Angewandte
Chemie
Frustrated Lewis Pairs
Facile Protocol for Catalytic Frustrated Lewis Pair Hydrogenation and
Reductive Deoxygenation of Ketones and Aldehydes**
Tayseer Mahdi and Douglas W. Stephan*
Abstract: A series of ketones and aldehydes are reduced in
toluene under H2 in the presence of 5 mol% B(C6F5)3 and
either cyclodextrin or molecular sieves affording a facile metal-
free protocol for reduction to alcohols. Similar treatment of
aryl ketones resulted in metal-free deoxygenation yielding
aromatic hydrocarbons.
be mediated by an aluminum alkoxide catalyst through the
Meerwein, Ponndorf and Verley (MPV) mechanism.[19] Alter-
natively, NaBH4 and LiAlH4 can be used as stoichiometric
reagents to hydrogenate unsaturated functional groups.[20]
Berkessel and co-workers[21] reported the first metal-free
reduction of benzophenone using H2 and tBuOK as the
catalyst at 100 atm of H2 and 2008C. However, the emergence
of FLPs allowed catalytic metal-free hydrogenations under
more mild conditions. In 2009, the group of Privalov[22]
computationally predicted that catalytic ketone hydrogena-
tion should be possible using B(C6F5)3 as the catalyst.
Although in assessing this prediction, Repo et al.[23] found
only stoichiometric deoxygenation of aromatic carbonyls.
Wang et al.[24] approached the catalytic ketone hydrogenation
challenge computationally, suggesting that a bifunctional
amine-borane FLP catalyst would be viable. In our own
attempts to effect ketone reduction we found that treatment
of dialkylketones with B(C6F5)3 and H2 in toluene led to the
stoichiometric formation of C6F5H and borinic esters of the
form RR’CHOB(C6F5)2.[25] In addition, the stoichiometric
reduction of carbonyl groups by N/B[26] and P/B[27] FLPs,
including regioselectivity studies using deuterium and tritium
labeling experiments have been reported.[28]
I
n the latter part of the 19th and early 20th centuries,
Sabatier[1] uncovered the ability of amorphous metals to
catalyze the hydrogenation of organic substrates. About 60
years later, Wilkinson[2] discovered the ability of homoge-
neous transition metal complexes to catalyze the hydro-
genation of olefins. Since these two seminal findings, hydro-
genation catalysis has found use in a myriad of products for
modern society. Among the outstanding developments are
the remarkably selective asymmetric hydrogenation catalysts
developed by Noyori[3] and Knowles.[4] Despite the power of
these technologies, research efforts prompted by cost, toxicity
and low abundance have focused on the development of first-
row transition metal-based catalysts.[5] An alternative strategy
to hydrogenation catalysis based on main-group compounds
has emerged in the last decade.[6] These systems known as
frustrated Lewis pairs (FLPs) are derived from combinations
of main-group Lewis acids and bases in which steric or
electronic features preclude quenching of the acidic and basic
components allowing the two reagents to act concurrently
effecting the heterolytic cleavage of H2. Moreover, these FLP
systems were first shown to effect the catalytic hydrogenation
of imines, protected nitriles, aziridines[7] and subsequently
extended to other catalysts[8] and substrates including enam-
ines,[9] silyl enol ethers,[10] N-heterocycles,[11] olefins,[12] poly-
arenes,[13] fulvenes,[14] and alkynes.[15] In related work, the
aromatic hydrogenation of N-phenyl amines to give cyclo-
hexylammonium derivatives was demonstrated[16] and this
concept was extended to effect the reduction of pyridines[17]
and a variety of N-heterocycles.[18]
In rather dramatic recent findings, our group[29] and that of
Ashley[30] simultaneously found that the use of ethereal
solvents for FLP-catalyzed reductions of ketones and alde-
hydes resulted in effective hydrogenations. In these cases, the
role of the solvent was proposed to hydrogen bond to the
À
transient protonated ketone precluding protonation of the B
C bond, thus allowing catalysis to proceed effectively. In the
present study, we further FLP based hydrogenations of
ketones and aldehydes, exploring reductions in toluene with
the addition of an oxygen containing material such as a-
cyclodextrin (a-CD) or molecular sieves (MS). Use of these
materials provides a heterogeneous Lewis base for H2
activation and hydrogen bonding, thus yielding a facile
catalytic protocol for ketone and aldehyde reduction and
the reductive deoxygenation of aryl ketones using H2.
In the case of carbonyl substrates, there are well
established main-group routes to ketone reductions. For
example, transfer hydrogenation from a sacrificial alcohol can
The ketone 3-methyl-2-butanone was combined with an
equivalent of a-CD and 5 mol% B(C6F5)3 in toluene and
heated at 608C under H2 (60 atm). After 12 h, quantitative
reduction to the product 3-methyl-2-butanol was evidenced
by 1H NMR spectroscopy, revealing a diagnostic multiplet at
3.27 ppm corresponding to the presently formed CH group
and broad singlet at 1.82 ppm assignable to the OH group
(Table 1, entry 1). Under similar conditions, a series of methyl
alkyl ketones (entries 2–6), dialkyl ketones (entries 7–9), aryl
(entries 10–14), benzyl (entries 15–19) and cyclic ketones
(entries 20–22) were hydrogenated in high yields. In addition,
the catalytic reduction of aldehydes was similarly performed
[*] T. Mahdi, Prof. Dr. D. W. Stephan
Department of Chemistry, University of Toronto
80 St. George St, Toronto, Ontario, M5S 3H6 (Canada)
E-mail: dstephan@chem.utoronto.ca
[**] We gratefully acknowledge the support of NSERC of Canada. D.W.S.
is grateful for the award of a Canada Research Chair. T.M. is grateful
for the award of an NSERC postgraduate scholarship and for
productive discussions with Dr. Roman Dobrovetsky.
Supporting information for this article is available on the WWW
Angew. Chem. Int. Ed. 2015, 54, 8511 –8514
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
8511