Reduction of hydroxy-functionalised carbaboranyl carboxylic acids to tertiary alcohols by organolithium reagents

Article abstract of DOI:10.1039/c3dt52826j

Reduction of hydroxy-functionalised carbaboranyl carboxylic acids by organolithium reagents yields the corresponding tertiary alcohols. This is in contrast to exo-polyhedral C-C bond cleavage of unsubstituted carbaboranyl carboxylic acids upon reaction with lithium organyls. The proposed dimeric contact ion pairs may also explain the formation of tertiary alcohols instead of the expected ketones.

Full text of DOI:10.1039/c3dt52826j

Volume 43 Number 13 7 April 2014 Pages 4911–5232
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Hey-Hawkins et al.
Reduction of hydroxy-functionalised carbaboranyl carboxylic acids to
tertiary alcohols by organolithium reagents

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Reduction of hydroxy-functionalised carbaboranyl
carboxylic acids to tertiary alcohols by
organolithium reagents†
Cite this: Dalton Trans., 2014, 43,
4935
Received 8th October 2013,
Accepted 8th November 2013
Wilma Neumann, Markus Hiller, Peter Lönnecke and Evamarie Hey-Hawkins*
DOI: 10.1039/c3dt52826j
www.rsc.org/dalton
Reduction of hydroxy-functionalised carbaboranyl carboxylic acids
by organolithium reagents yields the corresponding tertiary
alcohols. This is in contrast to exo-polyhedral C–C bond cleavage
of unsubstituted carbaboranyl carboxylic acids upon reaction with
lithium organyls. The proposed dimeric contact ion pairs may also
explain the formation of tertiary alcohols instead of the expected
ketones.
Scheme 1
Carbaboranyl alcohols are commonly synthesised by reaction
of C-lithiated derivatives with epoxides, aldehydes or
ketones to yield primary, secondary or tertiary alcohols,
respectively, while attempts to reduce carbaboranyl ketones
with Grignard or organolithium reagents to yield tertiary alco-
hols usually result in cleavage of the exo-polyhedral C–C bond
excess of the used organolithium reagent, although the latter
would be expected to react preferentially with carbon dioxide.
Reduction of carboxylic acids with organolithium reagents
typically results in the formation of the corresponding ketones
3
as main products; attack of the organolithium reagent at a
1
carboxylate leads to a geminal diol, which gives the corres-
ponding ketone upon acidic work-up. A tertiary alcohol cannot
be formed under these conditions, as elimination of an oxygen
atom would be required. Only a second reduction step after
of the cluster. Especially the use of organolithium reagents
leads to cleavage of the carbon–carbon bond, probably due to
1
e,f
formation of an unstable tertiary alkoxide. It was suggested
that the intermediate alcoholates are more stable when
formed by Grignard reagents, as O–Mg bonds are less polar
3
work-up of the ketone yields the tertiary alcohol. Thus, the
1
g
unexpected formation of a carbaboranyl alcohol seems to
involve a different mechanism.
than O–Li bonds.
Similar reactivity was reported for
1
f
carbaboranyl esters. Thus, exo-polyhedral C–C bond cleavage
should also be expected in the reaction of carbaboranyl car-
boxylic acids with organolithium reagents, as the electron-
deficient cluster highly activates the terminal carboxyl group
for facile reaction with the organolithium reagent resulting in
cleavage of the carboxylic acid rather than reduction.
We therefore further investigated this unique reactivity of
2
1-hydroxy-1,2-dicarba-closo-dodecaboranyl-2-carboxylic acid (1a)
with specific alkyl lithium reagents, which provides a synthetic
route towards selected tertiary carbaboranyl alcohols (Table 1).
However, during the carboxylation of the lithiated
-hydroxy-1,2-dicarba-closo-dodecaborane, formation of a side
product was observed, which was identified as the corres-
ponding tertiary alcohol of the targeted carbaboranyl car-
Table 1 Reduction of carbaboranyl carboxylic acids by organolithium
reagents
1
boxylic
acid, 1-hydroxy-1,2-dicarba-closo-dodecaboranyl-2-
2
carboxylic acid (salborin) (Scheme 1). This observation
suggests that the carboxylic acid was further reduced by an
Universität Leipzig, Institut für Anorganische Chemie, Johannisallee 29, 04103
Leipzig, Germany. E-mail: hey@uni-leipzig.de; Fax: +49-341-9739319;
Tel: +49-341-9736151
1
2
Reaction
R
R
Products
1
2
3
4
OH
H
OCH
OH
C
C
C
4
4
4
H
H
H
9
9
9
b + c (1 : 1)
c
c
†
Electronic supplementary information (ESI) available. CCDC 961910. For ESI
and crystallographic data in CIF or other electronic format see DOI: 10.1039/
c3dt52826j
3
CH
3
b + c (1 : 1)
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Scheme 2
Thus, the tertiary alcohol 1b could be selectively prepared diolate (Scheme 2). This assumption is further supported by
from pure salborin (1a) and n-BuLi and was fully characterised the fact that the respective 1-methoxy-1,2-dicarba-closo-dodeca-
including X-crystallography.‡ However, even use of a large boranyl-2-carboxylic acid (3a) did not give the corresponding
excess of n-butyllithium did not increase the yield of 1b to tertiary alcohol but only the decarboxylation product 3c in the
more than 50%. Furthermore, formation of the tertiary alcohol reaction with n-BuLi. Besides methylation of salborin (1a), also
1
b was always accompanied by formation of 1-hydroxy- addition of tetramethylethylenediamine (tmeda), which is
carbaborane 1c resulting from cleavage of the exo-polyhedral known to be an excellent Lewis base for the complexation of
C–C bond. Thus, full conversion of salborin (1a) always gives a lithium cations, noticeably decreased the formation of the ter-
1
: 1 mixture of 1b and 1c.
tiary alcohol 1b in the reaction of 1a with n-BuLi.
The proposed mechanism involving the formation of
Other organolithium reagents besides n-butyllithium were
dimeric contact ion pairs (Scheme 2) explains the formation of also employed in the reduction of salborin. While methyl-
the tertiary alcohol 1b together with 1-hydroxy-carbaborane lithium gave the corresponding tertiary alcohol 2-(1-hydroxy-
1
c.§ The formation of such dimers would allow transfer of an 1,2-dicarba-closo-dodecaboranyl)-propan-2-ol (4b) (Table 1),
oxygen atom of the intermediate geminal diol to the carboxy- the addition of sec- or tert-butyllithium as well as phenyl-
late group of a second lithiated salborin molecule. The result- lithium only resulted in decarboxylated 1-hydroxy-carbaborane
ing cleavage of the exo-polyhedral C–C bond would lead to 1c, that is, the steric properties of the organolithium reagent
elimination of lithium carbonate as well as formation of the also have a major influence on the reaction. Thus, sterically
corresponding ketone as intermediate and dilithiated 1c. The demanding reagents apparently promote exo-polyhedral C–C
highly reactive ketone is then further reduced to the tertiary bond cleavage by preventing formation of the proposed
alcohol 1b by n-butyllithium, and acidic work-up gives the dimeric contact ion pairs.
observed 1 : 1 mixture of 1b and 1c. The formation of hydro-
gen-bonded dimers by carbaboranyl carboxylic acids is well
4
known from crystal structures of different derivatives.
However, in solution and upon deprotonation, different inter-
actions can be expected.
Conclusions
Salborin (1a) mainly differs from other carbaborane deriva- 1-Hydroxy-1,2-dicarba-closo-dodecaboranyl-2-carboxylic
acid
tives which were reported to undergo exo-polyhedral C–C bond (salborin, 1a) reacted with n-butyllithium and methyllithium
1
cleavage upon reaction with organolithium reagents in the to give unexpectedly the corresponding tertiary alcohols 1b
substituent at the second carbon atom of the cluster, i.e., a and 4b in 1 : 1 mixtures with 1-hydroxy-carbaborane 1c, which
hydroxyl group. Indeed, when the reaction was carried out could be separated by column chromatography or crystallisa-
5
with 1,2-dicarba-closo-dodecaboranyl-1-carboxylic acid (2a),
tion. The proposed reaction mechanism involving the for-
only the unsubstituted cluster 2c was obtained by decarboxyla- mation of dimeric contact ion pairs also underlines the
tion (Table 1). Thus, the hydroxyl group seems to play an importance of the hydroxyl group in the 1-position of the
important role in the mechanism of reduction by preventing cluster in this process. Thus, carbaboranyl carboxylic acids
exo-polyhedral C–C bond cleavage in these compounds. without a hydroxyl group and the use of sterically demanding
According to the proposed mechanism, the hydroxyl group organolithium reagents led exclusively to exo-polyhedral C–C
could be involved in stabilising the intermediate geminal bond cleavage.
4936 | Dalton Trans., 2014, 43, 4935–4937
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(
3
d) L. I. Zakharkin and A. I. L’vov, Zh. Obshch. Khim., 1967,
7, 1154, [Russian; p. 1217]; (e) R. N. Grimes, Carboranes,
Acknowledgements
We thank the Fonds der Chemischen Industrie (FCI, doctoral
grant to W.N.) and the Graduate School Leipzig School of
Natural Sciences – Building with Molecules and Nano-objects
Elsevier, Amsterdam, 2nd edn, 2011, ch. 9.10, pp. 436–437;
(f) L. I. Zakharkin and A. I. L’vov, J. Organomet. Chem., 1966,
5, 313; (g) A. I. L’vov and L. I. Zakharkin, Izv. Akad. Nauk.
SSSR, Ser. Khim., 1967, 2527, [Russian; p. 2653];
(h) V. Terrasson, J. G. Planas, D. Prim, C. Viñas, F. Teixidor,
M. E. Light and M. B. Hursthouse, J. Org. Chem., 2008, 73,
(BuildMoNa) for their generous support. Furthermore, we
thank André Götze for support with the syntheses.
9
140; (i) V. Terrasson, J. G. Planas, D. Prim, F. Teixidor,
C. Viñas, M. E. Light and M. B. Hursthouse, Chem.–Eur. J.,
009, 15, 12030; ( j) V. Terrasson, Y. García, P. Farràs,
Notes and references
2
‡
3
3
3
0
30 10 2
Crystallographic data for 1b (MoKα radiation (λ = 0.71073 Å)): C11H B O , M =
02.45, orthorhombic, space group Pbca, a = 11.6357(9), b = 9.7575(8), c =
F. Teixidor, C. Viñas, J. G. Planas, D. Prim, M. E. Light and
M. B. Hursthouse, Cryst. Eng. Commun., 2010, 12, 4109;
3
1.537(4) Å, V = 3580.6(6) Å , Z = 8, T = 130(2) K, 25 019 reflections measured,
663 unique (Rint = 0.1138). Final R indices (all data): R
1 2
= 0.1001, wR =
(k) F. Di Salvo, B. Camargo, Y. García, F. Teixidor, C. Viñas,
.1356. Through OH⋯O donor–acceptor bonds chains are formed along the b axis.
J. G. Planas, M. E. Light and M. B. Hursthouse, Cryst. Eng.
Commun., 2011, 13, 5788.
The structure was solved by direct methods and all non-hydrogen atoms were
refined anisotropically. CCDC 961910 contains the supplementary crystallographic
data for this paper. These data can be obtained free of charge via www.ccdc.cam.ac. 2 M. Scholz, K. Bensdorf, R. Gust and E. Hey-Hawkins, Chem-
uk/conts/retrieving.html.
MedChem, 2009, 4, 746.
M. J. Jorgenson, Org. React., 1970, 18, 1.
§
In order to obtain spectroscopic evidence for the suggested intermediates,
3
4
1
11
1
7
time-resolved H, B{ H} and Li NMR spectra of the reduction reaction were
recorded. For this purpose, solutions of the lithium salt of salborin in Et O and
(a) A. J. Welch, U. Venkatasubramanian, G. M. Rosair, D. Ellis
and D. J. Donohoe, Acta Crystallogr., Sect. C: Cryst. Struct.
Commun., 2001, 57, 1295; (b) U. Venkatasubramanian, D. Ellis,
G. M. Rosair and A. J. Welch, Acta Crystallogr., Sect. C: Cryst.
Struct. Commun., 2003, 59, o559; (c) U. Venkatasubramanian,
D. Ellis, G. M. Rosair and A. J. Welch, Acta Crystallogr.,
Sect. C: Cryst. Struct. Commun., 2003, 59, o586;
2
n-BuLi in n-hexane were frozen out in an NMR tube. The NMR tube was allowed
to slowly warm up in the NMR spectrometer, which allowed data acquisition at
the starting point of the reaction. Despite very short measurement times (below
60 seconds) no signals of intermediates could be detected. The recorded spectra
either corresponded to those of the starting material or the reaction products.
This indicates that the rate of the reaction is too high to allow the detection of
intermediates on the NMR timescale.
(d) U. Venkatasubramanian, D. J. Donohoe, D. Ellis, B. T. Giles,
1
(a) R. N. Grimes, Carboranes, Elsevier, Amsterdam, 2nd edn,
011, ch. 9.9, pp. 427–430; (b) L. I. Zakharkin, Dokl. Akad.
Nauk. SSSR, 1965, 162, 817, [Russian]; (c) V. I. Stanko,
S. A. Macgregor, S. Robertson, G. M. Rosair, A. J. Welch,
A. S. Batsanov, L. A. Boyd, R. C. B. Copley, M. A. Fox,
J. A. K. Howard and K. Wade, Polyhedron, 2004, 23, 629.
2
A. I. Klimova, Yu. A. Chapovskii and T. P. Klimova, Zh. 5 R. A. Kasar, G. M. Knudsen and S. B. Kahl, Inorg. Chem.,
Obshch. Khim., 1966, 36, 1773, [Russian; p. 1779];
1999, 38, 2936.
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Dalton Trans., 2014, 43, 4935–4937 | 4937