Expanding the Boundaries of Water-Tolerant Frustrated Lewis Pair Hydrogenation: Enhanced Back Strain in the Lewis Acid Enables the Reductive Amination of Carbonyls

Article abstract of DOI:10.1002/anie.201703591

The development of a boron/nitrogen-centered frustrated Lewis pair (FLP) with remarkably high water tolerance is presented. As systematic steric tuning of the boron-based Lewis acid (LA) component revealed, the enhanced back-strain makes water binding increasingly reversible in the presence of relatively strong base. This advance allows the limits of FLP's hydrogenation to be expanded, as demonstrated by the FLP reductive amination of carbonyls. This metal-free catalytic variant displays a notably broad chemoselectivity and generality.

Full text of DOI:10.1002/anie.201703591

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Accepted Article
Title: Expanding the Boundary of Water Tolerant Frustrated Lewis Pair
Hydrogenation: Enhanced Back Strain in the Lewis Acid Enables
the Reductive Amination of Carbonyls
Authors: Tibor Soos, Éva Dorkó, Márk Szabó, Bianka Kótai, Imre
Pápai, and Attila Domján
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To be cited as: Angew. Chem. Int. Ed. 10.1002/anie.201703591
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10.1002/anie.201703591
Angewandte Chemie International Edition
COMMUNICATION
Expanding the Boundary of Water Tolerant Frustrated Lewis Pair
Hydrogenation: Enhanced Back Strain in the Lewis Acid Enables
the Reductive Amination of Carbonyls
Éva Dorkó[a], Márk Szabó[b], Bianka Kótai[a], Imre Pápai[a], Attila Domján[b] and Tibor Soós*[a]
Abstract: We report here the development of a boron/nitrogen
centered frustrated Lewis pair (FLP) with remarkable high water
tolerant property. As systematic steric tuning of the boron-based
Lewis acid (LA) component revealed, the enhanced back-strain
engenders water binding increasingly reversible in the presence of
relatively strong base. This advance allows to expand the limit of
FLP’s hydrogenation as demonstrated by the FLP reductive amina-
tion of carbonyls. This metal-free catalytic variant displays a notable
broad chemoselectivity and generality.
sensitive toward moisture. The catalyst deactivation by water,
however, is more than an interaction of water and the LA, it is
actually an FLP reaction. Thus, the strength of the water binding
to boron center can be significantly enhanced by deprotonation
of the added LBs, (the Brønsted acidity of H2O-B(C6F5)3 is
comparable to HCl (pKa=8.4 (MeCN)).
[8]
This leveraging effect of LBs is well illustrated by the obser-
vation that the archetypal LA, B(C6F5)3 can only form a water
tolerant FLP hydrogenation catalyst as long as a rather weakly
basic solvent, such as 1,4–dioxane is applied as an LB.[4e] Thus,
in the presence of a stronger LB, even such as THF, the
B(C6F5)3 LA is irreversible inhibited. To minimize the limiting
interference of water in the presence of more basic oxygen-
centered LB, the deliberate combination of steric and electronic
tuning for the Lewis acidic component are required. The em-
ployed enhanced steric shielding around the LA center serves to
prevent or retard the complexation ability with LBs (including
water),[9] while retaining the capacity of cleavage of the small
hydrogen molecule with oxygen-centered LBs.[4d,f]
Frustrated Lewis pairs (FLP) chemistry is a discrete activa-
tion mode that can be utilized for metal-free catalysis.[1] One of
these applications, the FLP hydrogenation[2,3], has sparked
scientific upheaval with a promise to develop metal-free hydro-
genation technology. Since the inception of this new paradigm,
the scope and utility of the FLP hydrogenation have been con-
tinually expanded and several key limitations have been solved.
This is aptly exemplified by the FLP reduction of carbonyl com-
pounds and the water tolerant hydrogenation of various ketones
and aldehydes.[4] Despite the progress in FLP hydrogenation,
water tolerance is still limited to boron/oxygen centered FLPs,
and the currently used boron-based Lewis acids (LA)
are,incompatible with water if more basic Lewis bases (LB),
such as amines or phosphines are incorporated into the FLP
hydrogenation catalyst.[5] This restrain is not merely a technical
concern, but it represents a major obstacle to expand the utility
of FLP hydrogenation toward hydrogenation-condensation tan-
dem reactions.[4f, 6] Herein, we show that it is possible to tackle
this constrain via developing a structurally well-designed boron-
based LA for FLP chemistry. The resulting FLP not only fulfilled
the premise of water tolerant boron/nitrogen centered FLP hy-
drogenation catalyst, but also enabled us to develop metal-free
FLP reductive amination of carbonyls[7] with hydrogen.
There have been also efforts to push the water-tolerance
limit of nitrogen-centered FLPs through the development of LAs.
One of the possible solutions is the change of the boron center
in FLPs into a heavier element to result in a still strong but softer
Lewis acid, as has been demonstrated by Ashley and co-
workers.[5]. Other noteworthy advance in the boron series is the
recent development of a non-fluorinated boron LA B(3,5-
Cl2C6H3)3 for FLP promoted reductive amination of carbonyls
with silanes. As Fasano and Ingleson has recently recog-
nized,,[6d] the electronic tuning alone afforded a weaker LA that
can tolerate water even in presence of alkyl amines. Albeit an
important step forward, the applicability of this boron/nitrogen
centered FLP catalyst appears to be limited, the cumulative
LA/LB strength was efficient for silane activation, but not for H2
heterolysis. Consequently, the issue of water tolerant bo-
ron/nitrogen centered FLP hydrogenation, which can be used in
hydrogenation-condensation tandem reactions, has remained
unresolved.
From the appearance of the FLP hydrogenation, the catalytic
procedures were overwhelmingly accomplished with B(C6F5)3 as
a sterically overcrowed LA combined with nitrogen, phosphorous
or oxygen centered LBs. The high oxophilicity of the boron cen-
ter, however, renders these hydrogenation catalysts extremely
Based on the above, it seems that the electronic tuning in
borane series reached its limit and we anticipated that the steric
effects could be considered as a major factor to improve further
the water tolerance of boron-centered Lewis acids. However, the
efficiency of any structural modifications is hampered by the
gaps of understanding how the varying front- and back-strain[10]
affect the LAs strength and reactivity. We thus attempted to
achieve an insight via screening a series of boranes with gradu-
ally different local steric environments around the boron atom.
We selected tris(2-chloro-6-fluoroaryl)borane I, as a starting
point for this study and devised to enhance its front- and back-
strain by the stepwise exchange of fluorine to chlorine atoms.
[a]
[b]
É. Dorkó, B. Kótai, Prof. Dr. I. Pápai, Dr. T. Soós
Institute of Organic Chemistry, Hungarian Academy of Sciences,
Research Centre for Natural Sciences
Magyar tudósok körútja 2, 1117 Budapest (Hungary)
E-mail: soos.tibor@ttk.mta.hu
M. Szabó, Dr. A. Domján
NMR Research Laboratory of IC, Hungarian Academy of Sciences,
Research Centre for Natural Sciences
Magyar tudósok körútja 2, 1117 Budapest (Hungary)
Supporting information for this can be found under:
This article is protected by copyright. All rights reserved.

10.1002/anie.201703591
Angewandte Chemie International Edition
COMMUNICATION
energy of isodesmic reaction LAH- + B(C6F5)3 → LA + B(C6F5)3H-. Lower
energy value refers to weaker Lewis acidity as compared to B(C6F5)3.
For the synthesis of these asymmetrically substituted boranes (I,
II and III, see Scheme 1.) a scalable procedure was developed
based on previously described method.[4d]
Perhaps more surprising is the finding that the trend within
the series is not linear and even one chlorine-fluorine replace-
ment exerts such a cumulative steric penalty in Lewis acid II that
it practically impedes the dative adduct formation with Et3P=O
probe. In an effort to distinguish between the two steric factors,
we computed the relative thermodynamic hydricity[13] of boranes
I-III via DFT calculations taking the archetypal LA B(C6F5)3 as a
reference compound (entry 3).[14] As hydride anion (H–) is the
smallest possible LB, the steric penalty to reach the boron cen-
ter (front-strain) is minimal. Therefore, the strength of hydride
binding is determined by the electronic effect and the steric
penalty emerging upon the pyramidalization of the boron, the
back-strain. The computational data indicate that the relative
hydricity decreases only slightly within the series and no such a
drastic drop can be observed as in the acidity scale measured
by the Gutmann-Beckett method. Consequently, the difference
in acidity trends is due to front-strain that serves to traverse the
complexation of a larger LB. An additional way to interpret the
above data (entry 1 and entry 3) is to view these bulky boranes
as a structurally “spring-loaded” system. Whereas each F–Cl
replacement increases the electrophilicity of the borane, the
increment of electrophilicity is counterweighted as the gradually
growing back-strain increasingly strives to push back the boron
center into the original sp2 state
Cl
F
0.3 eq. BF3*OEt2, THF, 0o
C
B
F
Cl
F
Br
Cl
i
F
Cl PrMgCl
Cl
F
THF
I, 40%
BF3K
84%
B
a)
b)
F
Cl
Cl
Cl
Cl
Cl
0.5 eq.
THF, 0o
F
Cl
II, 55%
C
Cl
Cl
c)
d)
e)
f)
MgBr
BF3
K
Cl
Cl
B
F
Cl
Cl
F
Cl
2 eq.
Cl
80%
THF, 0o
C
III, 70%
Scheme 1. Synthesis of halogenated boranes. Conditons: a) 1.1 eq. BuLi in
THF; b) 1,5 eq. Br2; c) 1.1 eq. BuLi in THF, -78°C; d) 2 eq. B(OMe)3; e) 1.4 eq.
1M HCl, 0°C; f) 4 eq. KHF2 in MeOH/H2O.
As LA strength is situation dependent and likely not possible
to determine on an absolute sense, we used multiple methods to
gain detailed knowledge about the synthesized boranes. First,
we performed a cyclic voltammetry (CV) study of I-III to gauge
the electronic consequences of the successive replacement of
fluorine atom with chlorine (Table 1, entry 1). These reduction
potentials can be considered as the approximate electrophilicity
of the boron centers in absence of the steric effect, as previous
electrochemical studies on sterically congested boranes sug-
gested.[11] From this study, an additive relationship was observ-
able, the reduction potential of boranes was found to shift to less
negative potentials and the voltammetry became more reversi-
ble as the number of chlorine substituents increased around the
boron center. This tendency is consistent with the greater elec-
tron-withdrawing capacity and steric demand of chlorine.
A final evaluation of these boranes was the study of their
water complexation ability in the presence of a relatively strong
aliphatic amine base. In these NMR studies DABCO was used
1
as a non-coordinating base and conclusions rest upon H, 10B,
19F, DOSY, NOESY and EXSY NMR results. First, detailed
structural information were obtained by means of 1H single-pulse,
DOSY and NOESY experiments about BAr3-H2O-DABCO com-
plexes (See the Supporting Information). The NMR studies
indicate that DABCO and water form a 1:1:1 complex with all I-III
boranes.
Next, Gutmann-Beckett method[12] was used to assess the
relative Lewis acidity of I-III boranes (entry 2). This empirical
method gave a reverse order within the series, so the most
fluorinated borane I formed the strongest dative adduct. Thus,
the increasing sterical strain (both front- and back-strain) engen-
dered by the fluorine-chlorine exchange counters the gains
made by the increasing electron-withdrawing power of more
chlorine substituents.
Table 1. Evaluation of relative Lewis acidity of boranes I-III.
Entry
Method
I
II
III
Figure 1. a) 10B NMR of the boranes I–III in DABCO/H2O/borane I–III com-
plexes at 45°C (signals at 5.0 ppm are dative complexes). b) 1H NMR signal of
DABCO in the same ternary aqua complexes at 45°C and the free DABCO
(signal at 2.09 ppm is due to solvent).
1
2
3
Cyclic Voltammetry[a]
Gutmann-Beckett[b]
Relative hydricity[c]
-2.1 V
77%
-2.0 V
5%
-1.9 V
4%
Further and more significant structural dynamics of ternary
aqua complexes is revealed from 1H and 10B NMR studies at
45°C (Figure 1). Whereas DABCO/H2O/borane I adduct remains
intact at this temperature, the other two ternary aqua complexes
considerably dissociate to free borane II and III (45% and 60%
respectively). Accordingly, these borane II or III/DABCO pairs
can be used for FLP activations in presence of equimolar water,
-15.3
kcal/mol
-16.0
kcal/mol
-17.2
kcal/mol
[a] Reduction potentials (in V) measured by CV, for borane I only the Eox can
be determined. [b] Relative %, the 0% and 100% reference points are the 31P
NMR chemical shift of Et3P=O and its adduct with B(C6F5)3. [c] Gibbs free
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10.1002/anie.201703591
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COMMUNICATION
as free borane and DABCO are available for hydrogen cleavage.
To gain further insight, 2D EXSY NMR spectroscopy[15] was
used to explore quantitatively the dynamic behaviour of water
dissociation. This method enabled us to determine rate con-
stants and activation parameters of the dissociation of the ter-
nary aqua complexes of boranes II and III (see Supporting In-
formation). Whereas the stability of the DABCO/H2O/borane II
and III complexes is similar, there is a significant difference in
kinetics as the exchange rate is nearly 20 times higher for the
aqua complex of borane III (11.0 vs. 0.57 s-1 at 35oC, see in
Supporting Information). This can be correlated with the in-
creased steric profile of III, especially, the enhanced back-strain
may play a key role.
3[b]
80°C
72h
78%
99%
99%
4[b]
55°C
80°C
72h
72h
0%
0%
14%
99%
5[b][c]
-
44%
t
[a] Reaction condition: 0.25 mmol Bu-benzaldimine (1), 4 bar H2, 10 mol%
borane, 10 mol% DABCO, toluene, 24h. [b] Reaction condition: 0.25 mmol
benzaldehyde (3) and 0.25 mmol benzylamine, 20 bar H2, 10 mol% borane,
toluene, 100 mg molecular sieves. [c] Reactions run without molecular sieves.
R2 R3
R2 R3
N
N
O
10 mol% III
toluene
20 bar H2, 80oC
+ H2O
+
:
After identifying borane/amine FLPs with water tolerance,
we conducted some preliminary experiments to ascertain their
utility in FLP hydrogenations. First, the metal-free reduction of
tert-butylbenzaldimine (1) to tert-butylbenzylamine (2) was
probed under inert conditions. Gratifyingly, all I–III boranes were
found to be amenable to promote the reduction at 80°C with
DABCO base (Table 2, entry 1), however, there was a difference
at room temperature reductions (entry 2). This result is con-
sistent with the sterical accessibility and hydricity of the applied
LAs.
R1
H
H
1
R1
26-95%
H
1
Ph
H
O
HN
Ph
HN
HN
Ph
HN
Ph
H
HN
Ph
H
H
MeO
MeOOC
54% (99%)
H
6
7
8
9
10
78% (99%) 90% (99%)
90% (99%)
88% (99%)
Ph
HN
Ph
Ph
Ph
Ph
HN
HN
HN
HN
Cl
H
H
H
H
H
N
O
S
Cl
11
95% (99%)
13
94% (99%)
14
12
15
33% (42%)
31% (63%)
86% (99%)
Next, our major objective, the prospect of water tolerant
FLP hydrogenation was probed in reductive amination reaction.
The reaction of benzaldehyde (3) with benzylamine (4) was
selected as a test reaction using 10 mol% borane catalysts in
the presence of molecular sieves. To our delight, the desired
catalytic reduction could be performed selectively, no competing
reduction to benzylalcohol occurred and water was compatible
with boranes at 80°C. As expected, the presence of water had a
significant impact on the FLP catalysts’ performance, the reac-
tions slowed down and a reverse order in efficiency was ob-
served (entry 3). Notably, the application of catalyst III allowed to
run the reaction at lower temperature (55°C, entry 4) and, most
importantly, without water-scavenger (entry 5). Thus, borane
catalyst III is a superior catalyst to I and II, it can tolerate even
10 equivalents of water in FLP promoted reductive amination.
Finally, it is important to note that the presence of water might
be advantageous as the borane-water adduct can function as a
Bronsted acid catalyst in an auto-tandem hydrogenation pro-
cess.[4f]
Ph
Ph
H
HN
HN
HN
HN
H
F
N
Ph
Ph
Ph
H
H
H
Br
18, 26% (66%)
19
16
20
17
54% (99%)
89% (99%)
17% (25%)
80% (99%)
tBu
HN
N
H
Ph
Ph
N
H
Ph
N
N
Ph
Ph
H
H
21, 61% (93%)
22, 68% (93%)
23, 93% (99%)
24, 60% (85%)
N
N
H
N
H
H
H
HN
HN
Ph
H
Ph
H
25
29
66% (99%)
27
28
30
26
50% (69%)
91% (99%) 39% (50%)
76% (99%)
61% (73%)
N
HN
Ph
N
N
H
Ph
N
Ph
H
H
33, 81%
(R,S):(S,S)
1:2
34, 55%
31
64% (91%)
35
32
(S,R):(R,R)
1:2
78% (99%)
90% (99%)
Scheme 2. FLP reductive amination of carbonyl compounds using borane
III as a catalyst. The applied reaction condition: 80°C, 72 h, toluene, 20 bar H2,
isolated yields and (conversions).
Table 2. Conversions of FLP reduction of imine 1 and FLP reductive amination
with borane I-III.
Having identified borane III as a competent, as well as water
tolerant LA for FLP reductive amination, we next focused on
exploring its scope and limitation. We were pleased to find that a
wide array of amines and carbonyls can undergo FLP promoted
reductive amination with high selectivity, no side reactions,
especially no carbonyl reduction to alcohol, could be detected.
This can be correlated with the renewable borohydride character
of the catalyst. As shown in Scheme 2, both aliphatic and aro-
matic amines can be used as LB in the reductive coupling (6, 7)
the developed FLP is highly tolerant of a wide range of function-
al groups, thus ether (8, 9) and ester (10), as well as heteroaro-
matic rings (11-13) do not irreversible inhibit the catalysis. More-
over, the method displays high chemoselectivity, it tolerates
several functionalities that are prone to reduction, including
Entry
T [°C]
t[h]
I.
II.
III.
10 mol% I, II, or III
10 mol% DABCO
4 bar H2, toluene, 24h
Test reaction a):
inert reaction
condition
N
H
N
1
2
10 mol% I, II, or III
Test reaction b):
non-inert reaction
condition
NH
2 20 bar H2, toluene,
72h, molecular sieves
O
+
Ph
H2O
Ph
N
+
H
3
4
5
24h
24h
99%
0%
1[a]
2[a]
80°C
r.t.
99%
62%
99%
21%
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10.1002/anie.201703591
Angewandte Chemie International Edition
COMMUNICATION
[2]
For reviews, see: a) D. W. Stephan, S. Greenberg, T. W. Graham, P.
Chase, J. J. Hastie, S. J. Geier, J. M. Farrell, C. C. Brown, Z. M. Heiden,
G. C. Welch, M. Ullrich, Inorg. Chem. 2011, 50, 12338–12348; b) D. W.
Stephan, Org. Biomol. Chem. 2012, 10, 5740–5746; c) T. Soós, Pure
Appl. Chem. 2011, 83, 667–675; d) J. Paradies, Synlett, 2013, 777-780;
e) L. J. Hounjet, D. W. Stephan, Org. Process Res. Dev. 2014, 18,
385–391; f) L. Shi, Y.-G. Zhou, ChemCatChem 2015, 7, 54–56.
chlorine (14, 15), bromine (16), cyclopropyl (18), olefin (19, 21,
22) and acetylene (20). The reduction of imines of sterically
hindered amines such as tert-butylamine and diisopropyl-amine
are slower; therefore these products (24, 28) can be isolated
with only moderate yields. As a further proof for versatility, we
found that chiral secondary amines can be used in this protocol,
as only negligible racemization was observed in 1-phenylethyl
products 29 and 30. It was expected and then observed that the
steric demand of the reducing agent affects the outcomes of the
reductions. Thus, cinnamaldehyde can be chemoselectively
reduced to allylamine derivative 22 without the saturation of the
olefinic group. Furthermore, 4-tBu-cyclohexanone was trans-
formed selectively to the corresponding cis-amino derivative 32,
so the transiently formed bulky borohydride attacks the corre-
sponding imine equatorially. We also assumed that the steric
contribution of the reducing agent could be used to secure dia-
stereoselectivity in chirality transfer reactions. Thus, the reduc-
tive amination of methyl-ethylketone with enantiopure 1-
phenylethylamines was probed. Despite the moderate diastere-
omeric ratio, 2:1, it is a promising result for substrates having
such a small steric difference (33, 34). Finally, the double meth-
ylation of primary amine was accomplished using formaldehyde
(35). Notably, the water tolerance of the developed FLP allowed
using 37% aqueous solution of formaldehyde. Thus, even aque-
ous two-phase (water-toluene) reaction can be performed with
high conversion.
[3]
[4]
For mechanism, see: a) T. A. Rokob, A. Hamza, A. Stirling, T. Soós, I.
Pápai, Angew. Chem. Int. Ed. 2008, 47, 2435–2438; b) T. A. Rokob, A.
Hamza, I. Pápai, J. Am. Chem. Soc. 2009, 131, 10701–10710; c) S.
Grimme, H. Kruse, L. Goerigk, G. Erker, Angew. Chem. Int. Ed. 2010,
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a) M. Lindqvist, N. Sernala, V. Sumerin, K. Chernichenko, M. Leskelä;
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Tang, D. W. Stephan, Dalton Trans. 2014, 43, 15723–15726; b) D. J.
Scott, M. J. Fuchter, A. E. Ashley, J. Am. Chem. Soc. 2014, 136,
15813–15816; c) T. Mahdi, D. W. Stephan, J. Am. Chem. Soc. 2014,
136, 15809–15812; d) Á. Gyömöre, M. Bakos, T. Földes, I. Pápai, A.
Domján, T. Soós, ACS Catal. 2015, 5, 5366–5372; e) D. J. Scott, T. R.
Simmons, E. J. Lawrence, G. G. Wildgoose, M. J. Fuchter, A. E. Ashley,
ACS Catal. 2015, 5, 5540–5544; f) M. Bakos, Á. Gyömöre, A. Domján,
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[5]
[6]
D. J. Scott, N. A. Phillips, J. S. Sapsford, A. C. Deacy, M. J. Fuchter, A.
E. Ashley, Angew. Chem. Int. Ed. 2016, 55, 14738–14742.
Auto-tandem condensation-reduction FLP reactions using silane reduc-
ing agents a) M.-C. Fu, R. Shang, W.-M. Cheng, Y. Fu, Angew. Chem.
Int. Ed. 2015, 54, 9042–9046; b) V. Fasano, J. E. Radcliffe, M. J. Ingle-
son, ACS Catal. 2016, 6, 1793−1798; c) M. R. Tiddens, R. J. M. K.
Gebbink, M. Otte, Org. Lett. 2016, 18, 3714–3717; d) V. Fasano, M. J.
Ingleson, Chem. Eur. J. 2017, 23, 2217–2224.
In conclusion, as the systematic steric tunings revealed, the
modulation of back-strain is an important design element to
tackle one of key constrains of B/N centered FLP hydrogenation,
the water inhibition. The enhanced back-strain of LA upon com-
plexation makes water binding increasingly reversible. In this
way, we can maintain the preferential hydrogen activation ability
while suppressing the interference of the water with FLP. The
utility of this structurally fine-tuned FLP catalyst was demon-
strated in reductive amination of carbonyls. This novel metal-free
method displays a notable broad chemoselectivity and generality.
[7]
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1; c) S. Gomez, J. A. Peters, T. Maschmeyer, Adv. Synth. Catal. 2002,
344, 1037–1057; d) Chiral Amine Synthesis, Ed. T. C. Nugent, Wiley-
VCH, 2010. For selected catalytic examples, see: e) V. I. Tararov, R.
Kadyrov, T. H. Riermeier, C. Fischer, A. Börner, Adv. Synth. Catal.
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ter, S. Rudolph, Org. Lett. 2006, 8, 741–744; g) R. I. Storer, D. E. Car-
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Acknowledgements
The authors acknowledge financial support from National Re-
search, Development and Innovation Office (grants K-116150
and K-115660). The authors thank László Gulyás for HRMS
measurements and Tamás Pajkossy for CV measurements.
Keywords: frustrated Lewis pairs, water tolerant, strain, reduc-
tive amination, dynamic NMR
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We report here the development of a
boron/nitrogen centered frustrated
Lewis pair with remarkable high water
tolerant property. As systematic steric
tuning of the boron-based Lewis acid
component revealed, the enhanced
back-strain engenders water binding
increasingly reversible in the presence
of relatively strong base. This advance
allows to expand the limit of FLP’s
hydrogenation as demonstrated by the
FLP reductive amination of carbonyls.
Éva Dorkó, Márk Szabó, Bianka Kótai,
Imre Pápai, Attila Domján and Tibor
Soós*
Page No. – Page No.
Expanding the Boundary of Water
Tolerant Frustrated Lewis Pair Hy-
drogenation: Enhanced Back Strain
in the Lewis Acid Enables the Reduc-
tive Amination of Carbonyls
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