was protonated to monoenolate anion
12 and then the enolate anion 12 immediately cyclized
to O-anion 13 via an intramolecular aldol condensation
process. From the experimental results as shown in
Schemes 3 and 4, the formation of the stereoisomers of
2 seems to be determined by equilibrium between stere-
oisomers of the O-anion 13 in the cyclization step from
12. Thus, preliminary calculations for the four possible
stereoisomers of 13 were performed by the RHF/AM1
method to evaluate their thermodynamic stability (Figure
2).5,8 These computational results are in accordance with
the experimental observations. Thus, 13a is slightly more
stable than 13b, and these isomers 13a and 13b are
much more stable than the other isomers 13c and 13d .
F IGURE 1. Optimized structures of transition states for the
hydrocoupling of anion radicals 10 to 11.
(5) The calculations were carried out with use of 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., J r.; 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.; Gomperts, R.;
Martin, R. L.; Fox, D. J .; Keith, T.; Al-Laham, M. A.; Peng, C. Y.;
Nanayakkara, A.; Challacombe, M.; Gill, P. M. W.; J ohnson, 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.
F IGURE 2. Optimized structures and relative free energies
of four isomers of 13 by the RHF/AM1 method.
Con clu sion
(6) It was confirmed that the optimized structures had only one
imaginary frequency according to the vibration analysis. The imaginary
frequency was verified to be consistent with the intermolecular
homocoupling by displaying the vibrational mode with the Gauss View
program.
(7) Ab initio and DFT calculations for optimization of the transition
states have not been successful so far.
(8) It was confirmed that the optimized structures had no imaginary
frequency according to the vibration analysis. The relative free energies
shown in Figure 4 were based on the values after thermal correction.
This paper describes that the reductive hydrodimer-
ization of benzalacetones was efficiently accomplished by
electroreduction, using an undivided cell in Et4NOTs/
acetonitrile to give cyclized hydrodimers as mixtures of
two diastereomers. The electroreductive hydrodimeriza-
tion of benzalacetones gave linear dl-hydrodimers ste-
reoselectively according to kinetic control, and subse-
J . Org. Chem, Vol. 69, No. 3, 2004 961

Kise et al.
4a : Rf 0.35 (hexanes-ethyl acetate, 2:1). Colorless oil. IR
quent cyclization of the linear dl-hydrodimers produced
mixtures of two cyclopentanols under thermodynamic
control.
(neat) 3460, 1699, 1605, 1510, 835, 820, 733 cm-1 1H NMR
.
(CDCl3) δ 1.50 (s, 3 H), 1.88 (s, 3 H), 2.11 (dd, 1 H, J ) 7.0,
14.3 Hz), 2.39 (dd, 1 H, J ) 10.5, 14.3 Hz), 3.12 (d, 1 H, J )
11.9 Hz), 3.20 (dt, 1 H, J ) 7.0, 10.5 Hz), 3.57 (dd, 1 H, J )
10.5, 11.9 Hz), 3.83 (br s, 1 H), 6.83-6.99 (m, 4 H), 7.02-7.18
(m, 4 H). 13C NMR (CDCl3) δ 28.3 (q), 33.1 (q), 49.2 (t), 51,2
(d), 57.3 (d), 67.8 (d), 79.6 (s), 114.9 (d, J CCF ) 21.1 Hz), 115.5
(d, J CCF ) 21.1 Hz), 128.8 (d, J CCCF ) 7.8 Hz), 128.9 (d, J CCCF
) 7.8 Hz), 136.2 (s, J CCCCF ) 2.8 Hz), 138.7 (s, J CCCCF ) 3.3
Hz), 161.3 (s, J CF ) 242.1 Hz), 161.6 (s, J CF ) 243.3 Hz), 212.2
(s). Anal. Calcd for C20H20O2F2: C, 72.71; H, 6.10. Found: C,
72.84; H, 6.18.
Exp er im en ta l Section
Sta r tin g Ma ter ia ls. Benzalacetone (1) is commercially
available. Other benzalacetones in Table 2 were prepared by
reaction of aromatic aldehydes with acetone according to the
reported method.9
Typ ica l P r oced u r e for Con sta n t Cu r r en t Electr olysis.
A solution of benzalacetone (1) (146 mg, 1.0 mmol) and
Et4NOTs (1.5 g, 5.0 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 125 mA
at room temperature until almost all of 1 was consumed (150
C). The mixture was poured into water (50 mL) and extracted
with Et2O. The cyclic hydrodimers 2a (46%) and 2b (34%) were
isolated by column chromatography on silica gel (hexanes-
ethyl acetate). Small amounts of saturated ketone (4-phen-
ylbutane-2-one, <10%) and linear hydrodimer (probably meso,
<3%) were also detected.
4b: Rf 0.3 (hexanes-ethyl acetate, 2:1). Colorless oil. IR
(neat) 3435, 1699, 1605, 1512, 835, 793, 735 cm-1 1H NMR
.
(CDCl3) δ 1.41 (s, 3 H), 1.78 (br s, 1 H), 2.06-2.27 (m, 2 H),
2.16 (s, 3 H), 3.33-3.50 (m, 3 H), 6.84-6.93 (m, 4 H), 7.02-
7.14 (m, 4 H). 13C NMR (CDCl3) δ 26.6 (q), 33.1 (q), 50.1 (d),
50.8 (t), 55.1 (d), 71.1 (d), 79.6 (s), 115.0 (d, J CCF ) 20.6 Hz),
115.2 (d, J CCF ) 20.6 Hz), 128.6 (d, J CCCF ) 7.8 Hz), 129.0 (d,
J CCCF ) 7.8 Hz), 137.1 (s, J CCCCF ) 2.8 Hz), 137.3 (s, J CCCCF
)
3.4 Hz), 161.3 (s, J CF ) 242.2 Hz), 161.4 (s, J CF ) 242.1 Hz),
209.5 (s). Anal. Calcd for C20H20O2F2: C, 72.71; H, 6.10.
Found: C, 72.96; H, 6.21.
2a : Rf 0.6 (hexanes-ethyl acetate, 2:1). White solid. Mp
5a : Rf 0.59 (hexanes-ethyl acetate, 1:2). Pale yellow oil. IR
113-114 °C. IR (KBr) 3449, 1711, 1493, 762, 743, 696 cm-1
.
(neat) 3497, 1701, 1591, 1518, 1464, 914, 808, 764, 733 cm-1
.
1H NMR (CDCl3) δ 1.51 (s, 3 H), 1.85 (s, 3 H), 2.18 (dd, 1 H, J
) 7.3, 13.8 Hz), 2.40 (dd, 1 H, J ) 10.8, 13.8 Hz), 3.17 (d, 1 H,
J ) 11.6 Hz), 3.29 (dt, 1 H, J ) 7.3, 10.8 Hz), 3.65 (dd, 1 H, J
) 10.8, 11.6 Hz), 3.88 (br s, 1 H), 7.08-7.30 (m, 10 H). 13C
NMR (CDCl3) δ 28.4 (q), 33.1 (q), 49.4 (t), 51.7 (d), 58.0 (d),
67.9 (d), 79.7 (s), 126.1 (d), 126.8 (d), 127.4 (d), 127.6 (d), 128.1
(d), 128.5 (d), 140.8 (s), 143.2 (s), 212.9 (s). Anal. Calcd for
1H NMR (CDCl3) δ 1.50 (s, 3 H), 1.89 (s, 3 H), 2.15 (dd, 1 H, J
) 7.0, 14.3 Hz), 2.37 (dd, 1 H, J ) 10.3, 14.3 Hz), 3.12 (d, 1 H,
J ) 11.9 Hz), 3.18 (dt, 1 H, J ) 10.3, 14.3 Hz), 3.52 (dd, 1 H,
J ) 7.0, 10.3 Hz), 3.79 (s, 3 H), 3.80 (s, 3 H), 3.81 (s, 3 H), 3.84
(s, 3 H), 3.97 (br s, 1 H), 6.53-6.88 (m, 6 H). 13C NMR (CDCl3)
δ 28.1 (q), 32.9 (q), 48.8 (t), 51.1 (d), 55.6 (q), 57.6 (d), 67.4 (d),
79.3 (s), 110.6 (d), 111.1 (d), 119.1 (d), 119.4 (d), 133.2 (s), 135.9
(s), 147.1 (s), 147.5 (s), 148.5 (s), 212.7 (s). Anal. Calcd for
C
20H22O2: C, 81.60; H, 7.53. Found: C, 81.58; H, 7.54.
2b: Rf 0.43 (hexanes-ethyl acetate, 2:1). White solid. Mp
C
24H30O6: C, 69.54; H, 7.30. Found: C, 69.47; H, 7.28.
127-128 °C. IR (KBr) 3477, 1688, 1601, 1493, 764, 745, 698
1
cm-1. H NMR (CDCl3) δ 1.42 (s, 3 H), 1.83 (s, 1 H), 2.15 (s, 3
5b: Rf 0.53 (hexanes-ethyl acetate, 1:2). Pale yellow oil. IR
(neat) 3508, 1705, 1591, 1514, 1464, 914, 810, 764, 731 cm-1
.
H), 2.11-2.33 (m, 2 H), 3.40-3.60 (m, 3 H), 7.08-7.23 (m, 10
H). 13C NMR (CDCl3) δ 26.6 (q), 33.0 (q), 50.5 (d), 50.9 (t), 55.5
(d), 71.2 (d), 79.7 (s), 126.2 (d), 126.4 (d), 127.3 (d), 127.6 (d),
128.1 (d), 128.3 (d), 141.7 (s), 209.6 (s). Anal. Calcd for
1H NMR (CDCl3) δ 1.41 (s, 3 H), 2.05-2.28 (m, 2 H), 2.17 (s,
3 H), 3.37-3.47 (m, 3 H), 3.77 (s, 3 H), 3.78 (s, 3 H), 3.81 (s, 6
H), 6.60-6.75 (m, 6 H). 13C NMR (CDCl3) δ 26.4 (q), 32.9 (q),
49.9 (q), 50.3 (t), 55.1 (d), 55.6 (q), 70.8 (d), 79.2 (s), 110.6 (d),
110.9 (d), 119.0 (d), 119.3 (d), 134.4 (s), 134.5 (s), 147.2 (s),
148.3 (s), 209.7 (s). Anal. Calcd for C24H30O6: C, 69.54; H, 7.30.
Found: C, 69.40; H, 7.22.
C
20H22O2: C, 81.60; H, 7.53. Found: C, 81.53; H, 7.55.
Lin ea r m eso-h yd r od im er of 1: Rf 0.55 (hexanes-ethyl
acetate, 2:1). White solid. Mp 138-140 °C. IR (KBr) 1711,
1601, 1495, 768, 706 cm-1 1H NMR (CDCl3) δ 1.74 (s, 6 H),
.
6a : Rf 0.45 (hexanes-ethyl acetate, 2:1). White solid. Mp
2.31-2.42 (m, 2 H), 2.59-2.72 (m, 2 H), 3.30-3.43 (m, 2 H),
7.17-7.36 (m, 10 H). 13C NMR (CDCl3) δ 30.7 (q), 46.8 (d),
48.8 (t), 126.8 (d), 128.2 (d), 128.6 (d), 142.4 (s), 207.1 (s). Anal.
Calcd for C20H22O2: C, 81.60; H, 7.53. Found: C, 81.49; H,
7.47.
191-193 °C. IR (KBr) 3464, 1697, 1597, 1508, 795, 775 cm-1
.
1H NMR (CDCl3) δ 1.62 (s, 3 H), 1.71 (s, 3 H), 2.28 (dd, 1 H, J
) 7.6, 14.0 Hz), 2.72 (dd, 1 H, J ) 10.8, 14.0 Hz), 3.45 (d, 1 H,
J ) 10.8 Hz), 4.14 (s, 1 H), 4.41-4.54 (m, 1 H), 5.02 (t, 1 H, J
) 10.8 Hz), 7.17-7.47 (m, 6 H), 7.53-7.95 (m, 8 H). 13C NMR
(CDCl3) δ 28.6 (q), 33.3 (q), 46.0 (d), 50.0 (d and t), 68.6 (d),
79.9 (s), 122.8 (d), 122.9 (d), 123.4 (d), 124.1 (d), 124.9 (d), 125.2
(d), 125.4 (d), 125.7 (d), 125.9 (d), 126.6 (d), 127.3 (d), 128.5
(d), 131.9 (s), 132.2 (s), 133.5 (s), 133.7 (s), 137.5 (s), 139.5 (s),
213.3 (s). Anal. Calcd for C28H26O2: C, 85.25; H, 6.64. Found:
C, 85.20; H, 6.65.
3a : Rf 0.33 (hexanes-ethyl acetate, 2:1). Colorless oil. IR
(neat) 3474, 1701, 1612, 1583, 1514, 1464, 831 cm-1. 1H NMR
(CDCl3) δ 1.57 (s, 3 H), 1.76 (s, 3 H), 2.13 (dd, 1 H, J ) 7.3,
13.8 Hz), 2.36 (dd, 1 H, J ) 10.3, 13.8 Hz), 3.09 (d, 1 H, J )
11.9 Hz), 3.19 (dt, 1 H, J ) 7.3, 10.3 Hz), 3.53 (dd, 1 H, J )
10.3, 11.9 Hz), 3.74 (s, 3 H), 3.76 (s, 3 H), 3.93 (s, 1 H), 6.70-
6.81 (m, 4 H), 6.99-7.05 (m, 2 H), 7.07-7.13 (m, 2 H). 13C NMR
(CDCl3) δ 28.4 (q), 32.7 (q), 49.4 (t), 50.6 (d), 54.8 (d), 56.7 (d),
67.9 (d), 79.1 (s), 113.3 (d), 113.6 (d), 128.1 (d), 128.2 (d), 132.6
(s), 135.0 (s), 157.6 (s), 157.9 (s), 212.2 (s). Anal. Calcd for
6b: Rf 0.3 (hexanes-ethyl acetate, 2:1). White solid. Mp
194-196 °C. IR (KBr) 3435, 1701, 1597, 1508, 800, 793, 777
1
cm-1. H NMR (CDCl3) δ 1.47 (s, 3 H), 2.12 (s, 3 H), 2.21 (dd,
C
22H26O4: C, 74.55; H, 7.39. Found: C, 74.38; H, 7.35.
1 H, J ) 11.3, 13.2 Hz), 2.47-2.56 (m, 1 H), 3.62 (d, 1 H, J )
8.4 Hz), 4.75-4.97 (m, 2 H), 7.23-7.43 (m, 6 H), 7.55 (d, 1 H,
J ) 7.6 Hz), 7.58 (d, 1 H, J ) 7.6 Hz), 7.65-7.71 (m, 3 H),
7.79 (d, 1 H, J ) 7.3 Hz), 7.97-8.05 (m, 1 H), 8.18 (d, 1 H, J
) 7.8 Hz). 13C NMR (CDCl3) δ 26.3 (q), 33.3 (q), 45.1 (d), 47.9
(d), 51.6 (t), 72.0 (d), 80.1 (s), 122.9 (d), 122.99 (d), 123.30 (d),
124.1 (d), 124.9 (d), 125.1 (d), 125.3 (d), 125.38 (d), 125.41 (d),
125.6 (d), 126.5 (d), 126.8 (d), 128.4 (d), 131.9 (s), 132.1 (s),
133.5 (s), 133.6 (s), 137.9 (s), 138.9 (s), 210.5 (s). Anal. Calcd
for C28H26O2: C, 85.25; H, 6.64. Found: C, 85.17; H, 6.60.
3b: Rf 0.23 (hexanes-ethyl acetate, 2:1). Colorless oil. IR
1
(neat) 3449, 1701, 1612, 1583, 1514, 1464, 831, 731 cm-1. H
NMR (CDCl3) δ 1.39 (s, 3 H), 1.86 (br s, 1 H), 2.04-2.16 (m, 1
H), 2.14 (s, 3 H), 2.18-2.28 (m, 1 H), 3.32-3.47 (m, 3 H), 3.729
(s, 3 H), 3.732 (s, 3 H), 6.70-6.77 (m, 4 H), 7.00-7.08 (m, 4
H). 13C NMR (CDCl3) δ 26.5 (q), 32.9 (q), 49.6 (q), 50,9 (t), 54.7
(d), 55.0 (q), 71.3 (d), 79.2 (s), 113.5 (d), 113.6 (d), 128.1 (d),
128.4 (d), 133.7 (s), 133.8 (s), 157.8 (s), 210.0 (s). Anal. Calcd
for C22H20O4: C, 74.55; H, 7.39. Found: C, 74.45; H, 7.43.
7a : Rf 0.41 (hexanes-ethyl acetate, 2:1). White solid. Mp
137-139 °C. IR (KBr) 3462, 1682, 1632, 1599, 1508, 862, 835,
(9) Drakes, N. L.; Allen, P., J r. Organic Synthesis; Wiley: New York,
1941; Vol. I, pp 77-78.
1
819, 746 cm-1. H NMR (CDCl3) δ 1.58 (s, 3 H), 1.83 (s, 3 H),
962 J . Org. Chem., Vol. 69, No. 3, 2004

dl-Hydrocoupling of Benzalacetones by Electroreduction
2.32 (dd, 1 H, J ) 7.0, 14.3 Hz), 2.52 (dd, 1 H, J ) 10.5, 14.3
Hz), 3.35 (d, 1 H, J ) 11.9 Hz), 3.60 (dt, 1 H, J ) 7.0, 10.5
Hz), 3.94 (dd, 1 H, J ) 10.5, 11.9 Hz), 4.08 (s, 1 H), 7.32-7.44
(m, 5 H), 7.48-7.56 (m, 3 H), 7.60-7.81 (m, 6 H). 13C NMR
(CDCl3) δ 28.3 (q), 33.2 (q), 49.4 (t), 51.9 (d), 58.1 (d), 67.8 (d),
79.90 (s), 125.1 (d), 125.5 (d), 125.6 (d), 125.95 (d), 126.02 (d),
126.1 (d), 126.5 (d), 127.3 (d), 127.4 (d), 127.49 (d), 127.53 (d),
128.0 (d), 128.4 (d), 132.1 (s), 132.4 (s), 133.17 (s), 133.24 (s),
138.1 (s), 140.7 (s), 212.8 (s). Anal. Calcd for C28H26O2: C,
85.25; H, 6.64. Found: C, 85.12; H, 6.54.
(CDCl3) δ 0.16 (s, 9 H), 1.69 (s, 3 H), 2.11 (s, 3 H), 2.22 (dd, 1
H, J ) 10.8, 13.0 Hz), 2.35 (d, 1 H, J ) 8.1, 13.0 Hz), 3.00 (d,
1 H, J ) 10.8 Hz), 3.11 (dt, 1 H, J ) 8.1, 10.8 Hz), 3.96 (t, 1 H,
J ) 10.8 Hz), 7.00-7.24 (m, 10 H). 13C NMR (CDCl3) δ -2.3
(q), 30.6 (q), 31.3 (q), 51.0 (d), 51.2 (t), 53.5 (d), 70.8 (d), 81.9
(s), 126.19 (d), 126.21 (d), 127.3 (d), 127.4 (d), 128.1 (d), 128.2
(d), 141.4 (s), 142.2 (s), 207.1 (s).
2b′: Rf 0.4 (hexanes-ethyl acetate, 5:1). Colorless oil. 1H
NMR (CDCl3) δ 0.24 (s, 9 H), 1.40 (s, 3 H), 2.04-2.11 (m, 1
H), 2.15 (s, 3 H), 2.36-2.42 (m, 1 H), 3.44-3.53 (m, 1 H), 7.09-
7.22 (m, 10 H). 13C NMR (CDCl3) δ 2.3 (q), 26.4 (q), 32.8 (q),
50.4 (t), 50.7 (d), 54.5 (d), 72.5 (d), 82.3 (s), 126.1 (d), 126.2
(d), 127.3 (d), 127.6 (d), 128.1 (d), 142.3 (s), 209.3 (s).
Desilyla tion of 2a ′. To a solution of 2a ′ (110 mg, 0.3 mmol)
in dry THF (2.5 mL) was added a 1 M solution of Bu4NF in
THF (0.33 mL, 0.33 mmol). After being stirred for 1 h at room
temperature, the mixture was quenched with AcOH (0.02 mL,
0.33 mmol) and evaporated. The residue was column chro-
matographed on silica gel (hexanes-ethyl acetate) to give 2a
(50%) and 2b (43%).
X-r a y Cr ysta llogr a p h ic An a lysis. All measurements were
made on a Rigaku RAXIS imaging plate area detector with
graphite monochromated Mo KR radiation. The structure was
solved by direct methods with SIR92 and expanded by using
Fourier techniques with DIRDIF99. The non-hydrogen atoms
were refined anisotropically. Hydrogen atoms were refined
isotropically. All calculations were performed with the Crys-
talStructure crystallographic software package.
Cr ysta l Da ta for 2a . C20H22O2, FW 294.39, triclinic, P1h (no.
2), colorless block, a ) 5.726(1) Å, b ) 9.535(2) Å, c ) 16.038(3)
Å, R ) 82.246(3)°, â ) 89.04(1)°, γ ) 76.988(7)°, V ) 845.1(3)
Å3, T ) 298 K, Z ) 2, Dcalcd ) 1.157 g/cm3, µ ) 0.73 cm-1, GOF
) 1.002. The final cycle of full-matrix least-squares refinement
on F2 was based on 3663 observed reflections and 222 variable
parameters and converged with unweighted and weighted
agreement factors of R1 ) 0.096 and wR2 ) 0.100.
Cr ysta l Da ta for 6a . C28H26O2, FW 394.51, monoclinic,
P21/c (no. 14), colorless block, a ) 14.908(2) Å, b ) 8.2274(9)
Å, c ) 18.524(2) Å, â ) 109.164(3)°, V ) 2146.1(4) Å3, T ) 298
K, Z ) 4, Dcalcd ) 1.221 g/cm3, µ ) 0.75 cm-1, GOF ) 1.001.
The final cycle of full-matrix least-squares refinement on F2
was based on 2364 observed reflections and 297 variable
parameters and converged with unweighted and weighted
agreement factors of R1 ) 0.038 and wR2 ) 0.034.
Cr ysta l Da ta for 6b. C28H26O2, FW 394.51, orthorombic,
Pbca (no. 61), colorless block, a ) 13.392(2) Å, b ) 10.953(1)
Å, c ) 28.412(2) Å, V ) 4167.2(8) Å3, T ) 298 K, Z ) 8, Dcalcd
) 1.258 g/cm3, µ ) 0.77 cm-1, GOF ) 0.982. The final cycle of
full-matrix least-squares refinement on F2 was based on 4757
observed reflections and 298 variable parameters and con-
verged with unweighted and weighted agreement factors of
R1 ) 0.041 and wR2 ) 0.041.
7b: Rf 0.28 (hexanes-ethyl acetate, 2:1). White solid. Mp
176-178 °C. IR (KBr) 3506, 1688, 1634, 1601, 1508, 853, 822,
1
746 cm-1. H NMR (CDCl3) δ 1.49 (s, 3 H), 1.89 (s, 1 H), 2.17
(s, 3 H), 2.27-2.41 (m, 2 H), 3.52-3.63 (m, 1 H), 3.77-3.92
(m, 2 H), 7.30-7.45 (m, 6 H), 7.54-7.60 (m, 2 H), 7.62-7.76
(m, 6 H). 13C NMR (CDCl3) δ 26.6 (q), 33.2 (q), 50.8 (d), 51.0
(t), 55.8 (d), 71.2 (d), 79.9 (s), 125.2 (d), 125.3 (d), 125.68 (d),
125.72 (d), 125.77 (d), 125.84 (d), 126.4 (d), 127.3 (d), 127.4
(d), 127.5 (d), 127.9 (d), 128.1 (d), 132.20 (s), 132.24 (s), 133.2
(s), 139.2 (s), 139.3 (s), 209.7 (s). Anal. Calcd for C28H26O2: C,
85.25; H, 6.64. Found: C, 85.15; H, 6.61.
8a : Rf 0.67 (hexanes-ethyl acetate, 1:1). Pale yellow oil. IR
(neat) 3462, 1701, 1595, 1506, 926, 804, 735 cm-1 1H NMR
.
(CDCl3) δ 1.47 (s, 3 H), 2.02 (s, 3 H), 2.16 (dd, 1 H, J ) 7.3,
13.8 Hz), 2.24-2.34 (m, 1 H), 3.19 (d, 1 H, J ) 11.6 Hz), 3.44-
3.56 (m, 1 H), 3.54 (br s, 1 H), 3.87 (dd, 1 H, J ) 9.7, 11.3 Hz),
6.02-6.05 (m, 2 H), 6.23-6.28 (m, 2 H), 7.28-7.30 (m, 1 H),
7.34-7.36 (m, 1 H). 13C NMR (CDCl3) δ 28.0 (q), 32.1 (q), 41.0
(d), 46.2 (t), 47.0 (d), 65.0 (d), 79.2 (s), 104.8 (d), 106.4(d), 109.9
(d), 110.2 (d), 141.0 (d), 141.4 (d), 153.9 (s), 156.0 (s), 211.1
(s). Anal. Calcd for C16H18O4: C, 70.06; H, 6.61. Found: C,
69.89; H, 6.53.
8b: Rf 0.42 (hexanes-ethyl acetate, 1:1). Pale yellow oil. IR
(neat) 3437, 1705, 1597, 1508, 924, 806, 735 cm-1 1H NMR
.
(CDCl3) δ 1.34 (s, 3 H), 2.14 (dd, 1 H, J ) 9.5, 13.5 Hz), 2.24
(s, 3 H), 2.28 (dd, 1 H, J ) 8.1, 13.5 Hz), 3.43 (d, 1 H, J ) 9.5
Hz), 3.58-3.80 (m, 2 H), 5.98-6.02 (m, 2 H), 6.21-6.26 (m, 2
H), 6.28-6.30 (m, 2 H). 13C NMR (CDCl3) δ 25.9 (q), 32.3 (q),
40.4 (d), 45.3 (d), 47.5 (t), 67.6 (d), 79.4 (s), 105.0 (d), 105.7
(d), 109.9 (d), 110.1 (d), 141.1 (d), 141.2 (d), 154.6 (s), 155.6
(s), 208.7 (s). Anal. Calcd for C16H18O4: C, 70.06; H, 6.61.
Found: C, 68.82; H, 6.48.
Isom er iza tion of 2. A mixture of 2a or 2b (100 mg, 0.34
mmol) and t-BuOK (11 mg, 0.034 mmol) in dry THF (5 mL)
was stirred at room temperature for 3 days. The mixture was
diluted with 1 M HCl (10 mL) and extracted with Et2O. The
products 2 and 9 were isolated by column chromatography on
silica gel (hexanes-ethyl acetate).
9: Rf 0.8 (hexanes-ethyl acetate, 2:1). Pale yellow oil. IR
(neat) 1678, 1616, 1601, 1495, 700 cm-1 1H NMR (CDCl3) δ
.
1.91 (s, 3 H), 2.21-2.24 (m, 3 H), 2.63-2.75 (m, 1 H), 2.99-
3.13 (m, 1 H), 3.14-3.24 (m, 1 H), 4.18-4.25 (m, 1 H), 7.02-
7.07 (m, 2 H), 7.11-7.33 (m, 8 H). 13C NMR (CDCl3) δ 16.7
(q), 30.1 (q), 47.4 (t), 53.1 (d), 62.2 (d), 126.4 (d), 126.5 (d), 126.9
(d), 127.0 (d), 128.5 (d), 128.7 (d), 137.7 (s), 144.2 (s), 144.8
(s), 153.1 (s), 198.8 (s).
Ack n ow led gm en t. One of the authors (N.K.) is
grateful to the Electric Technology Research Foundation
of Chugoku for financial support.
Silyla tion of 2. A solution of 2a (100 mg, 0.34 mmol),
chlorotrimethylsilane (0.13 mL, 1 mmol), and triethylamine
(0.14 mL, 1 mmol) in dry THF (2.5 mL) was stirred for 20 h.
After the solvent was removed in vacuo, dry Et2O (10 mL) was
added to the residue. Insoluble solid was filtered off and the
filtrate was evaporated. The crude mixture was purified by
column chromatography on silica gel (hexanes-ethyl acetate)
to give 2a ′ in 90% yield.
Su p p or tin g In for m a tion Ava ila ble: Crystallographic
1
CIF files for 2a , 6a , and 6b; a PDF file of H and 13C NMR
spectra of 2a , 2b, 6a , and 6b, X-ray crystallographic structures
(ortep) of 2a , 6a , and 6b, and the results of calculations shown
in Figures 1 and 2. This material is available free of charge
via the Internet at http://pubs.acs.org.
2a ′: Rf 0.6 (hexanes-ethyl acetate, 5:1). Colorless oil. IR
(neat) 1715, 1701, 1603, 1497, 841, 762, 698 cm-1
.
1H NMR
J O035280Q
J . Org. Chem, Vol. 69, No. 3, 2004 963