Metal-free hydrogenation of electron-poor allenes and alkenes

Article abstract of DOI:10.1002/anie.201205348

The poorer, the better: A metal-free catalytic procedure for the reduction of electron-poor allenes and alkenes has been developed. The method employs a frustrated Lewis pair based catalyst. 1,4-Diazabicyclo[2.2.2]octane (DABCO)/B(C₆F₅)₃ was shown to be the best combination in optimization studies. Copyright

Full text of DOI:10.1002/anie.201205348

Angewandte
Chemie
DOI: 10.1002/anie.201205348
Frustrated Lewis Pairs
Metal-Free Hydrogenation of Electron-Poor Allenes and Alkenes**
Blanca Inꢀs, David Palomas, Sigrid Holle, Sebastian Steinberg, Juan A. Nicasio, and
Manuel Alcarazo*
In memory of Anna Rufinska
Since their discovery, the chemistry of frustrated Lewis pairs
(FLPs) has flourished, and they show remarkable reactivity
towards the activation of small molecules. Thus, it has been
[1]
[2]
À
À
À
B
reported in recent years that bonds such as C O, C H,
H,[3] S S, C C, or Si H can be activated by using this
elegant concept. In spite of this, their arguably most
remarkable application is still the heterolytic cleavage of
H2,[7] and the subsequent development of metal-free catalytic
hydrogenations of a number or organic polar substrates, such
as imines,[8] enamines,[9] nitrogenated heterocycles,[10] or silyl
enol ethers[11] by employing H2 rather than Hantzsch
esters.[12,13] Surprisingly, despite all of these achievements,
the FLP-promoted catalytic hydrogenation of electron-poor
unsaturated systems is still underdeveloped.[14] Herein, in an
attempt to address this clear limitation, we describe our
efforts towards the catalytic reduction of allenes. These
studies indicate that electron-deficient allenes are the most
adequate substrates for hydrogenation, probably following
a Michael-type hydride addition to the allene. Moreover, we
have also extended this method to the hydrogenation of
electron-poor alkenes, such as alkylidene malonates.
[4]
[5]
[6]
À
À
À
At first glance it seemed to us that allenes, owing to the
higher reactivity derived from their two adjacent double
bonds, could be appropriate substrates for a preliminary
screening of reaction conditions. Thus, tetraphenylallene
1 was exposed to mixtures of PhNMe2 or Ph2NMe/B(C6F5)3
(15 mol%) and H2 (60 bar).[15] Interestingly, consumption of
1 was observed, and two new products 2 and 3 could be
isolated from the reaction mixtures after column chromatog-
raphy (Scheme 1). While the formation of alkene 3 clearly
indicates that reduction of allenes is possible by FLP
chemistry, the detection of 2 suggests the existence of
a competing reaction pathway. Thus, it can be envisaged
that first 1 is protonated at the central carbon atom, and
subsequent hydride transfer to the transient cation produces
Scheme 1. Reactivity of electron-neutral allenes towards FLPs and the
molecular structure of 5 and 7 in the solid state (hydrogen atoms
omitted for clarity; ellipsoids set at 50% probability).[18] Reagents and
conditions (yields): a) B(C6F5)3/Ph2NMe (15 mol%), toluene, 808C,
3 days, 2 (63%), 3 (22%) or B(C6F5)3/PhNMe2 (15 mol%), toluene,
808C, 3 days, 2 (0%), 3 (96%); b) B(C6F5)3 (15 mol%), toluene, RT, 5
(97%); c) B(C6F5)3, toluene, RT, 7 (78%).
3. Alternatively, intramolecular Friedel–Crafts alkylation
affords 2. Furthermore, it should not be excluded that the
undesired transformation of 1 into 2 may be directly
promoted by B(C6F5)3 without the participation of any
proton, because: 1) allene 4 cleanly cycloisomerizes into 5
solely in the presence of catalytic amounts of B(C6F5)3, and
2) the allene–borane complex 7 is obtained when the more
electron-rich allene 6 is employed as a substrate.[16,17]
To overcome this inherent drawback, an electron-defi-
cient allene 8 that is unable to interact with the borane
through the central carbon atom was chosen as new model
substrate. In this case, after subjection to the hydrogenation
[*] Dr. B. Inꢀs, Dr. D. Palomas, S. Holle, S. Steinberg, J. A. Nicasio,
Dr. M. Alcarazo
Max-Planck-Institut fꢁr Kohlenforschung
45470 Mꢁlheim an der Ruhr (Germany)
E-mail: alcarazo@mpi-muelheim.mpg.de
[**] Generous financial support from the Fonds der Chemischen
Industrie and the European Research Council (ERC Starting grant
agreement no. 277963) is gratefully acknowledged. We also thank
Prof. A. Fꢁrstner for constant encouragement and the NMR
spectroscopy and X-ray crystallography departments of our institute
for excellent support.
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201205348.
Angew. Chem. Int. Ed. 2012, 51, 12367 –12369
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
12367

.
Angewandte
Communications
Table 2: Catalytic hydrogenation of electron deficient allenes: Reaction
conditions (808C, 60 bar), the reduced product was indeed
obtained in very good yield ,and no traces of cyclized products
were detected. Interestingly, despite the fact that the for-
mation of ester–B(C6F5)3 complexes is known, this process is
probably reversible under the studied conditions and does not
seem to affect the desired hydrogenation.[19] Screening of
different bases revealed DABCO to be the most suitable for
this transformation (Table 1 and Figure 1). With this opti-
scope.[a]
Entry
Allene
Product
Yield [%][b]
1
2
3
4
5
10; R,R’=Ph
11; R,R’=p-(Me)Ph
12; R,R’=p-(F)Ph
13; R,R’=p-(OMe)Ph
14; R-R’=3,5-di(F)-9-fluorene
15
16
17
18
19
75
65
94
Table 1: Catalytic hydrogenation of allene 8: Lewis base optimization.[a]
68
43[c]
Entry Allene
Base
Product
Yield [%][b]
[a] Reaction conditions: Toluene, 808C, 3 days; H2 60 bar and DABCO/
B(C6F5)3 (15 mol%). [b] Yields of isolated product. [c] The low yields are
probably due to dimerization of the allene at the working conditions.
1
2
3
4
5
tBu3P
Mes3P
2,6-lutidine
DABCO
DABCO[d]
64
66
90[c]
93
92
37 in very good yields. Moreover, reactions were faster and
the catalysts charge could be reduced to 10 mol% (Table 3).
To the best of our knowledge, this is the first systematic study
on the reduction of electron-deficient unsaturated species
employing FLPs.[14]
[a] Reaction conditions: Toluene, 808C, 3 days. H2 60 bar and Lewis
base/B(C6F5)3 (20 mol%). [b] Yields of isolated product. [c] Conversion
from GC. [d] DABCO/B(C6F5)3 (15 mol%).
Table 3: Catalytic hydrogenation of alkylidene malonates.[a]
Entry
Alkene
Product
Yield [%][b]
1
2
3
4
5
6
7
8
9
20; R=Ph
29
30
31
32
33
34
35
36
37
92
91
93
91
96
79
81
79
88
21; R=2-naphthyl
22; R=p-(CF3)Ph
23; R=p-(F)Ph
24; R=p-(OMe)Ph
25; R=iPr
26; R=(CH2)6CH3
27; R=Cy
28; R=(CH2)2Ph
Figure 1. Molecular structure of 9 in the solid state (except for the
À
newly formed C H bonds, hydrogen atoms omitted for clarity;
[a] Reaction conditions: Toluene, 808C, 24 h; H2 60 bar and DABCO/
B(C6F5)3 (10 mol%). [b] Yields of isolated product.
ellipsoids set at 50% probability).[17]
mized catalytic mixture in hand, we explored the scope of this
method further, and to this end a representative set of diaryl
substituted allenes 9–12 containing substituents of different
electronic nature was synthesized and submitted to the
optimized conditions (Table 2).
The results compiled in Table 2 deserve further comment.
With the exception of 14, which probably dimerizes,[20] all of
the substrates behaved well; however, higher yields were
obtained when electron-withdrawing groups were placed on
the aryl substituents. Furthermore, the hydrogenation seems
Finally, some considerations about the plausible reaction
mechanism will be mentioned. It has been proposed that the
FLP-promoted reduction of imines and electron-rich alkenes
is initiated by protonation of the substrate, followed by
hydride transfer.[21] However, a direct protonation of the
olefin moiety does not seem to be reasonable for the
substrates studied considering their electron-poor nature. In
an attempt to gain some evidence about the reaction pathway,
some additional experiments were carried out. Thus, when
a mixture of alkene 20 and KHB(C6F5)3 38 was heated in
ClC6D5 under the same conditions developed for the catalytic
hydrogenation and subsequently quenched with DAB-
CO·HCl 39, only traces of 29 were detected, while most of
the starting material remained untouched. In sharp contrast,
an equimolar mixture of 20 and [HDABCO][DB(C6F5)3] 40[22]
already afforded 29% conversion of 20 into [D1]-29 after only
4 h. Although this reaction is not as clean as its catalytic
version, 1H NMR experiments reveal that the deuterated
product [D1]-29 bears the deuterium label at the b-position
(Scheme 2). These experiments demonstrate that: 1) the
À
to be quite selective; only the C C double bond directly
attached to the ester groups was affected under the reaction
conditions, while the more distant olefinic functionality
remained untouched. In view of this reactivity, we decided
to study whether the additional activation provided by the
allene moiety was necessary to accomplish the desired
hydrogenations or if a structurally simpler alkylidene malo-
nate could also undergo the same transformation. Thus,
compounds 20–28 were submitted to reduction conditions,
and they afforded the corresponding saturated products 29–
12368 www.angewandte.org
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2012, 51, 12367 –12369

Angewandte
Chemie
a single carbon center, see: G. D. Frey, V. Lavallo, B. Donnadieu,
W. W. Schoeller, G. Bertrand, Science 2007, 316, 439 – 441.
[8] a) P. A. Chase, G. C. Welch, T. Jurca, D. W. Stephan, Angew.
Chem. 2007, 119, 8196 – 8199; Angew. Chem. Int. Ed. 2007, 46,
8050 – 8053; b) P. A. Chase, T. Jurca, D. W. Stephan, Chem.
Commun. 2008, 1701 – 1703; c) C. F. Jiang, O. Blacque, H. Berke,
˝
Chem. Commun. 2009, 5518 – 5520; d) G. Eros, H. Mehdi, I.
Pꢁpai, T. A. Rokob, P. Kirꢁly, G. Tꢁrkꢁnyi, T. Soꢀs, Angew.
Chem. 2010, 122, 6709 – 6713; Angew. Chem. Int. Ed. 2010, 49,
6559 – 6563.
Scheme 2. Plausible mechanism of the FLP-promoted hydrogenation.
Reagents and conditions (GC conversions): a) ClC6D5, 808C, 4 h; [D1]-
29 (29%).
[9] P. Spies, S. Schwendemann, S. Lange, G. Kehr, R. Frçhlich, G.
Erker, Angew. Chem. 2008, 120, 7654 – 7657; Angew. Chem. Int.
Ed. 2008, 47, 7543 – 7546.
[10] S. J. Geier, P. A. Chase, D. W. Stephan, Chem. Commun. 2010,
46, 4884 – 4886.
hydride from the borohydride moiety is transferred at the
electrophilic position of the substrate, and 2) the
[HDABCO]+ cation plays an active role. Even though these
are still preliminary results, they can be rationalized assuming
an initial activation of the substrate by the [DABCOH]+
moiety through a hydrogen bond, followed by nucleophilic
attack of the hydride (Scheme 2).
In conclusion, after studying the reactivity of allenes of
different electronic nature towards B(C6F5)3, the hydrogena-
tion of organic compounds employing FLP-based catalysis
could be extended to electron-poor allenes and alkylidene
malonates. Efforts to fully explore the scope and the
mechanism of this metal-free hydrogenation are underway
and will be reported in due course.
[11] H. D. Wang, R. Frçhlich, G. Kehr, G. Erker, Chem. Commun.
2008, 5966 – 5968.
[12] a) J. W. Yang, M. T. Hechavarria Fonseca, B. List, Angew. Chem.
2004, 116, 6829 – 6832; Angew. Chem. Int. Ed. 2004, 43, 6660 –
6662; b) J. B. Tuttle, S. G. Ouellet, D. W. C. MacMillan, J. Am.
Chem. Soc. 2006, 128, 12662 – 12663; c) M. Rueping, A. R.
Antonchick, T. Theissmann, Angew. Chem. 2006, 118, 3765 –
3768; Angew. Chem. Int. Ed. 2006, 45, 3683 – 3686.
[13] Asymmetric versions of some of these transformations have
been also recently developed; see: a) D. Chen, J. Klankermayer,
Chem. Commun. 2008, 2130 – 2131; b) D. Chen, Y. T. Wang, J.
Klankermayer, Angew. Chem. 2010, 122, 9665 – 9668; Angew.
Chem. Int. Ed. 2010, 49, 9475 – 9478.
[14] Only a couple of single examples have been described, namely
the reductions of carvone (see Ref. [8d]) and an ynone: a) B. H.
Xu, G. Kehr, R. Frçhlich, B. Wibbeling, B. Schirmer, S. Grimme,
G. Erker, Angew. Chem. 2011, 123, 7321 – 7324; Angew. Chem.
Int. Ed. 2011, 50, 7183 – 7186. During the review process of this
manuscript, new examples have been described: b) J. S. Reddy,
B. H. Xu, T. Mahdy, R. Frçhlich, G. Kehr, D. W. Stephan, G.
Erker, Organometallics 2012, 31, 5638 – 5649.
[15] The ability of PhNMe2 in combination to B(C6F5)3 to form FLPs
that are able to activate H2 has been recently reported: T. Voss,
T. Mahdi, E. Otten, R. Frçhlich, G. Kehr, D. W. Stephan, G.
Erker, Organometallics 2012, 31, 2367 – 2378. The reported
acidity of the diaryl ammonium cation [Ph2NH2]C+(pKa=0.78 in
H2O) suggest that [Ph2MeNH]+ should be able to protonate
allene 1.
Received: July 6, 2012
Revised: August 31, 2012
Published online: November 4, 2012
Keywords: alkylidene malonates · allenes ·
.
frustrated Lewis pairs · metal-free hydrogenation
[1] a) S. J. Geier, D. W. Stephan, J. Am. Chem. Soc. 2009, 131, 3476 –
3477; b) G. C. Welch, J. D. Masuda, D. W. Stephan, Inorg. Chem.
2006, 45, 478 – 480.
[2] M. A. Dureen, D. W. Stephan, J. Am. Chem. Soc. 2009, 131,
8396 – 8397.
[3] M. A. Dureen, A. Lough, T. M. Gilbert, D. W. Stephan, Chem.
Commun. 2008, 4303 – 4305.
[4] M. A. Dureen, G. C. Welch, T. M. Gilbert, D. W. Stephan, Inorg.
Chem. 2009, 48, 9910 – 9917.
[16] For the interaction of alkenes with boranes, see: X. Zhao, D. W.
Stephan, J. Am. Chem. Soc. 2011, 133, 12448 – 12450.
[17] For the synthesis of 6, see: A. C. Dyker, V. Lavallo, B.
Donnadieu, G. Bertrand, Angew. Chem. 2008, 120, 3250 – 3253;
Angew. Chem. Int. Ed. 2008, 47, 3206 – 3209.
[5] a) J. S. J. McCahill, G. C. Welch, D. W. Stephan, Angew. Chem.
2007, 119, 5056 – 5059; Angew. Chem. Int. Ed. 2007, 46, 4968 –
4971; b) M. Ullrich, K. S. H. Seto, A. J. Lough, D. W. Stephan,
Chem. Commun. 2009, 2335 – 2337; c) C. M. Mçmming, G. Kehr,
B. Wibbeling, R. Frçhlich, B. Schirmer, S. Grimme, G. Erker,
Angew. Chem. 2010, 122, 2464 – 2467; Angew. Chem. Int. Ed.
2010, 49, 2414 – 2417.
[6] a) D. J. Parks, W. E. Piers, J. Am. Chem. Soc. 1996, 118, 9440 –
9441; b) D. J. Parks, J. M. Blackwell, W. E. Piers, J. Org. Chem.
2000, 65, 3090 – 3098; c) M. Alcarazo, C. Gomez, S. Holle, R.
Goddard, Angew. Chem. 2010, 122, 5924 – 5927; Angew. Chem.
Int. Ed. 2010, 49, 5788 – 5791; d) D. Chen, V. Leich, F. Pang, J.
Klankermayer, Chem. Eur. J. 2012, 18, 5184 – 5187.
[7] For theoretical mechanistic studies, see: a) T. A. Rokob, A.
Hamza, A. Stirling, T. Soꢀs, I. Pꢁpai, Angew. Chem. 2008, 120,
2469 – 2472; Angew. Chem. Int. Ed. 2008, 47, 2435 – 2438;
b) T. A. Rokob, A. Hamza, I. Pꢁpai, J. Am. Chem. Soc. 2009,
131, 10701 – 10710; c) S. Grimme, H. Kruse, L. Goerigk, G.
Erker, Angew. Chem. 2010, 122, 1444 – 1447; Angew. Chem. Int.
Ed. 2010, 49, 1402 – 1405; d) for the splitting of dihydrogen using
[18] CCDC 890483 (5), 890379 (7), 890482 (9), 890381 (33), and
890380 (34) contain the supplementary crystallographic data for
this paper. These data can be obtained free of charge from The
Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.
uk/data_request/cif.
[19] a) C. M. Conifer, D. J. Law, G. J. Sunley, A. J. P. White, G. J. P.
Britovsek, Organometallics 2011, 30, 4060 – 4066; b) D. J. Parks,
W. E. Piers, M. Parvez, R. Atencio, M. J. Zaworotko, Organo-
metallics 1998, 17, 1369 – 1377.
[20] For a comprehensive discussion regarding thermal rearrange-
ments of allenes, see: J. E. Baldwin, R. H. Fleming, Fortschr.
Chem. Forsch. 1970, 15, 281 – 310.
[21] D. W. Stephan, S. Greenberg, T. W. Graham, P. Chase, J. J.
Hastie, S. J. Geier, J. M. Farrel, C. C. Brown, Z. M. Heiden, G. C.
Welch, M. Ullrich, Inorg. Chem. 2011, 50, 12338 – 12348, and
references therein.
[22] The synthesis of this compound is described in the Supporting
Information.
Angew. Chem. Int. Ed. 2012, 51, 12367 –12369
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org 12369