INDOLPhosphole and INDOLPhos Palladium-Allyl complexes in asymmetric allylic alkylations

Article abstract of DOI:10.1021/om801204a

The new INDOLPhosphole ligands 3a,b are obtained in good yield in a two-step synthetic sequence from 3-methylindole, (S)-BINOL, and the corresponding cyanophosphole. Palladium-allyl complexes have been prepared from INDOLPhosphole (3b) and INDOLPhos (1a)

Full text of DOI:10.1021/om801204a

2724
Organometallics 2009, 28, 2724–2734
INDOLPhosphole and INDOLPhos Palladium-Allyl Complexes in
Asymmetric Allylic Alkylations
Jeroen Wassenaar,† Steven van Zutphen,‡,§ Guilhem Mora,‡ Pascal Le Floch,‡
Maxime A. Siegler,| Anthony L. Spek,| and Joost N. H. Reek*,†
Van ‘t Hoff Institute for Molecular Sciences, UniVersity of Amsterdam, Nieuwe Achtergracht 166,
1018 WV Amsterdam, The Netherlands, Laboratoire “He´te´roe´le´ments et Coordination”, Ecole
Polytechnique, CNRS, 91128 Palaiseau Ce´dex, France, and Crystal and Structural Chemistry, BijVoet
Centre for Biomolecular Research, Faculty of Science, Utrecht UniVersity, Padualaan 8,
3584 CH Utrecht, The Netherlands
ReceiVed December 19, 2008
The new INDOLPhosphole ligands 3a,b are obtained in good yield in a two-step synthetic sequence
from 3-methylindole, (S)-BINOL, and the corresponding cyanophosphole. Palladium-allyl complexes
have been prepared from INDOLPhosphole (3b) and INDOLPhos (1a) of the type [Pd(INDOLPhos(p-
hole))(η3-C3H5)]PF6 and studied by multidimensional NMR spectroscopy and X-ray crystallography. The
allyl ligand undergoes a η3-η1-η3 isomerization in these complexes, which is selective when 1a is the
ligand. A tetrameric, boxlike structure, encapsulating a PF6- counteranion, is formed in the solid state in
the case of complex 5 ([Pd(3b)(η3-C3H5)]PF6). INDOLPhosphole ligands 3a,b and a small library of
INDOLPhos ligands were screened in the Pd-catalyzed asymmetric allylic alkylation of mono- and
disubstituted allylic acetates. The catalysts derived from these ligands were highly active, and
enantioselectivities were obtained for 1,3-diphenylprop-2-enyl acetate up to 90% ee. Cinnamyl acetate
was converted quantitatively with low regioselectivity (b/l ) 14/86) and good enantioselectivity up to
81% ee. In the case of disubstituted substrates, the absolute configuration of the product could be
rationalized by a model of selective attack on one of the enantiotopic termini in the Pd-allyl intermediate.
in the transition-metal complexes of hybrid ligands. This enables
specific binding of prochiral substrates, thus providing an
additional handle for enantiodiscrimination. Second, the facile
preparation resulting from the often modular synthetic sequence
in two or three steps allows for rapid scale-up for industrial
use and provides an economical advantage over conventional
chiral diphosphines.
Introduction
Chiral hybrid bidentate phosphine-phosphoramidite ligands
have recently gained much attention from the synthetic com-
munity for their use in highly efficient asymmetric catalytic
transformations.1 Along with the renaissance of chiral mono-
dentate ligands2 and the introduction of supramolecular bidentate
ligands,3 hybrid ligands are among the most significant develop-
ments in the field of asymmetric transition-metal catalysis in
the new millennium. In comparison to classical chiral bidentate
phosphines such as BINAP and DuPHOS, hybrid ligands offer
several advantages. First, the presence of two different phos-
phorus donor atoms, in addition to one or more chirality
elements, results in desymmetrization of the coordination sphere
In 2000, Leitner et al. introduced the first hybrid bidentate
phosphine-phosphoramidite QUINAPHOS and demonstrated
its use in the asymmetric Rh-catalyzed hydrogenation of
dimethyl itaconate and methyl 2-acetamidoacrylate.4 Up to now
several other chiral phosphine-phosphoramidites have been
* To whom correspondence should be addressed. E-mail: J.N.H.Reek@
uva.nl. Fax: +31 (0)20 525 6422. Tel: +31 (0)20 525 6437.
† University of Amsterdam.
(3) (a) Slagt, V. F.; van Leeuwen, P. W. N. M.; Reek, J. N. H. Chem.
Commun. 2003, 2474–2475. (b) Takacs, J. M.; Reddy, D. S.; Moteki, S. A.;
Wu, D.; Palencia, H. J. Am. Chem. Soc. 2004, 126, 4494–4495. (c) Breit,
B. Angew. Chem., Int. Ed. 2005, 44, 6816–6825. (d) Kleij, A. W.; Reek,
J. N. H. Chem. Eur. J. 2006, 12, 4219–4227. (e) Kuil, M.; Goudriaan, P. E.;
van Leeuwen, P. W. N. M.; Reek, J. N. H. Chem. Commun. 2006, 4679–
4681. (f) Sandee, A. J.; Reek, J. N. H. Dalton Trans. 2006, 3385–3391. (g)
Flapper, J.; Reek, J. N. H. Angew. Chem., Int. Ed. 2007, 46, 8590–8592.
(h) Kuil, M.; Goudriaan, P. E.; Kleij, A. W.; Tooke, D. M.; Spek, A. L.;
van Leeuwen, P. W. N. M.; Reek, J. N. H. Dalton Trans. 2007, 2311–
2320. (i) Sandee, A. J.; van der Burg, A. M.; Reek, J. N. H. Chem. Commun.
2007, 864–866. (j) Goudriaan, P. E.; van Leeuwen, P. W. N. M.; Birkholz,
M. N.; Reek, J. N. H. Eur. J. Inorg. Chem. 2008, 2939–2958. (k) Laungani,
A. C.; Slattery, J. M.; Krossing, I.; Breit, B. Chem. Eur. J. 2008, 14, 4488–
4502. (l) Moteki, S. A.; Takacs, J. M. Angew. Chem., Int. Ed. 2008, 47,
894–897. (m) Patureau, F. W.; Kuil, M.; Sandee, A. J.; Reek, J. N. H.
Angew. Chem., Int. Ed. 2008, 47, 3180–3183.
‡ Ecole Polytechnique.
§ Current address: Corning SAS, Corning European Technology Center,
77210 Avon, France.
| Utrecht University.
(1) (a) Amoroso, D.; Graham, T. W.; Guo, R. W.; Tsang, C. W.; Abdur-
Rashid, K. Aldrichim. Acta 2008, 41, 15–26. (b) Boeda, F.; Beneyton, T.;
Cre´visy, C. Mini-ReV. Org. Chem. 2008, 5, 96–127.
(2) (a) Claver, C.; Fernandez, E.; Gillon, A.; Heslop, K.; Hyett, D. J.;
Martorell, A.; Orpen, A. G.; Pringle, P. G. Chem. Commun. 2000, 961–
962. (b) Reetz, M. T.; Mehler, G. Angew. Chem., Int. Ed. 2000, 39, 3889.
(c) van den Berg, M.; Minnaard, A. J.; Schudde, E. P.; van Esch, J.; de
Vries, A. H. M.; de Vries, J. G.; Feringa, B. L. J. Am. Chem. Soc. 2000,
122, 11539–11540. (d) Minnaard, A. J.; Feringa, B. L.; Lefort, L.; De Vries,
J. G. Acc. Chem. Res. 2007, 40, 1267–1277. (e) Norman, D. W.; Carraz,
C. A.; Hyett, D. J.; Pringle, P. G.; Sweeney, J. B.; Orpen, A. G.; Phetmung,
H.; Wingad, R. L. J. Am. Chem. Soc. 2008, 130, 6840–6847. (f) Reetz,
M. T. Angew. Chem., Int. Ed. 2008, 47, 2556–2588. (g) Erre, G.; Enthaler,
S.; Junge, K.; Gladiali, S.; Beller, M. Coord. Chem. ReV. 2008, 252, 471–
491.
(4) (a) Francio, G.; Faraone, F.; Leitner, W. Angew. Chem., Int. Ed.
2000, 39, 1428. (b) Burk, S.; Francio, G.; Leitner, W. Chem. Commun.
2005, 3460–3462. (c) Diez-Holz, C. J.; Boing, C.; Francio, G.; Holscher,
M.; Leitner, W. Eur. J. Org. Chem. 2007, 2995–3002.
10.1021/om801204a CCC: $40.75
2009 American Chemical Society
Publication on Web 04/15/2009

INDOLPhosphole and INDOLPhos Pd-Allyl Complexes
Chart 1. Structure of INDOLPhos Ligands 1a-f
Organometallics, Vol. 28, No. 9, 2009 2725
Scheme 1. Synthesis of Indolylphospholes 2a,b
Scheme 2. Synthesis of INDOLPhospholes 3a,b
reported, such as ferrocene-based derivatives,5 PEAPhos,6
NOBIN-based derivatives,7 Me-AnilaPhos,8 ꢀ-amino alcohol
based derivatives,9 THNA-Phos,10 and HY-Phos.11 The ligands
have been employed in a range of asymmetric transformations,
including Rh- and Ru-catalyzed hydrogenation, hydroformyla-
tion, and Cu-catalyzed conjugate addition to enones. Our group
contributed to this field with the development of INDOLPhos
(1), which is based on a rigid 3-methylindole backbone, resulting
in a very small bite angle (Chart 1).12 Good to excellent
enantioselectivities were obtained using this ligand in Rh-
catalyzed hydrogenation and hydroformylation. It was observed
that the steric and electronic properties of the phosphine part
played a crucial role in obtaining high selectivities in these
transformations. Changing a diphenylphosphine for a diisopro-
pylphosphine results in some cases in an increase of enantio-
selectivity up to 90% ee. Encouraged by these findings, we
aimed to introduce more variation on this position. Phospholes,
unsaturated phosphorus-containing five-membered heterocycles,
exhibit steric and electronic properties different from those of
phosphines, making them suitable candidates to introduce more
variety on the INDOLPhos platform.13
used up to now in this reaction, despite their potential for direct
nucleophilic attack specifically at one position of the coordinated
allyl.15,16 However, excellent results in asymmetric allylic
alkylation have been obtained with diphosphites and
phosphite-phosphoramidites.17 Here, we introduce INDOL-
Phospholes as a new class of hybrid phosphole-phosphor-
amidite ligands and describe their synthesis, coordination
properties, and reactivity in Pd-catalyzed asymmetric allylic
alkylation. Furthermore, INDOLPhos palladium complexes are
described along with their catalytic performance in the asym-
metric allylic alkylation.
Results and Discussion
Ligand Synthesis. INDOLPhosphole ligands 3 were prepared
in a two-step procedure analogous to the synthesis of INDOL-
Phos ligands 1.12 Instead of reacting 3-methylindole with a
chlorophosphine, P-cyano 2,5-diphenyl (DPP) and 3,4-dimethyl
(DMP) phospholes were used as electrophiles. The cyanophos-
pholes were selected instead of their chloro and bromo deriva-
tives, which are very reactive and difficult to handle.18 In the
first step, the 3-methylindole NH is in situ protected with carbon
dioxide, which also acts as a directing group for the selective
deprotonation at the 2-position of the indole (Scheme 1).
Addition of the corresponding cyanophosphole gives indolylphos-
pholes 2a,b as yellow and white solids, respectively, in moderate
to good yields (71-84%), requiring no chromatographic
workup. Deprotonation of the NH of the indolylphospholes 2
at low temperature followed by condensation with (S)-bisnaph-
thol phosphorochloridite results in the formation of INDOL-
Phosphole ligands 3a,b (Scheme 2). They are obtained in
moderate yield (48-63%) after chromatographic purification
as yellow and white solids, respectively.
Phosphole derivatives were found to show excellent activity
in Pd-catalyzed allylic substitution, prompting us to investigate
the reactivity of the phosphole-containing INDOLPhos deriva-
tives in this transformation.14 To the best of our knowledge,
hybrid phosphine-phosphoramidite ligands have not been
(5) (a) Hu, X. P.; Zheng, Z. Org. Lett. 2004, 6, 3585–3588. (b) Jia, M.;
Li, X. S.; Lam, W. S.; Kok, S. H. L.; Xu, L. J.; Lu, G.; Yeung, C. H.;
Chan, A. S. C. Tetrahedron: Asymmetry 2004, 15, 2273–2278. (c) Hu, X. P.;
Zhuo, Z. Org. Lett. 2005, 7, 419–422. (d) Zeng, Q. H.; Hu, X. P.; Duan,
Z. C.; Liang, X. M.; Zheng, Z. Tetrahedron: Asymmetry 2005, 16, 1233–
1238.
(6) Huang, J. D.; Hu, X. P.; Duan, Z. C.; Zeng, Q. H.; Yu, S. B.; Deng,
J.; Wang, D. Y.; Zheng, Z. Org. Lett. 2006, 8, 4367–4370.
(7) Yan, Y. J.; Zhang, X. M. J. Am. Chem. Soc. 2006, 128, 7198–7202.
(8) Vallianatou, K. A.; Kostas, I. D.; Holz, J.; Borner, A. Tetrahedron
Lett. 2006, 47, 7947–7950.
(9) Boeda, F.; Rix, D.; Clavier, H.; Cre´visy, C.; Mauduit, M. Tetrahe-
dron: Asymmetry 2006, 17, 2726–2729.
(10) (a) Wang, D. Y.; Hu, X. P.; Huang, J. D.; Deng, J.; Yu, S. B.;
Duan, Z. C.; Xu, X. F.; Zheng, Z. Angew. Chem., Int. Ed. 2007, 46, 7810–
7813. (b) Qiu, M.; Hu, X. P.; Wang, D. Y.; Deng, J.; Huang, J. D.; Yu,
S. B.; Duan, Z. C.; Zheng, Z. AdV. Synth. Catal. 2008, 350, 1413–1418.
(11) Yu, S.-B.; Huang, J.-D.; Wang, D.-Y.; Hu, X.-P.; Deng, J.; Duan,
Z.-C.; Zheng, Z. Tetrahedron: Asymmetry 2008, 19, 1862.
(12) (a) Wassenaar, J.; Reek, J. N. H. Dalton Trans. 2007, 3750–3753.
(b) Wassenaar, J.; Kuil, M.; Reek, J. N. H. AdV. Synth. Catal. 2008, 350,
1610–1614.
(13) (a) Mathey, F. In Phosphorus-Carbon Heterocyclic Chemistry: The
Rise of a New Domain; Mathey, F., Ed.; Pergamon: Amsterdam, 2001; p
753. (b) Quin, L. D. In Phosphorus-Carbon Heterocyclic Chemistry: The
Rise of a New Domain; Mathey, F., Ed.; Pergamon: Amsterdam, 2001; p
219.
(15) For reviews on Pd-catalyzed allylic alkylation, see: (a) Trost, B. M.;
Van Vranken, D. L. Chem. ReV. 1996, 96, 395–422. (b) Trost, B. M.;
Crawley, M. L. Chem. ReV. 2003, 103, 2921–2943.
(16) Evans, L. A.; Fey, N.; Harvey, J. N.; Hose, D.; Lloyd-Jones, G. C.;
Murray, P.; Orpen, A. G.; Osborne, R.; Owen-Smith, G. J. J.; Purdie, M.
J. Am. Chem. Soc. 2008, 130, 14471–14473.
(17) (a) Die´guez, M.; Pa`mies, O.; Claver, C. J. Org. Chem. 2005, 70,
3363–3368. (b) Mata, Y.; Claver, C.; Die´guez, M.; Pa`mies, O. Tetrahedron:
Asymmetry 2006, 17, 3282–3287. (c) Pa`mies, O.; Die´guez, M.; Claver, C.
AdV. Synth. Catal. 2007, 349, 836–840. (d) den Heeten, R.; Swennenhuis,
B. H. G.; van Leeuwen, P. W. N. M.; de Vries, J. G.; Kamer, P. C. Angew.
Chem., Int. Ed. 2008, 47, 6602–6605.
(14) (a) Thoumazet, C.; Grutzmacher, H.; Deschamps, B.; Ricard, L.;
Le Floch, P. Eur. J. Inorg. Chem. 2006, 3911–3922. (b) Mora, G.;
Deschamps, B.; van Zutphen, S.; Le Goff, X. F.; Ricard, L.; Le Floch, P.
Organometallics 2007, 26, 1846–1855.
(18) Charrier, C.; Bonnard, H.; Mathey, F.; Neibecker, D. J. Organomet.
Chem. 1982, 231, 361–367.

2726 Organometallics, Vol. 28, No. 9, 2009
Wassenaar et al.
Figure 3. 1H VT NMR spectra (CD2Cl2, 500 MHz) of complex 5.
Figure 1. Section of the phase-sensitive 1H 2D NOESY spectrum
(CD2Cl2, 500 MHz, 298 K) for complex 4a. The blue off-diagonal
peaks arise from exchange, whereas the red peaks arise from NOE.
Figure 2. Exchange pathways interconverting isomers I and II of
complex 4a.
Scheme 3. Synthesis of Palladium-Allyl Complexes 4 and 5
Figure 4. Section of the phase-sensitive 1H 2D NOESY spectrum
(CD2Cl2, 500 MHz, 263 K) for complex 5. The blue off-diagonal
peaks arise from exchange, whereas the red peaks arise from NOE.
Synthesis of Palladium-Allyl Complexes. The coordination
properties of ligands 1a and 3b were investigated in their
cationic palladium-allyl complexes. Reaction of the ligand with
0.5 equiv of [Pd2(η3-C3H5)2Cl2] in dichloromethane followed
by abstraction of the chloride with AgPF6 afforded 4a and 5 as
pale yellow solids in good to excellent yield (79-99%, Scheme
3). Similarly, the bright yellow Pd-diphenylallyl complex 4b
was obtained in 60% yield using [Pd2(η3-1,3-diphenylallyl)2Cl2]
and 1a. The allyl complexes have been fully characterized by
NMR techniques (1H, 31P, 13C), mass spectrometry, and X-ray
crystallography. Phosphole 3a was also reacted with the
Pd-allyl chloride dimer, resulting in the formation of the desired
coordination compound in a complex product matrix from which
isolation proved impossible.
We reported previously that the 31P NMR signals of INDOL-
Phos ligands 1 exhibit large coupling constants in the range of
200 Hz.12a Their phosphole derivatives 3, on the other hand,
do not exhibit such large couplings, but the 31P NMR spectrum
of 3a exhibits two singlets. Two doublets are obtained for 3b
with a coupling constant of 43.1 Hz. The large difference in
these parameters can be attributed to the difference in electronic
properties of phospholes compared to phosphines.
NMR Study of Palladium-Allyl Complexes. Complexes
4a,b and 5 were studied by one- and two-dimensional NMR in
order to determine their structure in solution. Complex 4a
displays duplicated signals for all allyl protons and for some of
the protons on the INDOLPhos ligand. This effect can be
attributed to isomerism of the allyl fragment, which can adopt
two orientations (Figure 2). The isomers are able to interconvert

INDOLPhosphole and INDOLPhos Pd-Allyl Complexes
Organometallics, Vol. 28, No. 9, 2009 2727
Scheme 4. Mechanism of η3-η1-η3 Isomerization in
Complex 4a
Table 1. Thermodynamic Parameters for the η3-η1-η3
Isomerization in Complex 5
param
value
21.0
16.3
Eaa (kcal mol-1
)
a
∆Gq (kcal mol-1
)
∆Hq (kcal mol-1
∆Sq(kcal mol-1 K-1
kb (s-1
)
20.4
)
1.4 × 10-2
3.6
)
a At 298 K. b Rate of exchange at 293 K.
via a formal π-rotation involving a η3-η1-η3 isomerization. It
was found previously in JOSIPHOS19 and other bidentate
ligands containing different phosphorus donor atoms20 that this
isomerization is selective, involving opening of only one Pd-C
bond of the allyl fragment. In order to establish if such a
1
selectivity is also present in complex 4a, a phase-sensitive H
2D NOESY experiment was carried out (Figure 1). The
spectrum shows exchange peaks (blue) for the central proton
H2 of both isomers and their selective NOE contacts (red) with
the syn protons within each isomer. There is no exchange of
syn and anti protons at C3: i.e., H3s of isomer I becomes H3s of
isomer II and likewise for H3a. At C1, on the other hand,
syn-anti exchange does occur, interconverting H1s of isomer I
into H1a of isomer II and vice versa. The exchange pathways
are summarized in Figure 2.
The selective syn-anti exchange at C1, cis to the phosphora-
midite moiety, indicates that the η3-η1-η3 isomerization
follows a mechanism in which the Pd-C3 bond opens, forming
a η1 transition state wherein the C1-C2 bond rotates 180°,
completed by re-formation of the η3-allyl (Scheme 4). Impor-
tantly, the selective opening of the η3-allyl occurs cis to the
phosphine and can be rationalized by the greater steric bulk of
the diphenylphosphine, as was observed earlier in related
systems.19b The increased Pd-C3 bond length in the crystal
structure of 4a supports this observation (vide infra).
Figure 5. (top) Section of the phase-sensitive 1H 2D NOESY
spectrum (CDCl3, 500 MHz, 298 K) for complex 5. The blue off-
diagonal peaks arise from exchange, whereas the red peaks arise
from NOE. (bottom) Calculated lowest energy structure of 4b (DFT,
BP86, SV(P)): green for C, blue for N, red for O, orange for P,
aquamarine for Pd.
isomerization. At 20 °C, the rate of exchange is 3.6 s-1
.
However, this rate cannot be related to the catalytic experiments,
as substituted allyl ligands are known to isomerize much more
slowly, if at all.15a
The room-temperature 1H NMR spectrum of complex 5
exhibits broad signals for all protons except for the indole
backbone protons. A variable-temperature NMR study was
performed to analyze the dynamic process (Figure 3). The
broadening can be attributed to a faster η3-η1-η3 isomerization
compared to that for complex 4a, as individual signals are
obtained for the allyl protons of both isomeric complexes III
and IV. The coalescence temperature could unfortunately not
be established in CD2Cl2, the only suitable solvent with regard
to stability and solubility of the complex, due to its low boiling
point. Nevertheless, using line shape analysis at various tem-
peratures, the thermodynamic parameters for the isomerization
could be determined (Table 1). The free energy of activation is
found to be 16.3 kcal mol-1, which is in good agreement with
previous measurements of dynamic palladium-allyl com-
plexes.21 The positive entropy contribution results from the
additional degree of freedom gained from the intramolecular
The 1H 2D NOESY spectrum of complex 5 was recorded at
-10 °C (Figure 4). As for complex 4a, the central allyl protons
are exchanged in the η3-η1-η3 isomerization. All syn and anti
allyl protons of one isomer exhibit exchange peaks with the
signals for the other rotational isomer, although with low
intensity. This implies that the isomerization is unselective, and
Pd-C bond opening occurs at both termini of the allyl ligand.
The decreased steric demand of the 3,5-dimethylphosphole in
5 compared to the diphenylphosphine in 4a leads both donor
atoms (phosphoramidite and phosphole) to be similar in size
and, thus, no selective bond opening occurs.
The phenyl allyl complex 4b does not exhibit rotational
isomerism in solution or syn-anti interconversion. The 1H 2D
NOESY spectrum shows no off-diagonal exchange signals but
only signals arising from NOE (Figure 5). In spite of the severe
overlap of signals, the signals stemming from the phenylallyl
fragment could be assigned unambiguously. NOE contacts
(19) (a) Breutel, C.; Pregosin, P. S.; Salzmann, R.; Togni, A. J. Am.
Chem. Soc. 1994, 116, 4067–4068. (b) Pregosin, P. S.; Salzmann, R.; Togni,
A. Organometallics 1995, 14, 842–847.
(20) Camus, J. M.; Andrieu, J.; Richard, P.; Poli, R. Eur. J. Inorg. Chem.
2004, 1081–1091.
(21) Ferna´ndez-Gala´n, R.; Jalo´n, F. A.; Manzano, B. R.; Rodr´ıguez de
la Fuente, J.; Vrahami, M.; Jedlicka, B.; Weissensteiner, W.; Jogl, G.
Organometallics 1997, 16, 3758–3768.

2728 Organometallics, Vol. 28, No. 9, 2009
Wassenaar et al.
Figure 7. Displacement ellipsoid plot (50% probability level) of
one Pd complex of 5. Hydrogen atoms are omitted for clarity.
Selected bond distances (Å) and angles (deg): C(1)-C(2), 1.382(6);
C(2)-C(3), 1.357(6); Pd(1)-C(1), 2.170(3); Pd(1)-C(2), 2.157(4);
Pd(1)-C(3), 2.181 (4); Pd(1)-P(1), 2.2243(8); Pd(1)-P(2),
2.2870(9); P(1)-N(1), 1.680(3); P(2)-C(4), 1.794(3); C(2)-Pd(1)-
P(1), 138.34(13); C(2)-Pd(1)-P(2), 134.20(13); P(1)-Pd(1)-P(2),
85.80(3).
Figure 6. Displacement ellipsoid plot (50% probability level) of
one Pd complex of 4a. Hydrogen atoms are omitted for clarity.
Selected bond distances (Å) and angles (deg): C(1)-C(2), 1.393(9);
C(2)-C(3), 1.373(11); Pd(1)-C(1), 2.167(12); Pd(1)-C(2), 2.183(4);
Pd(1)-C(3), 2.218(15); Pd(1)-P(1), 2.2255(7); Pd(1)-P(2),
2.2844(7); P(1)-N(1), 1.688(2); P(2)-C(4), 1.812(3); C(2)-Pd(1)-
P(1), 134.15(13); C(2)-Pd(1)-P(2), 135.80(13); P(1)-Pd(1)-P(2),
87.93(3).
of the allyl ligand of one complex and the π-system of the indole
moiety of the adjacent complex. There is no evidence that
the tetrameric boxes are stable in solution. The presence of the
phosphole ligand might be important for the formation of the
box structure, which is not found in the crystal structure of 4a.
between one of the anti allyl protons (H1a) and the adjacent
phenyl ring with the downfield bisnaphthol protons (top left of
the NOESY spectrum) indicate that the phenyl group of the
allyl fragment points away from the bulk imposed by the chiral
bisnaphthol moiety. The contacts are confirmed by the DFT
calculated structure (BP86, SV(P)) shown in Figure 5, which
lies 0.5 kcal mol-1 lower in energy than the other possible
rotational isomer. According to the Boltzmann distribution, this
other isomer is accessible and, indeed, the 31P NMR spectrum
shows the presence of a second species in trace amounts (<2%),
which may be assigned to the second rotational isomer. As 4b
is the key catalytic intermediate in the allylic alkylation of rac-
1,3-diphenylprop-2-enyl acetate, nucleophilic attack at this
species leads to the product and determines the enantioselectivity
(vide infra).
X-ray Crystallography. Crystals of complexes 4a and 5
suitable for single-crystal X-ray diffraction were obtained by
slow diffusion of hexanes into a saturated dichloromethane
solution. Displacement ellipsoid plots for compounds 4a and 5
are shown in Figures 6 and 7, respectively. The relevant bond
distances and angles are listed in the corresponding figure
captions.
-
The remaining independent PF6 counteranions and lattice
solvent molecules (i.e., dichloromethane) are found to be
intercalated between the 2-D planes including the tetrameric
boxes. These counteranions are in short contact with the Pd
complexes via C-H · · · F interactions, which are comparable
with those found for other encapsulated anions.22
The structures of 4a and 5 both display a square-planar
geometry around the palladium atom. Differences in the
structures mainly arise from the increased bulkiness of the
diphenylphosphine compared to the phosphole. This is reflected
in the larger bite angle and Pd(1)-C(3) distance for 4a. In
addition, the phosphoramidite group in 5 is tilted out of the
coordination plane, which is probably the result of packing
effects which allow for the formation of the tetrameric box.
Palladium-Catalyzed Asymmetric Allylic Alkylation. The
catalytic activity of the Pd complexes of ligands 1a-f and 3a,b
was evaluated in the palladium-catalyzed asymmetric allylic
substitution. Preliminary experiments using nitrogen nucleo-
philes in this reaction such as aniline and benzylamine did not
yield the desired products. Therefore, dimethyl malonate was
chosen as the nucleophile in the alkylation of racemic allylic
acetates. Catalysts were generated in situ from [Pd2(η3-
C3H5)2Cl2] and the corresponding ligand.
In the crystal structure of 5, the four crystallographically
independent Pd complexes and two of the four independent
-
PF6 counteranions of the asymmetric unit form two-dimen-
sional (hereafter, 2-D) planes parallel to (001). Along these
-
planes, each PF6 counterion is encapsulated into a tetrameric
All ligands provided active catalysts for the allylic alkylation
of rac-1,3-diphenylprop-2-enyl acetate 6, a benchmark substrate
for new ligands in the asymmetric allylic alkylation (Table 2).
The reactivity and selectivity are highly affected by the ligand
substituents and nature of the phosphine donor group. For
INDOLPhos ligands 1a-d, which vary only in the type of
phosphine, similar reactivities are observed (entries 1-4).
Sterically more demanding phosphines give rise to higher ee’s
compared to diphenylphosphine, whereas the electronic proper-
ties seem to be less important. When substituents are introduced
box built of the four independent cations (Figure 8). The
formation of these tetrameric boxes can be attributed to weak
C-H · · · F intermolecular interactions (C · · · F distances (C )
carbon atoms of the allyl groups/phosphole rings/bisnaphthol
moieties) vary in the range 3.23-3.54 Å; all standard uncertain-
ties are lower than 0.01 Å) and the templating effect of the two
-
spherical PF6 counteranions. Within each tetrameric box, the
four independent Pd complexes are always found in close
contacts with each other. These contacts are found between (i)
one proton of the bisnaphthol moiety of one complex and the
π-system of the bisnaphthol moiety of the adjacent complex,
(ii) one indole proton of one complex and the π-system of the
bisnaphthol moiety of the adjacent complex, and (iii) one proton
(22) Li, C.; Pattacini, R.; Graff, R.; Braunstein, P. Angew. Chem., Int.
Ed. 2008, 47, 6856–6859.

INDOLPhosphole and INDOLPhos Pd-Allyl Complexes
Organometallics, Vol. 28, No. 9, 2009 2729
-
Figure 8. (a) Packing of one 2-D plane built of the four independent Pd complexes and two of the four independent PF6 counteranions,
the view being down the normal to (001) in the crystal structure of 5. The symmetry-independent residues are rendered in different colors.
-
The black outline corresponds to one tetrameric box. The disorder of one allyl ligand and of one PF6 counteranion and the H atoms are
omitted for the sake of clarity. (b) One tetrameric box in space-filling style (gray for C, blue for N, red for O, orange for P, yellow for F,
green for Pd) projected down the c* direction. The disorder of one allyl ligand is omitted for clarity.
Table 2. Pd-Catalyzed Allylic Alkylation of 6 with Ligands 1 and 3a
Table 3. Pd-Catalyzed Allylic Alkylation of 6 with Ligand 1ea
entry
solvent
conv. (%) (time (h))b
ee (%)c
1
2
3
4
5
6
CH2Cl2
THF
MeCN
EtOAc
toluene
i-PrOH
100 (8)
84 (4)
100 (1)
65 (4)
74 (4)
0 (22)
90
70
76
68
85
entry
ligand
conv. (%)b
ee (%)c
1
2
3
4
5
6
7
8
1a (R ) Ph, R′ ) H)
1b (R ) i-Pr, R′ ) H)
1c (R ) Cy, R′ ) H)
1d (R ) o-Tol, R′ ) H)
1e (R ) Ph, R′ ) SiMe3)
1f (R ) i-Pr, R′ ) Me)
3a (R1 ) Ph, R2 ) H)
3b (R1 ) H, R2 ) Me)
100
100
90
100
15
18
99
100
43
70
64
66
90
74
32
56
a Conditions: 0.5 mol % of [Pd2(η3-C3H5)2Cl2], 1.1 mol % of 1e,
room temperature, 3 equiv of dimethyl malonate, 3 equiv of BSA, pinch
of KOAc. b Conversion percentage of acetate, determined by GC. The
reaction time in hours is shown in parentheses. c Enantiomeric excess,
determined by chiral HPLC (Chiralcel-ODH).
Table 4. Pd-Catalyzed Allylic Alkylation of 8 with Ligands 1 and 3a
a Conditions: 0.5 mol % of [Pd2(η3-C3H5)2Cl2], 1.1 mol % of ligand,
CH2Cl2, room temperature, 3 equiv of dimethyl malonate, 3 equiv of
BSA, pinch of KOAc. b Conversion percentage of acetate after 1 h,
determined by GC. c Enantiomeric excess, determined by chiral HPLC
(Chiralcel-ODH). The S enantiomer was obtained in all cases.
entry
ligand
conv. (%)b
ee (%)c
at the 3- and 3′-positions on the bisnaphthol moiety, the
reactivity decreases, whereas the ee increases up to 90% (entries
5 and 6).
INDOLPhospholes 3a,b both give full conversion and enan-
tioselectivities of 32% and 56%, respectively (entries 7 and 8).
Surprisingly, the sterically less congested phosphole now gives
higher selectivity, which is in contrast with the trend observed
for INDOLPhos ligands 1a-d as discussed above.
From the screening experiments outlined above, it was
observed that ligand 1e gave rise to the highest enantioselectivity
but showed only 15% conversion after 1 h of reaction. However,
longer reaction times allow for quantitative formation of the
product. A solvent study using 1e as ligand was carried out,
with the aim of increasing activity while maintaining the high
selectivity (Table 3). Acetonitrile proves to be the only solvent,
giving a significantly higher rate compared to dichloromethane
(entry 3). However, the enantioselectivity drops to 76% ee. The
tradeoff in selectivity is not compensated by the gain in activity,
and we thus carried out all further experiments using dichlo-
romethane as solvent.
1
2
3
4
5
6
7
8
1a (R ) Ph, R′ ) H)
1b (R ) i-Pr, R′ ) H)
1c (R ) Cy, R′ ) H)
1d (R ) o-Tol, R′ ) H)
1e (R ) Ph, R′ ) SiMe3)
1f (R ) i-Pr, R′ ) Me)
3a (R1 ) Ph, R2 ) H)
3b (R1 ) H, R2 ) Me)
100
100
100
100
100
100
57
31
21
20
51
39
15
35
26
100
a Conditions: 0.5 mol % of [Pd2(η3-C3H5)2Cl2], 1.1 mol % of ligand,
CH2Cl2, room temperature, 3 equiv of dimethyl malonate, 3 equiv of
BSA, pinch of KOAc. b Conversion percentage of acetate after 1 h,
determined by GC. c Enantiomeric excess, determined by chiral GC
(Chiralsil DEX CB).
most cases in lower enantioselectivity and rate enhancement.15a
This is also observed for the catalysts generated from ligands 1
and 3. Remarkably, the enantioselectivities obtained with
arylphosphine-substituted ligands are lowered to a lesser extent
than with alkylphosphines (entries 1-6). In addition, substituents
on the bisnaphthol moiety are not beneficial for this substrate
(entries 5 and 6). The highest selectivity of 51% ee is reached
with the o-tolyl-substituted ligand 1d. When the performances
of phospholes 3a,b are compared, the more bulky 3a gives
higher selectivity, which is in contrast with the ligand effects
observed in the alkylation of 6. We speculate that the smaller
To investigate the effect of the structure of the substrate on
the catalytic performance, rac-1,3-dimethylprop-2-enyl acetate
(8) was subjected to the alkylation conditions (Table 4). It is
known that exchanging the Ph group for a Me group results in

2730 Organometallics, Vol. 28, No. 9, 2009
Wassenaar et al.
Table 5. Pd-Catalyzed Allylic Alkylation of 10 with Ligands 1 and
3a
highest reported to date and represents a lead for further
optimization.25
When the efficiency of INDOLPhos(phole) ligands in the
asymmetric allylic alkylation is compared to that of other hybrid
ligand systems such as phosphite-phosphoramidites, it can be
noted that our system is less active.17b,c The lower reactivity
can be explained in terms of electronic effects. Phosphines are
less π-acidic compared to phosphites, which leads to lower
reaction rates, as the rate-limiting step is reductive nucleophilic
attack.16 With respect to the enantioselectivity, INDOLPhos-
(phole)systemsgiveee’ssimilartothoseforphosphite-phosphor-
amidite ligands containing a rigid pyranoside sugar backbone.17b
Phosphite-phosphoramidite ligands containing a more simple
amino alcohol backbone, on the other hand, are more selective
than our system.17c These results indicate that a more flexible
backbone is beneficial for the enantioselectivity.
entry
ligand
conv. (%)b
ee (%)c
1
2
3
4
5
6
7
8
1a (R ) Ph, R′ ) H)
1b (R ) i-Pr, R′ ) H)
1c (R ) Cy, R′ ) H)
1d (R ) o-Tol, R′ ) H)
1e (R ) Ph, R′ ) SiMe3)
1f (R ) i-Pr, R′ ) Me)
3a (R1 ) Ph, R2 ) H)
3b (R1 ) H, R2 ) Me)
73
94
82
100
15
12
6
<1
19
26
44
50
38
<1
7
34
a Conditions: 0.5 mol % of [Pd2(η3-C3H5)2Cl2], 1.1 mol % of ligand,
CH2Cl2, room temperature, 3 equiv of dimethyl malonate, 3 equiv of
BSA, pinch of KOAc. b Conversion percentage of acetate after 1 h,
determined by GC. c Enantiomeric excess, determined by chiral GC
(Supelco ꢀ-DEX 225).
Mechanism of Enantiodiscrimination. It is known that, in
the case of 1,3-disubstituted substrates, enantiodiscrimination
results from preferential attack on one of the enantiotopic termini
of the allylpalladium complex.15b In the case of ligand 1a,
Pd-allyl complex 4b is the actual intermediate in the catalytic
cycle. As the structure in solution was assigned with NOESY
and DFT calculations (Figure 5), and no syn-anti interconver-
sion was observed, attack on this complex determines which
enantiomer is obtained. The other rotational isomer is observed
in trace amounts by NMR, and DFT calculations in the gas phase
indicate that it would be 0.5 kcal mol-1 higher in energy. Even
though it is present in trace amount, it cannot be excluded that
this second rotational isomer plays a role in the reaction, as it
is known that species which are present in only very low amount
can carry out most of the reaction flux.
Table 6. Pd-Catalyzed Allylic Alkylation of 12 with Ligands 1 and
3a
entry
ligand
conv. (%)b
13/14c
ee (%)d
1
2
3
4
5
6
7
8
1a (R ) Ph, R′ ) H)
1b (R ) i-Pr, R′ ) H)
1c (R ) Cy, R′ ) H)
1d (R ) o-Tol, R′ ) H)
1e (R ) Ph, R′ ) SiMe3)
1f (R ) i-Pr, R′ ) Me)
3a (R1 ) Ph, R2 ) H)
3b (R1 ) H, R2 ) Me)
100
100
100
100
100
100
80
9/91
5/95
5/95
14/86
11/89
5/95
10/90
7/93
12
<5
<5
81
<5
10
<5
<5
The stereochemical pathway of the reaction can be described
in terms of the diagram depicted in Scheme 5.26 Nucleophilic
attack can take place on either the major or minor Pd-allyl
complex. For the major isomer, rotation accompanied by
formation of the η2-alkene species favors pathway b toward the
S enantiomer. The steric bulk of the bisnaphthol hinders the
substrate rotation by having unfavorable steric interactions with
the newly formed tertiary substituent in the case of path a. If,
on the other hand, nucleophilic attack occurs on the minor
isomer, no preferred sense of rotation would be expected on
steric grounds.
100
a Conditions: 0.5 mol % of [Pd2(η3-C3H5)2Cl2], 1.1 mol % of ligand,
CH2Cl2, room temperature, 3 equiv of dimethyl malonate, 3 equiv of
BSA, pinch of KOAc. b Conversion percentage of acetate after 1 h,
determined by GC. c Branched-to-linear ratio, determined by GC.
d Enantiomeric excess, determined by chiral HPLC (Chiralcel-OJH).
Me substituents of 8 require a catalyst containing more steric
bulk compared to 6 to achieve efficient enantioselection.
Cyclic substrates are usually more difficult to alkylate with
high enantioselectivity. The small syn substituents, a proton in
most cases, poorly interact with the chiral steric environment
imposed by the ligand. Indeed, very low enantioselectivities are
obtained for most ligands in the allylic alkylation of 3-acetoxy-
cyclohexene (10) (Table 5). Only bulky ligands 1d-f are able
to induce significant enantioselection up to 50% ee (entries
4-6).
Monosubstituted linear substrates represent a challenge in
allylic alkylations, as both the regio- and enantioselectivity have
to be controlled. In contrast to Ir-catalyzed allylic alkylations,23
Pd-based catalysts give generally low branched to linear ratios
(b/l).24 Ligands 1 and 3 provide active catalysts for the allylic
alkylation of cinnamyl acetate 12 (Table 6). As expected for
Pd-based systems, the branched product 13 is formed in only
5-14% yield and low ee, except for ligand 1d. A good
enantioselectivity of 81% ee at a b/l of 14/86 is obtained by
using the o-tolyl-substituted INDOLPhos ligand 1d (entry 4).
Although the b/l is low, the enantioselectivity is among the
Experimentally, we found that the S enantiomer of the
alkylation product was formed in excess with all ligands. The
selective isomerization and crystal structure of 4a indicate a
labilization of the Pd-C3 bond (vide supra). These observations
support a mechanism following path b: i.e., attack on the C3
allyl terminus of the major allyl isomer. This mechanism is in
agreement with an early as well as a late transition state model.
The former is supported by the labilization of the Pd-C3 bond
and the latter by repulsive steric interactions during rotation of
the substrate upon nucleophilic attack.27 If the main reaction
flux is carried out by the minor allyl isomer, a much lower
enantiomeric excess would be expected, as rotation of the
substrate in both cases (paths c and d) is not predominantly
hindered by repulsive steric interactions. Therefore, we believe
that formation of the alkylation product proceeds by path b.
(25) Pretot, R.; Pfaltz, A. Angew. Chem., Int. Ed. 1998, 37, 323–325.
(26) von Matt, P.; Lloyd-Jones, G. C.; Minidis, A. B. E.; Pfaltz, A.;
Macko, L.; Neuburger, M.; Zehnder, M.; Ru¨egger, H.; Pregosin, P. S. HelV.
Chim. Acta 1995, 78, 265–284.
(23) Helmchen, G.; Dahnz, A.; Dubon, P.; Schelwies, M.; Weihofen,
R. Chem. Commun. 2007, 675–691.
(24) For a review on Pd-catalyzed asymmetric allylic alkylation of mono-
substituted substrates, see: Lu, Z.; Ma, S. M. Angew. Chem., Int. Ed. 2008,
47, 258–297.
(27) van Leeuwen, P. W. N. M. In Homogeneous Catalysis, Under-
standing the Art; Kluwer: Dordrecht, The Netherlands, 2004; pp 273-
281.

INDOLPhosphole and INDOLPhos Pd-Allyl Complexes
Organometallics, Vol. 28, No. 9, 2009 2731
Scheme 5. Enantiocontrol Provided by INDOLPhos(phole) Pd Catalysts
selectivity, up to 81% ee, but in a low b/l of 14/86. The results
show that hybrid ligands are able to induce moderate to good
enantioselectivities for a range of substrates in the asymmetric
allylic alkylation. The introduction of phosphole-containing
ligands did not lead to an increase in selectivity, which was
anticipated on the basis of the earlier successful application of
phospholes in the allylic substitution.
Conclusions
Phosphole-substituted INDOLPhos derivatives 3a,b have been
successfully synthesized and characterized. For 3b, the coor-
dination to palladium(II) was investigated in the palladium-
allyl complex 5 and compared to the corresponding INDOLPhos
palladium species 4a. In solution these complexes each exist
as two isomers in a 1:1 ratio, which interconvert through a
η3-η1-η3 isomerization. A selective isomerization was found
for 4a, where Pd-C bond opening only occurs trans with regard
to the diphenylphosphine donor group, due to steric effects. For
complex 5, no such selectivity has been found, which is
explained by the smaller phosphole substituent. As a result, the
steric demands of phosphole and phosphoramidite are similar,
and Pd-C bond opening occurs at both allyl termini. The rate
constant of the isomerization process for 5 is k ) 3.6 s-1. 4a
does not display dynamic behavior at room temperature, and
consequently its rate constant could not be determined.
In the solid state, complexes 4a and 5 display disorder in the
coordinated allyl fragments, confirming the rotational isomerism
observed in solution. Interestingly, the phosphole-containing
complex 5 forms a tetrameric box structure in the solid state,
which is templated by encapsulation of one PF6 counteranion.
The encapsulation is driven by eight C-H · · · F interactions
between hydrogen atoms located on the phosphole ligand and
the PF6 anion.
On the basis of the structural data for complexes 4a,b, the
formation of the S enantiomer in the case of 1,3-diphenylprop-
2-enyl acetate can be rationalized by a selective nucleophilic
attack cis to the phosphine in the Pd-allyl intermediate. In
contrast to the case for other C1-symmetrical ligands possessing
two different donor atoms, such as P-N ligands, the ratio of
isomeric Pd-allyl intermediates observed in solution is much
larger in our case (>50:1 vs 9:1).28 Analogously, however, the
enantioselectivity arises from the regioselective attack on the
major isomeric Pd-allyl complex. Our results from X-ray
crystallography and 2-D NMR spectrometry indicate that steric
rather than electronic effects play the dominant role in this step.
Experimental Section
General Considerations. All reactions were carried out under
an atmosphere of argon using standard Schlenk techniques. With
the exception of the compounds given below, all reagents were
purchased from commercial suppliers and used without further
purification. The following compounds were synthesized according
to published procedures: phosphorochloridite of (S)-(-)-2,2′-
INDOLPhospholes 3a,b and INDOLPhos ligands 1a-f were
evaluated in the Pd-catalyzed asymmetric allylic alkylation. For
1,3-disubstituted propenyl acetates, high activity was found
along with good enantioselectivity up to 90% ee. For cyclic
substrate 10, only moderate ee up to 50% was obtained. The
alkylation of cinnamyl acetate was achieved in good enantio-
(28) Helmchen, G.; Pfaltz, A. Acc. Chem. Res. 2000, 33, 336–345.

2732 Organometallics, Vol. 28, No. 9, 2009
Wassenaar et al.
bisnaphthol,29 1-cyano-3,4-dimethylphosphole,30 1-cyano-2,5-
diphenylphosphole,14b [Pd2(η3-1,3-diphenylallyl)2Cl2],26 rac-1,3-
diphenylprop-2-enyl acetate (6),31 rac-1,3-dimethylprop-2-enyl
acetate (8),32 and rac-3-acetoxycyclohexene (10).33 THF, pentane,
hexane, and diethyl ether were distilled from sodium benzophenone
ketyl; CH2Cl2, MeCN, EtOAc, i-PrOH, and MeOH were distilled
from CaH2, and toluene was distilled from sodium under nitrogen.
Melting points were recorded on a Gallenkamp melting point
apparatus and are uncorrected. NMR spectra (1H, 31P, and 13C) were
measured on a Varian INOVA 500 MHz or a Varian MERCURY
300 MHz spectrometer. Optical rotations were determined on a
Perkin-Elmer 241 polarimeter. High-resolution mass spectra were
recorded on a JEOL JMS SX/SX102A four-sector mass spectrom-
eter; for FAB-MS 3-nitrobenzyl alcohol was used as the matrix.
Gas chromatographic analyses were run on a Shimadzu GC-17A
apparatus. Chiral GC separations were conducted on an Interscience
Focus GC Ultra instrument. Chiral HPLC separations were con-
ducted on a Shimadzu 10A HPLC instrument, equipped with a UV
detector.
Synthesis of Indolylphosphole 2a. To a solution of 3-meth-
ylindole (126 mg, 0.96 mmol) in THF (5 mL) was added dropwise
0.40 mL of n-BuLi (2.5 M in hexanes) at -70 °C. The resulting
suspension was stirred at -70 °C for 20 min. Carbon dioxide was
bubbled through the suspension for 10 min to give a clear pale
yellow solution that was warmed to room temperature, after which
the solvent was removed in vacuo. The resulting white residue was
dissolved in THF (5 mL) to give a clear pale yellow solution, which
was cooled to -70 °C. To this solution was added 0.63 mL of
t-BuLi (1.6 M in pentanes), and the resulting orange solution was
stirred at -70 °C for 30 min. To this solution was added a solution
of 1-cyano-2,5-diphenylphosphole (250 mg, 0.96 mmol) in THF
(2 mL), and the reaction mixture was stirred for 1 h at -70 °C.
The resulting yellow solution was warmed to room temperature
and stirred for 16 h, after which it was washed with 5 mL of
degassed saturated aqueous NH4Cl. The organic layer was dried
over MgSO4 and filtered, and the solvent was removed in vacuo to
yield the product as a bright yellow solid. Yield: 293 mg (84%).
Mp: 144 °C. 1H NMR (CDCl3, 499.8 MHz, 298 K): δ (ppm) 7.57
(m, 5H), 7.51 (br s, 1H), 7.42 (d, JP,H ) 11.0 Hz, 2H), 7.29 (t, JH,H
) 7.5 Hz, 4H), 7.20 (t, JH,H ) 7.5 Hz, 2H), 7.13 (m, 2H), 7.07 (m,
1H), 2.76 (s, 3H). 13C NMR (CDCl3, 125.7 MHz, 298 K): δ (ppm)
150.29 (Cq), 138.46 (Cq), 136.20 (Cq, JP,C ) 16.5 Hz), 132.76 (CH,
29.0 Hz), 122.03 (Cq, JP,C ) 21.1 Hz), 121.95 (CH, JP,C ) 33.3
Hz), 119.29 (CH), 110.77 (CH), 18.07 (CH3, JP,C ) 3.8 Hz), 10.16
(CH3, JP,C ) 10.6 Hz). 31P{1H} NMR (CDCl3, 202.3 MHz, 298
K): δ (ppm) -37.70 (s). HRMS (FAB): m/z calcd for [M + H]+
C15H17NP 242.1099, found 242.1093.
Synthesis of INDOLPhosphole 3a. To a solution of in-
dolylphosphole 2a (70 mg, 0.19 mmol) in THF (3 mL) was added
dropwise 0.76 mL of n-BuLi (0.25 M in hexanes) at -70 °C. The
resulting orange solution was stirred for 10 min at -70 °C. To this
solution was added a solution of (S)-(-)-2,2′-bisnaphthol phos-
phorochloridite (67 mg, 0.19 mmol) in THF (1 mL) at -70 °C.
The reaction mixture was stirred for 1 h at -70 °C and then warmed
to room temperature. The resulting yellow solution was filtered
through a plug of SiO2 and concentrated in vacuo. The crude product
was further purified by SiO2 chromatography (5% EtOAc/hexane)
to give a bright yellow solid. Yield: 81 mg (63%). Mp: 147 °C.
[R]D20 ) +36.0° (c ) 0.5, CHCl3). 1H NMR (CDCl3, 499.8 MHz,
298 K): δ (ppm) 8.01-7.92 (m, 3H), 7.71 (d, JH,H ) 7.0 Hz, 1H),
7.60 (d, JH,H ) 7.5 Hz, 4H), 7.53 (d, JH,H ) 8.0 Hz, 1H), 7.50-7.22
(m, 15H), 6.81 (t, JH,H ) 7.5 Hz, 1H), 6.21 (br s, 1H), 6.11 (t, JH,H
) 8.0 Hz, 1H), 5.55 (br s, 1H), 2.92 (br s, 3H). 13C NMR (CDCl3,
125.7 MHz, 298 K): δ (ppm) 150.09 (Cq, JP,C ) 4.7 Hz), 148.73
(Cq), 136.87 (Cq, JP,C ) 16.0 Hz), 133.13 (Cq), 132.80 (Cq), 131.95
(Cq), 131.43 (Cq), 130.81 (CH), 130.48 (CH), 129.07 (CH), 129.01
(CH), 128.56 (CH, JP,C ) 22.4 Hz), 127.48 (CH), 127.35 (CH),
126.88 (CH, JP,C ) 9.7 Hz), 126.75 (CH), 126.62 (CH), 126.37
(CH), 125.49 (CH), 125.01 (CH), 122.94 (Cq), 121.91 (CH), 121.15
(CH), 121.01 (CH), 119.20 (CH), 116.16 (CH), 111.03 (CH), 11.40
(CH3). 31P{1H} NMR (CDCl3, 202.3 MHz, 298 K): δ (ppm) 148.57
(s), -32.66 (s). HRMS (FAB): m/z calcd for [M + H]+
C45H32NO2P2 680.1908, found 680.1906.
Synthesis of INDOLPhosphole 3b. The same procedure was
followed as for 3a, except for using indolylphosphine 2b (70 mg,
0.29 mmol) instead of 2a, 1.16 mL of n-BuLi (0.25 M in hexanes),
and 102 mg of (S)-(-)-2,2′-bisnaphthol phosphorochloridite (0.29
mmol) to give the product as a white solid. Yield: 77 mg (48%).
Mp: 167 °C. [R]D20 ) +188.0° (c ) 0.5, CHCl3). 1H NMR (CDCl3,
499.8 MHz, 298 K): δ (ppm) 8.02 (d, JH,H ) 8.5 Hz, 1H), 7.97 (d,
JH,H ) 8.0 Hz, 1H), 7.81 (d, JH,H ) 8.0 Hz, 1H), 7.52 (dd, JH,H
9.0 Hz, JH,H ) 4.0 Hz, 2H), 7.50-7.43 (m, 4H), 7.37 (d, JH,H
)
)
8.0 Hz, 1H), 7.34-7.30 (m, 2H), 6.82 (m, 2H), 6.76-6.68 (m, 2H),
6.39 (d, JH,H ) 8.5 Hz, 1H), 6.15 (t, JH,H ) 8.0 Hz, 1H), 2.49 (s,
3H), 2.12 (br s, 6H). 13C NMR (CDCl3, 125.7 MHz, 298 K): δ
JP,C ) 10.2 Hz), 129.04 (CH), 127.79 (CH), 126.36 (CH, JP,C
9.2 Hz), 124.25 (Cq), 124.01 (Cq), 123.72 (CH), 121.56 (Cq, JP,C
)
)
(ppm) 150.64 (Cq, JP,C ) 5.5 Hz), 148.98 (Cq), 141.09 (Cq, JP,C
)
16.5 Hz), 119.52 (CH), 119.28 (CH), 111.05 (CH), 10.47 (CH3,
JP,C ) 10.6 Hz). 31P{1H} NMR (CDCl3, 202.3 MHz, 298 K): δ
(ppm) -32.25 (s). HRMS (FAB): m/z calcd for [M + H]+ C25H21NP
366.1412, found 366.1414.
7.5 Hz), 133.22 (Cq), 132.94 (Cq), 131.91 (Cq), 131.52 (Cq), 130.84
(CH), 130.55 (CH), 129.92 (Cq, JP,C ) 27.0 Hz, JP,C ) 5.0 Hz),
129.18 (CH), 128.58 (CH, JP,C ) 10.9 Hz), 127.40 (CH), 126.89
(CH), 126.63 (CH), 126.48 (CH), 125.47 (CH), 125.06 (CH), 124.82
(Cq, JP,C ) 5.9 Hz), 123.81 (CH), 122.92 (Cq), 121.95 (CH), 121.76
(CH), 121.01 (CH), 118.74 (CH), 116.17 (CH), 18.14 (CH3), 10.80
(CH3, JP,C ) 14.3 Hz). 31P{1H} NMR (CDCl3, 202.3 MHz, 298
K): δ (ppm) 148.33 (d, JP,P ) 43.1 Hz), -37.03 (d, JP,P ) 43.1
Hz). HRMS (FAB): m/z calcd for [M + H]+ C35H28O2NP2
556.1595, found 556.1594.
Synthesis of Indolylphosphole 2b. The same procedure was
followed as for 2a, except for using 1-cyano-3,4-dimethylphosphole
(208 mg, 1.52 mmol) instead of 1-cyano-2,5-diphenylphosphole
and 200 mg of 3-methylindole (1.52 mmol) to give the product as
1
an off-white solid. Yield: 262 mg (71%). Mp: 117 °C. H NMR
(CDCl3, 499.8 MHz, 298 K): δ (ppm) 7.58 (d, JH,H ) 8.0 Hz, 1H),
7.41 (br s, 1H), 7.21 (m, 2H), 7.11 (t, JH,H ) 7.0 Hz, 1H), 6.47 (d,
Synthesis of Complex 4a, [Pd(1a)(C3H5)]PF6. To a solution
of INDOLPhos (1a; 100 mg, 0.16 mmol) in CH2Cl2 (4 mL) was
added [Pd2(η3-C3H5)2Cl2] (29 mg, 0.08 mmol) at room temperature.
The solution was stirred for 5 min. Silver hexafluorophosphate salt
(41 mg, 0.16 mmol) was then added, and the resulting suspension
was stirred for 30 min. Filtration over Celite and evaporation of
the solvent afforded the product as a white solid. Colorless needles
suitable for X-ray crystallographic analysis were obtained by slow
diffusion of hexanes into a saturated dichloromethane solution.
JP,H ) 38.5 Hz, 2H), 2.58 (s, 3H), 2.21 (d, JP,H ) 3.5 Hz, 6H). 13
C
NMR (CDCl3, 125.7 MHz, 298 K): δ (ppm) 150.45 (Cq), 150.38
(Cq), 137.93 (Cq), 129.11 (CH), 123,47 (CH), 122.90 (Cq, JP,C
)
(29) Buisman, G. J. H.; van der Veen, L. A.; Klootwijk, A.; de Lange,
W. G. J.; Kamer, P. C. J.; van Leeuwen, P. W. N. M.; Vogt, D.
Organometallics 1997, 16, 2929–2939.
(30) Holand, S.; Mathey, F. Organometallics 1988, 7, 1796–1801.
(31) Auburn, P. R.; Mackenzie, P. B.; Bosnich, B. J. Am. Chem. Soc.
1985, 107, 2033–2046.
(32) Moreno-Man˜as, M.; Ribas, J.; Virgili, A. J. Org. Chem. 1988, 53,
5328–5335.
(33) Jia, C. G.; Muller, P.; Mimoun, H. J. Mol. Catal. A: Chem. 1995,
101, 127–136.
20
Yield: 117 mg (79%). Mp: 174 °C dec. [R]D ) +263.0° (c )
1.0, CHCl3). 1H NMR (CD2Cl2, 499.8 MHz, 298 K): δ (ppm) 8.34
(d, JH,H ) 9.0 Hz, 0.5H), 8.32 (d, JH,H ) 9.0 Hz, 0.5H), 8.16 (t,
JH,H ) 7.5 Hz, 1H), 7.98 (t, JH,H ) 8.5 Hz, 1H), 7.81-7.54 (m,

INDOLPhosphole and INDOLPhos Pd-Allyl Complexes
Organometallics, Vol. 28, No. 9, 2009 2733
15H), 7.51-7.43 (m, 4H), 7.12 (t, JH,H ) 7.5 Hz, 1H), 6.86 (d,
JH,H ) 9.0 Hz, 0.5H), 6.75 (d, JH,H ) 9.0 Hz, 0.5H), 6.48 (m, 1H),
6.40 (d, JH,H ) 8.5 Hz, 0.5H), 6.37 (d, JH,H ) 8.5 Hz, 0.5H), 5.75
(tt, JH,H ) 14.0 Hz, JH,H ) 7.5 Hz, 0.5H), 5.47 (tt, JH,H ) 14.0 Hz,
Synthesis of Complex 5, [Pd(3b)(C3H5)]PF6. To a solution of
INDOLPhosphole (3b; 28.0 mg, 0.050 mmol) in CH2Cl2 (2 mL)
was added [Pd2(η3-C3H5)2Cl2] (9.2 mg, 0.025 mmol) at room
temperature. The solution was stirred for 15 min. Silver hexafluo-
rophosphate salt (12.7 mg, 0.050 mmol) was then added, and the
resulting suspension was stirred for 30 min. Filtration over Celite
and evaporation of the solvent afforded the product as a white solid.
Needles suitable for X-ray crystallographic analysis were obtained
by slow diffusion of hexanes into a saturated dichloromethane
solution. Yield: 42 mg (99%). Mp: 166 °C dec. [R]D20 ) +354.0°
(c ) 0.5, CHCl3). 1H NMR (CD2Cl2, 499.8 MHz, 263 K): δ (ppm)
8.29 (d, JH,H ) 9.0 Hz, 0.5H), 8.26, JH,H ) 9.0 Hz, 0.5H), 8.13 (t,
JH,H ) 8.5 Hz, 1H), 7.99 (t, JH,H ) 7.5 Hz, 1H), 7.80 (d, JH,H ) 9.0
Hz, 0.5H), 7.76 (d, JH,H ) 9.0 Hz, 0.5H), 7.72 (d, JH,H ) 9.0 Hz,
0.5H), 7.65-7.58 (m, 2H), 7.52-7.42 (m, 5H), 7.06 (t, JH,H ) 8.5
Hz, 2H), 6.67-6.44 (m, 2H), 6.42 (t, JH,H ) 7.5 Hz, 1H), 6.18 (d,
JH,H ) 8.5 Hz, 0.5H), 6.14 (d, JH,H ) 8.5 Hz, 0.5H), 5.62 (tt, JH,H
JH,H ) 7.0 Hz, 0.5H), 4.82 (t, JH,H ) 7.5 Hz, 0.5H), 4.68 (t, JH,H
)
8.5 Hz, 0.5H), 4.58 (m, 0.5H), 4.36 (m, 0.5H), 3.47 (m, 0.5H),
3.33 (t, JH,H ) 15.0 Hz, 0.5H), 3.22 (t, JH,H ) 15.0 Hz, 0.5H), 2.96
(m, 0.5H), 2.09 (s, 3H). 13C NMR (CD2Cl2, 125.7 MHz, 298 K): δ
(ppm) 149.50 (Cq, JP,C ) 6.4 Hz), 149.39 (Cq, JP,C ) 5.9 Hz), 147.11
(Cq, JP,C ) 5.2 Hz), 146.96 (Cq, JP,C ) 5.5 Hz), 139.18 (Cq), 136.73
(Cq), 133.58 (CH), 133.46 (CH), 133.31 (CH), 133.21 (CH), 133.10
(CH), 133.01 (Cq), 132.96 (CH), 132.91 (Cq), 132.86 (CH), 132.77
(CH), 132.73 (Cq), 132.68 (CH), 132.51 (CH), 132.42 (CH), 130.69
(CH, JP,C ) 12.2 Hz), 130.58 (CH, JP,C ) 12.3 Hz), 130.39 (CH,
JP,C ) 8.4 Hz), 130.30 (CH, JP,C ) 8.4 Hz), 129.52 (CH, JP,C
)
5.0 Hz), 129.21 (CH, JP,C ) 2.1 Hz), 128.09 (CH), 128.05 (CH),
127.64 (CH, JP,C ) 11.8 Hz), 127.38 (CH, JP,C ) 4.1 Hz), 127.24
(CH, JP,C ) 4.3 Hz), 127.04 (CH, JP,C ) 3.0 Hz), 126.78 (CH),
125.31 (CH, JP,C ) 6.3 Hz), 125.23 (CH, JP,C ) 6.4 Hz), 124.31
(CH), 124.24 (Cq), 122.46 (Cq), 121.15 (CH), 121.03 (CH), 120.18
(CH, JP,C ) 8.0 Hz), 115.65 (CH), 73.94 (CH2, JP,C ) 44.1 Hz),
73.89 (CH2, JP,C ) 45.1 Hz), 73.01 (CH2, JP,C ) 8.2 Hz), 72.80
(CH2, JP,C ) 8.0 Hz), 10.93 (CH3). 31P{1H} NMR (CD2Cl2, 202.3
MHz, 298 K): δ (ppm) 293.13 (septuplet, JP,F ) 710.1 Hz, PF6),
151.45 (d, JP,P ) 83.5 Hz, 0.5P), 151.42 (d, JP,P ) 83.5 Hz, 0.5P),
16.99 (d, JP,P ) 83.5 Hz, 0.5P), 16.86 (d, JP,P ) 82.3 Hz, 0.5P).
HRMS (FAB): m/z calcd for [M - PF6]+ C44H34O2NP2Pd 776.1116,
found 776.1119.
) 13.5 Hz, JH,H ) 6.5 Hz, 0.5H), 5.35 (tt, JH,H ) 13.5 Hz, JH,H
)
7.0 Hz, 0.5H), 4.34 (m, 1H), 4.26 (t, JH,H ) 9.0 Hz, 0.5H), 4.16
(m, 0.5H), 3.28 (m, 1H), 3.12 (t, JH,H ) 15.0 Hz, 0.5H), 2.89 (m,
0.5H), 2.35 (s, 1.5H), 2.34 (s, 1.5H), 2.32 (s, 3H), 2.04 (s, 3H).
13C NMR (CD2Cl2, 125.7 MHz, 298 K): δ (ppm) 156.24 (Cq),
150.01 (Cq), 147.63 (Cq), 139.09 (Cq), 136.64 (Cq), 133.30 (Cq),
132.95 (Cq), 132.87 (Cq), 132.68 (Cq), 132.59 (CH), 129.51 (CH),
129.21 (CH), 128.04 (CH), 127.65 (CH), 127.45 (CH), 127.22 (CH),
127.00 (CH), 126.15 (CH), 124.84 (CH), 124.41 (Cq), 124.09 (CH),
122.44 (Cq), 121.03 (CH), 120.82 (CH), 120.46 (CH), 120.14 (CH),
119.32 (CH), 115.63 (CH), 73.89 (CH2), 73.15 (CH2), 18.22 (CH3),
8.92 (CH3). 31P{1H} NMR (CD2Cl2, 202.3 MHz, 263 K): δ (ppm)
292.94 (septuplet, JP,F ) 711.5 Hz, PF6), 151.28 (d, JP,P ) 74.5
Hz, 0.5P), 151.17 (d, JP,P ) 75.1 Hz, 0.5P), 3.59 (d, JP,P ) 75.1
Hz, 0.5P), 3.47 (d, JP,P ) 74.4 Hz, 0.5P). HRMS (FAB): m/z calcd
for [M - PF6]+ C38H32O2NP2Pd 702.0958, found 702.0950.
Synthesis of Complex 4b, [Pd(1a)(1,3-diphenylallyl)]PF6. To
a solution of INDOLPhos (1a; 100 mg, 0.16 mmol) in CH2Cl2 (5
mL) was added [Pd2(η3-1,3-diphenylallyl)2Cl2] (53 mg, 0.08 mmol)
at room temperature. The solution was stirred for 15 min. Silver
hexafluorophosphate salt (41 mg, 0.16 mmol) was then added, and
the resulting suspension was stirred for 30 min. Filtration over Celite
gave a bright yellow solution. Hexanes (10 mL) was added to
precipitate a bright yellow solid. The solvent was removed by
syringe, and the product was dried in vacuo. Yield: 103 mg (60%).
Allylic Alkylation of rac-1,3-Diphenylprop-3-enyl Acetate
(6). A solution of [Pd2(η3-C3H5)2Cl2] (0.46 mg, 1.25 µmol) and
INDOLPhos(phole) ligand (2.75 µmol) in CH2Cl2 (1 mL) was
stirred for 30 min. Subsequently, a solution of rac-6 (63 mg, 0.25
mmol) in CH2Cl2 (1 mL), dimethyl malonate (86 µL, 0.75 mmol),
N,O-bis(trimethylsilyl)acetamide (185 µL, 0.75 mmol), and a pinch
of KOAc were added. The reaction mixture was stirred at room
temperature. After 1 h the reaction mixture was diluted with Et2O
(3 mL) and saturated aqueous NH4Cl (10 mL). The aqueous phase
was removed. To determine the conversion, a sample for GC
analysis was taken from the organic phase. The solvent was
removed in vacuo. To determine the ee by HPLC (Chiralcel-ODH,
0.5% 2-propanol/hexane, flow 0.5 mL/min), a sample was filtered
over SiO2, using hexanes as eluent.
20
1
Mp: 221 °C dec. [R]D ) +420.0° (c ) 1.0, CHCl3). H NMR
(CDCl3, 499.8 MHz, 298 K): δ (ppm) 8.19 (d, JH,H ) 9.0 Hz, 1H),
8.13 (d, JH,H ) 9.0 Hz, 1H), 8.01 (d, JH,H ) 8.5 Hz, 1H), 7.85 (d,
JH,H ) 8.0 Hz, 1H), 7.68-7.54 (m, 6H), 7.50 (t, JH,H ) 7.5 Hz,
2H), 7.37-7.22 (m, 8H), 7.05 (d, JH,H ) 8.5 Hz, 1H), 7.02 (t, JH,H
) 7.5 Hz, 2H), 6.94 (t, JH,H ) 7.5 Hz, 1H), 6.90 (d, JH,H ) 7.5 Hz,
2H), 6.81 (m, 3H), 6.65 (d, JH,H ) 7.5 Hz, 1H), 6.63 (d, 7.5 Hz,
1H), 6.26 (m, 3H), 6.19 (d, JH,H ) 6.5 Hz, 1H), 6.17 (m, 1H), 5.93
(d, JH,H ) 8.5 Hz, 1H), 5.77 (vt, J ) 10.0 Hz, 1H), 5.60 (vt, J )
15.0 Hz, 1H), 1.84 (s, 3H). 13C NMR (CDCl3, 125.7 MHz, 298
K): δ (ppm) 149.28 (Cq, JP,C ) 14.8 Hz), 147.14 (Cq, JP,C ) 5.4
Hz), 138.62 (Cq, JP,C ) 6.7 Hz), 137.34 (Cq, JP,C ) 5.0 Hz), 136.06
(Cq, JP,C ) 4.7 Hz), 135.48 (Cq, JP,C ) 12.7 Hz), 134.45 (CH),
134.34 (CH), 133.06 (CH), 132.82 (Cq), 132.60 (Cq), 132.54 (CH),
132.05 (Cq), 131.65 (CH, JP,C ) 2.5 Hz), 131.58 (CH), 131.34 (CH,
Allylic Alkylation of rac-1,3-Dimethylprop-3-enyl Acetate
(8). A solution of [Pd2(η3-C3H5)2Cl2] (0.46 mg, 1.25 µmol) and
INDOLPhos(phole) ligand (2.75 µmol) in CH2Cl2 (1 mL) was
stirred for 30 min. Subsequently, a solution of rac-8 (32 mg, 0.25
mmol) in CH2Cl2 (1 mL), dimethyl malonate (86 µL, 0.75 mmol),
N,O-bis(trimethylsilyl)acetamide (185 µL, 0.75 mmol), and a pinch
of KOAc were added. The reaction mixture was stirred at room
temperature. After 1 h the reaction mixture was diluted with Et2O
(3 mL) and saturated aqueous NH4Cl (10 mL). The aqueous phase
was removed. Conversion and ee were determined by chiral GC
(Chiralsil DEX CB, isothermal at 65 °C).
Allylic Alkylation of rac-3-Acetoxycyclohexene (10). A solution
of [Pd2(η3-C3H5)2Cl2] (0.46 mg, 1.25 µmol) and INDOLPhos(phole)
ligand (2.75 µmol) in CH2Cl2 (1 mL) was stirred for 30 min.
Subsequently, a solution of rac-10 (35 mg, 0.25 mmol) in CH2Cl2
(1 mL), dimethyl malonate (86 µL, 0.75 mmol), N,O-bis(trimeth-
ylsilyl)acetamide (185 µL, 0.75 mmol), and a pinch of KOAc were
added. The reaction mixture was stirred at room temperature. After
1 h the reaction mixture was diluted with Et2O (3 mL) and saturated
aqueous NH4Cl (10 mL). The aqueous phase was removed.
JP,C ) 11.8 Hz), 129.89 (CH, JP,C ) 12.2 Hz), 129.75 (Cq, JP,C
)
10.9 Hz), 129.19 (CH), 129.12 (CH), 128.72 (CH), 128.53 (CH),
128.30 (CH, JP,C ) 10.2 Hz), 127.63 (CH), 127.46 (CH), 127.34
(CH), 126.96 (CH), 126.37 (CH, JP,C ) 9.2 Hz), 126.08 (CH),
125.71 (Cq, JP,C ) 20.6 Hz), 125.70 (CH), 125.31 (Cq, JP,C ) 19.4
Hz), 123.39 (CH), 122.27 (Cq, JP,C ) 2.9 Hz), 121.84 (CH), 121.70
(Cq, JP,C ) 2.9 Hz), 120.37 (CH), 120.11 (CH), 115.65 (CH), 115.52
(CH), 94.21 (CH, JP,C ) 36.0, 5.9 Hz), 92.06 (CH, JP,C ) 24.9,
10.1 Hz), 10.45 (CH3). 31P{1H} NMR (CDCl3, 202.3 MHz, 298
K): δ (ppm) 293.76 (septuplet, JP,F ) 714.1 Hz, PF6), 146.02 (d,
JP,P ) 103.8 Hz), 12.83 (d, JP,P ) 103.8 Hz); a second set of signals
was observed in trace amounts (<2%) at δ (ppm) 145.42 (d, JP,P
) 108.6 Hz), 12.42 (d, JP,P ) 108.1 Hz). HRMS (FAB): m/z calcd
for [M - PF6]+ C56H42O2NP2Pd 928.1745, found 928.1738.

2734 Organometallics, Vol. 28, No. 9, 2009
Wassenaar et al.
Conversion and ee were determined by chiral GC (Supelco ꢀ-DEX
225, isothermal at 50 °C for 2 min, 3 °C/min to 190 °C).
anomalous dispersion effects in diffraction measurements on the
crystals. Geometry calculations were performed with the PLATON
program.41 Graphical illustrations were made using ORTEP-3
(2.02)42 and Mercury 1.4.2 (Build 2).43
Allylic Alkylation of Cinnamyl Acetate (12). A solution of
[Pd2(η3-C3H5)2Cl2] (0.46 mg, 1.25 µmol) and INDOLPhos(phole)
ligand (2.75 µmol) in CH2Cl2 (1 mL) was stirred for 30 min.
Subsequently, a solution of 12 (42 µL, 0.25 mmol) in CH2Cl2 (1
mL), dimethyl malonate (86 µL, 0.75 mmol), N,O-bis(trimethyl-
silyl)acetamide (185 µL, 0.75 mmol), and a pinch of KOAc were
added. The reaction mixture was stirred at room temperature. After
1 h the reaction mixture was diluted with Et2O (3 mL) and saturated
aqueous NH4Cl (10 mL). The aqueous phase was removed. To
determine the conversion, a sample for GC analysis was taken from
the organic phase. The solvent was removed in vacuo. To determine
the ee by HPLC (Chiralcel-OJH, 3.0% 2-propanol/hexane, flow 0.7
mL/min) a sample was filtered over SiO2, using hexanes as eluent.
X-ray Crystallography of 4a and 5. All reflection intensities
were measured at 110(2) K using a Nonius KappaCCD diffracto-
meter (rotating anode) with graphite-monochromated Mo KR
radiation (λ ) 0.710 73 Å) under the program COLLECT.34 The
program PEAKREF35 was used to refine the cell dimensions. Data
reduction was done using the program EVALCCD.36 The structure
of 4a was solved with the program DIRDIF0837 and that of 5 with
the program SHELXS-97.38 The two structures were refined on F2
with SHELXL-97.38 Analytical absorption corrections based on
crystal face indexing were applied to the data using SADABS39
(transmission ranges: for 4a, 0.80-0.92; for 5, 0.87-1.00). The
temperature of the data collection was controlled using the Oxford
Cryostream 600 system (manufactured by Oxford Cryosystems).
The H atoms were placed at calculated positions (AFIX 23 or AFIX
43 or AFIX 93 or AFIX 137) with isotropic displacement
parameters having values 1.2 or 1.5 times the Ueq value of the
attached C atom and were refined with a riding model. In the crystal
structure of 4a, the asymmetric unit contains two crystallographi-
cally independent Pd complexes, two hexafluorophosphate coun-
teranions, and two dichloromethane solvent molecules. The allyl
ligands are disordered, and their major components were refined
to 0.703(8) and 0.623(9). In the crystal structure of 5, the
asymmetric unit was modeled with four Pd complexes, four
hexafluorophosphate counteranions, and two dichloromethane
solvent molecules. One allyl ligand and one PF6- counteranion were
found to be disordered. The major component of the disordered
allyl ligand was refined to 0.718(8) and that of the disordered
counteranion to 0.717(6). One void, which probably contains very
disordered solvent molecules, was found at (-0.169, 0.748, 0.606).
The contribution of these solvent molecules was taken out for the
last stage of the refinement using the program SQUEEZE.40 For
both structures, the absolute configuration was established by the
structure determination of a compound containing a chiral reference
molecule of known absolute configuration and confirmed by
Data for 4a: C45H36Cl2F6NO2P3Pd, Mw ) 1006.96, colorless
block, 0.23 × 0.12 × 0.12 mm3, monoclinic, P21 (No. 4), a )
9.6088(2) Å, b ) 41.1341(6) Å, c ) 10.4629(2) Å, ꢀ ) 91.581(1)°,
V ) 4133.88(13) Å3, Z ) 4, Dexptl ) 1.618 g cm-3, µ ) 0.76 mm-1
.
74 134 measured reflections, 18 886 unique reflections (Rint
)
0.038), 16 822 observed reflections using the criterion I > 2σ(I).
1139 parameters refined with 217 restraints, R1/wR2 (I > 2σ(I))
0.033/0.056, R1/wR2 (all reflections) 0.043/0.058, S ) 1.06,
residual electron density between -0.47 and 0.58 e Å-3, Flack
parameter44 -0.018(10).
Data for 5: C38.5H33ClF6NO2P3Pd, Mw ) 890.42*, colorless
block, 0.19 × 0.19 × 0.16 mm3, triclinic, P1 (No. 1), a )
15.6617(4) Å, b ) 15.8329(4) Å, c ) 16.2065(5) Å, R )
98.715(1)°, ꢀ ) 92.600(1)°, γ ) 90.599(2)°, V ) 3967.63(19) Å3,
Z ) 4, Dexptl ) 1.491 g cm-3*, µ ) 0.72 mm-1*, 90 387 measured
reflections, 36 340 unique reflections (Rint ) 0.034), 32 022 observed
reflections using the criterion I > 2σ(I). 1989 parameters refined
with 421 restraints, R1/wR2 (I > 2σ(I)) 0.036/0.077, R1/wR2 (all
reflections) 0.046/0.080, S ) 1.06, residual electron density between
-0.68 and 0.87 e Å-3, Flack parameter44 -0.016(8). SQUEEZE
details: void of 319 Å3 per unit cell filled with 55 electrons per
unit cell. The asterisk indicates that the disordered solvent contribu-
tion was excluded.
DFT Calculations. The geometry optimization of complex 4b
was carried out with the Turbomole program45 coupled to the PQS
Baker optimizer.46 Geometries were fully optimized as minima at
the BP8647 level using the SV(P) basis set on all atoms.48
Acknowledgment. This work was supported by NRSC-C
and the European Union (RTN Revcat MRTN-CT-2006-
035866). We thank J. A. J. Geenevasen for assistance with
1H 2D NOESY experiments, J. W. H. Peeters for measuring
high-resolution mass spectra and W. I. Dzik for DFT
calculations. This work was also supported in part (A.L.S.)
by the Council for the Chemical Sciences of The Netherlands
Organization for Scientific Research (CW-NWO).
Supporting Information Available: Figures giving NMR
spectra of complexes 4a,b and 5 and CIF files giving crystal-
lographic data for 4a and 5. This material is available free of charge
via the Internet at http://pubs.acs.org.
OM801204A
(40) van der Sluis, P.; Spek, A. L. Acta Crystallogr., Sect. A 1990, 46,
194–201.
(34) COLLECT; Nonius BV, Delft, The Netherlands, 1999.
(35) Schreurs, A. M. M. PEAKREF; University of Utrecht, Utrecht, The
Netherlands, 2005.
(36) Duisenberg, A. J. M.; Kroon-Batenburg, L. M. J.; Schreurs,
A. M. M. J. Appl. Crystallogr. 2003, 36, 220–229.
(41) Spek, A. L. J. Appl. Crystallogr. 2003, 36, 7–13.
(42) Farrugia, L. J. J. Appl. Crystallogr. 1997, 30, 565.
(43) Macrae, C. F.; Edgington, P. R.; McCabe, P.; Pidcock, E.; Shields,
G. P.; Taylor, R.; Towler, M.; van de Streek, J. J. Appl. Crystallogr. 2006,
39, 453–457.
(37) Beurskens, P. T.; Beurskens, G.; de Gelder, R.; Garcia-Granda,
S.; Gould, R. O.; Smits, J. M. M. The DIRDIF2008 Program System;
Crystallography Laboratory, University of Nijmegen, Nijmegen, The
Netherlands, 2008.
(38) Sheldrick, G. M. Acta Crystallogr., Sect. A 2008, 64, 112–122.
(39) Sheldrick, G. M. SADABS 2006/1; University of Go¨ttingen,
Go¨ttingen, Germany, 2006.
(44) Flack, H. D. Acta Crystallogr., Sect. A 1983, 39, 876–881.
(45) Treutler, O.; Ahlrichs, R. J. Chem. Phys. 1995, 102, 346–354.
(46) Baker, J. J. Comput. Chem. 1986, 7, 385–395.
(47) (a) Perdew, J. P. Phys. ReV. B 1986, 33, 8822–8824. (b) Becke,
A. D. Phys. ReV. A 1988, 38, 3098–3100.
(48) Scha¨fer, A.; Horn, H.; Ahlrichs, R. J. Chem. Phys. 1992, 97, 2571–
2577.