Asymmetrie hydroformylation using Taddol-based chiral phosphine - Phosphite ligands

Article abstract of DOI:10.1021/om9009735

A small library of 17 modular and easily accessible phenol-derived chiral phosphine - phosphite ligands was evaluated in the asymmetric Rh-catalyzed hydroformylation of styrene. It was found that the stereochemical outcome of the reaction is highly dependent on the chiral phosphite moiety and the substituents on the phenolic backbone. Among the ligands studied, Taddol-based ligands of type 10 bearing bulky substituents in ortho-position to the phosphite performed best, with enantioselectivities of up to 85% ee and regioselectivities of ≥98:2. High-pressure NMR of the active catalyst [HRh(P-P)(CO)₂] (P-P = 10h) revealed an equatorial-apical coordination of the ligand at rhodium. Temperature dependency of the coupling constants observed during the experiment indicates equilibrium between the two equatorial-apical isomers, with the isomer in which the phosphite occupies the equatorial position being the dominant species.

Full text of DOI:10.1021/om9009735

478 Organometallics 2010, 29, 478–483
DOI: 10.1021/om9009735
Asymmetric Hydroformylation Using Taddol-Based Chiral
Phosphine-Phosphite Ligands
Tobias Robert,† Zohar Abiri,‡ Jeroen Wassenaar,‡ Albertus J. Sandee,‡ Steffen Romanski,†
†
Jorg-Martin Neudorfl, Hans-Gunther Schmalz,* and Joost N. H. Reek*
,†
,‡
€
€
€
†
€
Department fu€r Chemie, Universitat zu Koln, Greinstrasse 4, D-50939 Koln, Germany and
€
€
‡Van’t Hoff Institute for Molecular Sciences, University of Amsterdam, Nieuwe Achtergracht 166,
1018 WV Amsterdam, The Netherlands
Received November 8, 2009
A small library of 17 modular and easily accessible phenol-derived chiral phosphine-phosphite
ligands was evaluated in the asymmetric Rh-catalyzed hydroformylation of styrene. It was found that
the stereochemical outcome of the reaction is highly dependent on the chiral phosphite moiety and
the substituents on the phenolic backbone. Among the ligands studied, Taddol-based ligands of type
10 bearing bulky substituents in ortho-position to the phosphite performed best, with enantioselec-
tivities of up to 85% ee and regioselectivities of g98:2. High-pressure NMR of the active catalyst
[HRh(P-P)(CO)2] (P-P = 10h) revealed an equatorial-apical coordination of the ligand at rhodium.
Temperature dependency of the coupling constants observed during the experiment indicates
equilibrium between the two equatorial-apical isomers, with the isomer in which the phosphite
occupies the equatorial position being the dominant species.
Introduction
hydroformylation of styrenes (up to 95% ee).5 This chiral
phosphine-phosphite ligand in combination with Rh(I) was
the first efficient and general catalyst and still is a benchmark
in this area.6 Nevertheless, the regioselectivity (iso/n) of
BinaPhos is only 90%, and simultaneous control of enantio-
and regioselectivity remains an open challenge. Inspired by
these results, several structurally different phosphine-
phosphite ligands were synthesized and applied in the Rh-
catalyzed asymmetric hydroformylation. The most success-
ful ligands reported in the literature for this type of reaction
are displayed in Figure 1 (2,7 3,8 and 49). However, in spite of
their structural analogy to BinaPhos (1), these biphenyl-
or binaphthol-based ligands never achieved comparable
enantioselectivities (up to 71% ee with 4). Phosphine-
phosphoramidite ligands, on the other hand, have been
successfully applied in the hydroformylation of styrene,
giving enantioselectivities up to 99% ee.10
Transition metal-catalyzed hydroformylation of terminal
olefins is one of the most important homogeneous-catalytic
transformations in industry.1 Exploiting this method, several
million tons of oxo products are synthesized every year. The
asymmetric hydroformylation2 leads to optically active
branched aldehydes, which are valuable precursors for in-
stance in the synthesis of biologically interesting molecules.3
Over the last decades several transition metal complexes
bearing different phosphorus ligands, such as phospholanes,
phosphines, and phosphites, have been applied in the asym-
metric hydroformylation.2,4 A major breakthrough was
achieved in 1993 by Takaya and Nozaki, who discovered
the high activity and selectivity of BinaPhos (1) in the
*Corresponding authors. E-mail: j.n.h.reek@uva.nl; schmalz@
uni-koeln.de.
Although the catalytic asymmetric hydroformylation
opens a convenient and atom-economic entry to important
chiral intermediates from inexpensive feedstock, there is to
date no application on an industrial scale. In order to meet
(1) (a) Selected reviews: Breit, B. In Topics in Current Chemistry, Vol.
279; Krische, M. J., Ed.; Springer Verlag: Berlin, 2007; pp 139-172, and
references therein. (b) Rhodium Catalyzed Hydroformylation, Vol. 22;
Claver, C.; van Leeuwen, P. W. N. M., Eds.; Kluwer Academic Publishers:
Dordrecht, The Netherlands, 2000.
(2) Selected reviews: (a) Klosin, J.; Landis, C. R. Acc. Chem. Res.
2007, 40, 1251–1259. (b) Nozaki, K. In Comprehensive Asymmetric
Catalysis, Vol. 1; Jacobsen, E. N.; Pfaltz, A.; Yamamoto, H., Ed.; Springer
Verlag: Berlin, 1999; pp 381-413. (c) Agbossou, F.; Carpentier, J.-F.;
Mortreux, A. Chem. Rev. 1995, 95, 2485–2506.
(3) (a) Leighton, J. L. In Modern Rhodium-Catalyzed Organic Reac-
tions; Evans, P. A., Ed.; Wiley-VCH: New York, 2005; pp 93-110; (b)
Botteghi, C.; Paganelli, S.; Marchetti, M. Chirality 1991, 3, 355–369. (c)
Tanaka, R.; Nakano, K.; Nozaki, K. J. Org. Chem. 2007, 72, 8671–8676. (d)
Thomas, P. J.; Axtell, A. T.; Klosin, J.; Peng, W.; Rand, C. L.; Clark, T. P.;
Landis, C. R.; Abboud, K. A. Org. Lett. 2007, 9, 2665–2668. (e) Liu, P.;
Jacobsen, E. N. J. Am. Chem. Soc. 2001, 123, 10772–10773.
(5) Sakai, N.; Mano, S.; Nozaki, K.; Takaya, K. J. Am. Chem. Soc.
1993, 115, 7033–7034.
(6) (a) Nozaki, K.; Sakai, N.; Nanno, T.; Higashijima, T.; Mano, S.;
Horiuchi, T.; Takaya, H. J. Am. Chem. Soc. 1997, 119, 4413–4423. (b)
Nozaki, K.; Itoi, Y.; Shibahara, F.; Shirakawa, E.; Ohta, T.; Takaya, H.;
Hiyama, T. J. Am. Chem. Soc. 1998, 120, 4051.
(7) Deerenberg, S.; Kamer, P. C. J.; van Leeuwen, P. W. N. M.
Organometallics 2000, 19, 2065–2072.
ꢁ
(8) Pamies, O.; Net, G.; Ruiz, A.; Claver, C. Tetrahedron: Asymmetry
2001, 12, 3441–3445.
ꢀ
ꢀ
(9) Rubio, M.; Suarez, A.; Alvarez, E.; Bianchini, C.; Oberhauser,
W.; Peruzzini, M.; Pizzano, A. Organometallics 2007, 26, 6428–6436.
(10) (a) Yan, Y.; Zhang, X. J. Am. Chem. Soc. 2006, 128, 7198–
7202. (b) Wassenaar, J.; Reek, J. N. H. Dalton Trans. 2007, 3750–3753.
(c) Zhang, X.; Cao, B.; Yan, Y.; Yu, S.; Ji, B.; Zhang, X. Chem. Eur. J.,
2009, Early view (DOI: 10.1002/chem.200902238).
(4) (a) Sakai, N.; Nozaki, K.; Mashima, K; Takaya, H. Tetrahedron
Asymmetry 1992, 3, 583. (b) Babin, J.E.; Whiteker, G. T. (Union Carbide
Chem. Plastics Technol. Co.) WO 93/03839, 1993; Chem Abstr. 1993, 16,
ꢀ
ꢁ
2929. (c) Dieguez, M.; Pamies, O.; Claver, C. Tetrahedron: Asymmetry
2004, 15, 2113–2122.
r
pubs.acs.org/Organometallics
Published on Web 12/18/2009
2009 American Chemical Society

Article
Organometallics, Vol. 29, No. 2, 2010 479
Scheme 1a
a Conditions: (a) NBS, cat. i-Pr2NH, rt; (b) DABCO, ClPAr2,
BH3 THF; (c) n-BuLi; (d) DABCO, PCl3, chiral diol.
3
By screening the ligand library of 10 and 11 highly active
catalysts were identified for both the Rh-catalyzed asym-
metric hydroboration12 and Cu-catalyzed asymmetric 1,4-
addition.13 Furthermore, the substituents R1-R4 at the
ligand backbone were found to exert a crucial influence on
the selectivities. Convinced of the potential of this ligand
class and considering the fact that phosphine-phosphite
ligands seem to be privileged for this type of reaction, we
decided to investigate their performance also in the Rh-
catalyzed asymmetric hydroformylation of styrene.
Figure 1. Chiral phosphine-phosphite ligands applied in the
Rh-catalyzed asymmetric hydroformylation.
Results and Discussion
A first screening was carried out with 0.1 mol % of
Rh(acac)(CO)2 and 0.4 mol % of the chiral ligand in toluene
at 50 °C and 20 bar of syngas pressure in a synthesis robot
(18 h reaction time). The conditions, similar to those re-
ported by M. Rubio et al.,9 gave promising results, with
enantioselectivites up to 81% ee (Table 1). Regioselectivity
was very good in all cases (>98% of the branched aldehyde),
while conversions did not exceed 60% under the indicated
conditions.
Interestingly, the best results were obtained with Taddol-
based ligands 10h-j, resulting in enantioselectivities up to
81% ee (Table 1 and Figure 3). It is apparent that a bulky
substituent in position R1 is crucial in this case to achieve
high enantioselectivities. It is noteworthy that the use of
Binol-based ligands resulted in almost all cases in low
conversion, and only traces of the desired product were
observed in these experiments. Importantly, our results
represent the first successful application of Taddol-based
chiral phosphine-phosphite ligands in the asymmetric hy-
droformylation of styrene.14
In order to study the influence of the phosphite and
phosphine moiety on the ligand performance, ligands of
type 12 and 13 (Figure 2) were synthesized following our
established synthetic scheme.11 However, more sterically
demanding Taddol derivatives gave rise to lower enantios-
electivies (Table 1, entries 15 and 16) as compared to the
corresponding ligands of type 10. In order to optimize the
catalytic system, we studied different reaction conditions
Figure 2. Chiral phosphine-phosphite ligands of type 10-13.
Unless indicated otherwise, R1-R4 = H.
industrial requirements, high catalytic activity at moderate
temperatures, broad substrate scope, and excellent control of
regio- as well as enantioselectivity are necessary. Further-
more, the catalytic system has to be economically competi-
tive; therefore efficient and inexpensive ligand syntheses are
crucial. As the most successful systems such as BinaPhos do
not match all of these requirements, further investigations
are required. In the endeavor to identify new and potent
ligands for this transformation, modular (diversity-oriented)
ligand architectures can be very helpful. Some of us recently
reported a new modular synthesis of ligands of type 10 and 11
(Figure 2).11 The structures are easily accessible within four
synthetic steps starting from inexpensive substituted phenols
(Scheme 1). A high degree of variation of the ligand back-
bone can be obtained just by using different phenols.
€
(12) Werle, S.; Fey, T.; Neudorfl, J.-M.; Schmalz, H.-G. Org. Lett.
2007, 9, 3555–3558.
(13) Robert, T.; Velder, J.; Schmalz, H.-G. Angew. Chem., Int. Ed.
€
(11) (a) Velder, J.; Robert, T.; Weidner, I.; Neudorfl, J.-M.; Lex, J.;
Schmalz, H.-G. Adv. Synth. Catal. 2008, 350, 1309-1315. For earlier
modular approaches to this ligand class see: (b) Blume, F.; Zemolka, S.;
Fey, T.; Kranich, R.; Schmalz, H.-G. Adv. Synth. Catal. 2002, 344, 868–883.
(c) Kranich, R.; Eis, K.; Geis, O.; Mu€hle, S.; Bats, J. W.; Schmalz, H.-G.
Chem.-Eur. J 2000, 6, 2874–2894.
2008, 47, 7718–7721.
(14) (a) Seebach, D.; Beck, A. K.; Imwinkelried, R.; Roggo, S.;
Wonnacott, A. Helv. Chim. Acta 1987, 70, 954. Selected reviews: (b)
Seebach, D.; Beck, A. K.; Heckel, A. Angew. Chem. 2001, 113, 96. Angew.
Chem. Int. Ed. 2001, 40, 92. (c) Pellissier, H. Tetrahedron 2008, 64, 10279.

480 Organometallics, Vol. 29, No. 2, 2010
Table 1. First Screening Results of 10-12 as Ligands in the Rh-Catalyzed Hydroformylation of Styrenea
Robert et al.
entry
ligand
conv (%)
15:16
% ee (conf)
1
2
3
4
5
6
7
8
10a
10b
10c
10d
10e
10f
10g
10h
10i
1
36
34
33
37
61
34
47
60
35
38
0
<3 (n.d.)
36 (S)
33 (S)
17 (S)
6 (R)
60 (S)
44 (S)
80 (S)
81 (S)
80 (S)
37 (S)
98:2
98:2
98:2
98:2
98:2
98:2
98:2
98:2
98:2
98:2
9
10
11
12
13
14
15
16
10j
11a
11b
11c
11d
12a
12b
0
0
5
19
99:1
99:1
51 (S)
59 (S)
a Reaction conditions: 0.4 mol % L*, 0.1 mol % Rh(acac)(CO)2, 20 bar H2/CO, toluene, 50 °C, 18 h in a synthesis robot.
Table 2. Rh-Catalyzed Hydroformylation of Styrene at 20 °C and
20 bar of Syngasa
entry
ligand
conv (%)
10:11
% ee (conf)
1
2
3
4
5
6
7
10e
10f
10h
10i
5
3
9
4
4
2
1
18
77
99:1
99:1
99:1
99:1
99:1
99:1
99:1
>99:1
97:3
12 (S)
68 (S)
85 (S)
85 (S)
80 (S)
60 (S)
50 (S)
83 (S)
80 (S)
10j
Figure 3. Most selective Taddol-derived phosphine-phosphite
ligands 10h-j.
12a
12b
13a
10h
8b
9b,c
(syngas pressure, temperature, and reaction time). Lower
temperatures led to an increase in enantioselectivity up to
85% ee, however, with low conversions after 18 h reaction
time (Table 2). Lowering the syngas pressure to 10 bar at
35 °C resulted in a significantly better conversion (Table 2,
entry 9). This is in line with type I kinetics, in which
generally a negative order in CO is observed.1b The use
of ligand 13a bearing a substituted phosphine moiety did
not have a major influence on the enantioselectivity
(Table 2, entry 8).
As the bulky ortho-substituent apparently plays an im-
portant role in the stereochemical outcome of the reaction,
further experiments were conducted in order to obtain more
information about the structure of the free ligands and the
corresponding metal complexes. Phosphorous NMR re-
vealed interdependency between the size of substituent R1
and the 4JPP couplings of the free ligand, as the values of the
coupling constants increase with the steric bulk of the
substituents (Table 3). This suggests that the substituent on
the phenol ring acts as a handle to fine-tune the ligand
conformation, i.e., the relative orientation of the two phos-
phorus donor atoms. This allows precise control over the
positioning of steric bulk in the corresponding complexes
(shaping the pocket), which seems crucial in order to achieve
high enantioselectivities.
a Reaction conditions: 0.4 mol % L*, 0.1 mol % Rh(acac)(CO)2, 20
bar syngas, toluene, 50 °C, 18 h in a synthesis robot; b Reaction
performed at 35 °C in an autoclave. c 10 bar H2/CO was used.
Table 3. Chemical Shifts and Coupling Constants of Selected
Ligands
4
ligand
substituents
δ (P(OR)3) [ppm] δ (PR3) [ppm] JPP [Hz]
10a
10b
10e
10f
10h
10i
R1 = H
135.3
145.9
147.3
145.8
144.5
138.4
138.2
-16.7
-18.0
-17.9
-18.1
-17.3
-20.4
-18.8
13.3
66.8
60.5
67.0
87.5
128.1
151.3
R1 = Me
R2/R3 = (CH)4
R1 = iPr
R1 = Ph
R1 = tBu
10j
R1 = R3 = tBu
square-planar Rh(I) is the complex to which the decisive
alkene coordination takes place during the catalytic cycle,
we decided to study the corresponding Pd(II) complexes.
These were easily prepared by reaction of selected ligands
with PdCl2(PhCN)2. Suitable crystals for X-ray diffraction
were obtained by slow diffusion of n-hexane into a chloro-
form solution of the Pd complex of 10b and 10i (Figures 4
and 5). Space-filling models (Figure 6) of the two complexes
clearly illustrate the large structural differences between the
two PdCl2 complexes. Apparently, the size of the substitu-
ent at the phenyl ring has a major influence on the structure
Unfortunately, Rh complexes with ligands of type 10 did
not give suitable crystals for X-ray diffractometry. As a

Article
Organometallics, Vol. 29, No. 2, 2010 481
˚
Figure 4. ORTEP drawing of complex [Pd(10b)Cl2]. Selected bond distances [A] and angles [deg]: Pd(1)-P(1) = 2.2065(8); Pd(1)-P(2) =
2.2438(7); Pd(1)-Cl(1) = 2.3382(8); Pd(1)-Cl(2) = 2.3631(7); Pd(1)-C(30) = 4.775(3); P(1)-Pd(1)-P(2) = 89.54(3); P(1)-Pd(1)-P-
(2)-C(3) = 154.68(12); P(1)-Pd(1)-P(2)-C(9) = -85.89(11).
˚
Figure 5. ORTEP drawing of complex [Pd(10i)Cl2]. Selected bond distances [A] and angles [deg]: Pd(1)-P(1) = 2.2143(14);
Pd(1)-P(2) = 2.2333(17); Pd(1)-Cl(1) = 2.3356(16); Pd(1)-Cl(2) = 2.3250(16); Pd(1)-C(23) = 3.529(6); P(1)-Pd(1)-P(2) =
90.17(5); P(1)-Pd(1)-P(2)-C(37) = 97.5(2); P(1)-Pd(1)-P(2)-C(43) = -144.20(18).

482 Organometallics, Vol. 29, No. 2, 2010
Robert et al.
Figure 6. Space-filling models of [Pd(10b)Cl2] and [Pd(10i)Cl2].
coupling constants of complex [Rh(H)(10h)(CO)2] are
given in the caption.
Upon changing the temperature, the phosphorus-hydride
coupling constants change. At 45 °C, coupling constants of
JH-P1 = 93.2 and JH-P2 = 50.7 Hz are obtained, and at low
temperature (<-50 °C in toluene-d8) the hydride signal
broadens substantially. In addition, the phosphine signal in
the 31P NMR spectrum exhibits significant broadening already
at room temperature. This temperature dependence of the
coupling constants indicates a fast equilibrium between the
two ea (equatorial-apical) isomers A and B, as observed for
other phosphine-phosphite ligand systems.7-9 Isomer A, in
which the phosphine occupies the apical position trans to the
hydride, is preferred, as the smaller JH-P is observed for the
phosphite. Interconversion of the isomers is likely to occur
through a Berry pseudorotation,15 which scrambles the posi-
tion of phosphine and phosphite. Preference for the A isomer is
also observed for other phosphine-phosphites, as described
by van Leeuwen,7 Claver,8 and Pizzano.9
The presence of two active hydroformylation species may
seem counterintuitive considering the high enantioselectiv-
ities obtained with ligand 10h (up to 85% ee). However, it
may well be that one isomer is far more active in the
hydroformylation, possibly the minor isomer B. Analo-
gously to the Halpern and Brown mechanism in asymmetric
hydrogenation,16 the least stable isomer may give the fastest
migratory insertion and thus carries the main flux of the
reaction. Conversely, both species may be active but give rise
to the same enantiomeric product.
1
Figure 7. (Top) Hydride region of the H NMR spectrum of
[Rh(H)(10h)(CO)2] at 25 °C, δ -9.13, JH-Rh = 10.1, JH-P1
95.6, JH-P2 = 45.8. (Bottom) Section of 1H-coupled 31P NMR
spectrum of [Rh(H)(5h)(CO)2], δP1 25.5, δP2 145.5, JP1-P2
=
=
76.3, JP2-Rh = 218.2, JP2-H = 45.0 (P1 = phosphine, P2 =
phosphite, chemical shifts and coupling constants are given in
ppm and Hz, respectively).
of the complex in the crystalline state, which neverthe-
less should reflect the preferred conformation in solution.
Due to the steric bulk of the tert-butyl substituent in
the palladium complex of 10i, the Taddol moiety is forced
to adopt a conformation in which one phenyl substituent
˚
comes rather close to the metal center (3.53 A in axial
orientation).
In order to obtain more detailed information about
the active hydroformylation species, high-pressure NMR
studies with ligand 10h were carried out. A single set of
signals, consistent with the formula [Rh(H)(10h)(CO)2],
was observed at 25 °C, when mixing 3 equiv of 10h with
[Rh(acac)(CO)2] under conditions similar to the hydrofor-
mylation experiments (5 bar H2/CO, 4 h incubation at
50 °C, benzene-d6). The resulting 1H NMR spectrum exhi-
bits one hydride signal at -9.13 ppm as a doublet-of-
doublets-of-doublets (Figure 7, top). The signals in the
31P NMR spectrum were obscured by the peaks stemm-
ing from the free ligand and were therefore recorded at a
Rh/L ratio of 1:1 (Figure 7, bottom). Chemical shifts and
Conclusion
Rhodium(I) complexes of a series of chiral phosphine-
phosphite ligands have been evaluated in the asymmetric
(15) Casey, C. P.; Paulsen, E. L.; Beuttenmueller, E. W.; Proft, B. R.;
Petrovich, L. M.; Matter, B. A.; Powell, D. R. J. Am. Chem. Soc. 1997,
119, 11817.
(16) (a) Chan, A. S. C.; Halpern, J. J. Am. Chem. Soc. 1980, 102, 838–
840. (b) Chan, A. S. C.; Pluth, J. J.; Halpern, J. J. Am. Chem. Soc. 1980, 102,
5952–5954. (c) Halpern, J. Science 1982, 217, 401–407. (d) Landis, C. R.;
Halpern, J. J. Am. Chem. Soc. 1987, 109, 1746–1754. (e) Brown, J. M.;
Chaloner, P. A. Tetrahedron Lett. 1978, 1877–1880. (f) Brown, J. M.;
Chaloner, P. A. J. Am. Chem. Soc. 1980, 102, 3040–3048.

Article
Organometallics, Vol. 29, No. 2, 2010 483
hydroformylation of styrene. High regioselectivies (>98%)
and good enantioselectivities of up to 85% ee have been
achieved using Taddol-based ligands of type 10. A drastic
influence of the substituent size in ortho-position to the phos-
phite on the enantioselectivity is observed. Structural studies
on Pd complexes of ligands 10b and 10i have shown that the
size of this substituent translates in steric congestion around
the metal center via a conformational arrangement of the
Taddol moiety. High-pressure NMR studies of the rhodium-
hydrido bis-carbonyl species with ligand 10h revealed the
presence of two ea isomers, A and B, which interconvert
rapidly on the NMR time scale, probably by Berry pseudo-
rotations. In the most stable isomer, A, the phosphine occupies
the apical position trans to the hydride, as has been observed
previously for other phosphine-phosphites.7-9 Further stu-
dies aimed at elucidating the mechanistic implications of these
observations will be reported in due time.
(121.6 MHz, CDCl3) δ 10.78 (s, PR3), 82.91 (s, P(OR)3); IR
(ATR) ν~ 3056 (w), 2990 (w), 2929 (w), 2228 (w), 1573 (w), 1493
(w), 1447 (m), 1435 (m), 1409 (w), 1383 (w), 1253 (w), 1213 (m),
1154 (m), 1098 (m), 1050 (m), 1009 (s), 996 (s), 909 (s), 852 (w),
726 (s), 697 (s), 661 (w); MS (ESI) m/z (%) 928.7 ([M - Cl-]þ, m/
z 923-935), 893.3 ([M - 2Cl-]þ, m/z 888-898). Anal. Calcd for
C50H44Cl2O5P2Pd: C, 62.29; H, 4.60. Found: C, 61.59; H, 4.66.
Synthesis of the Complex [Pd(10i)Cl2]. Ligand 10i (49.7 mg,
60.0 μmol) and [PdCl2(PhCN)2] (23.0 mg, 60.0 μmol) were
dissolved in toluene (2.5 ml) and stirred for 90 min at RT.
Hexane was then added to precipitate the Pd(II) complex. After
centrifugation, the precipitate (product) was washed with hex-
ane and dried in vacuo to afford the Pd(II) complex [Pd(10i)Cl2]
(55 mg, 54.0 μmol, 90%) as a gray solid: 1H NMR (600 MHz,
CDCl3) δ [ppm] 0.48 (s, 3H, CH3), 0.84 (s, 3H, CH3), 0.88 (s, 9H,
CH3), 5.32 (d, J = 7.4 Hz, 1H, OCH), 6.25 (d, J = 7.4 Hz, 1H,
OCH), 6.58 (Ψt, J = 8.7 Hz, 1H), 7.05 (Ψdt, J1 = 7.8 Hz, J2 =
1.3 Hz, 1H), 7.09-7.20 (m, 8H), 7.07-7.69 (m, 21H), 7.92 (Ψd,
J = 7.3 Hz, 2H); 31P{1H} NMR (121.5 MHz, CDCl3) δ 9.94 (d,
J = 6.6 Hz, PR3), 91.53 (d, J = 6.6 Hz, P(OR)3); IR (ATR) ν~
3057 (w), 2986 (w), 2933 (w), 2226 (w), 1494 (w), 1480 (w), 1447
(m), 1435 (m), 1403 (m), 1392 (w), 1382 (w), 1232 (w), 1214 (w),
1164 (w), 1112 (m), 1099 (m), 1050 (m), 1031 (m), 1006 (s), 995
(s), 912 (m), 887 (m), 855 (m), 742 (s), 725 (s), 695 (s); MS (ESI)
m/z (%) 1006.2 ([M - Cl-]þ, m/z 1000-1013), 970.8 ([M -
Cl-]þ, m/z 965-977, 100), 935.3 ([M - 2Cl-]þ, m/z 930-941,
25). Anal. Calcd for C53H50Cl2O5P2Pd: C, 63.26; H, 5.01.
Found: C, 62.53; H, 5.11.
Interestingly, Taddol-based ligands proved to be superior
to corresponding Binol-based ligands in the current study.
Our results suggest that this tartaric acid-derived chiral diol
should be generally considered as an alternative to bi-
naphthyl- and biphenyl-derived compounds for this kind
of transformation.
Experimental Section
X-ray Structure Determinations. Suitable crystals for a single-
crystal X-ray structure analysis were grown by slow diffusion of
n-hexane into a chloroform solution of [Pd(10b)Cl2] and
[Pd(10i)Cl2]. A summary of crystallographic data is reported
in the Supporting Information.
General Comments. All experiments were carried out under
inert conditions. Solvents were dried using standard methods.
Hydroformylation reactions were carried out in a Chemspeed
Accelerator synthesis robot or a stainless steel autoclave and
monitored by chiral GC. High-pressure NMR experiments were
recorded on a Varian Inova 500 MHz spectrometer. Ligands of
type 10 and 11 were prepared as published.11 Preparation of the
new ligands 12a, 12b, and 13a is described in the Supporting
Information.
Typical Hydroformylation Procedure. All reagents, solvents,
and starting materials were placed in the synthesis robot, which
then generated stock solutions of all the compounds under inert
atmosphere. After transferring all solutions, the reaction vessels
were pressurized with 20 bar of syngas, heated to 50 °C, and
shaken for 16 h. Conversion, regioselectivity, and enantioselec-
tivity were monitored by gas chromatography on chiral sta-
tionary phase.
Synthesis of the Complex [Pd(10b)Cl2]. Ligand 10b (47.2 mg,
60.0 μmol) and [PdCl2(PhCN)2] (23.0 mg, 60.0 μmol) were
dissolved in toluene (2.5 ml) and stirred for 90 min at RT.
Hexane was then added to precipitate the Pd(II) complex. After
centrifugation, the precipitate (product) was washed with hex-
ane and dried in vacuo to afford the Pd(II) complex [Pd(10b)Cl2]
(57 mg, 59.0 μmol, 99%) as a gray solid: 1H NMR (300 MHz,
CDCl3) δ [ppm] 0.26 (s, 3H, CH3), 0.99 (s, 3H, CH3), 1.27 (s, 3H,
CH3), 5.54 (Ψt, J = 7.3 Hz, 2H, OCH), 6.53 (Ψt, J = 9.0 Hz,
1H), 6.88 (Ψdt, J1 = 7.6 Hz, J2 = 1.2, 1H), 6.97-7.06 (m, 3H),
7.07-7.69 (m, 26 H), 7.84 (Ψt, J = 7.4 Hz, 2H); 31P{1H} NMR
Intensity data for complexes [Pd(10b)Cl2] and [Pd(10i)Cl2]
were collected on a Nonius KappaCCD diffractometer, using a
˚
Mo KR1 graphite monochromator (λ = 0.71073 A). The
structures were solved by direct methods (SHELXS97) and
refined against all F2 data by full-matrix least-squares techni-
ques (SHELXL97).
HP NMR Experiments. In a typical experiment a 5 mm
sapphire high-pressure NMR tube was filled with a solution of
[Rh(acac)(CO)2] (4.0 mg, 0.016 mmol), ligand (0.047 mmol),
and benzene-d6 (0.5 ml). The tube was purged three times with 5
bar of H2/CO (1:1), pressurized with 5 bar of H2/CO (1:1), and
left for 4 h at 50 °C. After cooling to room temperature the
NMR spectra were recorded. For VT-NMR, benzene-d6 was
replaced by toluene-d8.
Acknowledgment. This work was carried out in the
context of Cost D40 and supported by the European
Commission (Ligbank).
Supporting Information Available: CIF files giving crystal-
lographic data, procedures and analytical data of synthesized
ligands and Pd complexes, and NMR spectra. This material is
available free of charge via the Internet at http://pubs.acs.org.