Scope and selectivity of heterogeneous Rh0-catalyzed tandem dehydrocoupling/hydrogenation using Me2NHA·BH 3 as a stoichiometric H2 source

Article abstract of DOI:10.1002/ejoc.201001332

The catalytic dehydrocoupling of Me₂NHA·BH ₃ (1) by Rh/Al₂O₃ (2) has been shown to act as an efficient hydrogenation and reduction system for a variety of organic substrates. A range of functional groups have been reduced, but chloro, bromo and iodo substituents, epoxide and nitrile groups were found to be stable under the reaction conditions, allowing chemoselective hydrogenation reactions to be performed. This reduction has also been shown to proceed cleanly under atmospheric air for a few representative examples of alkene and nitro functional groups. The use of dimethylamine-borane in a the presence of Rh⁰ has been shown to function as an efficient hydrogenation/reduction system for a variety of organic substrates. This system has been shown to be mild by comparison to other reduction systems with epoxide, halide and nitrile groups unaffected under the reaction conditions used.

Full text of DOI:10.1002/ejoc.201001332

SHORT COMMUNICATION
DOI: 10.1002/ejoc.201001332
Scope and Selectivity of Heterogeneous Rh0-Catalyzed Tandem
Dehydrocoupling/Hydrogenation Using Me2NH·BH3 as a Stoichiometric H2
Source
Matthew E. Sloan,[a] Anne Staubitz,[a][‡] Kajin Lee,[a] and Ian Manners*[a]
Keywords: Amine–borane / Hydrogenation / Dehydrocoupling / Reduction
The catalytic dehydrocoupling of Me2NH·BH3 (1) by Rh/
Al2O3 (2) has been shown to act as an efficient hydrogenation
and reduction system for a variety of organic substrates. A
range of functional groups have been reduced, but chloro,
bromo and iodo substituents, epoxide and nitrile groups were
found to be stable under the reaction conditions, allowing
chemoselective hydrogenation reactions to be performed.
This reduction has also been shown to proceed cleanly under
atmospheric air for a few representative examples of alkene
and nitro functional groups.
These systems required the reaction to be carried out in a
closed vessel, and are therefore classed as tandem dehydro-
genation/hydrogenation reactions. Ketones and imines were
also used in a similar system, using a Ru catalyst and pyr-
rolidine–borane, but no attempts were reported to assess
the scope of this reaction.[9]
Introduction
The reduction of functional groups is an essential tool
for the design and synthesis of new compounds, and has
found many uses in synthetic chemistry.[1] Traditional
routes often using high pressures of H2 and transition metal
catalysts, or hydride reducing agents, such as NaBH3CN,
LiAlH4 and NaBH4, can be experimentally dangerous or
may require specialist equipment.[1,2] Lewis-base adducts of
borane have found use as reducing agents, with BH3·THF
and BH3·SMe2 being the most ubiquitous,[1] however these
reagents are also highly pyrophoric, and in the case
of BH3·SMe2 malodorous, and require handling under
inert conditions. By comparison, amine–borane adducts,
RxH3–xN·BH3, possess a much stronger coordination bond
and are often thermally and hydrolytically stable. Many
amine–borane adducts are available commercially[3] or al-
ternatively, are easily synthesized from BH3·THF and the
corresponding amine.[4]
We have previously communicated the use of hetero-
geneous Rh0, generated from [Rh(μ-Cl)(1,5-cod)]2,[5] or
homogeneous “Cp2Ti”[6] catalyzed dehydrocoupling[7] of
Me2NH·BH3 (1), with concomitant hydrogenation of cyclo-
hexene, 1-octene, and 1,5-cyclooctadiene in closed, one-pot
systems (Scheme 1). In both of these systems isolation of
the products was complicated by the presence of soluble
ligands from the catalyst. For example, cyclooctane is
formed upon reduction of [Rh(μ-Cl)(1,5-cod)]2 to Rh0.[8]
Scheme 1. Tandem dehydrocoupling of 1 and hydrogenation of cy-
clohexene by Rh colloids.
By comparison, there are also transition metal-catalyzed
dehydrogenation/hydrogenation reactions that can be per-
formed in open vessels, indicating a fundamentally different
mechanism and which are classed as true hydrogen transfer
reactions. For example, Couturier and co-workers have re-
ported the Pd-catalyzed methanolysis of Me3N·BH3 and
tBuNH2·BH3,[10] and their utilization as hydrogen transfer
reagents for the hydrogenation of a range of organic com-
pounds, such as nitrobenzenes to anilines (Scheme 2).[11]
Scheme 2. Pd-catalyzed methanolysis of Me3N·BH3 and reduction
of functionalized nitrobenzene.
[a] School of Chemistry, University of Bristol,
Cantocks Close, Bristol, BS8 1TS, UK
Berke and co-workers have reported the ReI-catalyzed
dehydrocoupling/dehydrogenation of 1 and subsequent hy-
drogenation of a range of olefins.[12] Both of these workers
performed the reactions in open systems, indicating that
molecular H2 is not involved in the reaction. These reac-
tions can therefore be regarded as transfer hydrogenation
Fax: +44-117-929-0509
E-mail: ian.manners@bristol.ac.uk
[‡] Present address: Otto-Diels-Institut für Organische Chemie,
Christian-Albrechts-Universität Kiel, Otto-Hahn-Platz 3,
24118 Kiel, Germany
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201001332.
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Eur. J. Org. Chem. 2011, 672–675

Rh0-Catalyzed Tandem Dehydrocoupling/Hydrogenation
reactions. Reactions concerning the reduction of various Table 1. Functional groups stable under reaction conditions.
other organic functional groups have been reported.[13] Re-
cently, several groups have reported a third class of hydro-
genation reactions, under metal free conditions. In these
cases, a pair of bulky Lewis acids and Lewis bases cannot
form a classical adduct for steric reasons, but may activate
small molecules such as hydrogen, and have been termed
frustrated Lewis-pair-catalyzed hydrogen-transfer reac-
tions.[14] Herein we report further investigation of the dehy-
drogenation of 1 and tandem hydrogenation of various or-
ganic functional groups.
Results and Discussion
To eliminate the complication of soluble byproducts
formed from catalyst ligand dissociation/decomposition we
elected to use heterogeneous Rh/Al2O3 (2), which can be
easily reisolated from the reaction by filtration. In a typical
reaction, 2 was added to a solution of 1 and the organic
substrate in diethyl ether, toluene or THF, which resulted
in vigorous bubbling in all cases. The reaction vessel was
quickly sealed and stirred vigorously under an atmosphere
of argon for 48 h, unless otherwise noted. Isolation of the
reaction products was achieved by column chromatog-
raphy.[15] The substrates chosen for this study have pre-
viously been reported to undergo transition metal catalyzed
reduction.[11,16]
[a] 5 mmol substrate, 7.5 mmol 1, 0.15 mmol 2, 5 mL of diethyl
ether. [b] 5 mmol substrate, 12.5 mmol 1, 0.15 mmol 2, 5 mL of
diethyl ether.
naphthalene as a substrate, which was cleanly hydrogenated
using 1.5 equiv. of 1 in 48 h, yielding 2-ethylnaphthalene
(Table 2, Entry 1).
Table 2. Substrates that undergo clean hydrogenation/reduction.
Initial studies by our group were limited to alkene re-
duction. In order to broaden the scope of the reaction and
test its limitations we first investigated the reactivity of sev-
eral functional groups. In comparison to the alcoholysis hy-
drogenation route reported by Couturier and co-workers,[11]
which was found to ring-open 1,2-epoxydodecane and
dechlorinate 4-chlorodiphenyl ether, the tandem dehydroge-
nation/hydrogenation route appears to be milder. The at-
tempted ring-opening of 1,2-epoxydodecane and dehaloge-
nation of 4-chlorodiphenyl ether resulted in reisolation of
pure starting material after column chromatography
(Table 1, Entries 1 and 2). Because Ar–Br and Ar–I bonds
are generally more reactive and more easily reduced,[17] we
[a] 5 mmol substrate, 7.5 mmol 1, 0.15 mmol 2, 5 mL of toluene.
[b] 5 mmol substrate, 12.5 mmol 1, 0.15 mmol 2, 5 mL of diethyl
ether. [c] 5 mmol substrate, 17.5 mmol 1, 0.15 mmol 2, 5 mL of
diethyl ether. [d] Reaction carried out in air.
Due to the observed stability of epoxide and halide func-
also tested the reduction of 4-bromodiphenyl ether (Table 1, tionalities under these conditions, we exploited the reactiv-
Entry 3) or 5-chloro-2-iodoaniline (Table 1, Entry 4), which ity of unsaturated carbon–carbon bond to carry out chemo-
also resulted in the isolation of starting material. This high selective hydrogenations. Addition of 2.5 equiv. of 1 to a
tolerance of Ar–X bonds makes this reaction procedure mixture of 4-chlorostyrene and 2 was found to yield 1-
very interesting for synthetic schemes where one wishes to chloro-4-ethylbenzene after 48 h (Table 2, Entry 2). Similar
retain these important functional groups, for example in results were observed with (Ϯ)-limonene oxide under the
cross-coupling reactions. Further to this, aryl nitrile groups, same conditions, where hydrogenation of the isopropylene
which also reacted under Couturier’s conditions,[11,18] were moiety was achieved while leaving the epoxide intact and
found to be stable, with no reduction of 3,4-dimethoyxbenz- without changing the diastereomeric ratio of the cis/trans
ylnitrile after 48 h in the presence of 2.5 equiv. of 1 (Table 1, mixture of alkyl groups (Table 2, Entry 3).
Entry 5).
The reduction of nitro groups was found to proceed
The reduction of non-polar, unsaturated carbon–carbon cleanly, with addition of 3.5 equiv. of 1 to a mixture of 2-
bonds is often achieved by carrying out reactions under nitrofluorene and 2 yielding 2-aminofluorene quantitatively
high partial pressures of H2, which requires the use of high after 48 h (Table 2, Entry 4).
pressure apparatus.[1] To investigate the hydrogenation ac-
The reduction of internal alkene and alkyne functional
tivity of the dehydrocoupling system, we used 2-vinyl- groups did not proceed smoothly. For example the re-
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673

M. E. Sloan, A. Staubitz, K. Lee, I. Manners
SHORT COMMUNICATION
duction of diphenylacetylene resulted in the isolation of a nature of hydrogen substituents all of which could result in
mixture of hydrogenation products after 7 days with a different reaction mechanism. Hydrogenation of only the
2.5 equiv. of 1. The purification attempt by column alkene moiety of 4-chlorostyrene and (Ϯ)-limonene oxide
chromatography failed to separate diphenylethane and was achieved due to the chemoselective nature of this sys-
trans-diphenylethene, which were present in a 1:0.8 ratio by tem. Attempts to hydrogenate the internal alkene, in ethyl
NMR (Table 3, Entry 1). Similarly the attempted hydrogen- trans-4-bromocinnamate, and alkyne, in 1,2-diphenylacet-
ation of ethyl trans-4-bromocinnamate in the presence of ylene, were frustrated by low reactivity and poor product
2.5 equiv. of 1 after 7 days only resulted in partial conver- separation.
sion to ethyl 3-(4-bromophenyl)propionate. Attempted pu-
Supporting Information (see also the footnote on the first page of
1
this article): H and 13C NMR spectroscopic data for all reaction
rification of the crude reaction by column chromatography
failed to separate the product from starting material
(Table 3, Entry 2).
products.
Acknowledgments
Table 3. Partially hydrogenated products.
M. E. S., A. S. and K. L. thank the Engineering and Physical Sci-
ences Reasearch Council (EPSRC) for funding. I. M. thanks the
European Union (EU) for a Marie Curie Chair and the Royal Soci-
ety for a Wolfson Research Merit Award.
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Received: September 24, 2010
Published Online: December 27, 2010
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