588 Bull. Chem. Soc. Jpn., 75, No. 3 (2002)
© 2002 The Chemical Society of Japan
the maximum rotation of each chiral alcohol11 [α]D20 −0.439°
(neat, l = 0.01) for (S)-ꢀb11a; [α]D20 −45.45° (c 5.15, chloro-
form) for (S)-ꢂb11b; [α]D22 −45.2° (c 4.8, benzene) for (S)-
ꢃb11a; [α]D22 −0.200° (neat, l = 0.01) for (S)-ꢄb11a; [α]D25
−24.6° (neat) for S-ꢅb11c; [α]D22 +25.9° (c 2.2, benzene) for
(R)-ꢁb11d]. The absolute configuration of alcohols ꢀb–ꢁb
was found to be S.
bromide. The TBA•BF4 and DET were prepared by reported
methods,13,14 and were dried under a vacuum and kept in a desic-
cator. DMF was dried by a reported method15a and kept over acti-
vated molecular sieves (4 Å) under nitrogen gas.
A typical preparativescale electroreduction of acetophenone
has been described as under: 1.2 g acetophenone in 40 mL DMF
+ H2O (90:10) containing 0.1 M TBA•BF4 and 10 mM DET•BF4
was taken as a catholyte. A porous diaphragm was used as a cell
divider, and to it 20 mL DMF–H2O (90:10) containing 0.1 M
TBA•BF4 was added, which served as an anolyte. A Hg pool (36
cm2) was used as a cathode and Pt foil (9 cm2) served as an anode.
A charge corresponding to 2 F mol−1 was transferred at an applied
potential of −1.48 V vs Ag –AgCl.
After electrolysis, the solvent was removed under pressure (50
°C, 35 mm). To it water (~30 mL) was added, and the organic
product(s) were extracted with ether (3 × 30 mL). The combined
ethereal layer was dried over anhydrous sodium sulfate, filtered,
and the solvent was removed. Distillation of mass under reduced
pressure, 79–83 °C at 3 mm Hg (reported15b 79 °C at 3 mm Hg),
afforded 540 mg of pure ꢀb (yield 46%, mp 46–47 °C) [α]D22
−0.240° (neat, l = 0.01) in 55% ee assigned by a comparison of
the known rotation value, [α]D20 −0.439° (neat, l = 0.01)11a. The
remaining mass upon recrystallization afforded pinacol ꢀa (45%).
Preliminary CV studies on the reduction of ꢀ at mercury film
coated on a Pt wire (freshly prepared) in DMF containing 0.1
M TBA•BF4 showed a reduction peak at Ep −1.52 V vs Ag/
AgCl (ip = 8.75 µA). Upon the addition of 10 mM DET,
when CV was recorded two peaks appeared, viz Ep1 −1.14 V
(peak current, ip1 = 4.50 µA) and at Ep2 − 1.48 V (ip2 = 13.25
µA). The first peak at Ep1 −1.14 disappeared in repeated
scans, and was thus identified as being due to the adsorption of
DE+. The second peak i.e. Ep2 −1.48, due to the reduction of
compound ꢀ, was slightly shifted anodically with an increase in
ip2, indicating that the transfer of an electron from the cathode
to a ketone becomes more facile upon the addition of DET.
The effect of the concentration of DET on the cathodic reduc-
tion of ꢀ was then studied in DMF–Water (90:10) at a mercury
pool at a potential of −1.48 V vs Ag–AgCl using 0.1 M
TBA•BF4 by passing charge corresponding to 2 F mol−1. ꢀa/ꢀb
was obtained in 50%/42%, 45%/46%, 48%/48%, and 46%/
49% at DET concentrations 1 mM, 5 mM, 10 mM, and 20
mM, respectively. Compound ꢀb was found to have ee in 40%,
50%, 55%, 51%, and 45%, respectively, establishing that the
inductor concentration, viz DET, does not significantly effect
the yield of ꢀa and its optical yield and thus suggesting strong
adsorption of DET on the surface of the cathode.12
Financial assistance from DST, New Delhi is gratefully ac-
knowledged.
References
1
“Stereoselective synthesis,” Mihaly Nogradi, VCH, Wein-
heim, New York (1995).
Based on the above mentioned preliminary investigations, it
appears that the DET is adsorbed on the surface of the cathode
in a certain specific orientation, such that the H of –OH (of
DE+) remains towards the catholyte, and the oxygen of the
protonated k-etone (>C=O+–H ꢀ >C+–O–H) forms a hy-
drogen bridge with H (of –OH) of the adsorbed DET. Upon
electron transfer the intermediates (Aꢀ and Bꢀ) are formed. In-
termediate Aꢀ (ion pair) undergoes dimerization exclusively in
DMF to give racemic/meso ꢀa. The radical Bꢀ either undergoes
further electron transfer to give a carbanion (the electron is
transferred to nearest p orbital as ketone (s) is in certain specif-
ic orientation towards cathode) or dimerization. The addition
of a proton to carbanion in such a situation yields, the S-isomer
selectively. The above preposition finds further support from
an observation in the case of the reduction of ketone ꢁ, where
the corresponding alcohol ꢁb shows a loss of considerable
enantioselectivity (5%), as the bulky group –C(CH3)3 appears
to create a hinderance for a specific orientation on the surface
of the cathode.
2
3
4
5
6
7
H.U. Blaser, Tetrahedron Asymmetry, 2, 843 (1991).
H.U. Blaser, Chem. Rev., 92, 935 (1992).
H. Brunner, Top. Stereochem., 18, 129 (1988).
R.W. Murray, Acc. Chem. Res., 13, 135 (1980).
A. Tellac, Bull. Soc. Chim. Fr., 5, 743 (1985).
T. Komori and T. Nonaka, J. Am. Chem. Soc., 106, 2656
(1984), and the references cited therein.
D. Seebach and H.A. Dei, Angew. Chem., Int. Ed. Engl.,
14, 634 (1975).
8
9
L. Horner and W. Brich, Justus Liebigs Ann. Chem., 1977,
1354. Chem. Abstr., 88, 29464 (1978).
10 L. Horner and W. Brich, Chem. Ber., 111, 574 (1978).
11 a) R. Noyori, I. Tomino, Y. Tanimoto, and M. Nishizawa, J.
Am. Chem. Soc., 106, 6709 (1984). b) R.H. Pickard and J.
Kenyon, J. Chem. Soc., 105, 1115 (1914). c) D. Nasipuri and G.
Sarker, J. Ind. Chem. Soc., 44, 165 (1967). d) J.P. Vigneron and I.
Jacquet, Tetrahedron, 32, 939 (1976).
12 a) M. Jubault, E. Raoult, and D. Pletier, Electrochim. Ac-
ta., 19, 865 (1974). b) J. Kopilov, E. Kariv, and L.L. Miller, J.
Am. Chem. Soc., 99, 3450 (1977). c) M. Jubault, J. Chem. Soc.,
Chem. Commun., 1980, 953.
Detailed mechanistic studies of the process are being con-
ducted and will be addressed later.
13 a) W.N. Olmstead, Z. Margulin, and F.G. Bordwell, J. Org.
Chem., 45, 3295 (1980). b) W.C. Burrette, H.W. Johnson, Jr., and
D.T. Sawyer, Anal. Chem., 56, 1890 (1984).
Experimental
Electrochemical studies were carried out on a Wenking poten-
tiostat LB 72 M, a voltage scan generator VSG 72 and a Rikadenki
X–Y recorder (model 101 T). The chiral auxillary viz. DET was
synthesized by first refluxing (1R,2S) - ephedrine with methyl io-
dide (1:2) in alcohol for 10 h to give N,N-dimethylephedrinium
14 T. Hiyama, T. Mishima, H. Sawada, and H. Nozaki, J. Am.
Chem. Soc., 97, 1626 (1975).
15 “Vogel’s Textbook of Practical Organic Chemistry,” ed by
B.S. Furniss, A.J. Hannaford, P.W.G. Smith, and A.R. Tatchell
(1996), a) p. 409, b) p. 525.