Supramolecular control of ligand coordination and implications in hydroformylation reactions

Article abstract of DOI:10.1002/anie.201101653

The coordination mode of a monodentate phosphoroamidite ligand in a rhodium complex can be switched from equatorial to axial by a unique supramolecular pseudo encapsulation (see scheme). The axial complex has higher activity and selectivity in the challenging asymmetric hydroformylation of internal alkenes. Copyright

Full text of DOI:10.1002/anie.201101653

Communications
DOI: 10.1002/anie.201101653
Coordination Chemistry
Supramolecular Control of Ligand Coordination and Implications in
Hydroformylation Reactions**
Rosalba Bellini, Samir H. Chikkali, Guillaume Berthon-Gelloz,* and Joost N. H. Reek*
Coordination chemistry and organometallic chemistry have
intensely fuelled the field of transition metal catalysis, and
knowledge-based ligand design is, next to combinatorial and
high-throughput experimentation, a leading approach to
develop new catalytic systems. For the industrially important
hydroformylation reaction, ligand effects have been studied
in detail, also with the aid of high-pressure spectroscopy
techniques, (for example, HP NMR and HP-IR).[1] The active
species in this reaction is a trigonal bipyramidal complex, with
a hydride on the axial position. The classical Wilkinsonꢀs
dissociative mechanism, based on triphenyl phosphine as
ligand, is widely accepted and explains most observations
made to date. Two coordination complexes have been
observed with either the ligands coordinated in the equato-
rial–equatorial (eq-eq) or in the equatorial–axial (eq-ax)
mode (Scheme 1).
high enantioselectivity is attributed to the exclusive formation
of a single active species, in which the ligand coordinates in
eq-ax mode to the transition-metal center.
Monodentate ligands have been much less applied in
these transformations, as lower selectivities are anticipated
owing to lower control over coordination modes. However,
because of their simple structure, their synthesis is generally
much less elaborate, making these ligands potentially cheaper
and enabling the preparation of large ligand libraries, which
are required to rapidly find new active and selective catalysts
by rapid screening technologies. Application of very bulky
monodentate phosphite (p-accepting) ligands demonstrated
that these form very active catalysts that are also active in the
hydroformylation of internal alkenes, albeit with significant
isomerization.[5] Spectroscopy experiments on such systems
indicate that only one phosphite ligand coordinates to the
metal center in the equatorial plane. Along the same lines,
Breit et al. have reported the use of bulky phosphabenezenes
in hydroformylation catalysis.[6] In situ high-pressure NMR
investigations demonstrate the prevalent formation of a
monophosphine rhodium complex in which the ligand is
located in equatorial position whereas the hydride occupies
the axial site, which accounts for the reported activity and
selectivity.
Scheme 1. Different coordination modes of a triphenylphosphine rho-
dium catalyst. eq-eq=both equatorial, eq-ax=equatorial/axial.
Recently, we have introduced a ligand-template approach
for the supramolecular encapsulation of transition-metal
complexes.[7] Ligand-template tris-3-pyridylphosphine coor-
dinates zinc(II) porphyrins exclusively to the nitrogen donor
atom, whereas the phosphorus atom coordinates to the
catalytically active rhodium. The rhodium complex formed
under hydroformylation conditions has only one phosphorus
atom coordinated in the equatorial plane, and this catalyst
system displayed unprecedented regioselectivity in the hydro-
formylation of unfunctionalized terminal and internal
alkenes. Based on these results, we explored the use of
chiral analogues, that is, typically based on the bis(naphthol)
skeleton (Scheme 2). Herein, we present the remarkable
supramolecular control over the coordination chemistry of
these chiral pyridine-containing phosphoroamidite ligands
and the effect in the asymmetric rhodium-catalyzed hydro-
formylation of unfunctionalized internal alkenes by this
unusual coordination complex.
Monodentate phosphoroamidites (S)-1a–b were synthe-
sized in just two steps (Scheme 3).[8,9] To ascertain that ligands
(S)-1a bind to two zinc(II) porphyrin building blocks (2), we
measured the binding constants and performed a Job plot
analysis. The UV/Vis titration experiment revealed binding
constants of K1 = 1.8 ꢁ 103 LmolÀ1 and K2 = 1.7 ꢁ 103 LmolÀ1
for the first and second porphyrin binding, respectively, to (S)-
1a. The similarity between these constants indicate that the
Van Leeuwen et al. elegantly demonstrated that bidentate
phosphorus ligands with wide bite angles predominantly lead
to the formation of the eq-eq rhodium complex, resulting in
highly selective rhodium-catalyzed hydroformylation of 1-
octene, and promoting the formation of the linear aldehyde
product.[2] In the field of asymmetric hydroformylation, the
most promising class of ligands are hybrid phosphines and
phosphites or phosphoroamidites.[3] A real breakthrough in
this field was achieved by Takaya, Nozaki et al. with the
discovery of Binaphos, which gives ee values of up to 95% for
a wide range of substrates.[4] The reason for the exceptionally
[*] R. Bellini, Dr. S. H. Chikkali, Dr. G. Berthon-Gelloz,
Prof. Dr. J. N. H. Reek
Van’t Hoff Institute for Molecular Sciences
University of Amsterdam
Science Park 904, 1098 XH, Amsterdam (The Netherlands)
E-mail: j.n.h.reek@uva.nl
Homepage: http//www.science.uva.nl/research/imc/Homkat/
[**] We acknowledge the Revcat RTN research-training network, Marie
Curie actions, and the NRSCC for financial support.
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201101653.
7342
ꢀ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2011, 50, 7342 –7345

(acac)CO2] as the metal precursor in [D8]toluene under
syngas (H2/CO 1:1) at a pressure of 5 bar (Figure 1). In line
with previously reports, the complex based on bulky ligand
(S)-1a is monoligated [Rh(H)(CO)31a] with the phosphorus
ligand in the equatorial position; an hydride signal centered at
d = À11.01 ppm is observed with a small PH coupling typical
of such a cis-[Rh(H)(CO)31a] complex. Much to our surprise,
in the presence of two equivalents of porphyrin 2, this signal
1
disappears and the HP H NMR shows new signals in the
hydride region; a double doublet centered at d = À10.3 ppm
with a large phosphorus coupling (JP-H = 180 Hz and JRh-H
=
6.1 Hz) indicating that in this complex the phosphorus donor
atom is located trans to the hydride. The 1H-{31P} NMR
spectrum shows a signal at d = À10.3 ppm, confirming the
large coupling between the phosphorus and the hydride. The
2D 1H-31P NMR spectra also supports the formation of a
complex with a very large H-P cou-
Scheme 2. The assembly of supramolecular ligand based on 4-pyridyl-
phosphoroamidite 1a and tetraphenyl zinc(II) porphyrin 2.
pling.[9] To the best of our knowledge,
this is the first example of a rhodium
complex in which a bulky monodentate
ligand is coordinated trans to the hy-
dride.
Importantly, we are able to control
the ligand coordination mode by addi-
tion of
a supramolecular template,
which triggers the ligand coordination
on rhodium from the cis position to
Scheme 3. Synthesis of phosphoroamidite ligands.
trans position with respect to the hy-
dride. This supramolecular control of
binding events are independent and no cooperativity is
observed as previously with the tris-3-pyridylphosphine.[7b]
The Job plot analysis of NMR spectroscopy experiments in
[D8]toluene confirmed the formation of a 1:2 complex
between (S)-1a and template 5.[9]
cis versus trans coordination was demonstrated for a variety
of systems, extending to zinc(II) salphen templates, and to the
3-pyridyl, bisnaphthol, and phosphoramidite and phosphite
analogues of 1a, showing that this behavior is rather
general.[9]
To investigate the coordination behavior of (S)-1a to
rhodium under catalytically relevant conditions, we studied
the complexes formed by high-pressure (HP) NMR spectros-
copy. Rhodium complexes were prepared in situ using [Rh-
Using high-pressure IR spectroscopy, we studied the
formation of complexes cis-[Rh(H)(CO)31a] and trans-
[Rh(H)(CO)31a(2)2] under actual catalytic conditions, using
20 bar of syngas (H2/CO 1:1) and concentrations identical to
Figure 1. High Pressure NMR spectra of cis-[Rh(H)(CO)31a] and trans-[Rh(H)(CO)3(1a(2)2)].
Angew. Chem. Int. Ed. 2011, 50, 7342 –7345
ꢀ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
7343

Communications
Table 1: Results of the hydroformylation of trans-2-octene.[a]
those in catalysis experiments.[12] In the presence of [Rh-
(acac)CO2] and ligand (S)-1a, the tris(carbonyl) rhodium
hydride complex cis-[Rh(H)(CO)31a] was obtained, as was
evident from the three peaks in the carbonyl region, namely
2054, 2000, and 1982 cmÀ1. The rhodium complex formed in
the presence of (S)-1a and two equivalents of porphyrin 2
shows three absorption bands that are shifted to higher
wavenumbers (2055, 2022, 1998 cmÀ1),[9] in line what we
expected as the CO is a stronger p-accepting ligand than the
phosphoroamidite. This change also suggests that CO disso-
ciation from the trans-[Rh(H)(CO)31a(2)2] complex might be
faster, enhancing the alkene coordination step and possibly
increasing the reaction rate.
To find out if the change in coordination mode would
affect the catalytic performance, we used both complexes cis-
[Rh(H)(CO)31a] and trans-[Rh(H)(CO)31a(2)2] as catalyst
for the asymmetric hydroformylation of internal alkenes.[10,11]
We have chosen this reaction as 1) it is very challenging to
introduce functional groups in non-functionalized alkenes, so
success will lead to new enabling technology; 2) we previously
demonstrated that encapsulation can lead to unusual regio-
selective reactions;[7] and 3) monodentate phosphoramidite
ligands have been demonstrated to provide selective rhodium
catalyst for the asymmetric hydroformylation of functional-
ized alkenes.[10c]
Entry
Ligand
Conv.
[%][b]
Isom.
[%][c]
6b/6a[b,d]
6a
ee [%][e]
1
2
3
4
5
6
PPh3
(R,S)-Binaphos
(S)-1b
(S)-1b, 2 equiv 2
(S)-1a
(S)-1a(2)2
6
5
4
4
4
4
0
1.24
1.51
1.42
1.45
1.41
0.96
0
0
55
12
11
12
56
11 (R)[f]
10 (R)[f]
25 (R)[f]
45 (R)[f]
[a] [Rh]=1 mm in toluene, ligand/rhodium=9, trans-2-octene/rho-
dium=200, 258C, 20 bar, 84 h. [b] Percentage conversion calculated
using the GC method. [c] Percentage isomerization. [d] Ratio of the
products 6b and 6a. [e] Enantiomeric excess of product 6a. [f] The
absolute configuration was determined by comparing the GC traces with
the that from the enantiopure aldehydes (R)-6a and (S)-6a. For detailed
synthesis of (R)-6a and (S)-6a, see the Supporting Information.
mance is associated to this change in coordination mode. In
line with this, control experiments using ligand (S)-1b
(Table 1, entry 3 and 4) that lacks the pyridyl group shows
that these complexes give rise to low activity and the product
6a is produced in low ee, regardless of the presence of zinc(II)
porphyrin 2. This demonstrates that template 2 does therefore
not interfere directly with the rhodium-catalyzed hydro-
formylation. Furthermore, the increase in ee was also
observed when the coordination mode was changed using
phosphite and phosphoramidite analogues of 1a.
To determine whether this unusual template effect in (S)-
1a is more general, we investigated the AHF of a trans-2-
hexene and trans-2-heptene, and the templated ligands also
provide higher activity and enantioselectivity for these
substrates compared to the non-templated analogues.[9]
In summary, we have presented a new class of mono-
dentate phosphoramidite ligands for which the coordination
mode to rhodium can be controlled in a unique supramolec-
ular fashion, providing a new tool to control the activity and
selectivity of a transition metal catalyst. In situ high-pressure
NMR and IR studies under hydroformylation conditions
demonstrate the formation of the first rhodium hydride
complex in which the phosphorus donor atom of the ligand is
trans to the hydride, but only after coordination of zinc(II)
porphyrin moieties to the pyridyl moieties of the ligand. In
absence of these zinc(II) porphyrins, the common monoli-
gated rhodium hydrido complexes are formed with the ligand
in the equatorial plane, in cis orientation to the hydride.
Interestingly, the supramolecular change to the unusual
coordination is reflected in higher activity and selectivity
when these complexes are applied to the very challenging
asymmetric hydroformylation of unfunctionalized internal
alkenes.
The ligand (S)-1a and (S)-1a(2)2 as well as some control
ligands (PPh3,(R,S)-Binaphos and (S)-1b) were studied in the
rhodium-catalyzed asymmetric hydroformylation (AHF) of
trans-2-octene (5a) under syngas (H2/CO = 1/1) at 20 bar
pressure and at 258C in toluene (1 mm) (Scheme 4).[9]
Scheme 4. Hydroformylation of trans-2-octene.
The challenging character of this reaction is clear from the
results obtained with the rhodium catalyst derived from
triphenylphosphine, which only gave low conversions and
significant amount of isomerization (Table 1, entry 1). The
rhodium-catalyst-based (R,S)-Binaphos (Table 1, entry 2)
gave useful conversion (55%) but no significant ee%.
Complex [Rh(H)(CO)31a] provided the product with an
ee of 25%, albeit at relatively low conversion (12%, Table 1,
entry 5) Interestingly, in the presence of the template 2, and
thus with complex [Rh(H)(CO)31a(2)2], an increase in both
conversion (54%) and enantioselectivity (45%) is observed
(Table 1, entry 6). This indicates that the change of coordi-
nation mode improves the catalyst performance in this
challenging reaction both in terms of activity and selectivity.
In line with this finding, we explored a small series of various
zinc(II)-based templates, and regardless of the structure of
the template, in all cases the ee increases to the same 45%.[9]
This suggests that the dominant effect in change of perfor-
Received: March 7, 2011
Revised: April 28, 2011
Published online: June 22, 2011
Keywords: coordination mode · hydroformylation · isomers ·
.
molecular recognition · supramolecular chemistry
7344
www.angewandte.org
ꢀ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2011, 50, 7342 –7345

126, 1526 – 36; c) M. Kuil, T. Solter, P. W. N. M. van Leeuwen,
J. N. H. Reek, J. Am. Chem. Soc. 2006, 128, 11344 – 5; d) A. W.
Kleij, M. Kuil, D. M. Tooke, A. L. Spek, J. N. H. Reek, Inorg.
Chem. 2005, 44, 7696 – 7698; e) A. W. Kleij, M. Lutz, A. L. Spek,
P. W. N. M. van Leeuwen, J. N. H. Reek, Chem. Commun. 2005,
3661 – 3663; f) A. W. Kleij, J. N. H. Reek, Chem. Eur. J. 2006, 12,
4219 – 4227.
[1] P. W. N. M. van Leeuwen, C. Claver in Rhodium-Catalyzed
Hydroformylation, Kluwer Academic Publishers, Dordrecht,
2000.
[2] a) M. Kranenburg, Y. E. M. van der Burgt, P. C. J. Kamer,
P. W. N. M. van Leeuwen, Organometallics 1995, 14, 3081 –
3089; b) L. A. van der Veen, P. H. Keeven, G. C. Schoemaker,
J. N. H. Reek, P. C. J. Kamer, P. van Leeuwen, M. Lutz, A. L.
Spek, Organometallics 2000, 19, 872 – 883.
[3] a) S. Deerenberg, P. C. J. Kamer, P. W. N. M. van Leeuwen,
Organometallics 2000, 19, 2065 – 2072; b) O. Pꢂmies, G. Net, A.
Ruiz, C. Claver, Tetrahedron: Asymmetry 2001, 12, 3441 – 3445;
c) M. Rubio, A. Suꢃrez, E. ꢄlvarez, C. Bianchini, W. Ober-
hauser, M. Peruzzini, A. Pizzano, Organometallics 2007, 26,
6428 – 6486; d) Y. Yan, X. Zhang, J. Am. Chem. Soc. 2006, 128,
7198 – 7201; e) S. Chikkali, R. Bellini, G. Berthon-Gelloz, J. I.
van der Vlugt, B. de Bruin, J. N. H. Reek, Chem. Commun. 2010,
46, 1244 – 1246; f) X. Zhang, B. Cao, Y. Yan, S. Yu, B. Ji, X.
Zhang, Chem. Eur. J. 2010, 16, 871 – 877; g) T. Robert, Z. Abiri, J.
Wassenaar, A. J. Sandee, S. Romanski, J. M. Neudꢅrfl, H. G.
Schmalz, J. N. H. Reek, Organometallics 2010, 29, 478 – 483; h) J.
Wassenaar, B. de Bruin, J. N. H. Reek, Organometallics 2010, 29,
2767 – 2776; i) G. Franciꢆ, F. Faraone, W. Leitner, Angew. Chem.
2000, 112, 1486 – 1488; Angew. Chem. Int. Ed. 2000, 39, 1428 –
1430.
[4] a) K. Nozaki, N. Sakai, T. Nanno, T. Higashijima, S. Mano, T.
Horiuchi, H. Takaya, J. Am. Chem. Soc. 1997, 119, 4413 – 4423;
b) K. Nozaki, T. Matsuo, F. Shibahara, T. Hiyama, Organo-
metallics 2003, 22, 594 – 600; c) D. A. Castillo Molina, C. P.
Casey, I. Mꢇller, K. Nozaki, C. Jꢈkel, Organometallics 2010,
29, 3362 – 3367.
[5] P. W. N. M. van Leeuwen, C. F. Roobeek, J. Organomet. Chem.
1983, 258, 343 – 350.
[6] B. Breit, R. Winde, T. Mackewitz, R. Paciello, K. Harms, Chem.
Eur. J. 2001, 7, 3106 – 3121.
[8] a) N. Kudo, M. Perseghini, G. C. Fu, Angew. Chem. 2006, 118,
1304 – 1306; Angew. Chem. Int. Ed. 2006, 45, 1282 – 1284; b) C. J.
OꢀBrien, E. A. B. Kantchev, C. Valente, N. Hadei, G. A. Chass,
A. Lough, A. C. Hopkinson, M. G. Organ, Chem. Eur. J. 2006,
12, 4743 – 4748; c) M. Bartoszek, M. Beller, J. Deutsch, M.
Klawonn, A. Kockritz, N. Nemati, A. Pews-Davtyan, Tetrahe-
dron 2008, 64, 1316 – 1322; d) G. Erre, K. Junge, S. Enthaler, D.
Addis, D. Michalik, A. Spannenberg, M. Beller, Chem. Asian J.
2008, 3, 887 – 894.
[9] For details, see the Supporting Information.
[10] For hydroformylation, see: a) B. Breit, W. Seiche, Synthesis 2001,
1 – 36; b) B. Breit, Top. Curr. Chem. 2007, 279, 139 – 172; c) Z.
Hua, V. C. Vassar, H. Choi, I. Ojima, Proc. Natl. Acad. Sci. USA
2004, 101, 5411 – 5416; d) B. Breit, E. Fuchs, Chem. Commun.
2004, 694 – 695; e) E. Fuchs, M. Keller, B. Breit, Chem. Eur. J.
2006, 12, 6930 – 6939; f) M. L. Clarke, Curr. Org. Chem. 2005, 9,
701 – 718; g) N. Sakai, K. Nozaki, H. Takaya, J. Chem. Soc.
Chem. Commun. 1994, 395 – 396; h) R. I. McDonald, G. W.
Wong, R. P. Neupane, S. S. Stahl, C. R. Landis, J. Am. Chem. Soc.
2010, 132, 14027 – 14029.
ˇ
[11] For alternative supramolecular control, see: a) T. Smejkal, B.
Breit, Angew. Chem. 2008, 120, 317 – 321; Angew. Chem. Int. Ed.
ˇ
2008, 47, 311 – 315; T. Smejkal, B. Breit, Angew. Chem. 2008, 120,
4010 – 4013; Angew. Chem. Int. Ed. 2008, 47, 3946 – 3949; b) P.
Dydio, W. Dzik, M. Lutz, B. de Bruin, J. N. H. Reek, Angew.
Chem. 2011, 123, 416 – 420; Angew. Chem. Int. Ed. 2011, 50, 396 –
400.
[12] For high-pressure IR studies, see: a) P. C. J. Kamer, A. van Rooy,
G. C. Schoemaker, P. W. N. M. van Leeuwen, Coord. Chem. Rev.
2004, 248, 2409 – 2424; b) C. Kubis, R. Ludwig, M. Sawall, K.
Neymeyr, A. Bꢅrner, K. D. Wiese, D. Hess, R. Franke, D. Selent,
ChemCatChem 2010, 2, 287 – 295.
[7] a) V. F. Slagt, J. N. H. Reek, P. C. J. Kamer, P. W. N. M. van
Leeuwen, Angew. Chem. 2001, 113, 4401 – 4404; Angew. Chem.
Int. Ed. 2001, 40, 4271 – 4274; b) V. F. Slagt, P. C. J. Kamer,
P. W. N. M. van Leeuwen, J. N. H. Reek, J. Am. Chem. Soc. 2004,
Angew. Chem. Int. Ed. 2011, 50, 7342 –7345
ꢀ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
7345