Scope and Mechanisms of Frustrated Lewis Pair Catalyzed Hydrogenation Reactions of Electron-Deficient C￡C Double Bonds

Article abstract of DOI:10.1002/anie.201507298

Several phosphonium and ammonium triarylborohydrides, which are intermediates in hydrogenation reactions catalyzed by frustrated Lewis pairs, were synthesized in high yield under mild conditions from triaryl boranes, ammonium or phosphonium halides, and triethylsilane. The kinetics and mechanisms of the reactions of these hydridoborate salts with benzhydrylium ions, iminium ions, quinone methides, and Michael acceptors were investigated, and their nucleophilicity was determined and compared with that of other hydride donors.

Full text of DOI:10.1002/anie.201507298

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Angewandte
Communications
International Edition: DOI: 10.1002/anie.201507298
German Edition: DOI: 10.1002/ange.201507298
Reaction Mechanisms
Scope and Mechanisms of Frustrated Lewis Pair Catalyzed
=
Hydrogenation Reactions of Electron-Deficient C C Double Bonds
Varvara Morozova, Peter Mayer, and Guillaume Berionni*
Dedicated to Professor Paul Knochel on the occasion of his 60th birthday
Abstract: Several phosphonium and ammonium triarylboro-
hydrides, which are intermediates in hydrogenation reactions
catalyzed by frustrated Lewis pairs, were synthesized in high
yield under mild conditions from triaryl boranes, ammonium
or phosphonium halides, and triethylsilane. The kinetics and
mechanisms of the reactions of these hydridoborate salts with
benzhydrylium ions, iminium ions, quinone methides, and
Michael acceptors were investigated, and their nucleophilicity
was determined and compared with that of other hydride
donors.
the Mayr reactivity scale[3] can be hydrogenated by the use of
a combination of tris(1-naphthyl)phosphane (C10H7)3P and
B(C6F5)3 as the catalyst.[4]
On the other hand, hydrogenation reactions of nitro-
alkenes and acrylates were not catalyzed by FLPs derived
from B(C6F5)3 (1a), but proceeded smoothly when a Lewis
pair derived from the less acidic borane B(2,6-F2C6H3)3 (1c)
was employed (Scheme 2).[5] Analogously, Alcarazo and co-
H
ydrogenation reactions catalyzed by frustrated Lewis
pairs (FLPs) have attracted great attention in recent years, as
these reactions avoid the use of metal catalysts and show
unusual selectivity and functional-group tolerance.[1] The
heterolytic cleavage of H2 is only possible when the Lewis
acidity of Ar3B and the Lewis basicity of R3D (D = P or N)
exceed a certain strength, and when the formation of Lewis
acid–base adducts is counteracted by steric shielding
(Scheme 1).[2] Grimme, Paradies, and co-workers demon-
strated that hydrogenation reactions of EDG-substituted
=
C C double bonds proceed through initial protonation, and
Scheme 2. Synthesis of the ammonium and phosphonium hydrido-
borates 7a–c, with the yields of the isolated products. [a] The salt 7c-
nBu4N+ was obtained by using nBu4N+ ClÀ instead of 3. TMP=2,2,6,6-
tetramethylpiperidine.
that substrates with nucleophilicity parameters 1 < N < 5 on
workers explored the catalytic hydrogenation of electron-
poor alkenes with FLPs derived from differently fluorinated
triaryl boranes and 1,4-diazabicyclo[2.2.2]octane (DABCO)
and found that only B(2,4,6-F3C6H2)3 (1b) and B(2,6-F2C6H3)3
(1c) showed catalytic activity.[6] In agreement with Paradies
and co-workers, they observed that these less Lewis acidic
boranes were more efficient in the hydrogenation of electron-
deficient alkenes than B(C6F5)3 (1a).[6] However, systematic
mechanistic and kinetic studies to rationalize these observa-
tions have not yet been reported.
Scheme 1. Mechanism of the FLP-catalyzed hydrogenation of electron-
=
poor (top) and electron-rich (bottom) C C double bonds. EWG=elec-
To explore the scope and mechanism of hydrogenation
reactions proceeding through initial hydride transfer
(Scheme 1, top), we employed the benzhydrylium method[3]
to quantify the nucleophilic reactivity of the hydride donors
tron-withdrawing group; EDG=electron-donating group.
À
À
[*] V. Morozova, Dr. P. Mayer, Dr. G. Berionni
HB(C6F5À)3 (7a), HB(2,4,6-F3C6H2)3 (7b), and HB(2,6-
F2C6H3)3 (7c), which are intermediates in FLP-catalyzed
hydrogenation reactions. The tetraethylammonium triaryl-
borohydrides (7a–c)-Et4N+ were synthesized by mixing
equimolar amounts of a triaryl borane 1a–c, triethylsilane
(2), and Et4N+BrÀ (3) in CH2Cl2 (Scheme 2, top) according to
a procedure reported by Piers and co-workers.[7] When 3 was
Department Chemie, Ludwig-Maximilians-Universität München
Butenandtstrasse 5-13, 81377 München (Germany)
E-mail: guillaume.berionni@cup.uni-muenchen.de
Homepage: http://www.cup.uni-muenchen.de/oc/mayr/
Supporting information and ORCID(s) from the author(s) for this
article are available on the WWW under http://dx.doi.org/10.1002/
anie.201507298.
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replaced with a secondary or tertiary ammonium or phos-
phonium chloride 4–6 (Scheme 2, bottom), the corresponding
triarylborohydrides 7, which were previously synthesized by
the cleavage of H2 by FLPs,[5,6] were obtained in good yield in
analytically pure form.
In the solid state, the triarylborohydride 7b-Et4N+ fea-
tured short intramolecular interactions (about 2.55 Š)
between the BH1 hydride and F1, F6, and F9 of the
fluorinated aryl rings (Figure 1a), like in the pentafluorinated
Scheme 3. Reactions of 7a–c with the benzhydrylium tetrafluoro-
borates 8a,c and yields of the products. For the X-ray crystal structure
of 9-Et4N+, see the Supporting Information.[9,10]
hydride quantitatively at 208C to the benzhydrylium center of
8a and 8c (Scheme 3).[9,10]
Next, the kinetics of the reactions of the triarylborohy-
drides 7a–c with the electrophiles 8b–h were studied under
pseudo-first-order conditions ([7] @ [8]). Monoexponential
decay of the absorbance of 8b–h was observed in all cases
(Figure 2), and plots of kobs versus the concentration of 7a–c
gave the second-order rate constants k2 of these reactions
(Table 2).
Figure 1. X-ray crystal structures of a) 7b-Et4N+ (at 293 K) and
b) 7c-iPr2EtNH+ (at 100 K), with ellipsoids set at the 30% probability
level.[9] For bond lengths and angles, see the Supporting Information.
À
[8]
analogue nBu4N+HB(C6F5)3
.
X-ray diffraction analysis of
7c-TMPH+ (see the Supporting Information) agreed with
that recently described by Paradies and co-workers, who
obtained the same compound by heterolytic H2 cleavage,[5]
with the exception of the BH···HN distance, which we
measured to be 1.97 Š at 173 K,[9] and which was 1.91 Š at
100 K.[5] A considerably shorter H···H distance (1.77 Š) was
found for 7c-iPr2EtNH+ (Figure 1b), which was recrystallized
from CH2Cl2; this shorter H···H distance indicates a stronger
proton…hydride interaction.[9]
To quantify the hydride-donating ability of 7a–c and the
effect of different counterions, we studied the kinetics of their
reactions with the benzhydrylium ions 8a–h (Table 1), which
are employed as reference electrophiles of known electro-
philicity.[3] The formation of the diaryl methanes 10 and 11
shows that the triarylborohydrides 7a–c transferred their
Figure 2. Exponential decay of the time-dependent absorbance of 8 f at
l=616 nm during the reaction of 7c-Et4N+ (2.28”10À3 m) with 8 f
(6.5”10À6 m) in MeCN at 208C (kobs =7.3 sÀ1). Inset: linear correlation
between kobs and the concentration of 7c-Et4N+ (k2 =2.99”103 mÀ1 sÀ1).
Plots of the k2 values of the reactions of triarylborohy-
drides 7 with the electrophiles 8 against their E parameters
(Table 1) were linear (Figure 3), thus indicating the applic-
ability of Equation (1) for determining the nucleophilicity
Table 1: Structures, absorption maxima lmax, and electrophilicity
parameters E for the benzhydrylium ions 8a–h used as reference
electrophiles in this study.[3]
parameters
N and sN of the triarylborohydrides 7a–c
(Table 2). The almost identical second-order rate constants
k2 of the reactions of 7c-nBu4N+, 7c-Et4N+, 7c-tBu3PH+, 7c-
À
TMPH+, and 7c-iPr2EtNH+ with 8 f-BF4 (Table 2 and
lmax [nm][a]
E[b]
Scheme 4) show that the counterion has only a small effect
on the reaction rate. According to Equation (1), the slopes of
these correlation lines give the sensitivity parameters sN of 7.
X=NMe(CH2CF3)
X=N(CH2CH2)2O
X=NMe2
8a
8b
8c
8d
8e (n=2)
8 f (n=1)
586
611
605
612
620
616
À3.85
À5.53
À7.02
À7.69
À8.22
À8.76
À
À
These values were similar to those of other B H, Sn H, and
[11]
X=N(CH2)4
À
Si H hydride donors (0.6 < sN < 0.8).
logðk2Þ ¼ sNðN þ EÞ
ð1Þ
8g (n=2)
8h (n=1)
642
632
À9.45
Whereas the triarylborohydrides 7b-Et4N+ and 7c-Et4N+
exhibit similar nucleophilicity (N ꢀ 14), thus showing that the
para fluorine atom plays a negligible role, the pentafluoro-
phenyl derivative 7a-Et4N+ (N = 10.04) is considerably less
À10.04
[a] In MeCN, from Ref. [3a,b]. [b] From Ref. [3a].
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Table 2: Second-order rate constants k2 of the reactions of triarylboro-
hydrides (7a–c)-X+ with 8b–h in MeCN at 208C, and nucleophilicity N
and nucleophile-specific sensitivity parameters sN for 7a–c.
[a]
Ar2CH+
k2 [mÀ1 sÀ1
]
N, sN
7a-Et4N+
8b
8c
8d
8e
1.98”103
1.40”102
5.50”101
2.03”101
10.04, 0.73
Scheme 4. Second-order rate constants k2 (mÀ1 sÀ1) for the hydride-
transfer reaction from hydridoborate 7c with various counterions and
the benzhydrylium ion 8 f in MeCN at 208C.
7b-Et4N+
7c-Et4N+
8d
8 f
8h
8.48”103
1.51”103
3.02”102
14.13, 0.61
13.97, 0.66
8e
8 f
8g
8h
6.31”103
2.99”103
8.20”102
4.34”102
7c-nBu4N+
7c-TMPH+
8d
8e
8 f
8g
9.85”103
5.44”103
2.35”103
7.26”102
13.90, 0.65
14.24, 0.65
8e
8 f
8g
8h
8.34”103
3.60”103
1.05”103
5.95”102
7c-tBu3PH+
8d
8 f
8h
1.53”104
3.26”103
6.60”102
14.86, 0.58
14.94, 0.58
7c-iPr2EtNH+
8 f
8h
3.59”103
6.59”102
[a] For the determination of N and sN, see Figure 3 and the Supporting
Information.
Figure 4. Comparison of nucleophilicity parameters N (sensitivity
parameters sN in italics) of the triarylborohydrides 7a–c with those of
amino and N-heterocyclic carbene boranes (CH2Cl2) and other boro-
hydrides (DMSO).[11]
These nucleophilicity parameters can be used to ration-
alize the observations reported by the research groups of
Paradies and Alcarazo, that hydrogenation reactions of
alkylidene malonates, sulphones, and nitroolefins proceed
slower with FLPs derived from the strong Lewis acid 1a than
with those derived from 1b and 1c.[5,6] The low nucleophilicity
of 7a (N = 10.04) also accounts for the failure of the
stoichiometric reaction of (C6F5)3BHÀK+ with diethyl-2-
benzylidenemalonate (E = À20.55),[12] as recently described
by Alcarazo and co-workers.[6,12]
As the sN values of 7a–c are in a narrow range, thus
indicating that their relative nucleophilicity depends little on
the reactivity of the electrophile, the N values in Table 2 can
be used for a direct comparison with other classes of hydrides.
As shown in Figure 4, 7b-Et4N+ and 7c-Et4N+ are slightly less
nucleophilic than sodium borohydride, NaBH4 (N =
14.74),[11,13] and are among the most reactive hydride donors
so far quantified by Equation (1). The hydridoborate 7a-
Et4N+ has the same nucleophilicity as the pyridine!BH3
complex.[11]
Figure 3. Correlation of the logarithm of the second-order rate con-
stants k2 for the reactions of triarylborohydrides 7c-NEt4+ ( ), 7b-
&
+
+
~
*
NEt4 ( ), and 7a-NEt4 ( ) with the benzhydrylium tetrafluoroborates
8b–h in MeCN at 208C with the electrophilicity parameters E of 8b–h
from Table 1.[3]
nucleophilic (Figure 4). The presence of two meta fluorine
substituents thus reduces the hydride-donating ability of 7a
by a factor of approximately 104 and restricts the scope of
hydrogenation with FLPs derived from tris(pentafluorophe-
1H NMR spectroscopic monitoring of the stoichiometric
reactions of 7c-X+ with the Michael acceptors 12 and 14 in
CD3CN showed that hydride transfer to the benzylidene
=
nyl)borane (1a) to the most electrophilic C C double bonds.
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Table 3: Second-order rate constants k2 of the reactions of 7c-TMPH+
with quinone methides 12b,c, Michael acceptors 14a–c, and a,b-
unsaturated iminium ions 18a,b in MeCN at 208C.[16]
calc
Electrophile
lmax
[nm][a]
E[a]
k2
k2
k2
/
exp[b]
[mÀ1 sÀ1
]
12b
12c
14a
381
415
385
À11.87
À12.18
À11.32
15.2
2.28
10.8
2.02
5.33[c]
2.85[c]
0.347[d]
137[d]
14b
317
À9.15
10.6
23.1
192
14c
18a
306
348
À9.42
À9.80
58.8
475
1.62
650[d]
1.18[d]
18b
355
À7.37
42600
0.685
Scheme 5. Reactions of triarylborohydride 7c-X+ with electron-deficient
calc
[a] From Ref. [16]. [b] The value k2 was calculated from Equation (1).
[c] Counterion: Et4N+. [d] Counterion: nBu4N+. Tf=trifluoromethane-
sulfonyl.
=
C C double bonds in MeCN (or CD3CN) at 208C, and characterization
or isolation of the intermediate boron enolate. For details, see the
Supporting Information.
carbon atom was accompanied by the coordination of Ar3B to
the enolate oxygen atom (Scheme 5). Upon aqueous workup,
the products 13 and 16 were obtained. As the protodebor-
ylation of 15-TMPH+ or 17-TMPH+ with regeneration of the
FLP catalyst TMP/1c is very slow (not observed after 5 h in
CD3CN at 208C), we conclude that this step may be rate
shown to be almost independent of the counterion, but are
strongly affected by the substitution pattern of the Ar3B
catalyst. The nucleophilicity parameters of the triarylborohy-
drides were compared with those of other hydride donors and
used to analyze the synthetic potential of frustrated Lewis
pair catalyzed hydrogenation reactions of electron-deficient
=
determining in many FLP-catalyzed hydrogenation reactions
C C double bonds.
[14]
=
of acyl-substituted C C double bonds. In the reaction of
7c-Et4N+ with 14b, the resulting boron enolate 17-Et4N+
(d(11B) = À3.0 ppm) could even be isolated and fully charac-
terized.[15]
Acknowledgements
To examine the potential of the N and sN values of 7a–c
(Table 2) to predict the scope of reactions with electron-poor
We thank the Deutsche Forschungsgemeinschaft (SFB 749,
project B1) for financial support, Prof. Dr. H. Mayr, Prof. Dr.
P. Knochel, and Dr. A. R. Ofial for helpful discussions, and
Dr. S. Stephenson for assistance with NMR spectroscopy.
Prof. F. Terrier (Versailles, France), Dr. S. Lakhdar (Caen,
France), Dr. I. Makarov, Dr. K. Moriya, F. An, and E. Follet
(LMU, Munich) are also acknowledged for helpful comments.
=
C C double bonds, we measured the kinetics of their
reactions with several Michael acceptors and iminium ions
of known electrophilicity E.[16] As shown in Table 3, the k2
values of the reactions of the triarylborohydride 7c with the
quinone methides 12b,c and the iminium ions 18a,b are in
good agreement with the rate constants calculated from the
tabulated electrophilicities E[16] and from the N and sN values
of 7a–c (Table 2) obtained from Equation (1). In contrast, the
measured k2 values of the reactions with the Michael accept-
ors 14a–c are 50–200 times lower than predicted, which is
slightly outside the confidence range of Equation (1) (factor
Keywords: frustrated Lewis pairs · hydride donors · kinetics ·
nucleophilicity · reaction mechanisms
How to cite: Angew. Chem. Int. Ed. 2015, 54, 14508–14512
Angew. Chem. 2015, 127, 14716–14720
=
ꢁ
10–100). Activation of the C O or C N group of these
electrophiles by coordination with TMPH+ (pKa(MeCN)
ꢀ 11) can be excluded, since, in this case, the experimental
reaction rates would be higher than the calculated reaction
rates.[6,14]
In conclusion, several FLP–H2 salts were obtained by
hydrogen-free synthesis and were used for kinetic and
mechanistic studies. The reaction rates of hydride transfer
to benzhydrylium ions and Michael acceptors have been
[1] a) D. W. Stephan, G. Erker, Angew. Chem. Int. Ed. 2015, 54,
6400 – 6441; Angew. Chem. 2015, 127, 6498 – 6541; b) D. W.
Stephan, G. Erker, Angew. Chem. Int. Ed. 2010, 49, 46 – 76;
Angew. Chem. 2010, 122, 50 – 81.
[2] a) D. W. Stephan, Acc. Chem. Res. 2015, 48, 306 – 316; b) D. W.
Stephan, J. Am. Chem. Soc. 2015, 137, 10018 – 10032; c) D. W.
Stephan, Org. Biomol. Chem. 2008, 6, 1535 – 1539.
[3] a) H. Mayr, T. Bug, M. F. Gotta, N. Hering, B. Irrgang, B. Janker,
B. Kempf, R. Loos, A. R. Ofial, G. Remennikov, H. Schimmel, J.
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Communications
Am. Chem. Soc. 2001, 123, 9500 – 9512; b) H. Mayr, B. Kempf,
A. R. Ofial, Acc. Chem. Res. 2003, 36, 66 – 77.
[11] M. Horn, L. H. Schappele, G. Lang-Wittkowski, H. Mayr, A. R.
Ofial, Chem. Eur. J. 2013, 19, 249 – 263.
[12] For the electrophilicity parameters E of alkylidene malonates,
see: O. Kaumanns, R. Lucius, H. Mayr, Chem. Eur. J. 2008, 14,
9675 – 9682. According to Equation (1), the calculated second-
order rate constant of the stoichiometric reaction reported by
Alcarazo and co-workers (Ref. [6]) is 2 ” 10À8 mÀ1 sÀ1, which
corresponds to a half-life of more than 1.5 years at 208C with
a 1m concentration of the reagents.
[4] L. Greb, P. OÇa-Burgos, B. Schirmer, S. Grimme, D. W. Stephan,
J. Paradies, Angew. Chem. Int. Ed. 2012, 51, 10164 – 10168;
Angew. Chem. 2012, 124, 10311 – 10315.
[5] L. Greb, C.-G. Daniliuc, K. Bergander, J. Paradies, Angew.
Chem. Int. Ed. 2013, 52, 5876 – 5879; Angew. Chem. 2013, 125,
5989 – 5992.
[6] a) B. InØs, D. Palomas, S. Holle, S. Steinberg, J. A. Nicasio, M.
Alcarazo, Angew. Chem. Int. Ed. 2012, 51, 12367 – 12369; Angew.
Chem. 2012, 124, 12533 – 12536; b) J. Nicasio, S. Steinberg, B.
InØs, M. Alcarazo, Chem. Eur. J. 2013, 19, 11016 – 11020.
[7] a) J. M. Blackwell, D. J. Morrison, W. E. Piers, Tetrahedron 2002,
58, 8247 – 8254; b) simultaneous to our investigations, a similar
method was reported: W. L. Nie, C. Tian, M. Borzov, L. Maksim,
Q. Liu, H. Hu, W. Hu, Y. Jiang, K. Li, H. Gong, G. Chen, CN
104262374A, 2015.
[13] The reactivity differÀence of about 5 orders of magnitude
between 7a and BH4 corresponds to a DG° value of approx-
imately 8 kcalmolÀ1, which is smaller than the recently calcu-
lated theoretical value of 15 kcalmolÀ1: Z. M. Heiden, A. P.
Lathem, Organometallics 2015, 34, 1818 – 1827.
[14] More Brønsted acidic counterions than TMPH+, such as
DABCO-H+ and 2,6-lutidinium, may, however, activate Michael
acceptors through a R3N+H···O/N H-bonding interaction and
may protonate the intermediate boron enolate faster than
TMPH+ (see Ref. [5,6]).
[8] E. J. Lawrence, V. S. Oganesyan, D. L. Hughes, A. E. Ashley,
G. G. Wildgoose, J. Am. Chem. Soc. 2014, 136, 6031 – 6036.
[9] CCDC 1413309 (7b-Et4N+), 1413310 (7c-TMPH+), 1413311 (7c-
iPr2EtNH+), and 1413312 (9-Et4N+) contain the supplementary
crystallographic data for this paper. These data can be obtained
free of charge from The Cambridge Crystallographic Data
Centre.
[15] So far, only one boron enolate and an analogous nitronate
formed during the FLP-catalyzed hydrogenation of an ynone
and a nitrostyrene, respectively, have been characterized; see
Ref. [5] and: B.-H. Xu, G. Kehr, R. Frçhlich, B. Wibbeling, B.
Schirmer, S. Grimme, G. Erker, Angew. Chem. Int. Ed. 2011, 50,
7183 – 7186; Angew. Chem. 2011, 123, 7321 – 7324.
[16] For the electrophilicity parameters E of the electrophiles 12, 14,
and 18, see the reactivity database of E parameters: http://www.
cup.lmu.de/oc/mayr/DBintro.html. Kinetics of the reactions of
7c-TMPH+ with nitrostyrenes were not measurable owing to
UV/Vis overlap of their absorbances with those of the inter-
mediate nitronates.
[10] The fluoroborate 9–Et4N+ was formed by the abstraction of
À
a fluoride atom from the BF4 counterion by the released
B(C6F5)3; see: a) K. S. Coleman, J. Fawcett, D. A. J. Harding,
E. G. Hope, K. Singh, G. A. Solan, Eur. J. Inorg. Chem. 2010,
4130 – 4138; b) M. Alcarazo, C. Gomez, S. Holle, R. Goddard,
Angew. Chem. Int. Ed. 2010, 49, 5788 – 5791; Angew. Chem. 2010,
122, 5924 – 5927; for a higher-quality X-ray crystal structure of
[FB(C6F5)3]À, see: c) S. Kronig, E. Theuergarten, D. Holschu-
macher, T. Bannenberg, C. G. Daniliuc, P. G. Jones, M. Tamm,
Inorg. Chem. 2011, 50, 7344 – 7359.
Received: August 5, 2015
Published online: October 23, 2015
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