2070
J . Org. Chem. 1998, 63, 2070-2071
Novel Con cep t for Efficien t
Tr a n sition -Meta l-Ca ta lyzed Rea ction s:
A High ly Dia ster eoselective
Tita n ocen e-Ca ta lyzed P in a col Cou p lin g
u n d er Bu ffer ed P r otic Con d ition s
Andreas Gansa¨uer* and Daniel Bauer
Institut fu¨r Organische Chemie der Georg-August-Universita¨t,
Tammannstr. 2, 37077 Go¨ttingen, Germany
Recently, a great deal of attention has been devoted to
the development of catalytic reactions from stoichiometric
transformations. Since the first report on the use of TMSCl
to effect a McMurry coupling catalytic in titanium powder,1
this concept was successfully applied in a number of reac-
tions.2-4 Although powerful in most cases, this method has,
however, two disadvantages. First, after hydrolysis during
work-up hexamethyldisiloxane is generated in stoichiometric
amounts that can not be readily recycled and must be
disposed of as waste. Second, silylation frequently is the
slowest step in the catalytic cycle, and therefore, TMSCl and
similarily active or even more reactive silylating reagents,
e.g., TMSOTf, have to be employed to render the reaction
catalytic.
F igu r e 1. Titanocene-catalyzed pinacol couplings under buffered
protic conditions.
Herein, we address these disadvantages and disclose our
results on the first example of achieving catalytic turnover
by protonation of the metal-oxygen bond. Protonations are
amongst the fastest reactions, and therefore, catalytic turn-
over could be increased compared to silylation. The proton
donor used in the catalytic reaction should be readily re-
covered by protonation of the formed base with a strong acid.
These advantages over silylation should become especially
important in large-scale applications.
F igu r e 2. Pyridine hydrochlorides used in this study.
as stoichiometric reductant at 0.1 M concentration in THF
with 3-5 as proton donors. The results of these studies are
summarized in Table 1.
We decided to probe this novel concept in designing titano-
cene-catalyzed pinacol couplings5 as part of our ongoing
program directed towards the development of transition-
metal-catalyzed radical reactions (Figure 1). To achieve our
goal, the utilized acid must be strong enough to protonate
the titanium-oxygen bond. However, the stoichiometric re-
ductant, i.e. a metal powder, should not be oxidized or the
catalyst deactivated by complexation of the corresponding
base. Clearly, this sets limitations on the acidity, i.e., the
pKa value, the steric accessibility of the acid, and the donor
strength of the corresponding base. For our purpose, an
ideal class of acids seemed to be pyridine hydrochlorides.
According to their pKa values in water, e.g., 5.25 for pyri-
dine hydrochloride6 (3), 6.65 for 2,6-lutidine hydrochloride6
(4), 7.43 for 2,4,6-collidine hydrochloride6 (5), protona-
tion of titanocene alkoxides seemed to be readily possible
(Figure 2).
The effect of substitution on the pyridine hydrochlorides’
ability to enable catalytic reactions was dramatic. Com-
mercial pyridine hydrochloride 3 as acid did not lead to
detectable conversion to products. No titanium(III) reagent
was formed (Table 1, entry 1). 2,6-Lutidine hydrochloride
4 gave the 1,2-diol in 75 % yield but with low diastereose-
lectivity of 82:18 in favor of 1 (Table 1, entry 2). Gratify-
ingly, collidine hydrochloride 5 led to a noticeable improve-
ment in diastereoselectivity (95:5), albeit with a reduced
yield of 68% (Table 1, entry 3). A small amount of benzyl-
alcohol was also formed, and about 20 % of benzaldehyde
remained unreacted. It is reasonable to assume that the
reason for the superiority of 5 for achieving catalytic
turnover with high diastereoselectivity is a combination of
its inability to promote electron transfer from Mn to ben-
zaldehyde and its weak complexation tendency with tita-
nium. When Zn was used instead of Mn diastereoselectivity
decreased dramatically (Table 1, entry 4). Other metals
used as stoichiometric reductants, e.g., Al, did not lead to
catalytic turnover. Compared to the ability of Zn/TMSCl or
Mn/TMSCl to initiate pinacol couplings of aldehydes7 and
ketones, our stoichiometric reductive system Mn/5 did not
react with aliphatic or aromatic ketones at all and only very
sluggishly with aliphatic aldehydes or benzaldehyde (Table
1, entry 5) without the presence of a catalyst. The reason
for the superiotity of Mn as stoichiometric reductant com-
pared to Zn is unclear at present; however, Zn induces the
uncatalyzed reaction significantly faster than Mn (Table 1,
entry 6) presumably, because the formed ZnCl2 is a stronger
lewis acid than MnCl2. Thus, Mn/5 constitutes an ideal
Initial experiments were conducted with benzaldehyde,
3 mol % titanocene dichloride as precatalyst, and manganese
* To whom correspondence should be addressed. Tel.: +49/551-393240.
Fax: +49/551-392944. E-mail: agansae@gwdg.de.
(1) Fu¨rstner, A.; Hupperts, A. J . Am. Chem. Soc. 1995, 117, 4468.
(2) (a) Fu¨rstner, A.; Shi, N. J . Am. Chem. Soc. 1996, 118, 2533. (b)
Fu¨rstner, A.; Shi, N. J . Am. Chem. Soc. 1996, 118, 12349.
(3) (a) Hirao, T.; Hasegawa, T.; Muguruma, Y.; Ikeda, I. J . Org. Chem.
1996, 61, 366. (b) Nomura, R.; Matsuno, T.; Endo, T. J . Am. Chem. Soc.
1996, 118, 11666. (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.
(4) Corey, E. J .; Zheng, G. Z. Tetrahedron Lett. 1997, 38, 1045.
(5) For stoichiometric pinacol couplings initiated by low-valent titanium
reagents, see: (a) Raubenheimer, H. G.; Seebach, D. Chimia 1986, 40, 12.
(b) Handa, Y.; Inanaga, J . Tetrahedron Lett. 1987, 28, 5717. (c) Barden, M.
C.; Schwartz, J . J . Am. Chem. Soc. 1996, 118, 5484.
(6) Handbook of Chemistry and Physics, 78th ed.; CRC Press: Boca
Raton, FL, 1997; pp 8-45-8-55.
(7) (a) So, J .-H.; Park, M.-K.; Buodjouk, P. J . Org. Chem. 1988, 53, 5871.
(b) Gansa¨uer, A.; Bauer, D. Unpublished results.
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Published on Web 03/12/1998