A supramolecular catalyst for regioselective hydroformylation of unsaturated carboxylic acids

Article abstract of DOI:10.1002/anie.200703192

(Chemical Equation Presented) The quest to capture the catalytic power of enzymes is one of the great challenges of modern chemistry. A novel system inspired by the principles of enzymatic catalysis combines recognition of the substrate and transition-metal catalysis (see scheme; Do = donor, FG = functional group) and mimics enzyme properties - high efficiency, substrate selectivity, and reaction-site selectivity.

Full text of DOI:10.1002/anie.200703192

Angewandte
Chemie
DOI: 10.1002/anie.200703192
Supramolecular Catalysis
A Supramolecular Catalyst for Regioselective Hydroformylation of
Unsaturated Carboxylic Acids**
ˇ
ˇ
Tomµs Smejkal and Bernhard Breit*
Natural enzymes efficiently combine molecular recognition
and catalysis in one functional assembly. Reactions within
enzyme–substrate complexes have much higher rate con-
stants than corresponding bimolecular reactions.[1] High
degrees of regio- and stereoselectivity are achieved by
orientation of the substrate and precise positioning of the
reaction site in a favorable orientation relative to the catalytic
center. Of particular importance for substrate binding by
enzymes is the guanidine functional group of arginine. Over
70% of enzyme substrates and cofactors are anions, and the
guanidinium group forms strong ion pairs with oxoanions,
such as carboxylates and phosphates.[2] Through multiple
noncovalent interactions within the active site, enzymes can
achieve astonishing levels of substrate selectivity. This
specificity, however, can also be a problem. Very often,
enzymes have a narrow substrate specificity and lack the
generality required for synthetic applications.
Homogeneous catalysis, especially with transition metals,
is one of the key tools of modern synthetic chemistry.
Traditionally, catalytic performance of an organometallic
complex is tuned by variation of the steric bulk and electronic
properties of the ligands. However, the emerging field of
supramolecular catalysis seeks to produce efficient and
selective catalysts by making use of specific molecular
interactions and the principles of supramolecular chemistry.[3]
Many research groups have attempted to combine non-
covalent substrate binding and transition-metal catalysis,
thereby aiming at enzymelike behavior. However, only a
few examples of successful catalysts showing selectivity and
rate enhancement in synthetically useful transformations
have been reported to date.[4,5] An early example came from
Hayashi et al., who reported asymmetric hydrogenation of
trisubstituted acrylic acids in the presence of a chiral (amino-
alkyl)ferrocenylphosphine rhodium catalyst. The high enan-
tioselectivity (greater than 97% ee) is ascribed mainly to the
attractive interaction between the amino group on the
ferrocenylphosphine ligand and the carboxyl group of the
substrate.[6] Very prominent results were recently achieved in
the design of oxidation catalysts. Breslow and co-workers
prepared metalloporphyrin catalysts with attached cyclodex-
trin groups. Steroid derivatives were bound by hydrophobic
interactions, and their regioselective hydroxylation was
achieved.[7] Crabtree, Brudvig, and co-workers have recently
reported a catalyst containing a dinuclear manganese core
and a ligand based on Kempꢀs triacid. In this example, the
carboxy group of the ligand can interact through hydrogen
bonds with the carboxy group of the substrate, leading to
specific substrate orientation and modified regioselectivity
for oxidation.[8]
Reactions that build molecular skeletons belong to the
most important in organic synthesis. Hydroformylation of
alkenes represents an ideal example of an atom-economic[9]
ꢀ
C C bond-forming reaction and leads to products containing
an aldehyde group, which is an ideal functionality for further
synthetic transformations. At the same time, hydroformyla-
tion is one of the most important industrial processes relying
on homogeneous catalysis.[10,11] Inspired by the selectivity of
biological systems, we introduced the concept of a temporary
substrate-bound catalyst-directing group. High regio- and
stereoselectivity has been achieved in a number of catalytic
transformations by equipping substrates with a covalently
attached ortho-diphenylphosphinobenzoate group (o-dppb,
Figure 1).[12] However, the requirement of a covalent ligand–
Figure 1. Concept of covalent and supramolecular catalyst-directing
groups. Do=donor; FG1,2=complementary functional groups.
ˇ
[*] T. Smejkal, Prof. Dr. B. Breit
substrate bond prevents the use of substoichiometric amounts
of the ligand. Therefore, subsequent efforts have been
directed towards the design of ligand moieties that can bind
and orientate the substrate through noncovalent interactions.
Herein, we report the synthesis of a new receptor-based
phosphine ligand, which furnishes a highly reactive catalyst
that leads to unusual regioselectivity in the rhodium-cata-
lyzed hydroformylation of unsaturated carboxylic acids. Our
strategy was to combine the structural features of phosphine
ligands (catalyst binding unit) with a guanidinium-based
recognition unit for carboxylic acids in one molecule.[13,14] The
Institut für Organische Chemie und Biochemie
Albert-Ludwigs-Universität Freiburg
Albertstrasse 21, 79104 Freiburg(Germany)
Fax: (+49)761-203-8715
E-mail: bernhard.breit@organik.chemie.uni-freiburg.de
[**] This work was supported by the Fonds der Chemischen Industrie,
the Alfried Krupp Award for younguniversity teachers of the Krupp
foundation (to B.B.). T.S. is grateful to the state of Baden-
Württembergfor a Landesgraduierten Fellowship. We thank Dr. M.
Keller for X-ray crystal structure analysis.
Supportinginformation for this article is available on the WWW
under http://www.angewandte.org or from the author.
Angew. Chem. Int. Ed. 2008, 47, 311 –315
ꢀ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
311

Communications
ligand architecture was designed employing molecular mod-
eling. Thus, installation of the acylguanidinium functional
group in the meta position with respect to the catalyst-binding
phosphine unit should allow for two-point binding and thus
conformational orientation of the substrate (Figure 2).
Figure 2. Catalyst design assisted by molecular modeling (Spartan Pro,
molecular mechanics force field (MMFF); ligands not participating in
the recognition are omitted for clarity) and hypothetical structure of
the hydrometalation transition state.
Synthesis of the acylguanidine-functionalized phosphine
ligand 1 (Scheme 1) was readily accomplished by coupling of
the diphenylphosphinopyridine carboxylic acid 2[15] with
mono-Boc-protected guanidine and subsequent deprotection
Figure 4. Hydroformylation of 3; [Rh(CO)2acac]/ligand/3=1:10:200
(1:5:200 for ligand 7); c0(3)=0.2m, THF (2 mL), 10 bar CO/H2 (1:1),
408C, 4 h. TOF (mole aldehyde per mole catalyst per hour) determined
from the gas consumption curve. Conversion (%) and regioselectivity
(4/5 ratio) was determined by 1H NMR spectroscopic analysis of the
reaction mixture. n.d.=not determined.
ligand xantphos (4,5-bis(diphenylphosphino)-9,9-dimethyl-
xanthene, 7)[17] showed very low activity (5% conversion).[18]
When the reaction was conducted without ligand (8, unmodi-
fied rhodium catalyst), moderate activity and selectivity for
the formation of the branched regioisomer (4/5 = 0.59) was
observed. With ligands 9 and 10, which may allow for
supramolecular substrate–ligand interactions, only minor
improvements were seen. However, the pyridylacyl-
guanidinium system 1 yielded an outstanding catalyst with
excellent activity (TOF = 250 hꢀ1) and regioselectivity (l/b >
23). Under optimized conditions, the linear aldehyde 4 was
obtained in excellent yield (95%) and high regioselectivity
(l/b>98:2).[19]
Obviously, the rhodium catalyst derived from ligand 1 is
unique in that it yields both a significant rate enhancement
(ca. eightfold compared to 6) and high regioselectivity for
hydroformylation. Both effects, however, are typical features
of substrate-directed reactions.[20] Thus, to clarify the role of
ligand 1 in this hydroformylation reaction, a number of
control experiments were undertaken.
Scheme 1. Synthesis of ligand 1: 1) Boc-guanidine (Boc=tert-butoxy-
carbonyl), N-methylmorpholine, 1-benzotriazolyloxytris(dimethylami-
no)phosphonium hexafluorophosphate, DMF, RT (80%); 2) trifluoro-
acetic acid, RT, then Na2CO3, H2O, CH2Cl2, 08C (87%).
catalyzed by trifluoroacetic acid. After neutralization, ligand
1 precipitated as a dichloromethane adduct. X-ray diffraction
analysis of the oxide of 1 confirmed the proposed conforma-
tion for the ligand (Figure 3).[16]
As a first test system, hydroformylation of vinylacetic acid
3 was studied (Figure 4). The industrially applied standard
[Rh(CO)2acac]/PPh3 (6) system displayed rather low activity
(TOF = 30 hꢀ1, left graph, acac = acetylacetonate), and a
typical regioselectivity (4/5 = 1.3, right graph) was observed.
Under the same conditions, the wide-bite-angle bisphosphine
As can be seen from Table 1, g,d-unsaturated acids, such
as pent-4-enoic acid (11), are hydroformylated much slower
and with worse selectivities than b,g-unsaturated acids
(entry 2, Table 1). Hence, the distance between the carboxylic
acid functionality and the reactive alkene group matters.
Furthermore, the combination of acylguanidine 13 and
triphenylphosphine 6 does not give the desired activity and
selectivity (entry 3, Table 1). This finding suggests that the
molecular-recognition unit and the catalytic unit must be an
integral part of the same molecule to achieve the interesting
catalytic activity and selectivity. Further evidence came from
Figure 3. Crystal structure of ligand 1 oxide.
312
www.angewandte.org
ꢀ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2008, 47, 311 –315

Angewandte
Chemie
Table 1: Control experiments.[a]
Scheme 2. Proposed substrate bindingin the rate- and selectivity-
determininghydrometalation step. The bold curve represents the
substrate bindingsite of ligand 1.
Entry Ligand
Substrate
Conversion Regioselectivity TOF
[%]
(l/b ratio)
[hꢀ1
]
1
2
3
1
1
3
11
3
100
73
20
23
250
49
12
29
34
3.6
1.5
1.1
1.4
Table 2: Hydroformylation of internal alkene 14.[a]
6/13 (1:1)
1
1
4[b]
5
12
50
12/AcOH (1:1) 58
[a] [Rh(CO)2acac]/ligand/substrate=1:10:200,
c0(substrate)=0.2m,
THF (2 mL), 10 bar CO/H2 (1:1), 408C, 4 h, R’=(CH2)nCOOR; [b] Sus-
pension (ligand 1 is practically insoluble in the reaction medium without
a carboxylic acid); all other runs were clear solutions.
Entry
Ligand
Conversion [%]
Regioselectivity (15/16)
1
2
6
1
20[b]
1:1.7
11:1
80.5[c]
the fact that methyl ester 12, which lacks the complementary
functionality, reacted slowly and with low selectivity (entries 4
and 5, Table 1).
[a] [Rh(CO)2(acac)]/ligand/14=1:10:50, c0(14)=0.2m, THF (4 mL),
6 bar CO/H2 (1:1), RT, 68 h. [b] Yield determined by NMR spectroscopy:
15 (4%), 16 (7%). [c] Yield determined by NMR spectroscopy: 15
(71.5%), 16 (6.5%).
If the interaction between the carboxylic acid and
guanidine groups is important for catalyst performance, the
addition of another carboxylic acid to the reaction medium
should lead to competition for the recognition site. Indeed,
when acetic or benzoic acid was added to the reaction mixture
(1–5 equivalents relative to 3), we observed inhibition and
aldehydes 15 and 16 was 83% (based on conversion, 15/16 =
11:1). Interestingly, the preference for formyl addition at the
4-position is the same as that observed for substrate 3, which
is in agreement with a directed catalytic process.
decreased selectivity (see the Supporting Information).[21]
A
mechanism in which the recognition event precedes the
catalytic reaction implies that for high substrate concentra-
tions, saturation should be achieved. Hydroformylation of 3
was therefore conducted at various substrate concentrations
(0.05–0.4m). Indeed, substrate saturation and even inhibition
was observed (see the Supporting Information).
On the basis of these results, we propose a mechanism
consisting of two consecutive steps analogous to enzyme
catalysis:
a) binding of the substrate to the ligand(s) of the rhodium
phosphine complex;
b) directed catalytic reaction within the supramolecular
substrate–catalyst complex.
Furthermore, using a catalyst containing a molecular-
recognition unit should provide a possibility for substrate
differentiation, which would be difficult to achieve with
classical catalysts. Thus, we carried out a competition experi-
ment in which a 1:1 mixture of terminal olefins of similar
reactivity was hydroformylated in the presence of
[Rh(CO)2acac]/1 catalyst (Table 3).
The ratio of products at low conversion indicates that the
substrate selectivity was at least 9.7 for 3/12 and 7.3 for 3/17.
Thus, our supramolecular catalyst can carry out a chemical
transformation selectively on a specific target in a mixture of
chemical substances. It was also possible to achieve complete
In this case, the rate- and selectivity-determining hydro-
metalation step[22,23] becomes intramolecular in nature, which
accounts for both the observed rate acceleration and the
unusual regioselectivity (Scheme 2).
Table 3: Hydroformylation of a 1:1 mixture of two substrates.[a]
If this hypothesis is correct, it would be interesting to
study the reactivity of internal alkenes, which under conven-
tional hydroformylation conditions give nearly equimolar
amounts of regioisomeric aldehydes. Thus, we investigated
the hydroformylation of (Z)-pent-3-enoic acid (14).
Using triphenylphosphine (6) as a ligand, hydroformyla-
tion proceeded sluggishly, and formation of 16 over 15 was
only slightly preferred (Table 2, entry 1). Using ligand 1,
unprecedented high selectivity in the hydroformylation of an
internal alkene was achieved.[24] Branched aldehyde 15 was
observed as the major reaction product together with an
increased conversion (20!80%) and significantly lower
amounts of side products (9!2.5%). The yield of isolated
Entry t [h] Substrates Conversion
Regioselectivity
3/(12 or 17) [%] (l/b ratio) 3, (12 or 17)
1
2
3
4
12
20
6
3, 12
3, 12
3, 17
58:6
50, n.d.
50, 2.3
50, n.d.
50, 3
100:28
22:<3
100:25
15.5 3, 17
[a] [Rh(CO)2(acac)]/1/3/12(17)=1:20:200:200, c0(3)=c0(12 or 17)=
0.13m, THF (6 mL), 4 bar CO/H2 (1:1), RT. n.d.=not determined.
Angew. Chem. Int. Ed. 2008, 47, 311 –315
ꢀ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
313

Communications
conversion of substrate 3; the conversion of the noncomple-
could be selectively prepared in high yield (80% as deter-
mined by NMR spectroscopy and 75% isolated product).
In conclusion, we have developed a new supramolecular
ligand system combining a guanidine receptor unit for
carboxylates and a triarylphosphine group as the donor for
a transition metal. For the first time we have shown that
supramolecular interaction between ligand and substrate
gives synthetically useful levels of selectivity and activity in
a transition-metal catalyzed reaction. Our ligand proved to
give superior activity, predictable regiocon-
trol, substrate selectivity, and reaction-site
selectivity in the rhodium-catalyzed hydro-
formylation of b,g-unsaturated acids. Future
efforts will be devoted to gaining a deeper
insight into the nature of the supramolecular
interactions within our system. Furthermore,
we propose that this general biomimetic
supramolecular strategy can be applied to
other catalytic reactions and classes of sub-
strates. Additionally, a study of our catalyst
may also contribute to the understanding of
enzyme catalysis.
mentary substrate was then as low as 28% (12) and 25% (17).
This unusual substrate selectivity might be used syntheti-
cally—a substrate molecule bearing several potential reaction
sites could be selectively functionalized with the help of the
directing effect. Substrate 18, which bears two alkene func-
tional groups at different distances from the acid moiety, was
prepared and subjected to hydroformylation (Scheme 3).
Using triphenylphosphine (6) as a ligand, rates of hydro-
Received: July 17, 2007
Revised: August 28, 2007
Published online: November 12, 2007
Scheme 3. Hydroformylation of 18; [Rh(CO)2acac]/ligand/18=1:10:150; c0(18)=0.2m,
THF (8 mL), 4 bar CO/H2 (1:1), 258C.
Keywords: enzyme mimics · guanidine ·
.
homogeneous catalysis · hydroformylation ·
molecular recognition
formylation of the two alkene functionalities are very similar
(see the Supporting Information). Regardless of when the
reaction was stopped, we obtained an intractable mixture of
[1] T. C. Bruice, F. C. Lightstone, Acc. Chem. Res. 1999, 32, 127 –
136.
several mono- and dihydroformylated products (19–23).
Using ligand 1, the “blue” (remote) alkene functional
group is hydroformylated with similar rate and selectivity
(l/b) as with ligand 6. Conversely, reaction of the “red” (b,g-)
alkene group is ten times faster (compared with 6) and highly
regioselective, which again is indicative of a directed process
(see Figure 5, which displays 1HNMR spectra of the reaction
mixture taken at different reaction times and highlights the
reaction-site selectivity). On a preparative scale, aldehyde 19
[2] a) J. W. Steed, J. L. Atwood, Supramolecular Chemistry, Wiley,
New York, 2000, pp. 200 – 204; b) S. Mangani, M. Ferraroni in
Supramolecular Chemistry ofAnions (Eds.: A. Bianchi, K.
Bowman-James, E. Garcia-Espaæa), Wiley, New York, 1997,
pp. 63 – 78; c) K. A. Schug, W. Lindner, Chem. Rev. 2005, 105,
67 – 114.
[3] a) C. Waloch, J. Wieland, M. Keller, B. Breit, Angew. Chem.
2007, 119, 3097 – 3099; Angew. Chem. Int. Ed. 2007, 46, 3037 –
ˇ
3039; b) T. Smejkal, B. Breit, Organometallics 2007, 26, 2461 –
2464; c) M. Weis, C. Waloch, W. Seiche, B. Breit, J. Am. Chem.
Soc. 2006, 128, 4188 – 4189; d) X.-B. Jiang, L. Lefort, P. E.
Goudriaan, A. H. M. de Vries, P. W. N. M. van Leeuwen, J. G.
de Vries, J. N. H. Reek, Angew. Chem. 2006, 118, 1245 – 1249;
Angew. Chem. Int. Ed. 2006, 45, 1223 – 1227; e) J. M. Takacs,
D. S. Reddy, S. A. Moteki, D. Wu, H. Palencia, J. Am. Chem. Soc.
2004, 126, 4494 – 4495; f) P. A. Duckmanton, A. J. Blake, J. B.
Love, Inorg. Chem. 2005, 44, 7708 – 7710; g) M. L. Clarke, J. A.
Fuentes, Angew. Chem. 2007, 119, 948 – 951; Angew. Chem. Int.
Ed. 2007, 46, 930 – 933; h) X.-B. Jiang, P. W. N. M. van Leeuwen,
J. N. H. Reek, Chem. Commun. 2007, 2287 – 2289; i) A. J.
Sandee, A. M. van der Burg, J. N. H. Reek, Chem. Commun.
2007, 864 – 866; perspectives on this emerging area: j) M. J.
Wilkinson, P. W. N. M. van Leeuwen, J. N. H. Reek, Org.
Biomol. Chem. 2005, 3, 2371 – 2383; k) B. Breit, Angew. Chem.
2005, 117, 6976 – 6986; Angew. Chem. Int. Ed. 2005, 44, 6816 –
6825.
1
Figure 5. Hydroformylation of 18 usingligand 1. H NMR spectra
(400 MHz, CDCl3) of the double-bond region: a) 0 h, b) 4 h, c) 8.5 h.
Signals from H2’ and H7 are marked with red and blue arrows,
respectively. Reaction-site selectivity and regioselectivity was deter-
mined by 1H NMR spectroscopic analysis of the reaction mixture.
[4] Older results are summarized in: a) M. T. Reetz, Top. Catal.
1997, 4, 187 – 200; b) G. J. Rowlands, Tetrahedron 2001, 57,
1865 – 1882.
314
www.angewandte.org
ꢀ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2008, 47, 311 –315

Angewandte
Chemie
[5] a) D. B. Grotjahn, Chem. Eur. J. 2005, 11, 7146 – 7153; b) F.
Goettmann, P. Le Floch, C. Sanchez, Chem. Commun. 2006,
2036 – 2038; see also: c) J. Larsen, B. S. Rasmussen, R. G. Hazell,
T. Skrydstrup, Chem. Commun. 2004, 202 – 203; d) S. Jónsson,
F. G. J. Odille, P.-O. Norrby, K. Wärnmark, Org. Biomol. Chem.
2006, 4, 1927 – 1948.
[6] T. Hayashi, N. Kawamura, Y. Ito, J. Am. Chem. Soc. 1987, 109,
7876 – 7878.
[7] a) J. Yang, R. Breslow, Angew. Chem. 2000, 112, 2804 – 2806;
Angew. Chem. Int. Ed. 2000, 39, 2692 – 2695; b) J. Yang, B.
Gabriele, S. Belvedere, Y. Huang, R. Breslow, J. Org. Chem.
2002, 67, 5057 – 5067.
[8] S. Das, C. D. Incarvito, R. H. Crabtree, G. W. Brudvig, Science
2006, 312, 1941 – 1943.
[9] B. M. Trost, Acc. Chem. Res. 2002, 35, 695 – 705.
[10] K. Weissermel, H.-J. Arpe, Industrial Organic Chemistry, Wiley-
VCH, Weinheim, 2003, pp. 127 – 144.
case of neutral anion receptors. a) C. Schmuck, Coord. Chem.
Rev. 2006, 250, 3053 – 3067; b) C. Schmuck, U. Machon, Chem.
Eur. J. 2005, 11, 1109 – 1118.
[15] A. C. Laungani, J. M. Slattery, I. Krossing, B. Breit, unpublished
results; see also the Supporting Information.
[16] CCDC-654290 contains 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.
[17] a) M. Kranenburg, Y. E. M. van der Burgt, P. C. J. Kramer,
P. W. N. M. van Leeuwen, K. Goubitz, J. Fraanje, Organometal-
lics 1995, 14, 3081 – 3089; b) C. J. P. Kamer, P. W. N. M. van
Leeuwen, J. N. H. Reek, Acc. Chem. Res. 2001, 34, 895 – 904.
[18] Using harsher conditions (808C, 20 h), complete conversion
could be also achieved for the xantphos ligand (TOF = 50 hꢀ1, 4/
5 = 15.5), although the yield (as determined by NMR spectros-
copy) of aldehyde products (4 + 5) drops to 90% (the main
byproduct is butyric acid (6%), probably formed by isomer-
ization (!a,b) and hydrogenation).
[11] B. Breit, W. Seiche, Synthesis 2001, 1 – 36.
[12] a) B. Breit, Acc. Chem. Res. 2003, 36, 264 – 275; b) B. Breit,
Chem. Eur. J. 2000, 6, 1519 – 1524; c) B. Breit in Organic
Synthesis Highlights, Vol. 5 (Eds.: H.-G. Schmalz, T. Wirth),
Wiley-VCH, Weinheim, 2003, pp. 68 – 81; d) B. Breit, C. Grü-
nanger, O. Abillard, Eur. J. Org. Chem. 2007, 2497 – 2503;
e) compare also R. Breslow, Acc. Chem. Res. 1980, 13, 170 – 177.
[13] a) F. P. Schmidtchen in Supramolecular Chemistry ofAnions
(Eds.: A. Bianchi, K. Bowman-James, E. Garcia-Espaæa), Wiley,
New York, 1997, pp. 105 – 115; b) M. D. Best, S. L. Tobey, E. V.
Anslyn, Coord. Chem. Rev. 2003, 240, 3 – 15; c) P. Blondeau, M.
Segura, R. PØrez-FernandØz, J. de Mendoza, Chem. Soc. Rev.
2007, 36, 198 – 210.
[14] Schmuck has recently described acylguanidinium receptors,
which form strong complexes with carboxylates even in highly
competitive media, such as water. The increased acidity of the
acylguanidinium moiety (pKa = 7–8 in water) compared to the
simple guanidinium analogue favors the formation of hydrogen-
bound ion pairs and hence improves the binding affinity. An
additional advantage of the guanidine-based system is that no
additional base is required to deprotonate the substrate as in the
[19] Hydroformylation of 3; [Rh(CO)2acac]/1/3 = 1:20:200, c0(3) =
0.39m, THF (5 mL), 4 bar CO/H2 (1:1), RT, 20 h.
[20] A. H. Hoveyda, D. A. Evans, G. C. Fu, Chem. Rev. 1993, 93,
1307 – 1370.
[21] Inhibition effects of carboxylic acids on the hydroformylation of
hex-1-ene has already been described, but the regioselectivity
was unaffected. E. Mieczyæska, A. M. Trzeciak, J. J. Ziółkowski,
J. Mol. Catal. 1993, 80, 189 – 200.
[22] P. W. N. M. van Leeuwen, C. P. Casey, G. T. Whiteker in
Rhodium Catalyzed Hydroformylation (Eds: P. W. N. M. van
Leeuwen, C. Claver), Kluwer Academic, Dordrecht, 2000,
pp. 63 – 75.
[23] a) J. J. Carbó, F. Maseras, C. Bo, P. W. N. M. van Leeuwen, J.
Am. Chem. Soc. 2001, 123, 7630 – 7637; b) S. A. Decker, T. R.
Cundari, J. Organomet. Chem. 2001, 635, 132 – 141.
[24] For regioselective hydroformylation of 2- and 3-octene using
another supramolecular strategy, see: M. Kuil, T. Soltner,
P. W. N. M. van Leeuwen, J. N. H. Reek, J. Am. Chem. Soc.
2006, 128, 11344 – 11345.
Angew. Chem. Int. Ed. 2008, 47, 311 –315
ꢀ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
315