Facile metal free regioselective transfer hydrogenation of polarized olefins with ammonia borane

Article abstract of DOI:10.1039/c0cc03163a

Transfer hydrogenation of polarized olefins bearing strongly electron-withdrawing groups on one side of the double bond was achieved with ammonia borane under mild conditions without using a catalyst. Mechanistic studies proved the character of the direct H transfers proceeding stepwise with a unique hydroboration intermediate and hydride before proton transfer.

Full text of DOI:10.1039/c0cc03163a

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Facile metal free regioselective transfer hydrogenation of polarized
olefins with ammonia boranewz
Xianghua Yang, Thomas Fox and Heinz Berke*
Received 10th August 2010, Accepted 6th December 2010
DOI: 10.1039/c0cc03163a
Transfer hydrogenation of polarized olefins bearing strongly
electron-withdrawing groups on one side of the double bond
was achieved with ammonia borane under mild conditions
without using a catalyst. Mechanistic studies proved the
character of the direct H transfers proceeding stepwise with a
unique hydroboration intermediate and hydride before proton
transfer.
donor, applying polarized olefins as hydrogen acceptors and
study the H transfer mechanism in detail.
2-Cyclohexylidenemalononitrile (1a) was used first to test
the reaction conditions. It was surprising to see that the 1 : 1
hydrogen transfer from AB to 1a can be completed within
10 min in THF at room temperature and at 10 1C in less than
1 h, with 2a as the only hydrogenated product and borazine
((BHNH)3, BZ) as the by far predominant dehydrocoupling
product (a small amount of polyborazine and cyclotribora-
zane were also observed).7 When the solvent was changed to
acetonitrile, 1 h was required to complete the hydrogenation at
room temperature. Benzene and chloroform were also tried: in
both cases, the reactions were slow presumably due to poor
solubility of AB in these solvents, but the rate was much faster
in the less polar solvent benzene (20 h) than in chloroform
(more than 3 days). Considering that 10 min is too fast for
proper pursuit of the reaction course at room temperature,
acetonitrile was selected for the model studies.
Transfer hydrogenation is a broadly applied method for
hydrogenation of unsaturated compounds using a source
other than gaseous H2.1 Concerning the mechanism for
transfer hydrogenations, they are commonly classified into
two groups:2 (a) direct hydrogen transfers from the hydrogen
donor to the acceptor species, and (b) an indirect mechanism,
by which the H atoms are transferred from the hydrogen
donor to the acceptor through mediation by catalytic or
non-catalytic centers.
A typical example for the first route is the aluminium
complex catalyzed Meerwein–Ponndorf–Verley reduction of
carbonyl substrates to alcohols, which was proposed to occur
through a six-membered transition state including the Lewis
acidic centers.3 The second type, often also called bifunctional
catalysis, is the preferred mechanism for metal catalyzed
hydrogen transfers, where a metal hydride intermediate and
a protic site are formed prior to the double H transfer to the
hydrogen acceptor. The widely applied Noyori and Shvo type
transfer hydrogenations are of this type.4 However, double H
transfers via the elementary process of direct transfer without
the presence of a metal center are rare.5
To test the chemical scope of this reaction, a series of
polarized olefins with two electron-withdrawing (EWD)
groups on one side of the double bond and on the other side
with H, alkyl or aryl substituents (1a–1k) were applied in the
reaction with AB in acetonitrile at room temperature. High
yields in the hydrogenated products were achieved (Table 1).
The required time for completion of the reactions varied
from several minutes to several days. Comparing the reaction
times of different olefins, it was found that alkyl groups
accelerate the hydrogen transfers, since the required times
for the olefins 1a–1e were less than those for 1f–1h (Table 1,
entries 1–8). Comparing the effect of the ester substituent with
the stronger EWD group CN, the latter seemed to activate the
olefin more (entries 1 to 2 and 9 to 11). Hydrogen substituents
also accelerated the reaction rates presumably imposing less
steric hindrance on the reactants (entries 6, 7 and 9).
We recently approached metal free transfer hydrogenation
of imines with ammonia borane (BH3NH3, AB) as the hydrogen
donor.6 By various mechanistic studies it was proven to
involve a concerted double H transfer. Herein, we will report
another direct H transfer reaction with AB as the hydrogen
To ensure the transfer hydrogenation to proceed with
‘polarity-match’ of the hydrogen donor and the acceptor,
reactions of three different olefins (1a, 1h and 1i) with selectively
deuterated AB adducts (BD3NH3 (AB(D)) and BH3ND3
(A(D)B)) were carried out. The reactions were pursued by
in situ 1H, 2H and 13C NMR spectroscopies, and only the
expected regio-orientation of the deuterated products was
observed. This confirmed regiospecificity in the hydrogen
transfer processes. The possibility of radical involvement in
the reaction course seemed less probable.
Institute of Inorganic Chemistry, University of Zurich,
¨
Winterthurerstr. 190, 8057 Zurich, Switzerland.
¨
E-mail: hberke@aci.uzh.ch; Fax: +41 4463 56802;
Tel: +41 4463 54681
w This article is part of a ChemComm ‘Hydrogen’ web-based themed
issue.
z Electronic supplementary information (ESI) available: Preparation
of starting materials, general transfer hydrogenation procedure, and
detailed NMR data for all mentioned compounds. See DOI: 10.1039/
c0cc03163a
c
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Table
1
Transfer hydrogenation reactions of various polarized
with AB(D) (see Fig. 1, kAB/kAB(D) = 1). Assuming that any
HB transfer in the RDS would cause some kind of DKIE a 1,
a DKIE of 1 is expected to indicate that the double H transfer
is stepwise and the HB transfer being fast occurring before or
after the RDS.8
olefins with ABa
For the reaction of 1a with A(D)B, a normal DKIE of
1.55 was obtained, indicating the participation of the breakage
of the N–H bond in the RDS. For BD3ND3 (A(D)B(D)), the
DKIE value was 1.61. This further addresses the fact that
the HN transfer is rate determining regardless of HB or DB in
the neighborhood.
Entry Olefin
Temperature Time
Yieldb (%)
1
1a rt
1 h
2 h
5 h
4 h
1 h
6 h
499 (86)
2
3
4
5
6
1b rt
1c rt
1d rt
1e rt
499
499
499
499
499
Since the reaction of a 1 : 1 molar mixture of AB and 1a in
THF was very fast at room temperature, a NMR sample with
1a in excess (AB to 1a 1 : 3) was prepared at low temperature
in THF-D8 and kept at ꢀ40 1C. A set of new signals appeared
in the NMR (Fig. 2, spectrum c), which apparently belong
to a reaction intermediate (3a), since they disappeared with
increasing temperature and prolonged reaction times.
Based on 1H, 13C NMR and DEPT (THF-D8, ꢀ40 1C), the
intermediate 3a is a hydrogenation product formed via
1,2-addition of a B–H bond across the olefinic double bond,
while the boron substituent went to the cyano substituted side;
the CCN atom is thus characterized by a very broad signal at
13C NMR due to the quadrapolar broadening influence of the
11B nucleus (Fig. 2). The newly formed –BH2NH3 unit with a
4-coordinate boron showing a broad triplet at ꢀ14 ppm in the
11B NMR (different from cyclotriborazane which should be a
sharp triplet at ꢀ11 ppm in the 11B NMR). A new broad signal
also developed at 5.15 ppm in the 1H NMR, having no
11B correlation, no (or invisible) NOE nor long range
1f
rt
rt
5 d
6 h
2 d
92
7
8
1g
60 1C
rt
499
98
1
correlations to other H or 13C NMR signals indicating that
1h
60 1C
0.5 h
499 (93)
this signal belongs to the HN nuclei of 3a. Given enough time
at low temperature, the intensities of the signals for 3a will
increase until the signal of AB had completely disappeared
from the 11B NMR spectrum, while the signals of 2a also
9
1i
1j
rt
rt
10 min 499 (90)
10
0.5 h
3 d
499
11
1k rt
98
a
Reactions in acetonitrile with a 1 : 1 molar ratio of 0.1 mmol olefin
b
to AB. Reactions pursued by 1H NMR and the yields were
established by GC-MS based on the amount of olefins, in brackets
were the isolated yields with a 1 mmol scale, all reactions were carried
out at least twice to ensure the results as reported.
In addition to these deuterium labelling studies, the primary
deuterium kinetic isotope effect (DKIE) was also investigated
in reactions with 1a. According to the kinetic conversion chart
of Fig. 1, which is based on 11B NMR experiments, the rate
constants (k) were simulated with a first order equation to
obtain the DKIE values. In our former study on the hydrogen
transfer from AB to imines, an inverse DKIE was observed
with AB(D) and a normal DKIE with A(D)B indicating that in
this case the cleavage of both HB and HN is involved in the rate
determining step (RDS).6 However, using the push–pull olefin
1a as the hydrogen-acceptor, a DKIE could not be observed
Fig. 1 Conversion chart of the reaction of 0.5 mmol 1a with 0.1 mmol
AB, AB(D), A(D)B or A(D)B(D) pursued by 11B NMR in CH3CN at
rt, derived from the intensities of AB of the 11B NMR spectra with
2 min intervals. The black squares stand for reactions with AB, red
circles for AB(D), blue triangles for A(D)B and orange triangles for
A(D)B(D). Simulated reaction half-life times were: t1/2(AB) = 309 s,
t
1/2(AB(D)) = 308 s, t1/2(A(D)B) = 480 s, t1/2(A(D)B(D)) = 499 s. For
9
first order reactions, the reaction constant k = 0.693/t1/2
,
thus
k
k
AB/kAB(D)
=
t1/2(AB(D))/t1/2(AB)
=
1.00, kAB/kA(D)B
=
1.55,
AB/kA(D)B(D) = 1.61.
c
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2054 Chem. Commun., 2011, 47, 2053–2055

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Scheme 1 Proposed reaction mechanism.
RDS, and the structure of the hydroboration intermediate
clearly indicated that HB transfer occurs before the HN
transfer. Thus, this double-H transfer can be defined as
stepwise and in a polar terminology with hydride before
proton transfer.
Fig. 2 Selected 13C NMR spectra (range of 24 to 45 ppm) in
THF-D8: (a) pure 1a, labeled with circles K; (b) pure 2a, labeled with
triangles .; (c) in situ spectrum for the reaction of 1a with AB
(2 to 1 molar ratio) at ꢀ40 1C: five new resonances from 3a appeared
(labeled with squares ’)—including a broad signal; (d) in situ spectrum
for the reaction of 1a with AB(D) at ꢀ40 1C: two triplets belonging to CD
(1JDC = 20 Hz) appeared as labeled with arrows k, and the broad
resonance became sharper; (e) in situ spectrum for the reaction of 1a with
A(D)B at ꢀ40 1C: only one triplet of 2a appeared.
We gratefully thank the Swiss National Science Foundation
and the University of Zurich for financial support.
Notes and references
1 D. Klomp, U. Hanefeld and J. A. Peeters, in Handbook of
Homogeneous Hydrogenation, ed. J. G. De Vries and
C. J. Elsevier, Wiley-VCH, Weinheim, Germany, 2007; S. Gladiali
and E. Alberico, Chem. Soc. Rev., 2006, 35, 226–236;
J. S. M. Samec, J.-E. Bakvall, P. G. Andersson and P. Brandt,
¨
Chem. Soc. Rev., 2006, 35, 237–248.
started to grow in. The same experiment was also carried out
in acetonitrile leading to similar observations but at lower rate.
From the related reactions of 1a with AB(D) and A(D)B at
ꢀ40 1C, 1H, 13C and 11B NMR spectra were taken. Comparing
the 13C NMR spectra with that of the reaction of 1a with AB,
it can clearly be seen that the HB (or DB) atom was in the
intermediate already transferred, while the HN (or DN) atom
was not, since a triplet due to C–D coupling (1JDC = 20 Hz)
was exclusively observed for the intermediate only when
AB(D) was used (Fig. 2, spectrum d).
2 H. Berke, ChemPhysChem, 2010, 11, 1837–1849; A. Comas-Vives,
G. Ujaque and A. Lledos, THEOCHEM, 2009, 903, 123–132.
´
3 H. Meerwein and R. Schmidt, Justus Liebigs Ann. Chem., 1925, 444,
221–228; W. Ponndorf, Angew. Chem., 1926, 39, 138–143; Verley,
Bull. Soc. Chim. Fr., 1925, 37, 871–874.
4 R. Noyori, T. Okhuma, M. Kitamura, H. Takaya, N. Sayo,
H. Kumobayashi and S. Akuragawa, J. Am. Chem. Soc., 1987,
109, 5856–5858; R. Noyori, in Asymmetric Catalysis In Organic
Synthesis, Wiley-Interscience, John Wiley & Sons, New York, 1994,
pp. 16–94; Y. Blum, D. Czarkie, Y. Rahamim and Y. Shvo,
Organometallics, 1985, 4, 1459–1461; Y. Shvo, D. Czarkie,
Y. Rahamim and D. F. Chodosh, J. Am. Chem. Soc., 1986, 108,
7400–7402 and references cited therein.
Based on all these mechanistic facts, a two-step hydrogen
transfer mechanism is proposed with fast initial hydroboration
forming intermediate 3 (Scheme 1).9 There are two possible
routes to 3, the ionic pathway A and the concerted pathway B.
Considering the solvent effect and comparing THF with
acetonitrile, the ionic pathway A is expected to work better in
the more polar solvent acetonitrile, while the concerted route B
seems to be in operation in the less polar solvent THF. Since the
reaction proceeds much faster in THF than in acetonitrile,
route B seems more reasonable. The RDS is the transfer
of the HN atom of AB, which could be transferred via an
intra-molecular mode as shown in 4 of Scheme 1, followed by
the elimination of the very reactive [BH2NH2], which will be
rapidly further dehydrogenated to BZ presumably in a similar
manner as the reaction of 1 with AB.
5 A review on uncatalyzed transfer hydrogenation reactions:
C. Ruchardt, M. Gerst and J. Ebenhoch, Angew. Chem., Int. Ed.
¨
Engl., 1997, 36, 1406–1430.
6 X. Yang, L. Zhao, T. Fox, Z.-X. Wang and H. Berke, Angew.
Chem., Int. Ed., 2010, 49, 2058–2062.
7 For reactions on amine-borane adducts see: A. Staubitz,
A. P. M. Robertson and I. Manners, Chem. Rev., 2010, 110,
4079–4124; A. Staubitz, A. P. M. Robertson, M. E. Sloan and
I. Manners, Chem. Rev., 2010, 110, 4023–4078 and references cited
therein.
8 J. H. Espenson, in Chemical kinetics and reaction mechanisms,
McGRAW-HILL, Inc., 2nd edn, 1995, pp. 214–228;
H. H. Limbach, in Hydrogen Transfer Reactions, ed. J. T. Hynes,
J. Klinman, H. H. Limbach and R. L. Schowen, Wiley-VCH,
Weinheim, Germany, 2007, vols. 1 & 2, ch. 6 and references cited
therein.
9 For mechanistic studies on dehydrocoupling of AB also see:
P. M. Zimmerman, A. Paul, Z. Zhang and C. B. Musgrave, Angew.
Chem., Int. Ed., 2009, 48, 2201–2205; W. J. Shaw, J. C. Linehan,
N. K. Szymczak, D. J. Heldebrant, C. Yonker, D. M. Camaioni,
R. T. Baker and T. Autrey, Angew. Chem., Int. Ed., 2008, 47,
7493–7496; X. Yang and M. B. Hall, J. Am. Chem. Soc., 2008, 130,
1798–1799; V. Pons, R. T. Baker, N. K. Szymczak,
D. J. Heldebrant, J. C. Linehan, M. H. Matus, D. J. Grant and
D. A. Dixon, Chem. Commun., 2008, 6597–6599 and references cited
therein.
In summary, we have demonstrated a very efficient metal
free transfer hydrogenation of polarized olefins substituted
with EWD groups on one side of the double bond with AB at
room temperature. Deuterium labelling studies confirmed
the regiospecificity in the H transfer processes. The DKIE
demonstrated that only the HN transfers get involved in the
c
This journal is The Royal Society of Chemistry 2011
Chem. Commun., 2011, 47, 2053–2055 2055