Tandem decarboxylative hydroformylation-hydrogenation reaction of α,β-unsaturated carboxylic acids toward aliphatic alcohols under mild conditions employing a supramolecular catalyst system

Article abstract of DOI:10.1039/c3cc45547e

A new atom economic catalytic method for a highly chemoselective reduction of α,β-unsaturated carboxylic acids to the corresponding saturated alcohols under mild reaction conditions, compatible with a wide range reactive functional groups, is reported. The new methodology consists of a novel tandem decarboxylative hydroformylation/aldehyde reduction sequence employing a unique supramolecular catalyst system.

Full text of DOI:10.1039/c3cc45547e

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Tandem decarboxylative hydroformylation – hydrogenation reaction of
α,β-unsaturated carboxylic acids toward aliphatic alcohols under mild
conditions employing a supramolecular catalyst system
Lisa Diab, Urs Gellrich, Bernhard Breit*a
5
Received (in XXX, XXX) Xth XXXXXXXXX 200X, Accepted Xth XXXXXXXXX 200X
First published on the web Xth XXXXXXXXX 200X
DOI: 10.1039/b000000x
desirable functional group transformation given the ease of
preparation of the starting material through decarboxylative
Knoevenagel condensation.12 However, today the mildest
45 method to effect this transformation employes a two step
procedure involving stoichiometric amounts of the reducing
agent lithium aluminum hydride followed by a catalytic
hydrogenation step of the intermediate allylic alcohol.7 Only a
few one step procedures are know. They require however
50 either stoichiometric reductants and/or harsh reaction
conditions, and thus lack compatibility with many functional
groups.8ꢀ11
A
new atom economic catalytic method for
a highly
chemoselective reduction of α,β-unsaturated carboxylic acids to
10 the corresponding saturated alcohols under mild reaction
conditions, compatible with a wide range reactive functional
groups is reported. The new methodology consists of a novel
tandem decarboxylative hydroformylation/aldehyde reduction
sequence employing a unique supramolecular catalyst system.
15
The development of new catalysts and catalytic reactions
which allow for clean and selective transformations is of
immense scientific importance.1 Inspired from natural
enzymes we recently merged principles of supramolecular
chemistry with transition metal catalysis, and developed a
20 series of supramolecular ligand systems (1ꢀ3, Schemes 1 & 2)
that combine structural features of phosphine ligands (the
metalꢀbinding unit) with an acyl guanidinium functionality for
the recognition of functional groups.2ꢀ6 Thus, a rhodium
catalyst based on ligand 1 furnished unprecedented high
25 regioselectivity upon hydroformylation of β,γꢀunsaturated
carboxylic acids.3 Furthermore, it enabled the first
In order to develop a catalyst system for this desirable
transformation that would operate under mild reaction
55 conditions and which would be compatible with a range of
reactive functional groups,
a
tandem decarboxylative
hydroformylation/aldehyde hydrogenation process (see
Scheme 2) based on our supramolecular acylguanidinium
catalysts was investigated.
decarboxylative
hydroformylation
of
α,βꢀunsaturated
carboxylic acids to furnish the corresponding linear aldehydes
in high chemoꢀ and regioselectivity in which the carboxylic
30 acid function acts as a traceless directing group.4 Beyond
hydroformylation, a rhodium catalyst based on the pyrrolyl
ligand 2 displayed high activity and chemoselectivity for
aldehyde reduction to the corresponding alcohol under
hydroformylation conditions, and ligand 3 could even be used
35 in a tandem hydroformylationꢀhydrogenation process.5
60
Scheme 2: Decarboxylative hydroformylation/hydrogenation reaction,
and supramolecular ligands employed in this study.
We commenced our studies examining the reaction of octꢀ2ꢀ
enoic acid (5) under standard hydroformylation conditions (15
65 bar CO/H2, 40°C). Using [Rh(CO)2(acac)]/PPh3 as a catalyst
the saturated carboxylic acid 6 was obtained as the only
product (Table 1, entry 1). A rhodium catalyst derived from
ligand 1, underwent the expected decarboxylative
hydroformylation cleanly. However, this catalyst converted
70 the aldehyde, nꢀoctanal (7) to the respective alcohol, nꢀoctanol
(8) very slowly (Table 1, entry 2). Employing pyrrol ligand 2,
a rather chemounselective catalyst was obtained, which
furnished a mixture of aldehyde 7, alcohol 8 and the
hydrogenation product 6 (Table 1, entry 3). Also, a catalyst
75 based on ligand 4 having the phosphine donor in the orthoꢀ
Scheme
1:
Supramolecular
catalysts
for
decarboxylative
hydroformylation and aldehyde reduction.
The chemoselective reduction of α,βꢀunsaturated carboxylic
40 acids towards the corresponding saturated alcohols has been
frequently employed in organic synthesis,7ꢀ11 and is a highly
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40 previously known methods for reduction of α,βꢀunsaturated
carboxylic acids. Furthermore, ether, silyl ether and free
hydroxy functions are compatible with this method as well.
On looking at the reaction kinetics of the rhodium catalyst
obtained from the mixture of ligands 1 and 2 compared with
45 the kinetic profile of the rhodium catalysts obtained from
ligands 1 and 2 separately, it becomes obvious that in case of
the ligand mixture a new kinetically active catalyst species is
formed which operates with significantly higher activity and
chemoselectivity (see supporting information for details). This
50 suggests that the kinetically active species is most likely a
heteroleptic [LnRh(I)(1)(2)] system. This rational is further
supported by the fact that upon mixing of 1 and 2 in the
presence of a platinum(II) salt and octenoic acid (5) and
monitoring this reaction by means of 31P NMR we observed
55 the formation of the cis coordinated heteroleptic complex
exclusively (see supporting information for details).
position showed very low activity (1% conversion) (Table 1,
entry 4). In contrast, benzene bridged ligand 3 provided a
catalyst, which furnished the desired nꢀoctanol (8)
quantitatively after 29 h reaction time (Table 1, entry 5). The
addition of small amounts of the strong acid CF3SO3H, which
had proved benefitial for supramolecular aldehyde reduction,5
was detrimental in this case, since reaction chemoselectivity
switched completely towards hydrogenation of the alkene
function to furnish saturated acid 6 (Table 1, entry 7).
10 To further improve the catalyst, we tested various ligand
mixtures. We postulated that each of the two catalytic steps
may need its own optimal catalyst. Rhodium catalysts derived
from ligand mixtures of 2 and 3 as well as 1 and 3,
respectively, did not give any improvement. However, the
15 best catalyst for the title reaction was obtained employing a
mixture of ligands 1 and 2. This new catalyst system is
significantly more active than the one derived from the single
ligands and allowed a reduction of the catalyst loading to 0.5
mol% (Table 1, compare entry 2, 3 and 11). Thus, under mild
20 reaction conditions 40°C, 15 bar of CO/H2 nꢀoctanol (8) was
obtained in quantitative yield and with complete
regioselectivity (>99:1).
5
Table 2: reduction of α,βꢀunsaturated acids
Conditions Conditions
Entry
1
Product
A[a,c]
Yield [%]
B[b,c]
Yield [%]
Table 1: Tandem decarboxylative hydroformylationꢀhydrogenation
reaction of octꢀ2ꢀenoic acid (R = nC5H9)
96
98
2
3
4
5
6
7
99
98
99
98
98
99
95
98
99
96
98
94
25
6
7
8
Entry[a]
Ligand
[Rh(CO)2acac]/L/5
[%]e
[%]e
[%]e
1
2
PPh3
1
1:10:100
1:10:100
1:10:100
1:10:100
1:10:100
1:10:100
1:10:100
1:5:5:100
1:5:5:100
1:5:5:100
1:5:5:200
99
0
0
88.5
15
0
0
11.5
55
0
3
2
29
<1
0
4
4
5
3
0
>99
88
7
6b
7d
8b
9b
10b
11c
3
0
12
0
3
93
24
0
2:3
1:3
1:2
1:2
0
76
79
99
99
8
9
95
99
97
98
21
0
0
0
0
[a] Conditions A: [Rh(CO)2acac]/3/substrate = 1:10:100, c0(substrate) =
60 0.2 M, CH2Cl2 (2 ml), 15 bar CO/H2 (1:1), 29 h, 40°C. [b] Conditions B:
same as for [a] but [Rh(CO)2acac]/1:2/substrate = 1/5:5/200, t = 26 h. [c]
isolated yield. Bn = benzyl, Bz = benzoyl, TBS = tertꢀbutyldimethylsilyl.
[a] Conditions: c0(substrate)= 0.2 M, CH2Cl2 (2 ml), 15 bar CO/H2 (1:1),
29 h, 40°C. [b] t = 24 h. [c] t =26 h. [d] The reaction was carried out with
5% of CF3SO3H. [e] Determined by 1H NMR of the crude reaction
mixture.
30
In order to gain first insights into the interplay of ligand 1 and
65 2 with the substrate 5 we optimized the structures of several
confomers and tautomers of the platindichloro complexes at
the PCMꢀB3LYP/LANL2DZꢀ6ꢀ31G(d,p) level. Indeed, the
heterodimeric platincomplex was found to be more stable than
the homodimeric complexes (Figure 1).
Having established the optimal catalysts and reaction
conditions, we tested the compatibility with various functional
groups. Thus, aliphatic unsaturated acids gave excellent
results (Table 2, entries 1&2). Interestingly, remote nonꢀ
35 conjugated internal double bonds in the substrate molecule
were not affected at all (Table 2, entry 3). A carboxylic ester
(entry 4), an aliphatic carboxylic acid function (entry 7) and
even a keto function (entry 9) remained completely untouched
by this catalyst system, which is impossible using all
2
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DOI: 10.1039/C3CC45547E
under syngas pressure, and which consists of a tandem
decarboxylative hydroformylation/aldehyde reduction
sequence. The only byproduct in this reaction is carbon
dioxide which renders the overall process highly atom
55 economic. Importantly, the mildness of the reaction conditions
allow using a chemoselectivity profile that is impossible for
know methods relying on stoichiometric reducing agents or
heterogeneous catalysts. Further studies will have to address
the reaction mechanism and ligand cooperativity observed
60 with this catalyst in more detail.
Figure 1: The free energy differences between the most stable homoꢀ and
heterodimeric complexes. The 3Dꢀstructure shows the most stable
heterodimeric complex.
Notes and references
a Institut für Organische Chemie, Albert-Ludwigs-Universität Freiburg,
Albertstr. 21, Freiburg i. Bg., Germany. Fax: +49-761-203-8715; Tel:
+49-761-203-6051; E-mail: bernhard.breit@chemie.uni-freiburg.de
65 † Electronic Supplementary Information (ESI) available: Experimental
details, kinetics, analytical data of new compounds, and details from DFT
calculations See DOI: 10.1039/b000000x/
5
Furthermore, previous DFT calculations indicated that the
pyrol based ligand 2 stabilizes the transition state for the
aldehyde reduction step by an additional hydrogen bond
between the NH group of the heteroaromatic ring and the
10 carbonyl oxygen.5a We than focused on a possible explanation
for the unusual high regioselectivity observed in the tandem
decarboxylative hydroformylation – hydrogenation reaction.
(see Table 1). The regioselectivity is established during the
hydrometallation step of the hydroformylation reaction. Since
15 experimental and theoretical results indicate that the
catalytically active species is most likely a heterodimeric
complex we focussed on rhodium complex bearing 1 and 2 in
the coordiantion sphere. The most stable probranched and
prolinear complexes are depicted in Figure 2.
1
2
B. M. Trost, Angew. Chem. Int. Ed. Engl., 1995, 34, 259.
For reviews on supramolecular catalysis see: Reviews on
supramolecular catalysis: Supramolecular Catalysis (Ed. P. W. N. M.
van Leeuwen), WileyꢀVCH, Weinheim, 2008; B. Breit, Angew.
Chem. Int. Ed., 2005, 44, 6816; c) M. J. Wilkinson, P.W. N. M. van
Leeuwen, J. N. H. Reek, Org. Biomol. Chem., 2005, 3, 2371; P.A.R.
Breuil, F.W. Patureau, J.N. H. Reek, Angew. Chem. Int. Ed., 2009,
48, 2162; F.W. Patureau, M. Kuil, J. Sandee, J.N. H. Reek, Angew.
Chem. Int. Ed., 2008, 47, 3180; L. Yong, F. Yu, H: YanꢀMei; C: Fei;
P. Jie, F. QingꢀHua, Tetrahedron Letters, 2008, 49, 2878.
T. Smejkal, B. Breit, Angew. Chem. Int. Ed., 2008, 47, 311; T.
Smejkal, D. Gribkov, J. Geier, M. Keller, B. Breit, Chem. Eur. J.,
2010, 16, 2470.
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75
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20
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4
5
T. Smejkal, B. Breit, Angew. Chem. Int. Ed., 2008, 47, 4010.
a) L. Diab, T. Smejkal, J. Geier, B. Breit, Angew. Chem. Int. Ed.,
2009, 48, 8022; b) D. Fuchs, G. Rousseau, L. Diab, U. Gellrich, B.
Breit, Angew. Chem. Int. Ed. 2012, 51, 2178.
85
6
7
For other approaches see: M. D. Pluth, R. G. Bergman, K. N.
Raymond, Science, 2007, 316, 85; S. Das, C. D. Incarvito, R. H.
Crabtree, G. W. Brudvig, Science, 2006, 312, 1941; F. Goettmann, P.
Le Floch, C. Sanchez, Chem. Commun., 2006, 2036; f) D. B.
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Belvedere, Y. Huang, R. Breslow, J. Org. Chem., 2002, 67, 5057; H.
K. A. C. Coolen, J. A. M. Meeuwis, P. W. N. M. van Leeuwen, R. J.
M. Nolte, J. Am. Chem. Soc., 1995, 117, 11906ꢀ11913.
M. M. Ponpipom, N. N. Girotra, R. L. Bugianesi, C. D. Roberts, G.D.
Berger, R. M. Burk, R. W. Marquis, W. H. Parsons, K. F. Bartizal, J.
D. Bergstom, M. ;. Kurtz, J. C. Onishi, D. J. Rew, J. Med. Chem.,
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Panico, M. S. Pappalardo, Farmaco Ed. Sci., 1982, 171; K. Schulze,
A.ꢀK. Habermann, H. Uhlig, K. Wyssuwa, J. Prakt. Chem., 1993,
335, 687; P. L. Coe, N. E. Milner, J. A. Smith, J. Chem. Soc., Perkin
Trans. 1, 1975, 654.
25
90
30
Figure 2: The free energy difference (5.8 kcal/mol) between the
95
probranched and the prolinear hydrometallation.
35 The prolinear hydrometallation is favored by 5.8 kcal/mol,
explaining the high regioselectivity experimentally observed (
> 99:1). In order to understand this strong preference of the
prolinear hydrometallation we calculated the LUMO of the
model substrate hydrogenꢀbound to an acylguanidin at the
40 PCMꢀMP2/6ꢀ31G(d,p)//PCMꢀB3LYP/6ꢀ31G(d,p) level of
theory. Indeed, the largest coefficent of the LUMO is located
at the carbon atom in βꢀposition to the carboxyl group.
Therefore, the regioselectivity seems to arise from an orbital
control.
100
8
9
With NaBH4 and methanesulfonic acid: S. R. Wann, P. T. Thorsen,
M. M. Kreevoy, J. Org. Chem. 1981, 46, 2579.
With LiAlH4: M. Barbier, E. Lederer, C. R. Acad. Sci., 1960, 250,
4467.
105 10 With a heterogeneous rhodium/molybdenum catalyst at 150°C and
100 atm of hydrogen gas: D.ꢀH. He, N. Wakasa, T. Fuchikami,
Tetrahedron Lett., 1995, 36, 1059.
11 With SmI2 and Sm(OTf)3: Y. Kamochi, T. Kudo, Tetrahedron Lett.,
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45
In summary, we have developed a new catalytic method that
enables a highly chemoselective reduction of α,βꢀunsaturated
carboxylic acids to the corresponding saturated alcohols.
Heart of the methodology is a supramolecular catalyst that is
50 formed from ligands 1 and 2 in the presence of rhodium(I)
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