Unexpected cleavage of tetrahydrofuran by catalytic reductive lithiation

Article abstract of DOI:10.1039/b312972a

DBB, an electron transporter, can open THF at room temperature under sonication without any Lewis acid activation. This feature was successfully exploited in the straightforward synthesis of bis-silanes.

Full text of DOI:10.1039/b312972a

Unexpected cleavage of tetrahydrofuran by catalytic reductive lithiation†
Stéphane Streiff, Nigel Ribeiro and Laurent Désaubry*
UMR 7509, Centre de Neurochimie, 5, rue Blaise Pascal, 67084 Strasbourg Cedex, France.
E-mail: desaubry@chimie.u-strasbg.fr; Fax: +33 (0)3 88 60 76 20; Tel: +33 (0)3 88 45 67 33
Received (in Cambridge, UK) 21st October 2003, Accepted 16th December 2003
First published as an Advance Article on the web 13th January 2004
DBB, an electron transporter, can open THF at room tem-
perature under sonication without any Lewis acid activation.
This feature was successfully exploited in the straightforward
synthesis of bis-silanes.
This author showed that refluxing a mixture of biphenyl and lithium
in THF affords some butanol after hydrolysis of the reaction
system. At that temperature, 4-lithiobutoxide decomposed, and its
formation was not quantified. Later, Cohen showed that, in
presence of boron trifluoride etherate, LiDBB cleaves THF
5
Over the past two decades, reductive lithiations catalyzed by
electron transporters, such as naphthalene or 1,4A-di-tert-butylbi-
phenyl (DBB), have been established as some of the most general
instantaneously at a temperature as low as 278 °C. This reactivity
stems from the complexation of the oxygen atom by this strong
Lewis acid. More recently, Yus and coworkers reported that the
dilithium naphthalene dianion reacts slowly with THF at room
temperature for 24 hours, affording after hydrolysis small amounts
of butanol as well as products of condensation of naphthalene with
THF.6
1
and versatile methods of organolithium production. Reductive
lithiation of phenylthioethers, in particular, has found many useful
applications. These reactions are performed in THF. The only
alternative solvent that has been used successfully is dimethyl
ether.2
During the course of our studies on the synthesis of allylsilanes
by catalytic reductive lithiation, we observed that allylthioethers
were deprotonated and not reduced, depending on reaction
conditions. The reductive lithiation of phenylthioethers has been
known for over 20 years, and our observation was in apparent
contradiction with previous reports.1,3 This led us to investigate the
cause of this aberrant behaviour.
We examined the conditions of formation of the reducing agent
LiDBB (Table 1). To prepare this reagent, an excess of lithium and
a catalytic amount of DBB were sonicated for less than 5 minutes
at room temperature to afford a dark-green solution (conditions A).
This was immediately cooled to the desired temperature. In the
second procedure (conditions B) the time of sonication was
extended to 1 h.
When we analyzed a solution of LiDBB prepared according to
conditions B, we were pleased to notice the formation of a
substantial amount of n-butanol (0.27 M). We quantitatively
monitored, after hydrolysis, the formation of n-butanol by GC (Fig.
1). The efficiency of this process accounts well for the deprotona-
tion of 1, as depicted in Scheme 1. Entry 4 in Table 1 shows that the
reductive lithiation of 1 is faster than its deprotonation by
4-lithiobutoxide at 242 °C. At 278 °C, it is the opposite (entry
3).
7
With few exceptions, DBB-catalyzed lithiations do not involve
extended sonication at room temperature, this may be why our
observation had not been reported.8
We took advantage of the property of DBB to catalyse the
reductive lithiation of both THF and thioethers, to synthesize the
bis-silane 4 (Scheme 2). Thioether 1 was first treated as in entry 1
in Table 1, to afford the intermediary adduct 3, which underwent a
subsequent reductive lithiation overnight before it was quenched by
TMSCl. The bis-silane 4 was obtained in 68% yield. This procedure
When LiDBB was prepared within 5 minutes, the reductive
lithiation of 1 occurred exclusively (Table 1, entries 1–2). On the
other hand, when it was prepared according to conditions B, we
obtained a substantial amount of silylated thioether 3 at 242 °C
(entry 4). This reaction was exclusive at 278 °C (entry 3). One
possible reason for these observations which came to mind is that
THF might be cleaved into 4-lithiobutoxide, which would deproto-
nate the thioethers. Such a reductive cleavage of THF has been
reported, albeit under more drastic conditions. Eisch was the first to
note that THF could be cleaved by lithium in presence of an arene.4
Table 1 Effect of the preparation of LiDBB on the reductive silylation of
thioether 1
Con-
ditions
Isolated
yield (%)
a
Entry
T/°C
2 : 3
Fig. 1 Formation of n-butanol after hydrolysis of 0.1 M solution of DBB
1
2
3
4
a
A
A
B
B
278
242
278
242
71
72
69
59
100 : 0
100 : 0
0 : 100
88 : 12
sonicated at r.t.
Conditions A: a mixture of Li and DBB in THF was sonicated for less than
5
minutes at r.t.; conditions B: sonication for 1 hour at r.t. 1 was then added
at the indicated temperature. When the medium recovered its dark-green
colour, TMSCl was added.
Scheme 1 Mechanism of formation of the silylated thioether 3.
†
Electronic supplementary information (ESI) available: experimental
procedures, THF cleavage kinetics and the synthesis of compounds 2, 3, 4
and 6. See http://www.rsc.org/suppdata/cc/b3/b312972a/
Scheme 2 (a) Li, cat. DBB, 278 °C, 4-lithiobutoxide, 30 min; (b) TMSCl,
278 °C; (c) 12 h, 278 °C; (d) TMSCl, 278 °C.
3
46
C h e m . C o m m u n . , 2 0 0 4 , 3 4 6 – 3 4 7
T h i s j o u r n a l i s © T h e R o y a l S o c i e t y o f C h e m i s t r y 2 0 0 4

is particularly convenient. Compared to other methods, it does not
require any preliminary titration and manipulation of a sensitive
reagent. The reappearance of the original dark-green colour
indicates that the deprotonation of the thioether is completed and
the chlorosilane may be added. When this colour reappears, the
reductive lithiation is completed and the second portion of TMSCl
is added.
Notes and references
1
For some reviews, see: (a) T. Cohen and M. Bhupathy, Acc. Chem. Res.,
1
989, 22, 152; (b) D. J. Ramon and M. Yus, Eur. J. Org. Chem., 2000,
2
25.
2
T. Cohen, T. Kreethadumrongdat, X. Liu and V. Kulkarni, J. Am. Chem.
Soc., 2001, 123, 3478.
3 (a) B. S. Guo, W. Doubleday and T. Cohen, J. Am. Chem. Soc., 1987,
109, 4710; (b) S. Marumoto and I. Kuwajima, J. Am. Chem. Soc., 1993,
Gratifyingly, we were able to apply the same strategy to
allylthioether 5 (Scheme 3). The bis-silane 6 was obtained in a 67%
yield. This synthesis represents therefore an improvement of the
1
15, 9021; (c) D. W. McCullough, M. Bhupathy, E. Piccolino and T.
Cohen, Tetrahedron, 1991, 47, 9727; (d) W. D. Abraham and T. Cohen,
J. Am. Chem. Soc., 1991, 113, 2313.
9
published procedures that involved two steps. This class of
4
5
J. J. Eisch, J. Org. Chem., 1963, 28, 707.
1
0
dinucleophilic reagents is useful in organic synthesis.
(a) B. Mudryk and T. Cohen, J. Am. Chem. Soc., 1991, 113, 1866. THF
cleavage can also be achieved with a catalytic amount of DBB or
naphthalene, see (b) D. J. Ramon and M. Yus, Tetrahedron, 1992, 48,
3
585. For other synthetic applications of THF cleavage, see (c) M.
Oikawa, H. Oikawa and A. Ichihara, Tetrahedron, 1995, 51, 6237; (d)
C. A. Dvorak and V. H. Rawal, Chem. Commun., 1997, 2381–2382.
M. Yus, R. P. Herrera and A. Guijarro, Chem. Eur. J., 2003, 8, 2574.
(a) R. Karaman and J. L. Fry, Tetrahedron Lett., 1989, 30, 4931; (b) C.
E. Neipp, J. M. Humphrey and S. F. Martin, J. Org. Chem., 2001, 66,
Scheme 3 (a) Li, cat. DBB, 278 °C, 4-lithiobutoxide, 30 min; (b)
TBDMSCl, 278 °C.
6
7
In summary, we have provided the first evidence that an electron
transporter can cleave THF at room temperature by sonication. This
feature was successfully exploited in the straightforward synthesis
of bis-silanes 4 and 6. Due to their usefulness in organic synthesis,
the reductive lithiation reactions are still the subject of intensive
development. Our finding that THF can be cleaved in mild
conditions should be taken into account in the design of new
lithiation reactions.
We are indebted to Professors Y. Nakatani and G. Ourisson for
their invaluable support. We are also grateful to Professor D. Uguen
for having suggested to us that opening of THF may account for our
observations. S. S. and N. R. are funded by a doctoral fellowship
from the Ministry of Research and Technology (MRT, France).
5
31.
8
THF derivatives substituted by a vinyl moiety undergo a smooth
reductive lithiation under mild conditions, see ref. 5a. For a review on
the reductive cleavage of small ring heterocycles, see: (a) M. Yus and F.
Foubelo, Rev. Heteroatom Chem., 1997, 17, 73. Epoxides and oxetanes
also undergo a reductive cleavage by LiDBB under smooth conditions,
for reviews, see: references 1b and 8a.
9
(a) T. Morita, Y. Okamoto and H. Sakurai, Tetrahedron Lett., 1980, 21,
8
35; (b) P. B. Hithcok, M. F. Lappert, W. P. Leung, D. S. Liu, T. C. W.
Mak and Z. X. Wang, J. Chem. Soc., Dalton Trans., 1999, 1257.
0 (a) H. O. House, P. C. Gaa and D. VanDerveer, J. Org. Chem., 1983, 48,
661; (b) F. Narjes, O. Bolte, D. Icheln, W. A. Konig and E.
1
1
Schaumann, J. Org. Chem., 1993, 58, 626; (c) A. Tubuland and M.
Santelli, Tetrahedron, 1988, 44, 3975.
C h e m . C o m m u n . , 2 0 0 4 , 3 4 6 – 3 4 7
347