Reductive pinacol coupling of aromatic carbonyl compounds catalytic in chromium(II)

Article abstract of DOI:10.1055/s-1998-1695

Reductive coupling of aromatic and heteroaromatic aldehydes and ketones bearing different functional groups to pinacols is effectively catalysed with 1-5 mol % of Cr(II) salts or chromocene in THF/DMF mixtures in the presence of manganese powder and trialkyl chlorosilanes. Excellent dl selectivity can be achieved albeit with lower yield using trialkylsilyl chlorides with bulky substituents.

Full text of DOI:10.1055/s-1998-1695

May 1998
SYNLETT
549
Reductive Pinacol Coupling of Aromatic Carbonyl Compounds Catalytic in Chromium(II)
*
Aleš Svatoš and Wilhelm Boland
Max-Planck Institute for Chemical Ecology, Tatzendpromenade 1a, D-07745 Jena, Germany
Fax: +49(0)3641-643663, e-mail: Boland@ice.mpg.de
Received 23 February 1998
Abstract: Reductive coupling of aromatic and heteroaromatic
aldehydes and ketones bearing different functional groups to pinacols is
effectively catalysed with 1-5 mol % of Cr(II) salts or chromocene in
THF/DMF mixtures in the presence of manganese powder and trialkyl
chlorosilanes. Excellent dl selectivity can be achieved albeit with lower
yield using trialkylsilyl chlorides with bulky substituents.
absence of chromium the reduction of the carbonyl compound 1a to
benzyl alcohol 2a became a significant side reaction.
1
Pinacol coupling is an important carbon-carbon forming reaction that
usually proceeds via single-electron transfer from a metal to a carbonyl
group generating the corresponding ketyl radical that can dimerise to
either dl or meso isomers of substituted glycols. Conventional single-
2
electron reductions require for stoichiometric amounts of metals (Mg,
3
4
2,5d
Zn ), metallic salts (SmI
TiX
) or combinations of both. To
2,
n
reduce the high amounts of toxic and sometimes environmentally
critical elements, more recently catalytic systems using non-
stoichiometric amounts of metal salts or organometallic complexes of V
or Ti, powered by cheap metals (Mg, Zn, Mn), were successfully
2a, 5a-c, 6
developed.
The limited solubility of CrCl and CrCl in unpolar organic solvents,
2
3
the demand for an aprotic environment to suppress the reduction of
aldehydes to alcohols and the reactivity of the trialkylsilyl chloride
restrict the choice of solvents considerably. Good to excellent results
were obtained with THF and THF/DMF mixtures. Best results with
respect to yield and reaction time were obtained in the binary solvent
THF/DMF (1:1, v:v). In pure THF the reaction was much slower (Table
2). DMF increases the oxidation potential and solubility of the
During our investigations of a catalytic cycle for chromium(II)-induced
olefinations of carbonyl compounds with 1-acetoxy-1-bromides we
7
observed the formation of substantial amounts of hydrobenzoin 3a in
8
reactions with benzaldehyde. This type of reductive pinacol coupling
9
promoted by chromium(II) is principally known, but was studied only
10
in aqueous acids. In fact, when benzaldehyde was treated in a binary
solvent mixture of THF/DMF with CrCl (5 mol %) and trimethylsilyl
3
12
7
chromium salts and is believed to catalyse the reduction of Cr(III) to
Cr(II).
chloride (TMSCl, 2.2 eq.) in the presence of Mn-dust according to the
6b
protocol of Fürstner, the corresponding hydrobenzoin was obtained in
good yield (Scheme 1). Here we report the scope and the limitations of
the novel ternary reagent system of chromium(II)/metal/R SiCl for
3
pinacol coupling with respect to reagent combinations, reaction
conditions and stereoelectronic aspects of the substrates employed
(Scheme 1).
To cope with the solubility problems, we studied alternatively the use of
chromocene (Cp Cr) in unpolar solvents like toluene and more polar
2
solvents like THF and acetonitrile (Table 2). Again, binary solvent
systems with DMF as the cosolvent proved to be superior and led to
enhanced transformation rates (entry 12). Pure acetonitrile was
ineffective.
Scheme 1
As shown above, the presence of trialkysilyl chlorides was essential for
the reaction (Table 1, entries 1 and 4). Besides the activation of the
metal surface and the cleavage of intermediary Cr-O bonds the trialkyl
The experiments listed in Table 1, entries 1-5, established the catalytic
effect of chromium and proved the addition of TMSCl as essential for
activation. Reactions proceeded generally well, and even in the presence
6
silylchlorides serve as a source of chloride counterions for the
of only 1 mol % of CrCl good yields were still obtained after prolonged
dissolving zinc or manganese metal. Moreover, in accord with previous
3
4,6a
reaction times (entry 6). With respect to the transfer of two electrons for
the whole process this corresponds to about 140 catalytic cycles for
chromium. When only metal dusts (Mn, Zn) and TMSCl were used, the
formation of the hydrobenzoin 3 (Mn-powder, entry 3) was either very
slow, or did not proceed to a noticeable extent (Zn-dust, entry 1). In the
proposals,
we assume that the trialkylsilyl chlorides will activate the
carbonyl groups by forming the Lewis acid-base adduct 4. The latter
facilitates the transfer of a single electron to the carbonyl carbon atom
generating the stabilised silylalkoxy radical 5 which is either further
reduced to the silylated alcohol 2 or dimerises to the silylated pinacols 3

550
LETTERS
SYNLETT
(Scheme 2). Evidence for the direct participation and the influence of
the silyl moiety on the dimerisation of the ketyl radicals can be seen in
the observation, that with the very bulky TBDPSCl the radical
recombination (entry 8) proceeds i) much slower and that, due to the
high steric constraints between the two approaching silylalkoxy
radicals, the radical is ii) reduced to a significant extent by a second
electron to yield the silylated benzyl alcohol. On the other hand, the
bulkiness of the TBDPSCl derived silylalkoxy radicals led to an
excellent dl selectivity (Table 1, entry 8), and supported thereby the
direct involvement of silyloxy-moieties in the dimerisation of the ketyl
radicals. To our knowledge this is the first example of a dramatic control
diastereoselectivity of the reaction is predominantly controlled by the
trialkylsilyl chloride used for the activation.
Acknowledgements:
Financial
support
by
the
Deutsche
Forschungsgemeinschaft, Bonn, and the Fonds der Chemischen
Industrie, Frankfurt, is gratefully acknowledged. We also thank the
BASF, Ludwigshafen, and the Bayer AG, Leverkusen, for their generous
supply of chemicals and solvents. Thanks are also due to the Alexander-
von-Humboldt foundation for a fellowship (1997-1998) for A.S. and
Mr. Claus Schreiber for assistance.
of diastereoselectivity by
pinacolisation reactions.
a trialkylsilyl chloride additive in
References and Notes:
(1) (a) Wirth, T. Angew. Chem. Int. Ed. Engl. 1996, 35, 61. (b)
Dushin, R.G. In Comprehensive Organometallic Chemistry II;
Hegedus, L.S. Ed.; Pergamon; Oxford, 1995; Vol. 12, pp 1071. (c)
Robertson, G.M. In Comprehensive Organic Synthesis; Trost,
B.M. Ed.; Pergamon; New York, 1991, Vol. 3, pp 563.
(2) (a) Maury, O.; Villiers, C.; Ephritikhine, M. New J. Chem. 1997,
21, 137. (b) Fürstner, A.; Csuk, R.; Rohrer, C.; Weidmann, H. J.
Chem. Soc. Perkin Trans. I 1988, 1729.
Scheme 2
(3) (a) Tsukinoki, T.; Kawaji, T.; Hashimoto, I.; Mataka, S.; Tashiro,
M. Chem. Lett. 1997, 235. (b) Banerjee, A.K.; Sulbaran de
Carrasco, M.C.; Frydrych-Houge, C.S.V.; Motherwell, W.B.
Chem. Commun. 1986, 1803.
The synthetic scope of the catalytic system was further evaluated by
using the carbonyl compounds 1c-i and the reagent combinations listed
in Table 3. As a matter of fact, the system tolerated functional groups at
the aromatic nucleus, and the corresponding pinacols were isolated in
synthetically useful yields throughout. The aliphatic aldehyde (1h)
proved to be inert, while the α,β-unsaturated cinnamyl aldehyde (1i)
yielded a complex mixture of products.
(4) (a) Yanada, R.; Negoro, N.; Yanada, K.; Fujita, T. Tetrahedron
Lett. 1997, 38, 3271. (b) Honda, T.; Katoh, M. J. Chem. Soc.
Chem. Commun. 1997, 369. (c) Akane, N.; Kanagawa, Y.;
Nishiyama, Y.; Ishi, Y., Chem. Lett. 1992, 2431. (d) Shiue, J.S.;
Lin. C.C.; Fang, J.M. Tetrahedron Lett. 1993, 34, 335. (e) Namy,
J.L.; Souppe, J.; Kagan, H.B. Tetrahedron Lett. 1983, 24, 765.
(5) (a) Lipski, T.A., Hilfiker, M.A., Nelson, S.G. J. Org. Chem. 1997,
62, 4566. (b) Gansäuer, A.. Chem. Commun. 1997, 457. (c)
Gansäuer, A. Synlett 1997, 363. (d) Barden, M.C.; Schwartz, J. J.
Am. Chem. Soc. 1996, 118, 5484.
(6) (a) Hirao, T.; Hasegawa, T.; Muguruma, Y.; Ikeda, I. J. Org.
Chem. 1996, 61, 366. (b) Fürstner, A; Shi, N. J. Am. Chem. Soc.
1996, 118, 12349. (c) Matsubara, S.; Horiuchi, M.; Takai, K.;
Utimoto, K. Chem. Lett. 1995, 259.
(7) (a) Knecht, M.; Boland, W. Synlett 1993, 837. (b) Knecht, M.
Dissertation, University Bonn, 1994.
(8) Svatoš, A.; Boland, W. unpublished results.
(9) Hodgeson, D.M. J. Organometall. Chem. 1994, 476, 1, see note in
ref. 6b.
Since the exchange of the organic ligands of complexes of
(10) (a) Davis, D.D.; Bigelow, W.B. J. Am. Chem. Soc. 1970, 92, 5127.
(b) Conant, J.B.; Cutter, H.B. J. Am. Chem. Soc. 1926, 48, 1016.
organometallic compounds can be used in principle to optimise and
6a,b
control the selectivity and reaction rate,
we also tested (BiPy) Cr(III)
3
(11) Handlír, K, Holecek, J, Klikorka, J. Z. Chem. 1979, 19, 265.
(12) Clerici, A.; Porta, O. J. Org. Chem. 1989, 54, 3872.
and compared commercial chromocene with a complex produced in situ
and Cr(III) salts (Table 3). The (BiPy) Cr(III) complex failed to
3
catalyse the pinacol formation, but chromocene induced pinacolisation
at comparable rates to Cr(III)-chloride. The ratio of the d,l/meso-
products was, however, not affected. To eliminate the possibility, that
General synthetic procedure: A dry 50 ml two-necked round-bottom
flask equipped with condenser and Teflon -faced stirrer bar, containing
®
the metal powder (15.3 mmol) and the chromium(III) salt or a
chromium complex (0.2 mmol), was sealed with a septum and
evacuated with stirring for 10 min (oil pump). Then, the flask was
purged with argon and solvent(s) (ca. 10 ml) containing dodecane as an
internal standard (100 µl) were added. After stirring for ca. 2 min the
chloro trialkylsilane (8.8 mmol) was injected over a period of ca. 1 min
resulting in a violent reaction and gas evolution. This mixture was
stirred at the reaction temperature (see Tables; generally 65°C) and the
neat carbonyl compound or a solution of the carbonyl compound in an
appropriate solvent (4 mmol) was injected within 1-2 min. Stirring was
this might be due to partially destroyed chromocene, which is known to
10
be strongly air-sensitive, the complex was prepared in situ from CrCl
2
-
+
and C H Na . As a matter of fact, the in situ production of the
5
5
catalytically active complex proved to be superior and provided a more
reactive catalyst (Table 3, entries 20 and 23).
In conclusion, the pinacol reductive coupling is effectively catalysed by
1-2 mol % Cr(II) salts or chromocene co-reduced with cheap manganese
powder. The coupling showed excellent selectivity for aromatic and
heteroaromatic aldehydes and ketones. The reaction rate and the

May 1998
SYNLETT
551
maintained as indicated in Tables and, after cooling to rt., the reaction
was stopped by slow addition of a mixture of water and ethyl acetate (5
ml each). Solids were removed by filtration, the organic phase was
separated, and the aqueous layer was extracted with ethyl acetate (3 ×
10 ml). The combined organic phases were washed with brine (10 ml),
dried over magnesium sulfate and the solvents were removed under
gradient of ether or ethyl acetate in petroleum ether. 1,2-diphenyl-1,2-
ethandiol (3a). Prepared (entry 5) from 1a (0.424 g, 4 mmol) in THF/
DMF (1:1, v:v) at 65 °C using manganese powder, TMSCl and CrCl (5
3
mol %). Yield: 0.32 g (74%). M.p. 109 °C. High resolution MS:
calculated for C
H O : 214.0994, found: 214.0984. MS (EI, m/z (%)):
14 12 2
+.
214 (M ,1), 197 (1), 180 (5), 108 (97), 107 (100), 91 (2), 79 (79), 77
13
1
1
reduced pressure. Crude mixtures were analysed by CG-MS and C, H
(46). H NMR (CDCl ): d,l, δ 2.2 (2H, bs, OH), 4.7 (2H, s, CH-O), 7.1-
3
2b
NMR spectroscopy and the dl/meso ratio was determined. Silyl
7.4 (10 H, m, Ar-H) meso: 2.2 (2H, bs, OH), 4.85 (2H, s, CH-O), 7.1-7.4
13
groups were cleaved off upon stirring of the reaction mixtures with a
solution of tetrabutylammonium fluoride in THF (1M, 1.2 equiv).
Products were purified by column chromatography on silica gel using a
(10 H, m, Ar-H). C NMR (CDCl ): d,l, δ 79.13, meso: 78.12. IR
3
(KBr): 3374 (OH), 3028, 2896 (=C-H), 1601, 1493 (Ar ring), 1336 (-
-1
OH), 1034 (C-O), 854, 697 (=CH) cm .