Reaction of frustrated lewis pairs with conjugated ynones-selective hydrogenation of the carbon-carbon triple bond

Article abstract of DOI:10.1002/anie.201101051

Frustrated, but not frustrating: Frustrated Lewis pairs (FLPs) can undergo selective 1,4-addition reactions with conjugated ynones (see scheme). Upon FLP dihydrogen activation selective hydrogenation of the carbon-carbon triple bond can be achieved, in one case even catalytically. Copyright

Full text of DOI:10.1002/anie.201101051

DOI: 10.1002/anie.201101051
Frustrated Lewis pairs
Reaction of Frustrated Lewis Pairs with Conjugated Ynones-Selective
Hydrogenation of the Carbon–Carbon Triple Bond
Bao-Hua Xu, Gerald Kehr, Roland Frꢀhlich, Birgit Wibbeling, Birgitta Schirmer, Stefan Grimme,
and Gerhard Erker*
Dedicated to Professor Siegfried Hꢁnig on the occasion of his 90th birthday
Frustrated Lewis pairs (FLPs), comprised of sterically
encumbered strong Lewis acids and Lewis bases, undergo a
variety of remarkable reactions.[1] They add to alkenes and
alkynes,[2] add to various carbonyl compounds, including
carbon dioxide,[3] and undergo unique 1,4-addition reactions
to conjugated enynes and diynes to yield zwitterionic
cumulene derivatives.[4] Most notably many FLPs split
dihydrogen heterolytically, some reversibly, and are able to
transfer the resulting P/B or N/B bonded H+/HÀ pair to
selected unsaturated substrates.[5] This ability has resulted in
the development of a small series of metal-free catalytic
hydrogenation processes; some frustrated Lewis pairs are
able to serve as hydrogenation catalysts for bulky imines,
Scheme 1.
enamines, or silylenolethers.[6] We have now found a signifi-
cant extension to the scope of FLPs in the metal-free
hydrogenation of organic substrates. This new development
is based on observations made upon treating phosphine/
borane FLPs with various conjugated ynones.
enolate tautomerization reaction. The eight-membered het-
erocyclic product 6 shows NMR signals at d = 22.5 ppm
(31P{1H}), d = À2.6 ppm (11B{1H}), and d = 4.35, 4.27 ppm (1H,
=
We had shown that the ethylene-bridged intramolecular
frustrated P/B Lewis pair 1a[7] underwent a clean 1,2-addition
reaction to the carbonyl group of trans-cinnamic aldehyde (to
give 2).[8] The reaction of 1a with the ynone 3a takes a
different course. At low temperature we observe the forma-
tion of the zwitterionic 1,4-addition product 7a, which upon
heating is converted into the isomer 4, the 1,2-addition
product of the FLP 1a to the carbon–carbon triple bond of 3a
(see Scheme 1). Compound 4 is characterized by typical
spectroscopic data [d(31P{1H}) = 7.8 ppm, d(11B{1H}) =
CH2). It was also characterized by X-ray diffraction (for
details see the Supporting Information).
The reactions of 1a with the non-enolizable ynones 3c–3e
proceeded with preferential formation of the eight-mem-
bered ring products. In these cases 1,4-addition results in the
formation of the cyclic allene derivatives 7c–7e, which were
isolated in good yields (see Scheme 2). These compounds
13
3
=
À1
À13.8 ppm, d( C(C O)) = 200.9 ppm (d, JPC = 22.7 Hz), IR
=
˜
n(C O) = 1643 cm ] and it was characterized by X-ray
diffraction (for details see the Supporting Information).
The reaction takes a slightly different course when 1a was
treated with the ynone 3b that formally has the CH3 and Ph
substituents exchanged. The reaction with this enolizable
acetylenic ketone gives a product that is derived from 1,4-
FLP-addition to the ynone framework coupled with an
Scheme 2.
[*] Dr. B.-H. Xu, Dr. G. Kehr, Dr. R. Frꢀhlich,[+] B. Wibbeling,[+]
B. Schirmer,[++] Prof. Dr. S. Grimme,[++] Prof. Dr. G. Erker
Organisch-Chemisches Institut der Universitꢁt Mꢂnster
Corrensstrasse 40, 48149 Mꢂnster (Germany)
Fax : (+49)251-8336503
were characterized by C,H elemental analysis, spectroscopy,
and X-ray crystal structure analysis (see Figure 1 for a
representative example; for further details see the Supporting
Information). Compound 7c (R1 = tBu) as a typical example
exhibits a non-planar eight-membered core structure (B1–O3
1.501(3) ꢀ, P1–C6 1.835(2) ꢀ) that contains a close to linear
allene substructure (C4–C5 1.324(3), C5–C6 1.311(3) ꢀ; angle
C4-C5-C6 172.7(2)8). Compound 7c features a typical allene
E-mail: erker@uni-muenster.de
[+] X-ray crystal structure analyses.
[++] Quantum chemical calculations.
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201101051.
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Scheme 3.
Figure 1. A view of the molecular structure of the cyclic allenic product
7c (R1 =tBu).
13C{1H} NMR resonance signals at d = 216.4 ppm (C5) and
d(31P{1H}) = 8.5 ppm and d(11B{1H}) = 0.7 ppm.
The analogous reactions can also be carried out with the
intermolecular frustrated Lewis pair PtBu3/B(C6F5)3 (1b).[5b]
Treatment of the FLP 1b with the ynone 3a in pentane at
room temperature went to completion within 24 h and we
isolated the acyclic 1,4-P/B addition product 8a in over 80%
yield. Its NMR spectra show resonance signals at d(31P{1H}) =
46.0 ppm and d(11B{1H}) = À2.3 ppm and it shows a typical
allenic sp-hybridized C atom 13C NMR resonance at d =
224.9 ppm. The X-ray crystal structure analysis features the
Figure 3. Molecular structure of the B(C6F5)3/ynone adduct 9a.
= =
linear central C C C moiety (C2–C3 1.322(3) ꢀ, C3–C4
1.302(3) ꢀ, angle C2-C3-C4 176.0 (2)8) to which the O-
B(C6F5)3 (C2–O1 1.359(3), O1–B1 1.490(3) ꢀ; angle C2-O1-
B1 123.8(2)8) and the PtBu3 units are attached (see Figure 2).
1.271(3), C2–C3 1.416(3), C3–C4 1.202(3) ꢀ; angle C2-C3-
C4 176.3(3)8)
The B(C6F5)3/ynone adducts 9a,c were subsequently
treated with PtBu3 to cleanly give the zwitterions 8a,c in
high yield. When brought back into solution (CD2Cl2, room
temperature) the compounds 8a and 8c showed the expected
NMR spectra, but the sterically congested system 8c showed a
pronounced equilibrium between the zwitterion and its
precursor compounds 9c and free tBu3P. This equilibrium is
markedly temperature dependent, varying from an 8c/
(9c+tBu3P) ratio of approximately 1:1 at room temperature
to approximately 10:1 at 233 K (for details see the Supporting
Information).
The reactions of the FLPs 1a and 1b with the ynones 3
were analyzed by state of the art DFT calculations.[10]
Inclusion of solvent effects in the calculations were tested
(for details see the Supporting Information) but led only to
minor changes in relative reaction energies. These calcula-
tions revealed (see Table 1) that the six-membered ring
product 4 and the eight-membered exocyclic boron-enolate
system 6, as well as the acyclic systems 8, are the respective
thermodynamically favored isomers, whereas the eight-mem-
bered heterocyclic 1,4-P/B addition products 7 are formed in
kinetically controlled reactions.
We had shown that the FLP 1a rapidly activates
dihydrogen by heterolytic splitting at ambient conditions to
yield the zwitterionic phosphonium/hydridoborate system
10a.[7] This system then transfers the H+/HÀ pair rapidly to the
carbon–carbon triple bond of the ynone 3c to yield the a,b-
unsaturated ketone 11 (Scheme 4). Typically, we treated one
molar equivalent of the FLP·H2 reagent 10a with two molar
Figure 2. A projection of the molecular structure of compound 8a.
The reaction of the FLP 1b with the ynones 3c and 3e
proceeded analogously to yield the 1,4-addition products (see
Scheme 3), 8c and 8e, respectively. Compound 8c was also
characterized by X-ray diffraction (see the Supporting
Information).
Treatment of the ynones 3a and 3c, respectively, with
B(C6F5)3 gave the respective Lewis acid adducts (9a, 9c).
They show characteristic NMR signals [9c: 11B{1H} d =
13
1
=
3.4 ppm; C{ H} (C O-[B]) d = 208.7 ppm, compared with
d = 194.1 ppm for 3c[9]]. Compound 9a was characterized by
X-ray diffraction (see Figure 3: B1–O1 1.570(3), O1–C2
7184
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Angew. Chem. Int. Ed. 2011, 50, 7183 –7186

Table 1: Reaction energies [kcalmolÀ1] for the formation of products
between the ynones 3 and the FLPs 1a and 1b, calculated with B2PLYP-
D3/def2-TZVP//TPSS-D3/def2-TZVP.
Variations of the Lewis acid and Lewis base components
eventually led to a catalytic variant of the ynone hydro-
genation reaction. Treatment of the FLP 13/PtBu3 with H2
gave the salt 14. This reacted with the ynone 3c to give the
hydrogenation product cis-11c in a stoichiometric reaction,
even under a hydrogen atmosphere. However, employing the
FLP 13/DABCO (20 mol%) resulted in catalytic hydrogena-
tion of 3c at elevated temperature (808C, 10 bar H2, 48 h) to
yield the enone trans-11c as the major product admixed with
minor amounts of cis-11c and the saturated ketone 15 (for the
result of a typical experiment see Scheme 6).[11]
FLP
product[a]
ynone
3a
3b
3c
3d
3e
4
6
7
À40.8
–
À27.9
À37.8
À40.5
À28.6
À37.6
–
À31.1
À38.8
–
À33.1
À38.5
–
À31.9
1a
8
À34.2
À7.5
–
–
À31.3
–
–
À34.9
À8.6
1b
16b
12.5
[a] The energy for the structure found in experiments is given in italics.
[b] The structure of 16 used for the calculation is analogous to 4, in which
1b was added to the triple bond of the ynone substrate (see the
Supporting Information).
Scheme 6.
Scheme 4.
Frustrated Lewis pairs have been known to be metal-free
catalyst for the hydrogenation of enamines, dienamines,
silylenolethers, bulky imines, and related compounds.[1,6] All
of these reactions probably proceed by a reaction sequence
characterized by initial protonation of the organic substrate
followed by hydride transfer to the resulting reactive cationic
species.[12] From this investigation and a related reaction
studied by Soꢁs et al,[13] there is now increasing evidence that
FLP induced hydrogenation can also be carried out with a,b-
unsaturated carbonyl compounds. The FLP reduction of the
activated carbon–carbon triple bonds probably follows a
reversed sequence which is initiated by hydride addition to
the b position of the substrate with subsequent protonation of
the resulting boron–enolate intermediate (see Scheme 7).
equivalents of the ynone 3c to isolate a mixture of 11c (45%
yield out of a maximum 50% possible yield) and the eight-
membered heterocycle 7c (40%). Monitoring the progress of
the reaction by NMR spectroscopy revealed that initially only
1
Ph
=
the cis-enone isomer cis-11c [ H NMR: d = 6.77 ( CH ), 6.48
=
=
( CH O) ppm (3JHH = 13 Hz)] was formed, which became
C
then subsequently slowly isomerized to trans-11c [1H NMR:
=
C
d = 7.64 ( CH ), 7.17 ( CH O) ppm (3JHH = 16 Hz)] under
Ph
=
=
the Lewis acidic reaction conditions.
Treatment of the intermolecular FLP tBu3P/B(C6F5)3 with
H2 at ambient conditions gave the salt [tBu3PH]+[HB-
(C6F5)3]À (10b).[5b] This heterolytic hydrogen activation prod-
uct cleanly transferred the H+/HÀ pair stoichiometrically to
the ynone 3e with formation of cis/trans-11e. The in situ
liberated free FLP 1b is efficiently trapped by the ynone to
give the 1,4-adduct (in this case: 8e). Again the cis-enone
product is found initially, which can be explained by a reaction
sequence of 1,4-hydridoborate addition to 3e to give the
allenic enolate intermediate (12) followed by preferred
subsequent protonation by the very bulky tBu3PH+ from the
less hindered side (Scheme 5).
Scheme 7. LA: Lewis acid, LB: Lewis base.
These results indicate that the potential applications frus-
trated Lewis pair chemistry are increasing steadily. It is going
beyond the mere activation of small molecules towards
applications in a broad range of fields of chemistry.
Scheme 5.
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Communications
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Experimental Section
=
General procedure for 4, 6, and 7: Mes2PCH CH2 (100 mg,
0.34 mmol) and HB(C6F5)2 (117 mg, 0.34 mmol) were dissolved in
pentane (6 mL) and stirred for 15 min. A solution of ynone (3)
(0.34 mmol) in CH2Cl2 (1 mL) was added at room temperature. After
the reaction mixture had been stirred for 24 h, the solid was isolated
by cannula filtration and washed with cold pentane. 4 (after reflux
(CH2Cl2) for 4 h): yield 64%; elemental analysis (%) calcd for
C42H34BF10OP·0.5C5H12: C 64.98, H 4.90; found: C 65.19, H 4.33;
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NMR 31P{1H}: d = 7.8 ppm; 11B{1H}: d = À13.8 ppm; C{ H} (C O):
d = 200.9 ppm. 6: yield 89%; elemental analysis (%) calcd for
C42H34BF10OP: C 64.14, H 4.36; found: C 63.32, H 4.22; NMR
13
1
=
31P{1H}: d = 22.5 ppm; 11B{1H}: d = À2.6 ppm; 13C{ H}/ H ( CH): d =
1
1
=
=
153.1/6.55, ( CH2) 102.8/4.35, 4.27 ppm. 7c: yield 88%; elemental
analysis (%) calcd for C45H40BF10OP: C 65.23, H 4.87; found: C 64.53,
H 4.80; NMR 31P{1H}: d = 8.5 ppm; 11B{1H}: d = 0.7 ppm; C{ H} (
13
1
=
=
C ): d = 216.4 ppm.
General procedure for 8: A pentane (3 mL) solution of PtBu3
(40 mg, 0.20 mmol) was added to a mixture of B(C6F5)3 (100 mg,
0.20 mmol) and the respective ynone 3 (0.20 mmol) in CH2Cl2 (4 mL).
After stirring the reaction mixture for 24 h, the solid was isolated by
cannula filtration and washed with cold CH2Cl2. 8e: yield 87%,
HRMS (ESI) exact mass for [M+Na]+ (C45H37BF15PONa): calcd m/z
943.2329, found 943.2311; NMR 31P{1H}: d = 41.5 ppm; 11B{1H}: d =
13
1
= =
À2.3 pm; C{ H} ( C ): d = 226.5 ppm.
General procedure for 11: 10 (0.2 mmol) and ynone 3 (0.4 mmol,
2 equiv) were dissolved in CH2Cl2 (10 mL). The solution was stirred
2 h at room temperature. Afterwards, the solvent (CH2Cl2) was
removed under vacuum and the residue was extracted with pentane
(3 ꢂ 20 mL) to give the P/B products as white solids. The organic
phase was separated and the solvent was removed under reduced
pressure. Purification by chromatography on silica gel provided
enone 11. Reaction of 10a with 3c afforded 7c: (40%) and cis-11c
(45%); Reaction of 10b with 3e afforded after heating to 508C for
30 min 8e (36%) and 11e (40%, the ratio of cis/trans is 1.3:1).
For additional experimental details see the Supporting Informa-
tion.
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Received: February 11, 2011
Revised: April 5, 2011
Published online: June 16, 2011
Keywords: 1,4-additions · allenes · frustrated Lewis pairs ·
.
hydrogenations · ynones
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