Highly Diastereoselective Pinacol Coupling of Secondary Aliphatic Aldehydes Induced by a Catalytic System Consisting of Vanadium Complex, Chlorosilane, and Zinc Metal

Full text of DOI:10.1021/jo980376j

2812
J . Org. Chem. 1998, 63, 2812-2813
Ta ble 1. Selectivity of th e F or m a tion of 1,2-Diola
High ly Dia ster eoselective P in a col Cou p lin g
of Secon d a r y Alip h a tic Ald eh yd es In d u ced by
a Ca ta lytic System Con sistin g of Va n a d iu m
Com p lex, Ch lor osila n e, a n d Zin c Meta l
Toshikazu Hirao,* Motoki Asahara,
Yasuaki Muguruma, and Akiya Ogawa
yield, % (dl/meso)
entry
cat.
solvent
2a
3a
Department of Applied Chemistry, Faculty of Engineering,
Osaka University, Yamada-oka, Suita, Osaka 565-0871, J apan
1
2
3
4
CpV(CO)4
CpV(CO)4
Cp2VCl2
Cp2VCl2
CpV(CO)4
Cp2VCl2
Cp2VCl2
Cp2VCl2
DME
THF
DME
THF
THF
THF
THF
THF
0
80 (63/37)
78 (91/9)
0
0
82 (88/12)
Received March 2, 1998
100 (88/12)
100 (92/8)
100 (96/4)
74 (70/30)
0
0
0
0
0
5b
6b
7c
8d
The reductive dimerization of carbonyl compounds, espe-
cially aldehydes and ketones, to give diols is an important
method for constructing vicinally functionalized carbon-
carbon bonds.1 For this purpose, low-valent metals such as
aluminum amalgam,2 titanium,3 vanadium,4 zinc,5 and
samarium6 have been employed conveniently. For example,
pinacol coupling reactions using TiCl3/Zn-Cu and [V2Cl3-
(THF)6]2[Zn2Cl6] are employed successfully for the synthesis
of paclitaxel7 and C2-symmetrical HIV protease inhibitors,8
respectively. To synthesize such complicated compounds,
the efficient control of the stereochemistry in the coupling
reactions is of great importance.3f,h,j,4 In addition, another
significant part of the pinacol coupling reaction includes the
construction of a catalytic system of low-valent metals. It
has recently been revealed that the use of chlorosilanes in
combination with catalytic amounts of a transition-metal
salt such as titanium and vanadium and a stoichiometric
reducing agent successfully effects the catalytic pinacol
coupling reactions.9,10 Among these catalytic reactions, the
low-valent titanium-catalyzed pinacol coupling of aromatic
aldehydes exhibits the excellent diastereoselectivity.10c-e
However, there are no examples of the highly diastereose-
lective pinacol coupling of simple aliphatic aldehydes in
39 (89/11)
a
Reaction conditions unless otherwise stated: aldehyde (2
mmol), catalyst (0.06 mmol), Zn (4 mmol), Me3SiCl (4 mmol),
solvent (7 mL), 20 °C, 13 h. PhMe2SiCl was used instead of
b
Me3SiCl. c 40 °C. -20 °C.
d
catalytic systems.11,12 Herein, we report a highly diastereo-
selective catalytic pinacol coupling of secondary aliphatic
aldehydes with the aid of Cp2VCl2/R3SiCl/Zn (eq 1).
A versatile catalytic system consisting of vanadium,
chlorosilane, and zinc worked well for the reductive coupling
of aliphatic aldehydes in dimethoxyethane (DME) to give
1,3-dioxolanes, but unfortunately, the diastereoselectivity of
the dioxolanes obtained was generally very low. For ex-
ample, 2-ethylbutanal (1a ) reacted with cat. CpV(CO)4, Me3-
SiCl, and zinc powder in DME at room temperature,
affording 1,3-dioxolane (3a ) in 80% yield with low selectivity
(dl/meso ) 63/37, see entry 1 in Table 1).9b,c By switching
the solvent simply from DME to THF, however, the product
selectivity dramatically changed, providing 1,2-diol (2a )
predominantly without formation of any olefinic products
and 1,3-dioxolane (entry 2). Similar dependence of the
product selectivity on the solvent was also observed with
Cp2VCl2 catalyst (entries 3-4). More interestingly, both
reactions of secondary aldehyde (1a ) in THF using cat. Cp2-
VCl2 and cat. CpV(CO)4 exhibited the excellent diastereo-
selectivity (entries 2 and 4). In the case of cat. Cp2VCl2,
the diastereoselectivity could be further enhanced by using
PhMe2SiCl in place of Me3SiCl (entry 6). The result suggests
that the bulkiness of the substituents on chlorosilanes
somewhat contributes to the diastereoselection. Elevated
temperature led to a significant decrease in both yield and
stereoselectivity of 2a (entry 7). At a lower temperature
(-20 °C), the product selectivity changed, giving 1,3-diox-
olane (3b) even in THF (entry 8).
(1) (a) Grame, M. R. In Comprehensive Organic Synthesis; Trost, B. M.,
Fleming, I., Eds.; Pergamon Press: Oxford, 1991; Vol. 3, p 563. (b) Wirth,
T. Angew. Chem., Int. Ed. Engl. 1996, 35, 61.
(2) Schreibmann, A. A. Tetrahedron Lett. 1970, 49, 4271.
(3) (a) Mukaiyama, T.; Sato, T.; Hanna, J . Chem. Lett. 1973, 1041. (b)
Tyrlik, S.; Wolochowicz, I. Bull. Chim. Soc. Fr. 1973, 2147. (c) McMurry, J .
E.; Fleming, M. P. J . Am. Chem. Soc. 1974, 96, 4708. (d) Corey, E. J .;
Danheiser, R. L.; Chandrasekaran, S. J . Org. Chem. 1976, 41, 260. (e)
Suzuki, H.; Manabe, H.; Enokiya, R.; Hanazaki, Y. Chem. Lett. 1986, 1339.
(f) Handa, Y.; Inanaga, J . Tetrahedron Lett. 1987, 28, 5717. (g) McMurry,
J . E. Chem. Rev. 1989, 89, 1513. (h) Barden, M. C.; Schwartz, J . J . Am.
Chem. Soc. 1996, 118, 5484. (i) Balu, N.; Nayak, S. K.; Banerji, A. J . Am.
Chem. Soc. 1996, 118, 5932. (j) Clerici, A.; Clerici, L.; Porta, O. Tetrahedron
Lett. 1996, 37, 3035.
(4) (a) Freudenberger, J . H.; Konradi, A. W.; Pedersen, S. F. J . Am. Chem.
Soc. 1989, 111, 8014. (b) Park, J .; Pedersen, S. F. J . Org. Chem. 1990, 55,
5924. (c) Konradi, A. W.; Pedersen, S. F. J . Org. Chem. 1992, 57, 28. (d)
Konradi, A. W.; Kemp, S. J .; Pedersen, S. F. J . Am. Chem. Soc. 1994, 116,
1316.
(5) (a) Motherwell, W. B. J . Chem. Soc., Chem. Commun. 1973, 935. (b)
So, J .-H.; Park, M.-K.; Boudjouk, P. J . Org. Chem. 1988, 53, 5871. (c)
Tanaka, K.; Kishigami, S.; Toda, F. J . Org. Chem. 1990, 55, 2981. (d)
Tsukinoki, T.; Kawaji, T.; Hashimoto, I.; Mataka, S.; Tashiro, M. Chem.
Lett. 1997, 235.
(6) (a) Namy, J . L.; Kagan, H. B. Tetrahedron Lett. 1983, 24, 765. (b)
Molander, G. A. Chem. Rev. 1992, 92, 29. (c) Taniguchi, N.; Kaneta, N.;
Uemura, M. J . Org. Chem. 1996, 61, 6088.
(7) (a) Nicolaou, K. C.; Liu, J .-J .; Yang, Z.; Ueno, H.; Guy, R. K.; Sorensen,
E. J .; Claiborne, C. F.; Hwang, C.-K.; Nakada, M.; Nantermet, P. G. J . Am.
Chem. Soc. 1995, 117, 634. (b) Shiina, I.; Nishimura, T.; Ohkawa, N.; Sakoh,
H.; Nishimura, K.; Saitoh, K.; Mukaiyama, T. Chem. Lett. 1997, 419.
(8) (a) Kammermeier, B.; Beck, G.; Holla, W.; J acobi, D.; Napierski, B.;
J endralla, H. Chem. Eur. J . 1996, 2, 307. (b) Kammermeier, B.; Beck, G.;
J acobi, D.; J endralla, H. Angew. Chem., Int. Ed. Engl. 1994, 33, 685.
(9) Fu¨rstner’s group and our group have independently demonstrated
the catalytic McMurry coupling reaction and pinacol coupling reaction,
respectively; see: (a) Fu¨rstner, A.; Hupperts, A. J . Am. Chem. Soc. 1995,
117, 4468. (b) Hirao, T.; Hasegawa, T.; Muguruma, Y.; Ikeda, I. J . Org.
Chem. 1996, 61, 366. (c) Hirao, T.; Hasegawa, T.; Muguruma, Y.; Ikeda, I.
Abstracts for the 6th International Kyoto Conference on New Aspects of
Organic Chemistry, 1994; p 175.
(10) For quite recent advances in the catalytic pinacol coupling, see: (a)
Nomura, R.; Matsuno, T.; Endo, T. J . Am. Chem. Soc. 1996, 118, 11666. (b)
Maury, O. Villiers, C. Ephritikhine, M. New J . Chem. 1997, 21, 137. (c)
Gansa¨uer, A. J . Chem. Soc., Chem. Commun. 1997, 457. (d) Gansa¨uer, A.
Synlett 1997, 363. (e) Lipski, T. A.; Hilfiker, M. A.; Nelson, S. G. J . Org.
Chem. 1997, 62, 4566.
(11) For the diastereoselective pinacol coupling of aliphatic aldehydes
by using a stoichiometric Nb(III), see: Szymoniak, J .; Besanc¸on, J .; Mo¨ıse,
C. Tetrahedron 1994, 50, 2841.
(12) Pedersen and co-workers reported a series of highly diastereoselec-
tive stoichiometric pinacol coupling of aliphatic aldehydes bearing chelating
groups.4
S0022-3263(98)00376-4 CCC: $15.00 © 1998 American Chemical Society
Published on Web 04/16/1998

Communications
J . Org. Chem., Vol. 63, No. 9, 1998 2813
Ta ble 2. Cp 2VCl2/R3SiCl/Zn -In d u ced P in a col Cou p lin g
Rea ction a
diastereoselectivity (entries 8-9). Contrary to this, the
intramolecular coupling reaction3g,9a,10e,11,13 of 1,5-diketone
(1j) successfully proceeded with excellent diastereoselectiv-
ity, as exemplified in eq 2.14
This successful result prompted us to examine catalytic
intramolecular cyclization of olefinic aldehydes,15 as indi-
cated in eq 3. When the reaction of δ,ꢀ-unsaturated alde-
hyde (1k ) with cat. Cp2VCl2/Me3SiCl/Zn was conducted in
THF at -20 °C,16 trace amounts of vicinal diol were formed,
and instead cyclic alcohol (5) was obtained as the major
product with excellent diastereoselectivity (eq 3). The result
is of great interest and may be explained by 5-exo-cyclization
of the corresponding ketyl radical anion, followed by chlo-
rination. In general, ketyl radical anions cyclize with
excellent trans selectivities, suggesting that electronic repul-
sion between the forming radical center and the negatively
charged ketyl oxygen is significant in the transition state
leading to the disfavored cis isomer.17 Considering also the
1,3-diaxial interaction between 2- and 6-methyl groups,
model A is the most favorable, giving R-methyl located cyclic
product (5) as the major product.
a
Reaction conditions unless otherwise stated: aldehyde (3
mmol), Cp2VCl2 (0.09 mmol), Zn (6 mmol), Me3SiCl (6 mmol), THF
b
(7 mL), 20 °C, 13 h. PhMe2SiCl was used instead of Me3SiCl.
c Isolated yield (%). -20 °C.
d
In summary, this work describes a novel catalytic pinacol
coupling of secondary aliphatic aldehydes with excellent
diastereoselection. In this catalytic system, the additive of
chlorosilane plays an important role in the construction of
catalytic systems and also assists the stereoselection. An
additive on the vanadium catalytic system also provides a
versatile synthetic tools with high stereoselectivity, as
exemplified by the highly stereoselective monodebromination
of gem-dibromocyclopropanes with the vanadium catalyst in
cooperation with diethyl phosphonate or triethyl phos-
phite.18,19 Further studies on the scope and precise mech-
anism are underway, as well as the construction of new
catalytic systems of low-valent metals.20
The representative results of the reductive coupling of
aliphatic aldehydes by using the cat. Cp2VCl2/R3SiCl/Zn are
shown in Table 2, which are strongly suggestive of a wide
range of secondary aldehydes that participate in the highly
diastereoselective pinacol coupling (entries 1-4). As well
as secondary aldehydes, catalytic reactions of primary
aldehydes in THF also provided the corresponding 1,2-diols
selectively in excellent yields; however, their diastereose-
lectivities were very low (entries 5-7). These results
strongly suggest that the diastereoselection is affected
strongly by the bulkiness of the R-position of aldehydes.
On the other hand, the catalytic pinacol coupling of
ketones such as acetophenone proceeded efficiently with low
Ack n ow led gm en t. This research was supported in
part by a Grant-in-Aid for Scientific Research on Priority
Areas from the Ministry of Education, Science and Culture,
J apan.
(13) (a) Corey, E. J .; Danheiser, R. K.; Chandrasekaran, S. J . Org. Chem.
1977, 42, 2655. (b) McMurry, J . E.; Kees, K. L. J . Org. Chem. 1977, 42,
2655. (c) Molander, G. A.; Kenny, C. J . J . Org. Chem. 1988, 53, 2134. (d)
McMurry, J . E.; Rico, J . G. Tetrahedron Lett. 1989, 30, 1169. (e) Raw, A.
S.; Pedersen, S. F. J . Org. Chem. 1991, 56, 830. (f) Chiara, J . L.; Cabri, W.;
Hanessian, S. Tetrahedron Lett. 1991, 32, 1125. (g) Hays, D. S.; Fu, G. C.
J . Am. Chem. Soc. 1995, 117, 7283.
(14) In the case of ketones, the formation of dioxolanes is very slow even
in DME, and therefore, DME can be employed as a solvent for the catalytic
pinacol coupling to give 1,2-diol. On the other hand, the catalytic pinacol
coupling reaction in THF at temperatures over 45 °C was accompanied by
a ring opening reaction of THF.
(15) For the reductive intramolecular cyclization using stoichiometric
amounts of SmI2, see: (a) Molander, G. A.; Kenny, C. J . Am. Chem. Soc.
1989, 111, 8236. (b) Molander, G. A.; Harring, L. J . Org. Chem. 1990, 55,
6171. (c) Molander, G. A.; McKie, J . A. J . Org. Chem. 1992, 57, 3132. For
V(II) induced reductive intramolecular cyclization, see: (d) Inokuchi, T.;
Kawafuchi, H.; Torii, S. J . Org. Chem. 1991, 56, 4983.
Su p p or tin g In for m a tion Ava ila ble: Analytical data on the
compounds prepared (IR, 1H NMR, 13C NMR, and mass spectra;
elemental analyses) and NMR spectra of 2e (8 pages).
J O980376J
(17) Curran, D. P.; Porter, N. A.; Giese, B. In Stereochemistry of Radical
Reactions; VCH Press: Weinheim, 1995.
(18) Hirao, T.; Hirano, K.; Hasegawa, T.; Ohshiro, Y.; Ikeda, I. J . Org.
Chem. 1993, 58, 6529.
(19) For some other catalytic system of early transition metals, see, for
example: (a) Fu¨rstner, A.; Shi, N. J . Am. Chem. Soc. 1996, 118, 2533. (b)
Corey, E. J .; Zheng, G. Z. Tetrahedron Lett. 1997, 38, 2045.
(20) For YbI2-catalyzed reduction with Al, see: Ogawa, A.; Ohya, S.;
Sumino, Y.; Sonoda, N.; Hirao, T. Tetrahedron Lett. 1997, 38, 9017.
(16) The same reaction at 20 °C provided 52% (R-Me/â-Me ) 60/40) of 5
(trans-isomer) with the formation of its cis-isomer (ca. 20%).