Versatile Catalytic Hydrogenation Using A Simple Tin(IV) Lewis Acid

Article abstract of DOI:10.1002/anie.201606639

Despite the rapid development of frustrated Lewis pair (FLP) chemistry over the last ten years, its application in catalytic hydrogenations remains dependent on a narrow family of structurally similar early main-group Lewis acids (LAs), inevitably placing limitations on reactivity, sensitivity and substrate scope. Herein we describe the FLP-mediated H₂activation and catalytic hydrogenation activity of the alternative LA iPr₃SnOTf, which acts as a surrogate for the trialkylstannylium ion iPr₃Sn⁺, and is rapidly and easily prepared from simple, inexpensive starting materials. This highly thermally robust LA is found to be competent in the hydrogenation of a number of different unsaturated functional groups (which is unique to date for main-group FLP LAs not based on boron), and also displays a remarkable tolerance to moisture.

Full text of DOI:10.1002/anie.201606639

Angewandte
Communications
Chemie
International Edition: DOI: 10.1002/anie.201606639
German Edition: DOI: 10.1002/ange.201606639
FLP Hydrogenation
Versatile Catalytic Hydrogenation Using A Simple Tin(IV) Lewis Acid
Daniel J. Scott, Nicholas A. Phillips, Joshua S. Sapsford, Arron C. Deacy, Matthew J. Fuchter,
and Andrew E. Ashley*
Abstract: Despite the rapid development of frustrated Lewis
pair (FLP) chemistry over the last ten years, its application in
catalytic hydrogenations remains dependent on a narrow
family of structurally similar early main-group Lewis acids
(LAs), inevitably placing limitations on reactivity, sensitivity
and substrate scope. Herein we describe the FLP-mediated H2
activation and catalytic hydrogenation activity of the alterna-
tive LA iPr3SnOTf, which acts as a surrogate for the
trialkylstannylium ion iPr3Sn+, and is rapidly and easily
prepared from simple, inexpensive starting materials. This
highly thermally robust LA is found to be competent in the
hydrogenation of a number of different unsaturated functional
groups (which is unique to date for main-group FLP LAs not
based on boron), and also displays a remarkable tolerance to
moisture.
activated olefins).[8] This constrained focus is far from ideal, as
examining and developing a wider variety of LAs can be
expected to produce novel FLP-catalyzed protocols that
display different substrate scope and/or more favorable
functional group tolerance.[9] For example, the application
of highly Lewis acidic boranes to the FLP-catalyzed hydro-
genation of organic carbonyls has been notably challenging:
whilst stoichiometric reductions were reported as early as
2007,[9] it took until 2014 until catalytic protocols were
developed.[10] This difficulty can be attributed to the strength
of the interaction between the alcohol (ROH) products and
the LAs, which renders the LA·ROH adducts strongly acidic
[cf. H2O·B(C6F5)3; pKa = 8.4 (MeCN), < 1 (H2O, est.)];[11]
consequently, these adducts are fundamentally incompatible
with the moderately strong N/P-centered LBs typically
incorporated into active FLP catalysts. Ultimately, turnover
can only be achieved when such LBs are strictly excluded, due
to the necessarily highly Brønsted acidic media [for example,
protonated ethers, pKa(H2O) ! 0].[10,12]
Since the formalization of the concept within the last
decade, great attention has been focused on the development
and study of frustrated Lewis pairs (FLPs): Lewis acid (LA)
and base (LB) combinations that fail to form the classically
expected strong adduct, typically because it is sterically
precluded.[1] The resulting combined reactivity has been
found to lead to a range of novel bond activation reactions
that do not require the involvement of a transition metal
(TM).[2] Of particular interest has been the activation and
cleavage of H2, which has allowed the development of the first
general methodology for TM-free catalytic hydrogenation.[3]
Computational investigations have suggested that the
primary requirements for successful activation of H2 by an
FLP are a sufficient cumulative LA/LB strength, and
a suitable steric profile.[4] One appealing aspect of FLP
chemistry is therefore the generality of the concept; indeed,
FLP-type reactions have been identified for a broad spectrum
of LAs and LBs.[2,5] Nevertheless inspection of the literature
reveals that, despite the apparent breadth of the field,
investigations into TM-free FLP-catalyzed hydrogenation
have focused overwhelmingly on a very narrow range of
LAs; thus far this has exclusively been achieved using B-
based acceptors[6] [predominantly (fluoroaryl)borane deriva-
tives, of which B(C6F5)3 is prevalent],[7] with the exception of
a single report using P-based LAs (for a limited range of
Based on the above, we were motivated to investigate
FLPs based on heavier p-block LAs, which have thus far
attracted scant attention for use in FLP applications.[13]
Specifically, our interest was drawn to stannylium ion
“R3Sn+” (R = alkyl) LAs;[14] these are isolobal with Ar3B
species commonly employed in FLP chemistry, and have been
calculated to possess similar hydride ion affinities (DGHÀ
=
65.83 and 64.95 kcalmolÀ1 for nBu3Sn-H and [H-B(C6F5)3]À
respectively),[15] suggesting that they ought to demonstrate
comparable reactivity in FLP H2 activation and hydrogena-
=
tion reactions. Furthermore, C O reductions by R3SnH in
protic media are well known to occur via ionic hydride
transfer.[16] Crucially, however, these LAs interact only much
more weakly with hydroxylic species [for example,
(nBu3Sn·xH2O)+; pKa(H2O) = 6.25].[17]
Manners et al. have previously investigated the use of
nBu3SnOTf (an nBu3Sn+ equivalent; Tf = CF3SO2) as a LA
partner in FLP chemistry,[13a] but reported that it was not
capable of activating H2 when combined with the strong
amine base TMP (2,2,6,6-tetramethylpiperidine) at 508C,
whereas the B(C6F5)3/TMP FLP readily cleaves H2, even at
room temperature;[18] this result was attributed to the poorer
electrophilicity of the Sn compound, and it is evident that the
Sn–OTf interaction is strong enough to substantially reduce
the Lewis acidity of the nBu3Sn+ fragment.
We envisioned that it should be possible to increase the
Lewis acidity, to the threshold necessary for favorable H2
heterolysis, by simply increasing the size of the alkyl groups
on Sn, thereby increasing the degree of “internal frustra-
tion”[19] between the R3Sn+ and TfOÀ moieties. To this end,
we targeted the bulkier trialkylstannyl compound iPr3SnOTf
([1]OTf), which was readily prepared via reaction of excess
[*] D. J. Scott, Dr. N. A. Phillips, J. S. Sapsford, A. C. Deacy,
Dr. M. J. Fuchter, Dr. A. E. Ashley
Department of Chemistry, Imperial College London
London, SW7 2AZ (UK)
E-mail: a.ashley@imperial.ac.uk
Homepage: http://www.ashleyresearchgroup.org.uk
Supporting information and the ORCID identification number(s) for
the author(s) of this article can be found under http://dx.doi.org/10.
1002/anie.201606639.
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Table 1: [1]OTf-catalyzed hydrogenation of imines.
Scheme 1. Synthesis of [1]OTf.
Entry[a] Substrate
R
R1
H
R2
Base t [h] Conversion
iPrMgCl and SnCl4 to generate iPr4Sn, followed by facile
protodealkylation with HOTf (Scheme 1). This straightfor-
ward and inexpensive two-step procedure furnishes pure
[1]OTf in good yield (42%, 2 steps), and can easily be
performed on a multi-gram scale. [1]OTf is a white solid that
shows moderate solubility in polar halogenated solvents and
its 119Sn{1H} spectrum shows a single broad resonance at d =
156 ppm (Dv1/2 = 130 Hz, CDCl3). The high chemical shift is
consistent with significant stannylium ion character, although
it is considerably upfield of the value reported for [nBu3Sn]-
[CB11Me12] (d = 454 ppm), which displays the least coordi-
nated trialkylstannylium core to date.[20] Gutmann–Beckett
Lewis acidity measurements support this conclusion,[21] indi-
cating increased electrophilicity in comparison with
[%][b]
1
2
3
4
5
6
7
2a
2b
2c
2c
2d
2e
2 f
H
H
H
H
H
H
4-Br
tBu
–
12
16
16
24
32
80
16
97
85
Me tBu
H
H
Me Ph
H
H
–
Ph
Ph
–
4
Col
Col
Col
>99
96
65
Ts
tBu Col
96
[a] 10 bar refers to initial pressure at RT. [b] Conversions determined by
1H NMR spectroscopic analysis (see the SI).
=
even PhCH NTs (2e; Ts = O2SC6H4Me, 4-toluenesulfonyl),
although the latter reaction is appreciably slower, presumably
as the substrate is less basic still (Table 1, entry 6). Notably,
[22]
nBu3SnOTf, although still lower than B(C6F5)3 {AN = 64.2
=
nBu3SnOTf; 68.0 [1]OTf; 78.1 B(C6F5)3}. [1]OTf has also been
characterized by 1H, 13C and 19F NMR spectroscopy, MS and
elemental analysis (see the Supporting Information (SI)).
Addition of DABCO (1,4-diazabicyclo[2.2.2]octane) to
[1]OTf (1:1) leads to an upfield shift in the 119Sn{1H}
resonance (which remains similarly broad) to 39 ppm, con-
sistent with a donor–acceptor interaction. However, the
the bromoaryl imine 2 f also undergoes efficient C N hydro-
genation (Table 1, entry 7); no evidence of hydrodebromina-
tion is observed during this reaction (no NMR resonances
attributable to 2a/3a, [1]Br or [1]2),[24] supporting the idea
that radical Sn species do not appear to be involved in this
reaction. Accordingly, we propose that hydrogenation occurs
via a polar mechanism analogous to that for related borane-
catalyzed systems:[1d,e,25] H2 activation by an FLP consisting of
[1]OTf/imine is followed by hydride transfer and release of
amine at elevated temperature (Figure S15). This is further
supported by the observation that pre-formed 2a·HOTf is
rapidly reduced by [1]H even at RT,[26] whereas the equivalent
reactions with unprotonated 2a, either alone or in the
presence of [1]OTf, do not lead to significant reduction at
1208C (see SI). Interestingly, there is evidence for autocatal-
ysis during the course of the reaction (16% conversion
observed after 3 h, 60% after 6 h); comparable observations
have been made by Paradies et al. for imine hydrogenations
catalyzed by B(2,6-F2C6H3)3, and are attributed to the
increased basicity of the product amines, relative to the
imine substrate, rendering H2 activation more favorable as
more product is formed.[25]
Following success in the hydrogenation of imines, we were
interested to see whether [1]OTf might also be capable of
mediating the hydrogenation of closely related carbonyl
compounds. Satisfyingly, when acetone (4a) is exposed to
reaction conditions similar to those used to hydrogenate 2c
catalytic conversion to 2-propanol (5a) is observed (Table 2,
entry 1). Whilst the reaction at 1208C is somewhat slow, at
1808C near-quantitative conversion can be observed within
32 h (Table 2, entry 2). Significantly, no evidence of catalyst
decomposition is observed in this homogeneous reaction,
either by 1H or 119Sn{1H} NMR spectroscopy,[27] in comparison
with analogous FLP protocols mediated by B(C6F5)3.[1f,28] To
the best of our knowledge this is the first example of
a catalytically active FLP system capable of tolerating such
conditions without degradation, and illustrates the impressive
1
corresponding H NMR spectrum shows only a single reso-
nance for the DABCO protons, suggesting rapid exchange
between an adduct and FLP. Admission of H2 (4 bar) leads to
the appearance of resonances in the room temperature
1H [5.12 ppm, SnH, 1J(119Sn/117Sn-1H) = 1471/1405 Hz;
10.93 ppm, NH] and 119Sn{1H} (À46 ppm) NMR spectra,
that are consistent with formation of iPr3SnH ([1]H) and
DABCO·HOTf, and hence H2 heterolysis by the N/Sn Lewis
pair. Further, conclusive proof for H2 activation is provided
by replacing H2 with D2, which causes the new 119Sn{1H}
resonance to split into a triplet [1:1:1, 1J(119Sn-2H) = 226 Hz],
and the new resonances in the 1H NMR spectrum to be
replaced by equivalent signals in the 2H spectrum. This
represents the first example of FLP H2 activation using a LA
based on Sn, or any p-block element beyond the 3rd row of the
periodic table.
Having demonstrated H2 activation, our focus shifted to
achieving catalytic hydrogenation using [1]OTf. Gratifyingly,
=
heating the archetypal FLP substrates PhCH NtBu (2a) and
=
PhC(Me) NtBu (2b) with 10 mol% [1]OTf to 1208C under
H2 (10 bar) led to conversion to the respective amines (3a and
3b; Table 1, entries 1 and 2). Conversely, the N-phenyl
=
analogue PhCH NPh (2c) is reduced far less effectively
(Table 1, entry 3), which is attributed to the reduced basicity
of both the imine and amine product, which makes H2
activation less favorable. Consistent with this interpretation,
addition of 2,4,6-collidine [Col; pKa(MeCN) = 14.98][23] as an
auxiliary base leads to a dramatic improvement in perfor-
mance (Table 1, entry 4), and also allows for reduction of the
=
related ketimine PhC(Me) NPh (2d; Table 1, entry 5), and
2
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Table 2: [1]OTf-catalyzed hydrogenation of ketones and aldehydes.
Entry[a] Substrate
R
R1
Base
t [h] Conversion
[%][b]
1[c]
2[d]
3[d]
4[d]
5[d]
6
4a
4a
4b
4c
4d
4a
4a
4a
4a
4a
Me
Me
Ph
tBu
2,6-Cl2C6H3
Me
Me
Me
Me
Me Col
Me Col
Me Col
96
32
48
48
32
16
16
78
97
91[f]
79
91
57
48
14
32
95
H
H
Col
Col
Me Col
Me Lut
7
8
Me DABCO 16
9
Me [1]OiPr[e] 16
10[g]
Me
Me Col
32
Scheme 2. a) Proposed mechanism for catalytic hydrogenation of 4a
using [1]OTf ([N]=2,4,6-collidine) and b) alternative H2 activation
using in situ generated [1]OiPr.
[a] 10 bar refers to initial pressure at RT. [b] Conversions determined by
1H NMR spectroscopic analysis (see the SI). [c] Reaction run at 1208C,
repressurized after 48 h. [d] Repressurized at 16 h intervals. [e] Gener-
ated in situ from [1]H and 4a (see the SI). [f] Based on consumption of
4b; reaction produces 5b in addition to 6 and 7 as side-products in a ca.
74:18:8 molar ratio (see the SI). [g] Using undried reagents, solvent and
catalyst (see the SI).
conversion is observed in its absence either at RT or 1208C.
Conversely, if [1]OTf is replaced by Col·HOTf, only slow
release of H2 is observed at RT.[32] In order for the final H+
transfer step to occur efficiently it should be recognized that
Col and [1]OiPr must be comparable in base strength and,
therefore, it may be envisaged that once [1]OiPr is formed in
the reaction mixture, it could also activate H2 in conjunction
with [1]OTf (Scheme 2b). In fact, catalytic hydrogenation can
be observed by substituting Col with [1]OiPr (generated in
situ from [1]H and 4a; Table 2, entry 9), thus demonstrating
its competence in this role. Even so, the reduced rate of
turnover in this reaction indicates that the auxiliary base does
play a beneficial role beyond simply facilitating formation of
some initial [1]OiPr, presumably by rendering H2 activation
more favorable.[33]
Clear tolerance of alcohol products suggested that these
reactions might also demonstrate appreciable moisture toler-
ance.[10,12] Remarkably, when the hydrogenation of model
substrate 4a (chosen over an imine to avoid hydrolysis) was
prepared on the open bench, with non-anhydrous reagents
and solvent, and using [1]OTf that had been exposed to air for
1 week, the reaction was observed to proceed without any
noticeable reduction in rate (Table 2, entry 10; details in SI).
This is unprecedented in FLP catalysis, where even the most
tolerant of previously reported reactions have been dramat-
ically slowed by adventitious H2O,[12] and suggests a major
advantage of using Sn-based LAs.
thermal stability of [1]OTf, which enables the use of more
forcing conditions in order to achieve an improved rate of
turnover. As well as 4a, other aliphatic and aromatic ketones
and aldehydes (4b—d) can be reduced under these conditions
(Table 2, entries 3–5). In the case of acetophenone (4b),
1H NMR spectroscopic analysis indicates formation of the
expected alcohol 5b, in addition to smaller quantities of
styrene (6) and a-methylbenzyl ether (7). Similar side-
reactions were observed in our previous attempts to reduce
4b using B(C6F5)3 in 1,4-dioxane,[10b,12c] but in those cases this
led to severe reductions in conversion and rate of turnover.
The ease and speed with which it was possible to apply this
system to carbonyl hydrogenation stands in contrast to the
extended period of development required before more
conventional B-based FLPs were successfully used in this
transformation.[10a,b] It is also noteworthy that the [1]OTf-
catalyzed reaction can proceed using a rather conventional,
moderately-strong, N-centered LB, which again contrasts
with B-based systems and is consistent with less acidic adducts
forming between the product alcohols (e.g. 5a) and [1]OTf.
The choice of LB is important to the outcome of the
hydrogenation of 4a (Table 2, entries 6–8), with inferior
results obtained using either a weaker or stronger base [2,6-
lutidine (Lut), DABCO; pKa(MeCN) = 14.13, 18.29].[29]
Given the low Brønsted basicity of 4a we propose
a slightly different mechanism for its reduction than for
2a,[30] with the substrate activated by [1]+ rather than via H-
bonding to [Col-H]+ (Scheme 2a).[16b] Evidence for this comes
from the significantly upfield-shifted 119Sn{1H} NMR reso-
nance (d = 92 ppm) observed upon addition of 4a (10 equiv.)
Finally, we investigated the use of [1]OTf in the catalytic
hydrogenation of compounds containing other unsaturated
functionalities; the heteroaromatic ring of acridine, and the
=
C C bonds in n-butyl acrylate and 1-piperidino-1-cyclohex-
ene could all be effectively reduced (yields 83–99%), further
demonstrating the versatility of this SnIV compound (Fig-
ure S33).
In summary, we have demonstrated the use of readily
accessible and inexpensive iPr3SnOTf as a main-group LA
[31]
À
to [1]OTf, indicative of Sn O binding.
A proposed
subsequent HÀ transfer from [1]H to adduct {[1]·4a}OTf, to
form [1]OiPr and regenerate [1]OTf, is supported by the
observation that [1]H is capable of reducing 4a in the
presence of [1]OTf even at RT, whereas no appreciable
=
=
=
catalyst for the hydrogenation of C C, C N and C O bonds;
this constitutes only the second example of an FLP hydro-
genation protocol utilizing a p-block LA not incorporating
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[5] S. A. Weicker, D. W. Stephan, Bull. Chem. Soc. Jpn. 2015, 88,
1003 – 1016.
boron, and the first such example shown to be applicable to
the reduction of a range of different functional groups.
Despite the ubiquity of Sn in industrial catalysis this also
represents, to the best of our knowledge, the first example of
homogeneous catalytic hydrogenation using a Sn-based
system of any kind.[34] Of particular interest is the ready
[6] A few examples of catalytic hydrogenation using TM-based
FLPs have also been reported. See: a) M. P. Boone, D. W.
Stephan, J. Am. Chem. Soc. 2013, 135, 8508 – 8511; b) A. T.
Normand, C. G. Daniliuc, B. Wibbeling, G. Kehr, P. Le Gendre,
G. Erker, J. Am. Chem. Soc. 2015, 137, 10796 – 10808; c) X. Xu,
C. G. Daniliuc, G. Erker, J. Am. Chem. Soc. 2015, 137, 4550 –
4557; d) N. S. Lambic, R. D. Sommer, E. A. Ison, J. Am. Chem.
Soc. 2016, 138, 4832 – 4842; e) S. R. Flynn, O. J. Metters, I.
Manners, D. F. Wass, Organometallics 2016, 35, 847 – 850.
[7] For catalytic hydrogenation using much weaker boranes paired
with strong bases, see: S. Mummadi, D. K. Unruh, J. Zhao, S. Li,
C. Krempner, J. Am. Chem. Soc. 2016, 138, 3286 – 3289.
[8] a) T. vom Stein, M. Perꢄz, R. Dobrovetsky, D. Winkelhaus, C. B.
Caputo, D. W. Stephan, Angew. Chem. Int. Ed. 2015, 54, 10178 –
10182; Angew. Chem. 2015, 127, 10316 – 10320; imine hydro-
genation is also known using an Al-based LA or a pyridylidene
as catalyst, but in both cases was reported not to proceed via an
FLP mechanism: b) J. A. Hatnean, J. W. Thomson, P. A. Chase,
D. W. Stephan, Chem. Commun. 2014, 50, 301 – 303; c) J. Auth, J.
Padevet, P. Mauleꢆn, A. Pfaltz, Angew. Chem. Int. Ed. 2015, 54,
9542 – 9545; Angew. Chem. 2015, 127, 9678 – 9681.
=
applicability of this protocol to C O bond hydrogenation, in
a reaction that displays an unparalleled level of H2O
tolerance. This neatly demonstrates the value of pursuing
alternative FLP LAs, and can be jointly attributed to the
formation of weakly acidic LA·ROH adducts; a thermally
robust [iPr3Sn]+ core, allowing access to high reaction
À
temperatures; and the stability of the Sn C bonds towards
protolytic cleavage for example, by H2O. Clearly there is
significant scope for variation of the triorganotin(IV) frame-
work in “R3Sn+” species; investigations into how this affects
their reactivity, functional group tolerance, and substrate
scope are currently underway.
Acknowledgements
[9] P. Spies, G. Erker, G. Kehr, K. Bergander, R. Frohlich, S.
Grimme, D. W. Stephan, Chem. Commun. 2007, 5072 – 5074.
[10] a) T. Mahdi, D. W. Stephan, J. Am. Chem. Soc. 2014, 136, 15809 –
15812; b) D. J. Scott, M. J. Fuchter, A. E. Ashley, J. Am. Chem.
Soc. 2014, 136, 15813 – 15816.
[11] C. Bergquist, B. M. Bridgewater, C. J. Harlan, J. R. Norton,
R. A. Friesner, G. Parkin, J. Am. Chem. Soc. 2000, 122, 10581 –
10590.
We thank GreenCatEng, Eli Lilly (Pharmacat consortium)
and the EPSRC for providing funding for a PhD studentship
(D.J.S.), and the Royal Society for a University Research
Fellowship (A.E.A.).
Keywords: catalysis · frustrated Lewis pairs · hydrogenation ·
[12] a) T. Mahdi, D. W. Stephan, Angew. Chem. Int. Ed. 2015, 54,
8511 – 8514; Angew. Chem. 2015, 127, 8631 – 8634; b) ꢁ. Gyç-
mçre, M. Bakos, T. Fçldes, I. Pꢂpai, A. Donjꢂn, T. Soꢆs, ACS
Catal. 2015, 5, 5366 – 5372; c) D. J. Scott, T. R. Simmons, E. J.
Lawrence, G. G. Wildgoose, M. J. Fuchter, A. E. Ashley, ACS
Catal. 2015, 5, 5540 – 5544; d) V. Fasano, J. E. Radcliffe, M. J.
Ingleson, ACS Catal. 2016, 6, 1793 – 1798.
[13] a) G. R. Whittell, E. I. Balmond, A. P. M. Robertson, S. K. Patra,
M. F. Haddow, I. Manners, Eur. J. Inorg. Chem. 2010, 3967 –
3975; b) S. Freitag, J. Henning, H. Schubert, L. Wesemann,
Angew. Chem. Int. Ed. 2013, 52, 5640 – 5643; Angew. Chem.
2013, 125, 5750 – 5754; c) S. Freitag, K. M. Krebs, J. Henning, J.
Hirdler, H. Schubert, L. Wesemann, Organometallics 2013, 32,
6785 – 6791; d) F. A. Tsao, L. Cao, S. Grimme, D. W. Stephan, J.
Am. Chem. Soc. 2015, 137, 13264 – 13267; e) Y. Yu, J. Li, W. Liu,
Q. Ye, H. Zhu, Dalton Trans. 2016, 45, 6259 – 6268; f) K. M.
Krebs, J.-J. Maudrich, L. Wesemann, Dalton Trans. 2016, 45,
8081 – 8088.
stannylium · tin
[1] For key publications, see: a) G. C. Welch, R. R. San Juan, J. D.
Masuda, D. W. Stephan, Science 2006, 314, 1124 – 1126; b) G. C.
Welch, D. W. Stephan, J. Am. Chem. Soc. 2007, 129, 1880 – 1881;
c) P. A. Chase, G. C. Welch, T. Jurca, D. W. Stephan, Angew.
Chem. Int. Ed. 2007, 46, 8050 – 8053; Angew. Chem. 2007, 119,
8196 – 8199; d) P. A. Chase, T. Jurca, D. W. Stephan, Chem.
Commun. 2008, 1701 – 1703; e) D. Chen, J. Klankermayer,
Chem. Commun. 2008, 2130 – 2131; f) A. E. Ashley, A. L.
Thompson, D. OꢀHare, Angew. Chem. Int. Ed. 2009, 48, 9839 –
9843; Angew. Chem. 2009, 121, 10023 – 10027; g) K. Cherni-
chenko, ꢁ. Madarꢂsz, I. Pꢂpai, M. Nieger, M. Leskelꢃ, T. Repo,
Nat. Chem. 2013, 5, 718 – 723; h) M.-A. Lꢄgarꢄ, M.-A. Courte-
manche, ꢅ. Rochette, F.-G. Fontaine, Science 2015, 349, 513 –
516.
[2] For reviews of FLP chemistry, see: a) “Frustrated Lewis Pairs”:
G. Erker, D. W. Stephan, Topics in Current Chemistry, Vols. I and
II, Springer, Berlin, 2013; b) D. W. Stephan, Acc. Chem. Res.
2015, 48, 306 – 316; c) D. W. Stephan, G. Erker, Angew. Chem.
Int. Ed. 2015, 54, 6400 – 6441; Angew. Chem. 2015, 127, 6498 –
6541; d) D. W. Stephan, J. Am. Chem. Soc. 2015, 137, 10018 –
10032.
[14] The use of “R3Sn+” LAs need not present excessive safety
concerns. While certain organotin(IV) species are highly toxic
(notably for R = Me), this is highly dependent on the organic
skeleton. See, for example: T. Gadja, A. Jancsꢆ, Met. Ions Life
Sci. 2010, 7, 111 – 151, and references therein.
[15] Z. M. Heiden, A. P. Lathem, Organometallics 2015, 34, 1818 –
1827.
[16] For example, see: a) K. Kamiura, M. Wada, Tetrahedron Lett.
1999, 40, 9059 – 9062; b) T. X. Yang, P. Four, F. Guibꢄ, G.
Balavoince, New J. Chem. 1984, 8, 611 – 614, and references
therein.
[17] C. G. Arnold, A. Weidenhaupt, M. M. David, S. R. Mꢇller, S. B.
Haderlein, R. P. Schwarzenbach, Environ. Sci. Technol. 1997, 31,
2596 – 2602.
[18] V. Sumerin, F. Schulz, M. Nieger, M. Leskelꢃ, T. Repo, B. Rieger,
Angew. Chem. Int. Ed. 2008, 47, 6001 – 6003; Angew. Chem.
2008, 120, 6090 – 6092.
[3] For reviews of FLP-catalyzed hydrogenation, 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) J.
Paradies, Angew. Chem. Int. Ed. 2014, 53, 3552 – 3557; Angew.
Chem. 2014, 126, 3624 – 3629; c) L. J. Hounjet, D. W. Stephan,
Org. Process Res. Dev. 2014, 18, 385 – 391.
[4] T. A. Rokob, A. Hamza, I. Pꢂpai, J. Am. Chem. Soc. 2009, 131,
10701 – 10710.
4
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[19] A similar strategy has been documented for silyium species:
obtained by mixing [1]OTf, collidine and 5a (10 equiv) at the
a) B. Mathieu, L. Ghosez, Tetrahedron 2002, 58, 8219 – 8226;
b) T. J. Herrington, B. J. Ward, L. R. Doyle, J. McDermott,
A. J. P. White, P. A. Hunt, A. E. Ashley, Chem. Commun. 2014,
50, 12753 – 12756.
same concentration in DCB.
[28] L. E. Longobardi, C. Tang, D. W. Stephan, Dalton Trans. 2014,
43, 15723 – 15726.
[29] a) I. Kaljurand, A. Kꢇtt, L. Soovꢃli, T. Rodima, V. Mꢃemets, I.
Leito, I. A. Koppel, J. Org. Chem. 2005, 70, 1019 – 1028; b) J. F.
Coatzee, G. R. Padmanabhan, J. Am. Chem. Soc. 1965, 87, 5005 –
5010.
[30] H. J. Campbell, J. T. Edward, Can. J. Chem. 1960, 38, 2109 – 2116.
[31] J. M. Blackwell, W. E. Piers, R. McDonald, J. Am. Chem. Soc.
2002, 124, 1295 – 1306.
[20] I. Zharov, B. T. King, Z. Havlas, A. Pardi, J. Michl, J. Am. Chem.
Soc. 2000, 122, 10253 – 10254.
[21] a) U. Mayer, V. Gutmann, W. Gerger, Monatsh. Chem. 1975, 106,
1235 – 1257; b) M. A. Beckett, G. C. Strickland, J. R. Holland,
K. S. Varma, Polymer 1996, 37, 4629 – 4631; c) G. C. Welch, L.
Cabrera, P. A. Chase, E. Hollink, J. D. Masuda, P. Wei, D. W.
Stephan, Dalton Trans. 2007, 3407 – 3414.
[22] A. E. Ashley, T. J. Herrington, G. G. Wildgoose, H. Zaher, A. L.
Thompson, N. H. Rees, T. Krꢃmer, D. OꢀHare, J. Am. Chem. Soc.
2011, 133, 14727 – 14740.
[32] If this reaction mixture is subsequently heated to 1208C very
slow formation of 5a is observed. In light of other results, this
reduction is most likely mediated by the [1]OTf formed upon H2
release from [1]H/Col·HOTf.
[33] The reduced rates of turnover with 2,6-lutidine and DABCO
relative to collidine can be attributed to less favorable H2
activation, and H+ transfer, respectively (see the SI). Evidence
that collidine is a slightly stronger base than [1]OiPr comes from
the observation that addition of collidine to a [1]OTf/5a mixture
[23] I. Kaljurand, A. Kꢇtt, L. Soovꢃli, T. Rodima, V. Mꢃemets, I.
Leito, I. A. Koppel, J. Org. Chem. 2005, 70, 1019 – 1028.
[24] W. Kitching, H. A. Olszovy, G. M. Drew, Organometallics 1982,
1, 1244 – 1246.
[25] a) S. Tussing, L. Greb, S. Tamke, B. Schirmer, C. Muhle-Goll, B.
Luy, J. Paradies, Chem. Eur. J. 2015, 21, 8056 – 8059; b) S.
Tussing, K. Kaupmees, J. Paradies, Chem. Eur. J. 2016, 22, 7422 –
7426.
[26] Interestingly, while this reaction proceeds initially very rapidly at
RT (reaching almost 50% conversion within minutes), the rate
drops quickly (e.g. only 65% conv. after 17 h), presumably due
to deprotonation of remaining 2a·HOTf by the more basic 3a.
[27] RT NMR spectroscopy on the final reaction mixture shows only
one set of Sn-iPr resonances and no unassigned peaks in the 1H
spectrum, and a single broad resonance at around 30 ppm in the
119Sn{1H} spectrum. A comparable 119Sn{1H} signal can be
1
leads to an upfield shift in the LA H and 119Sn resonances and
downfield shifts for the collidine 1H resonances, consistent with
deprotonation. Similar shifts in the collidine resonances are
observed during catalytic reactions (see the SI).
[34] We are aware of a single example of heterogeneous Sn-catalyzed
hydrogenation: S. Nishiyama, T. Kubota, K. Kimura, S. Tsuruya,
M. Masai, J. Mol. Catal. A 1997, 120, L17 – 22.
Received: July 8, 2016
Revised: August 5, 2016
Published online: && &&, &&&&
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Communications
FLP Hydrogenation
Less frustration with new FLP: The
simple Lewis acid iPr3SnOTf can be used
to activate H2 in conjunction with
common N-centered Lewis bases via
a frustrated Lewis pair (FLP) mechanism.
These FLP systems are effective for the
D. J. Scott, N. A. Phillips, J. S. Sapsford,
A. C. Deacy, M. J. Fuchter,
A. E. Ashley*
&&&& — &&&&
=
Versatile Catalytic Hydrogenation Using A
Simple Tin(IV) Lewis Acid
catalytic hydrogenation of a variety of C
=
=
C, C N, and even C O bonds and display
an unprecedented level of tolerance to
moisture.
6
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These are not the final page numbers!