3,5-Dialkyl effect on enantioselectivity in Pd chemistry: Applications involving both bidentate and monodentate auxiliaries

Article abstract of DOI:10.1021/om034381b

The structural 3,5-dialkylphenyl effect on enantioselectivity is demonstrated for several Pd-catalyzed reactions including a ring-opening transmetalation, Heck arylation, and allylic alkylation. For these homogeneously catalyzed reactions the observed enantiomeric excesses (ee's) are found to improve by more than 15%. The ligands tested include MeO-Biphep and a P,N-phosphino-oxazoline-bidentate ligand containing 3,5-di-tert-butylphenyl substituents. Further, several derivatives of the monodentate auxiliary MOP (CR)-2-diarylphosphino-1,1′-binaphthyl) have been modified to include 3,5-dialkylphenyl substituents and these auxiliaries have been tested in Pd-catalyzed enantioselective hydrosilylation chemistry. For some, but not all of these MOP ligands, enhanced ee's of the order of 40-50% are found. Variable-temperature and 2-D NMR studies have been carried out on new model complexes and reveal selected restricted rotation around a number of the P-C(ipso) aryl bonds. Solid-state structures for two of the new complexes, PdBrCp-NCCeHUXphosphino-oxazoline, 2b), 8b, and PdCl(C₆H ₄CH₂NMe₂)(MOP, 4b), 9b, have been determined.

Full text of DOI:10.1021/om034381b

Organometallics 2004, 23, 2295-2304
2295
3,5-Dia lk yl Effect on En a n tioselectivity in P d Ch em istr y:
Ap p lica tion s In volvin g Both Bid en ta te a n d Mon od en ta te
Au xilia r ies
Pascal Dotta, P. G. Anil Kumar, and Paul S. Pregosin*
Laboratory of Inorganic Chemistry, ETHZ, 8093 Zu¨rich, Switzerland
Alberto Albinati* and Silvia Rizzato
Department of Structural Chemistry (DCSSI) and Faculty of Pharmacy, University of Milan,
20133 Milan, Italy
Received December 17, 2003
The structural 3,5-dialkylphenyl effect on enantioselectivity is demonstrated for several
Pd-catalyzed reactions including a ring-opening transmetalation, Heck arylation, and allylic
alkylation. For these homogeneously catalyzed reactions the observed enantiomeric excesses
(ee’s) are found to improve by more than 15%. The ligands tested include MeO-Biphep and
a P,N-phosphino-oxazoline-bidentate ligand containing 3,5-di-tert-butylphenyl substituents.
Further, several derivatives of the monodentate auxiliary MOP ((R)-2-diarylphosphino-1,1′-
binaphthyl) have been modified to include 3,5-dialkylphenyl substituents and these
auxiliaries have been tested in Pd-catalyzed enantioselective hydrosilylation chemistry. For
some, but not all of these MOP ligands, enhanced ee’s of the order of 40-50% are found.
Variable-temperature and 2-D NMR studies have been carried out on new model complexes
and reveal selected restricted rotation around a number of the P-C(ipso) aryl bonds. Solid-
state structures for two of the new complexes, PdBr(p-NCC6H4)(phosphino-oxazoline, 2b),
8b, and PdCl(C6H4CH2NMe2)(MOP, 4b), 9b, have been determined.
In tr od u ction
the auxiliary (instead of the routine phenyl substituent)
enhances the ee’s in Heck and allylic alkylation chem-
istry. Specifically, we have used MeO-Biphep, 1,12 and
the phosphino-oxazolines, 2 (see Scheme 1),13,14 in the
There are now a number of readily available bidentate
chiral auxiliaries capable of achieving enantiomeric
excesses (ee’s) in excess of 90%, for a variety of enan-
tioselective transformations. The ligands Duphos1-3 and
Binap4 have been relatively successful in enantioselec-
tive homogeneous hydrogenation, whereas the TAD-
DOL5 series has been employed successfully in C-C
bond making reactions. Many chelating oxazoline
derivatives,6-11 with and without tertiary phosphine
donors, are now widely employed in a variety of catalytic
reactions.
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10.1021/om034381b CCC: $27.50 © 2004 American Chemical Society
Publication on Web 04/15/2004

2296 Organometallics, Vol. 23, No. 10, 2004
Dotta et al.
Sch em e 1
tert-butylphenyl and 3,5-dimethylphenyl substituents
can be effective and that Ru, Rh, and Ir catalysts also
show this 3,5-dialkyl effect on enantioselectivity.
For complexes of MeO-Biphep, 1,12 we have suggested
that this enhanced enantioselectivity arises due to
restricted rotation around the P-C(ipso) bonds of the
P(3,5-di-tert-butylphenyl) groups, as indicated in frag-
ment 3. This decrease in molecular freedom derives from
the restricted rotation due to the interaction of the
P-aryl substituent with the biaryl backbone and results
in a more rigid chiral pocket and thus improved cor-
relation between substrate and catalyst.
We report here (a) several new examples of this 3,5-
dialkyl effect on ee, involving palladium chemistry of
the ligands 1 and 2, (b) that the effect can be extended
to the monodentate auxiliary, MOP,20 4, and (c) new
detailed NMR and X-ray studies relevant to the P-C
restricted rotation for new complexes of 2 and MOP.
Resu lts
enantioselective Heck arylation of dihydrofuran (e.g., as
shown in eq 1), and found that 1b and 2b are signifi-
Rea ction s w ith 1a ,b a n d 2a ,b. Lautens and co-
workers21 have reported in detail on the Pd-catalyzed
ring-opening alkylation of the oxabenzonorbornadiene
shown in eq 2. The reaction is thought to involve a
cantly better than 1a and 2a in terms of enantioselec-
tivity with improvements of 10-20% rather routine.
Several other groups15-19 have found that both 3,5-di-
transmetalation from the dialkyl zinc to palladium,
followed by alkyl insertion into the complexed double
bond and Zn-assisted ring opening. One diastereomer
is strongly favored. The reaction conditions are mild and
yields are good. For dimethyl zinc, using (R)-Binap, (R)-
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3,5-Dialkyl Effect on Enantioselectivity in Pd Chemistry
Organometallics, Vol. 23, No. 10, 2004 2297
Ta ble 1. Resu lts in Alk yla tin g Rin g Op en in g of
Oxa ben zon or bor n a d ien ea
The allylic alkylation of cyclohexenyl acetate with
dimethyl malonate (eq 4) has been reported previously.26
reaction
time (h)
yield
(%)
ee
(%)
entry
R
ligand
1
2
3
4
5
Me
Me
Me
Et
(S)-1a
(R)-1a
(R)-1b
(R)-1a
(R)-1b
26
18
22
20
20
93
73
73
87
49c
57b
86
82.7
81.6
97.7
95.0
97.4
Although many auxiliaries do not work well with this
substrate, presumably because the Pd-allyl intermediate
formed (vida infra) is rather small and symmetric,
Trost26 has developed a ligand set that carries out this
transformation with high ee’s. Using [Pd(η3-C3H5)(2a ,b)]-
OTf as precursor, we find 36% ee with 2a and 56% ee
with 2b. While these data confirm that the 3,5-dialkyl
effect is present, they are a far cry from the 90% ee
known in the literature.
MOP Ch em istr y. The monodentate auxiliary MOP
((R)-2-diarylphosphino-1,1′-binaphthyl), 4a -6a , intro-
duced by Hayashi,20 has proven to be an interesting
ligand. While it has been used successfully in allylic
alkylation chemistry, much effort has been devoted to
its application to enantioselective hydrosilylation reac-
tions,20a,b,h e.g., the chemistry of eq 5.
Et
6
7
Me
Me
2a
2b
17
17
92.5
93.1
a
b
Catalyst loading: 5 mol % PdCl2(ligand). Formation of side
products. c Reaction not run to completion.
Tol-Binap, and the Pfaltz/Helmchen phosphino-oxazo-
line i-Pr-PHOX, Lautens reports ee’s of 67%, 76%, and
89%, respectively.
Using the two MeO-Biphep ligands, 1a ,b, with the
latter having the 3,5-di-tert-butylphenyl groups, we find
ee’s of ca. 81.6% and 97.7%, respectively, and show our
results in Table 1 (entries 2 and 3). Clearly, the effect
is working in this chemistry and the observed increase
lies within the range we have previously noted. The
same reaction with the P,N-auxiliaries 2a ,b gave ee’s
of 92.5% and 93.1% (entries 6 and 7), i.e, almost no
improvement. Similarly, using diethyl zinc22 and 1a ,b,
we find ee’s of 95.0% and 97.4% (entries 4 and 5). It
would appear that the effect is more pronounced where
there is more room for improvement.
The enantioselective Heck reaction has been the
subject of considerable interest. The classical test
substrate, suggested by Hayashi,23 is dihydrofuran, dhf,
although Overman and co-workers24 have reported on
several elegant intramolecular versions. For the Pd-
catalyzed Heck reaction of 2-naphthyl triflate with
dihydrofuran, i.e., eq 3, we find 79% ee with 2a and 98%
The standard MOP compounds, 4a -6a , were synthe-
sized according to the literature. In addition, we have
prepared the new MOP derivatives 4b-6b (with 3,5-
di-tert-butylphenyl groups).
Using these various auxiliaries, together with the
allyl complex [Pd(µ-Cl)(η3-C3H5)]2, gave quantitative
yields of the trichlorosilane, B, and good yields of the
alcohol, C, after oxidative workup with KF, and then
H2O2. In contrast to the Heck chemistry, the amount of
catalyst precursor employed was relatively small, usu-
ally 0.1%. The ee’s from the hydrosilylation reactions
with styrene (entries 1-7), 2-vinylnaphthalene (entries
8-12), and p-methoxystyrene (entries 13-15) are shown
in Table 2. The data, and related observations, reveal a
number of interesting points:
(a) For styrene, using the MeO-MOP, 5b (entries 3
and 4), and CN-MOP, 6b (entries 5 and 6), containing
the 3,5-di-substituted tert-butyl groups, there are >39%
improvements in the ee, relative to 5a and 6a . Never-
theless, the maximum ee is still modest. However, for
the unsubstituted H-MOP, 4b, there is a slight decrease
in ee, relative to 4a (entries 1 and 2), and both of these
ee values are much larger than for either MeO-MOP or
CN-MOP.27
ee with 2b. Interestingly, Pd2(dba)3 is the preferred Pd-
precursor, relative to Pd(OAc)2, in that the yields with
the former are much better. This was somewhat sur-
prising for us.12b,25 Using the dba precursor, one avoids
the reduction step; nevertheless, the reaction is still
quite slow. However, the observed ee with 2b, 98% (19%
more than with 2a ), is gratifying.
(22) Using diethyl zinc and 2a ,b, we find little or no reaction.
(23) Ozawa, F.; Kubo, A.; Matsumoto, Y.; Hayashi, T.; Nishioka, E.;
Yanagi, K.; Moriguchi, K. Organometallics 1993, 12, 4188-4196.
Hayashi, T. J . Organomet. Chem. 2002, 653, 41-45.
(b) For the 2-vinyl naphthalene and p-methoxy sty-
rene substrates, the use of the 3,5-dimethylphenyl
groups can be advantageous, e.g., there is a ca. 13%
(24) Oestreich, M.; Dennison, P. R.; Kodanko, J . J .; Overman, L. E.
Angew. Chem., Int. Ed. 2001, 40, 1439-1442. Overman, L. E.; Rosen,
M. D. Angew. Chem., Int. Ed. 2000, 39, 4596-4599. Overman, L. E.;
Link, J . T. In Metal Catalyzed Cross-Coupling Reactions; Diederich,
F., Stang, P. J ., Eds.; Wiley-VCH: Weinheim, Germany, 1998; pp 239-
266.
(26) Trost, B. M.; van Vranken, D. L. Chem. Rev. 1996, 96, 395.
Trost, B. M.; Rasdinov, R.; Grenzer, E. M. J . Am. Chem. Soc. 1997,
119, 7879-7880.
(27) We note that there is a change of enantiomer on going from 4
or 5 to 6. We believe this is related to differences in how these ligands
bind the Pd-atom and studies to support this idea on suitable models
are in progress.
(25) 31P and 19F NMR experiments with stoichiometric amounts of
the 2-naphthyl triflate substrate and Pd(OAc)2 and P,N-ligand, or Pd-
(dba)2 and P,N-ligand, suggest not much difference between these two
with respect to the rate of formation of the Pd-aryl and free triflate.
Consequently, the observed rate difference as a function of catalyst is
most likely not related to the oxidative addition reaction.

2298 Organometallics, Vol. 23, No. 10, 2004
Dotta et al.
Ta ble 2. Ca ta lytic Resu ltsa fr om th e
Hyd r osilyla tion Rea ction w ith MOP Liga n d s
time
(h)
yieldb of
B (%)
ee of
C (%)
entry
Ar
ligand
1
2
3
4
5
Ph
Ph
Ph
Ph
Ph
Ph
Ph
4a
4b
5a
5b
6a
6b
6b
4a
4b
4c
6a
6b
4a
4b
4c
20
16
16
43
2
100
100
100
100
100
100
100
100
100
95
92 (R)
88 (R)
7 (R)
57 (R)
42 (S)
81 (S)
86 (S)
77 (R)
55 (R)
80 (R)
32 (S)
66 (S)
67 (R)
38 (R)
80 (R)
6
2
7c
21
66
88
138
21
68
15
65
65
8c,d
9c,d
10c,d
11c,d
12c,d
13c
14c
15c
2-naphthyl
2-naphthyl
2-naphthyl
2-naphthyl
2-naphthyl
4-MeO-Ph
4-MeO-Ph
4-MeO-Ph
1
F igu r e 1. A section of the variable-temperature H NMR
100
100
100
99
spectra measured for 7b. The pseudoaxial 3,5-di-tert-
butylphenyl group demonstrates a higher barrier to rota-
tion than the pseudoequatorial analogue. The two weaker
doublets stem from the nonequivalent methyl groups of the
i-Pr group (CD2Cl2).
100
a
Catalyst loading: 0.05 mol % [Pd(µ-Cl)(η3-C3H5)]2, 0.2 mol %
ligand unless otherwise stated. Determined by NMR. c Run in
b
toluene (1 M). 0.2 mol % [Pd(µ-Cl)(η3-C3H5)]2, 0.8 mol % ligand
d
used.
increase in ee for the p-methoxy styrene with the 3,5-
dimethylphenyl groups (entry15), but the 3,5-di-tert-
butylphenyl groups result in marked decreases in ee.
For the 2-vinyl naphthalene, the results are mixed.
(c) When using the standard H-MOP, changing from
styrene to p-methoxy styrene results in decreased ee’s
(entries 1 and 2 vs 13 and 14), i.e., the substrate is
important.
(d) The reactions with the meta-substituted auxilia-
ries are usually slower.
Clearly, the choice of MOP ligand is important.
Further, although the 3,5-di-tert-butylphenyl substitu-
ent on the phosphine donor can be helpful, this ligand
modification is not always the best choice in terms of
improving the selectivity, i.e., in some cases the 3,5-
dimethylphenyl compound is better. Earlier, in the Pd-
catalyzed phenylation of dihydrofuran with phenyl
triflate,14a using 2a -c (2c is not shown in the scheme),
the observed ee increased “as expected”: phenyl (74%)
< 3,5-di-methylphenyl (86%) < 3,5-di-tert-butylphenyl
(98%).
F igu r e 2. 31P,1H correlation at 199 K for 7b showing the
five nonequivalent ortho protons (one from the naphthyl
backbone, four from the two rings) as a consequence of the
restricted rotation. Two of the three weaker correlations
stem from J values to the para protons, i.e, 5J (31P,1H)-
(CD2Cl2).
the aromatic region of the 31P,1H correlation at this
temperature. Apart from the four strong cross-peaks
from the now nonequivalent ortho protons (five, count-
ing the o-naphthyl analogue), three additional weak
cross-peaks are observed. Two of these (δ ca. 6.8 and
ca. 7.5) arise from the slightly broadened singlets due
to the para protons of the 3,5-di-tert-butylphenyl groups,
i.e., we are observing a rare example of a readily
NMR a n d Str u ctu r a l Stu d ies for th e P ,N Com -
p lexes. The effect on the solution dynamics of introduc-
ing the 3,5-di-tert-butylphenyl groups on the phosphorus
donor of 2b in the simple P,N complex, PdCl2(2b), 7b,
1
is shown in Figure 1. In the H NMR spectrum at 273
K one begins to see the effects of the P-C hindered
rotation on the tert-butyl proton signals of one of the
P-aryl rings. At 233 K the two tert-butyl groups are
clearly nonequivalent and well resolved (as are the ortho
protons, not shown). An analogous set of temperature-
dependent spectra for PdCl2(2a ), 7a , do not reveal any
restricted rotation at 233 K. At 213 K (at which
temperature the second P-aryl ring begins to experience
slow rotation around its P-C bond) the first set of tert-
butyl resonances are sharp. At 199 K, all four tert-butyl
groups are nonequivalent and resolved. Figure 2 shows
5
detectable five-bond, J (31P,1H), spin-spin interaction.
We also recorded variable-temperature1H NMR spec-
tra for the aryl complexes PdBr(p-NC-C6H4)(2a and 2b),
8a ,b, which stem from substitution reactions on Pd(Br)-
(p-NCC6H4)(TMEDA). Interestingly, we find no evidence
for significant differences in the barriers to rotation
about the P-C bonds in these two complexes. Given the
improved ee’s noted in the text, above, this observation
seemed strange. This NMR finding prompted us to
measure the structure of 8b in the solid state, via X-ray

3,5-Dialkyl Effect on Enantioselectivity in Pd Chemistry
Organometallics, Vol. 23, No. 10, 2004 2299
Ta ble 3. Selected Bon d Len gth s (Å) a n d Bon d
An gles (d eg) for 8b a n d 9b
8b
Pd-C(1L)
Pd-N(1)
1.989(4)
2.141(4)
2.277(1)
2.469(1)
1.822(4)
1.816(4)
1.837(4)
C(1L)-Pd-N(1)
C(1L)-Pd-P(1)
N(1)-Pd-P(1)
C(1L)-Pd-Br(1)
N(1)-Pd-Br(1)
P(1)-Pd-Br(1)
N(2)-C(7L)
176.6(2)
91.4(1)
91.5(1)
85.8(1)
91.5(1)
174.7(1)
1.149(7)
Pd-P(1)
Pd-Br(1)
P(1)-C(111)
P(1)-C(121)
P(1)-C(6)
9b
Pd-C(1L)
Pd-N(1)
2.007(4)
2.167(4)
2.256(1)
2.416(1)
1.455(6)
1.490(6)
1.492(6)
1.835(4)
P(1)-C(121)
1.834(4)
1.840(4)
81.1(2)
97.7(1)
176.8(1)
165.1(1)
91.8(1)
90.1(1)
P(1)-C(111)
Pd-P(1)
C(1L)-Pd-N(1)
C(1L)-Pd-P(1)
N(1)-Pd-P(1)
C(1L)-Pd-Cl(1)
N(1)-Pd-Cl(1)
P(1)-Pd-Cl(1)
Pd-Cl(1)
N(1)-C(8L)
N(1)-C(9L)
N(1)-C(7L)
P(1)-C(6)
F igu r e 3. An ORTEP view of the structure of the complex
PdBr(p-NCC6H4) (2b), 8b. Ellipsoids are drawn at 50%
probability.
diffraction, and an ORTEP view of this molecule is given
in Figure 3.
Solid -Sta te Str u ctu r e of 8b. Complex 8b reveals a
slightly distorted square-planar structure with the
bromide ligand in a trans position to the P-donor and
the p-cyano aryl η1 carbon atom trans to the oxazoline
nitrogen. As expected, On the basis of previous struc-
tures13,14a for complexes of 2, the oxazoline ring is
rotated ca. +98° with respect to the Br-Pd-N-P plane.
In conventional complexed PHOX ligands, the oxazoline
is approximately in the coordination plane. Further, the
p-cyano-aryl ligand is rotated ca. -71° with respect to
this same coordination plane. This is important in that
this aryl ligand now occupies space fairly remote from
the closest 3,5-di-tert-butylphenyl group, thereby ex-
plaining why no restricted rotation is found in solution.
The 31P, 1H, and 13C assignments for the two different
P(3,5-dialkylphenyl) rings in 9b,c were made by first
assigning both of the two spin systems (indicated by
arrows in 9), using proton-proton and phosphorus-
proton correlations, followed by NOE’s to assign the
remaining protons. Once the protons are assigned, the
two P-aryl rings can be distinguished via NOE’s. Figure
4 shows a slice through the NOESY spectrum for the
3,5-methylphenyl complex, 9c. The pseudoaxial ring in
the molecule is proximate to the binaphthyl backbone,
see fragment 10, and reveals eight different NOE’s
The immediate bonding distances about the Pd-atom
are fairly routine,28 allowing for the differing trans
influences of the four donors, e.g., the Pd-P separation,
2.277(1) Å, lies toward the lower end of the range for
this bond distance, due to the modest trans influence
of the bromide ligand, while the Pd-N bond length,
2.141(4) Å, is slightly long, due to the trans carbon-
donor. We note that the Br-Pd-C(1L) angle, at ca. 86°,
is rather small, suggesting that the p-cyano-aryl ligand
prefers a position remote from the relatively large P-aryl
substituents. A summary of the most relevant distances
and angle is given in Table 3.
NMR a n d Str u ctu r a l Stu d ies for th e MOP Com -
p lexes. To better understand the results from the
catalytic experiments using MOP, we have prepared
several simple MOP complexes, 9, derived from the well-
known chloro-bridged cyclometalated N,N′-dimethyl-
benzylamine.29-31
arising from the methyl groups, six from the backbone
plus two strong interactions involving the immediately
adjacent ortho and para protons. The pseudoequatorial
ring shows only four NOE’s from the methyl groups, two
very weak interactions to the backbone and, again, two
strong interactions involving the proximate ortho and
para protons.
(28) Orpen, A. G.; Brammer, L.; Allen, F. H.; Kennard, O.; Watson,
D. G.; Taylor, R. J . Chem. Soc., Dalton 1989, S1-S83.
(29) Ryabov, A. D.; Sakodinskaya, I. K.; Yatsimirsky, A. K. J . Chem.
Soc., Dalton Trans. 1985, 2629-2637.
(30) Dehand, J .; Pfeffer, M. Coord. Chem. Rev. 1976, 18, 327-352.
Pfeffer, M.; Fischer, J .; Mitschler, A.; Ricard, L. J . Am. Chem. Soc.
1980, 102, 6338.
The cis chloride ligand in 9 is not very bulky; however,
the aryl moiety associated with the cyclometalated ring
(31) Newcome, G. R.; Puckett, W. E.; Gupta, V. K.; Kiefer, G. E.
Chem. Rev. 1986, 86, 451-489.

2300 Organometallics, Vol. 23, No. 10, 2004
Dotta et al.
1
F igu r e 4. A slice through the H,1H NOESY spectrum of
the 3,5-dimethylphenyl MOP analogue, 9c. The pseudo-
axial aryl ring, associated with the low-frequency methyl
signal, reveals many more contacts to the aromatic back-
bone than does the pseudoequatorial analogue. Indeed, for
the methyl group at higher frequency, the two most intense
contacts stem from the adjacent ortho and para protons of
the 3,5-dimethylphenyl moiety and not from the interring
NOE’s (CD2Cl2).
F igu r e 6. An ORTEP view of the structure of the cyclo-
metalated Pd complex, 9b. Ellipsoids are drawn at 50%
probability.
To complement these NMR studies we have deter-
mined the solid-state structure of 9b using X-ray
diffraction methods.
Solid -Sta te Str u ctu r e of 9b. Figure 6 shows an
ORTEP view of the new MOP complex. Complex 9b
reveals a distorted square-planar structure with the
chloride ligand in a trans position to the C-donor and
the MOP P-donor trans to the dimethylamino nitrogen.
The coordination distances are fairly standard, although
both the Pd-N, 2.167(4) Å, and Pd-Cl, 2.416(1) Å,
separations are on the longish side,28 due to the rela-
tively strong trans influences of the P- and C-donors,
respectively.
The pseudoaxial P(3,5-di-tert-butylphenyl) group, iden-
tified via the torsion angle Cl(1)-Pd-P(1)-C(111) ) ca.
-83°, is found closest to the C,N-chelate ring in agree-
ment with the NMR studies. Interestingly, the binaph-
thyl backbone is positioned closest to the chloride ligand
(the torsion angle Cl(1)-Pd-P(1)-C(6) is ca. 34°). This
observation serves as a reminder that one is not certain
as to which of the possible MOP substituent fragments
actually approaches the position occupied by potential
substrate.
The bond angles about the Pd atom are interesting.
The C(1L)-Pd-N(1) angle at 81.1(2)° is, as expected,
fairly small, due to the five-membered ring. Conse-
quently, the remaining two ligands, Cl- and MOP, will
have a little more space. The N(1)-Pd-Cl(1) angle,
91.8(1)°, is only slightly opened; however, the C(1L)-
Pd-P(1) angle, 97.7(1)°, is relatively large. Since the
sum of the four angles from the various cis-positioned
ligands is 360.7°, it seems reasonable that the larger
97.7(1)° angle arises from steric crowding between the
MOP and the cyclometalated aromatic ring, again in
agreement with the NMR experiments. Indeed, the
ORTEP view suggests that the molecule is somewhat
congested in the area between the MOP and the C,N-
chelate ring. Despite the congestion, we note that the
three C-P-C angles are all fairly normal: C(6)-P(1)-
C(121) ) 100.3(2)°, C(6)-P(1)-C(111) ) 107.1(2)°, and
C(121)-P(1)-C(111) ) 104.0(2)°.
F igu r e 5. 1H NMR spectra measured as a function of
temperature for the complexes 9b and 9c in the methyl
region. For the 3,5-di-tert-butylphenyl complex (left) the
restricted rotation is clearly visible at 253 K, whereas for
the 3,5-dimethylphenyl compound (right) the restricted
rotation is recognized at 233 K; for 9c, the ca. 2.55 ppm
resonance stems from a N-methyl group (CD2Cl2).
lies approximately in the coordination plane and is thus
sterically significant with respect to the proximate MOP
ligand. Figure 5 shows sections of the appropriate
1
variable temperature H spectra for 9b (left side) and
9c (right side). At ambient temperature, the 18-proton
tert-butyl signal of the pseudoaxial ring in 9b is quite
broad, and at 273 K, broad but resolved. At 233 K all
four 9-proton signals are resolved. The spectra for the
dimethyl analogue, 9c, reveal the first set of resolved
methyl signals at 233 K, i.e., the barrier to rotation is
lower. The aryl protons of 9a begin to show well-resolved
ortho proton resonances from the P-aryl moieties below
200 K. Once again there is selective restricted rotation
induced by the presence of the 3,5-dialkyl groups.

3,5-Dialkyl Effect on Enantioselectivity in Pd Chemistry
Organometallics, Vol. 23, No. 10, 2004 2301
Discu ssion
The catalytic results support a substantial 3,5-dialkyl
effect on enantioselectivity based on the four different
Pd-catalyzed reactions presented. Moreover, given that
some few earlier studies on Ru(II),15a Rh(I),17 and Ir(I)15b
catalyzed hydrogenation, using 3,5-dialkyl-substituted
auxiliaries, all showed improved ee’s, we feel justified
in suggesting that the effect has some generality. It is
also noteworthy that the effect is operative for MOP, a
presumed monodentate auxiliary.
The >20% improvements in ee observed seem associ-
ated with reactions which, initially, gave only moderate-
to-poor ee’s. Moreover, it is not always the case that the
3,5-di-tert-butylphenyl groups on the phosphorus afford
the largest increases. In one or two examples, the 3,5-
dimethylphenyl substituents could be shown to induce
the desired improvement, whereas the tert-butyl ana-
logues proved to be worse in terms of ee. This brings us
to the solution studies.
ylphenyl analogue will occasionally be superior. The
energy difference, ∆∆Gq, associated with a 10% ee
improvement between ca. 80% and 90% is known to be
of the order of 1 kcal.32 Consequently, small structural
changes can be important. Undoubtedly, our structural
3,5-dialkyl effect on enantioselectivity is quite subtle,
but useful.
Exp er im en ta l Section
All water- or air-sensitive manipulations were carried out
under a nitrogen atmosphere. Pentane and ether were distilled
from NaK, THF and toluene from potassium, and CH2Cl2 from
CaH2. The MeO-Biphep ligands 1a and 1b were a gift from F.
Hoffmann-La Roche AG. The phosphino-oxazoline ligands 2a 33
and 2b,14 the MOP ligands, 4a ,34 4c,35 5a ,36 and 6a ,34 the
intermediates (R)-2-(bis(3,5-di-tert-butylphenyl)phosphinyl)-2′-
((trifluoromethane-sulfonyl)oxy)-1,1′-binaphthyl14 and (R)-2-
(bis(3,5-di-tert-butylphenyl)phosphinyl)-2′-(cyano)-1,1′-binaph-
thyl,14 and the complexes 7a ,32 7b,14 and 8a 13 were synthesized
according to the literature. NMR spectra were recorded with
Bruker DPX-250, -300, -400, and -500 MHz spectrometers at
room temperature unless otherwise noted. Chemical shifts are
given in ppm, coupling constants (J ) in Hertz. Elemental
analyses and mass spectroscopic studies were performed at
ETHZ.
The variable-temperature 1H NMR studies on the
model complexes, 7 and 9, which have additional ligands
occupying space on or near the coordination plane,
suggest that the 3,5-di-tert-butylphenyl groups induce
selective restricted rotation around the pseudoaxial aryl
P-C(ipso) bond. We suggest that the additional crowd-
ing due to the meta substituents will move part of the
tertiary phosphine toward the remaining ligands. This
will, in turn, make the ligand more intrusive with
respect to complexed olefin substrate, and thus, the
chiral pocket more selective. For complexes of the P,N
ligand, 2, a 3,5-dialkylphenyl substituent moves closer;
however, for MOP it is not yet certain which of the three
P-substituents is involved.
Cr ysta llogr a p h y. Colorless crystals of PdBr(p-CN-C6H4)-
(2b), 8b, suitable for X-ray diffraction, were obtained by
diffusion from a CH2Cl2/pentane mixture and are air stable.
Air-stable, yellow crystals of (C6H4CH2NMe2)Pd(4b)Cl, 9b,
were obtained from a methanol/water solution.
Crystals were mounted on a Bruker SMART diffractometer,
equipped with a CCD detector, for the unit cell and space group
determinations. Crystals of 8b were cooled, using a cold
nitrogen stream, to 200(2) K for the data collection; for 9b data
were collected at room temperature. Selected crystallographic
and other relevant data are listed in Table 4 and in the
Supporting Information (Table S1).
The observed normal barriers to rotation found in 8b
are not surprising since the aryl ligand is rotated away
from the coordination plane. For a hypothetical complex
related to 8b, but containing an in-plane olefin (a
possible transition state in the Heck reaction, see 10),
Data were corrected for Lorentz and polarization factors
with the data reduction software SAINT37 and empirically for
absorption with the SADABS program.38
the crowding would increase. If, instead, a five-coordi-
nate transition state were correct, e.g., Pd(Br or triflate)-
(phenyl or 2-naphthyl)(dhf)(2b), there would again be
increased steric interactions. For both coordination
numbers, we expect that higher barriers should be
observed. Unfortunately, we have never been able to
detect a dhf complex related to 10.
However, one can have too much of a good thing. In
the MOP hydrosilylation chemistry, the 3,5-di-tert-
butylphenyl groups are not advantageous. In 11, which
might be a relevant structure since the hydride migrates
to the methylene group, the styrene phenyl moiety
might well interact with the pseudoequatorial P-aryl
substituent (or the naphthyl backbone). If the P-sub-
stituent moves too close to the remaining ligands and
interferes with complexation and/or induces a change
in the transition state structure, then a reduced ee may
result. This is likely to be the reason the 3,5-dimeth-
The structures were solved by Patterson and Fourier
methods and refined by full-matrix least squares39 (the func-
2
tion minimized being ∑[w(Fo2 - (1/k)Fc )]). For both structures,
no extinction correction was deemed necessary. The scattering
factors used, corrected for the real and imaginary parts of the
(32) Sheldon, R. A. In Chirotechnology; Marcel Dekker: New York,
1993; pp 39-73.
(33) Selvakumar, K.; Valentini, M.; Wo¨rle, M.; Pregosin, P. S.;
Albinati, A. Organometallics 1999, 18, 1207-1215.
(34) Uozumi, Y.; Suzuki, N.; Ogiwara, A.; Hayashi, T. Tetrahedron
1994, 50, 4293-4302.
(35) Hayasji, T.; Hirate, S.; Kitayama, K.; Tsuji, H.; Torii, A.;
Uozumi, Y. J . Org. Chem. 2001, 66, 1441-1449.
(36) Uozumi, Y.; Tanahashi, A.; Lee, S.; Hayashi, T. J . Org. Chem.
1993, 58, 1945-1948.
(37) BrukerAXS, SAINT, Integration Software; Bruker Analytical
X-ray Systems: Madison, WI, 1995.
(38) Sheldrick, G. M. SADABS, Program for Absorption Correction;
University of Go¨ttingen: Go¨ttingen, Germany, 1996.
(39) Sheldrick, G. M. SHELX-97, Structure Solution and Refinement
Package; Universita¨t Go¨ttingen: Go¨ttingen, Germany, 1997.

2302 Organometallics, Vol. 23, No. 10, 2004
Ta ble 4. Exp er im en ta l Da ta for th e X-r a y Diffr a ction Stu d y of 8b‚H2Cl2 a n d 9ba
Dotta et al.
compd
formula
mol wt
collection T, K
diffractometer
cryst syst
space group (no.)
a, Å
8b‚CH2Cl2
62H70 BrCl2N2OPPd
1147.38
200(2)
9b
C
C57H67ClNPPd
938.94
293(2)
Bruker SMART CCD
monoclinic
P21 (no. 4)
14.6172(2)
12.7682(1)
17.5686(3)
111.713(1)
3046.28(7)
2
monoclinic
P21 (no. 4)
15.193(2)
10.700(1)
15.882(2)
92.449(3)
2579.5(5)
2
b, Å
c, Å
â, deg
V, Å3
Z
F
(calcd), g cm-3
1.251
11.13
1.209
4.78
µ, cm-1
radiation
Mo KR graphite monochrom., λ ) 0.71073 Å
1.56 < θ < 27.46
31530
13850
10925
θ range, (deg)
no. data collected
no. independent data
no. obsd reflns (no)
1.82 < θ < 26.02
24512
10137
8019
2
2
[|Fo| > 2.0σ(|F| )]
no. of param refined (nv)
abs structure (Flack’s) param
Rint
652
544
0.008(8)
0.0580
0.0448
0.1079
0.820
0.04(2)
0.0367
0.0379
0.0884
0.979
R (obsd reflns)a
Rw2 (obsd reflns)b
GOFc
R ) ∑(|Fo - (1/k)Fc|)/∑|Fo|. Rw ) [∑w(Fo - (1/k)Fc2)2/∑w |Fo | ]. c GOF ) [∑w(Fo - (1/k)Fc2)2/(no - nv)]1/2
.
a
b
2
2
2 2
2
anomalous dispersion, were taken from the literature.40 The
by using ω scans, in steps of 0.3 deg. For each of the 1878
collected frames, counting time was 15 s.
standard deviations on intensities were calculated in term of
statistics alone. Refining the Flack’s parameter tested the
handedness of the structure (cf. Table 4).41 All calculations
were carried out by using the PC version of SHELX-9739 and
ORTEP programs.42
Str u ctu r a l Stu d y of P d Br (p-CN-C6H4)(2b)‚CH2Cl2, 8b‚
CH2Cl2. The space group was unambiguously determined from
the systematic absences, while the cell constants were refined
by least squares, at the end of the data collection, using 2414
reflections (θmax e 22.5°). The data were collected (up to
sin(θ/λ) ) 0.649) by using ω scans, in steps of 0.3 deg. For each
of the 2142 collected frames, counting time was 20 s.
The t-Bu substituents on the phenyl rings show large
amplitude vibrational displacements that, nonetheless, could
be modeled satisfactorily by using anisotropic displacements
for the C atoms. However, for the carbons bound to atom C127,
two different orientations were clearly shown in the difference
Fourier maps. Thus, the two orientations were refined by using
isotropic displacement parameters for the disordered C atoms.
The occupancy factors, for the two orientations, are ap-
proximately equal (0.59 and 0.41, respectively). All other atoms
were refined by using anisotropic displacement parameters.
Toward the end of refinement, a highly disordered chla-
trated solvent molecule (CH2Cl2) was found in the difference
Fourier maps. Two different orientations were refined but the
resulting solvent geometry is poorly defined.
The contribution of the hydrogen atoms, in their calculated
positions (C-H ) 0.95 Å, B(H) ) 1.3/1.5 × B(Cbonded) Å2), was
included in the refinement by using a riding model. Upon
convergence (see Table S1) no significant features were found
in the difference Fourier map.
Str u ctu r a l Stu d y of (C6H4CH2NMe2)P d (4b)Cl, 9b. The
space group was unambiguously determined from the system-
atic absences, while the cell constants were refined by least
squares, at the end of the data collection, using 991 reflections
(θmax e 21.7°). The data were collected (up to sin(θ/λ) ) 0.617)
As in the previous case, the t-Bu substituents are disordered.
Two different orientations (with approximately equal weights)
for the carbon atoms bound respectively to atoms C118, C127,
and C128 were clearly shown in the difference Fourier maps,
and a disorder model was refined, as above. The remaining
t-Bu group was satisfactorily refined anisotropically.
Anisotropic displacement parameters were used for all other
atoms. The contribution of the hydrogen atoms, in their
calculated positions (C-H ) 0.95 Å, B(H) ) 1.3/1.5 × B(Cbonded
)
Å2), was included in the refinement by using a riding model.
Upon convergence (see Table S1) the final Fourier difference
map showed no significant peaks.
Syn th esis of th e P h osp h in e Oxid e (S)-2-(Bis(3,5-d i-
ter t-bu tylp h en yl)p h osp h in yl)-1,1′-bin a p h th yl. To a mix-
ture of (S)-2-trifluoromethanesulfonyloxy-1,1′-binaphthyl (1.38
g 3.43 mmol), palladium acetate (39 mg, 0.085 mmol), 1,4-bis-
(diphenylphosphino)butane (73 mg, 0.085 mmol), and bis(3,5-
di-tert-butylphenyl)phosphine oxide (1.76 g, 4.13 mmol) was
added 12 mL of DMSO and 2.35 mL of diisopropylethylamine
(1.77 g, 13.7 mmol). The mixture was heated with stirring at
100 °C for 20 h. After being cooled to room temperature, the
reaction mixture was concentrated under reduced pressure.
The residue was diluted with EtOAc, washed twice with water,
dried over Na2SO4, and concentrated under reduced pressure.
Chromatography on silica gel (hexane/EtOAc ) 3:1) gave 2.33
g (100%) of the product as a white solid. Anal. Calcd for C48
-
1
H
55OP: C, 84.92; H, 8.16. Found: C, 84.99; H, 8.09. H NMR
(CDCl3, 250 MHz): δ 7.78-7.99 (m, aromatic, 2H), 7.38-7.74
(m, aromatic, 8H), 7.17-7.29 (m, aromatic, 5H), 7.02-7.08 (m,
3
aromatic, 2H), 6.91 (d, J HH ) 8.0, aromatic, 1 H), 1.31 (s,
C(CH3)3, 18 H), 1.17 (s, C(CH3)3, 18 H). 13C NMR (CDCl3, 62.9
MHz): δ 35.0 (C(CH3)3), 34.7 (C(CH3)3), 31.4 (s, C(CH3)3), 31.2
(C(CH3)3). 31P NMR (CDCl3, 101.3 MHz): δ 27.9 (s). MS
(ESI): 679.1 (M+, 100%).
Syn th esis of (S)-2-(Bis(3,5-d i-ter t-bu tylp h en yl)p h os-
p h in o)-1,1′-bin a p h th yl, 4b. To a mixture of (S)-2-(bis(3,5-
di-tert-butylphenyl)phosphinyl)-1,1′-binaphthyl (2.32 g, 3.42
mmol) and triethylamine (9.7 mL, 69 mmol) in 50 mL of xylene
was added HSiCl3 (1.8 mL, 18.4 mmol). The mixture was
heated to 130 °C for 6 h. After being cooled to room temper-
ature, the mixture was diluted with ether and quenched with
(40) International Tables for X-ray Crystallography; Wilson, A. J .
C., Ed.; Kluwer Academic Publisher: Dordrecht, The Netherlands,
1992; Vol. C.
(41) Flack, H. D. Acta Crystallogr. 1983, A39, 876.
(42) Farrugia, L. J . J . Appl. Crystallogr. 1997, 30, 565.

3,5-Dialkyl Effect on Enantioselectivity in Pd Chemistry
Organometallics, Vol. 23, No. 10, 2004 2303
a small amount of saturated NaHCO3. The resulting suspen-
sion was filtrated over Celite and the Celite washed with
copious amounts of ether. After removal of the solvent, the
crude product was purified by chromatography on silica gel
(hexane/EtOAc ) 30:1) to give 2.20 g (97%) of the product as
a white solid. Anal. Calcd for C48H55P: C, 86.97; H, 8.36.
Found: C, 86.87; H, 8.25. 1H NMR (CDCl3, 250 MHz): δ 7.91-
8.03 (m, aromatic, 4H), 7.03-7.60 (m, aromatic, 15 H), 1.37
(s, C(CH3)3, 18 H), 1.25 (s, C(CH3)3, 18 H). 13C NMR (CDCl3,
62.9 MHz): δ 34.9 (C(CH3)3), 34.8 (C(CH3)3), 31.5 (C(CH3)3),
31.4 (C(CH3)3). 31P NMR (CDCl3, 101.3 MHz): δ -11.6 (s). MS
(ESI): 663.1 (M+, 100%).
aromatic, 3H), 6.90-7.56 (m, aromatic, 14 H), 3.57 (s, OCH3,
3H), 1.29 (s, C(CH3)3, 18 H), 1.21 (s, C(CH3)3, 18 H). 13C NMR
(CDCl3, 62.9 MHz): δ 56.0 (OCH3), 34.9 (C(CH3)3), 34.7
(C(CH3)3), 31.5 (C(CH3)3), 31.4 (C(CH3)3). 31P NMR (CDCl3,
101.3 MHz): δ -11.4 (s). MS (HiResMALDI): calcd 693.4220,
found 693.4195 (M+, 100%).
Syn th esis of (R)-2-(Bis(3,5-d i-ter t-bu tylp h en yl)p h os-
p h in o)-2′-(cya n o)-1,1′-bin a p h th yl, 6b. To a mixture of (R)-
2-(bis(3,5-di-tert-butylphenyl)phosphinyl)-2′-(cyano)-1,1′-bi-
naphthyl (0.42 g, 0.60 mmol) and triethylamine (1.7 mL, 12.1
mmol) in 12 mL of xylene was added HSiCl3 (0.31 mL, 3.1
mmol). The mixture was heated to 130 °C for 6 h. After being
cooled to room temperature, the mixture was diluted with
ether and quenched with a small amount of saturated NaH-
CO3. The resulting suspension was filtrated over Celite and
the Celite washed with copious amounts of ether. After
removal of the solvent, the crude product was purified by
chromatography on silica gel (hexane/EtOAc ) 9:1) to give 0.41
Syn th esis of (R)-2-(Bis(3,5-d i-ter t-bu tylp h en yl)p h os-
p h in yl)-2′-(h yd r oxy)-1,1′-bin a p h th yl. To a stirred solution
of 2.07 g of (R)-2-(bis(3,5-di-tert-butylphenyl)phosphinyl)-2′-
((trifluoromethane-sulfonyl)oxy)-1,1′-binaphthyl (2.50 mmol)
in a 2/1 mixture of 1,4-dioxane and methanol (15 mL) was
added 2 mL of an aqueous 3 M NaOH solution. The solution
was stirred for 24 h at room temperature. After addition of 3
mL of 3 M HCl and 100 mL of EtOAc, the organic phase was
separated and washed with water. Another 3 mL of 3 M HCl
was added to the aqueous phase, which was extracted once
again with EtOAc. The combined organic phases were dried
over MgSO4. Evaporation of the solvent followed by chroma-
tography (silica gel, hexane/EtOAc ) 5:1) gave 1.566 g (90%)
of the product as a white solid. Anal. Calcd for C48H55O2P: C,
82.96; H, 7.98. Found: C, 83.07; H, 8.16. 1H NMR (CD2Cl2,
250 MHz): δ 9.73 (s, OH, 1H), 6.85-8.05 (m, aromatic, 17 H),
6.37 (d, 3J HH ) 8.3, aromatic, 1H), 1.40 (s, C(CH3)3, 18 H), 1.14
(s, C(CH3)3, 18 H). 13C NMR (CD2Cl2, 62.9 MHz): δ 35.1
(C(CH3)3), 34.4 (C(CH3)3), 31.1 (C(CH3)3), 30.8 (C(CH3)3). 31P
NMR (CD2Cl2, 101.3 MHz): δ 31.0 (s). MS (ESI): 695.2 (M+,
100%).
g (99%) of the product as a white solid. Anal. Calcd for C49
-
H
54NP: C, 85.55; H, 7.91; N, 2.04. Found: C, 85.51; H, 7.91;
N, 1.92. 1H NMR (CDCl3, 250 MHz): δ 7.87-8.07 (m, aromatic,
4H), 7.81 (d, 3J HH ) 8.5, aromatic, 1H), 6.92-7.55 (m, aromatic,
13 H), 1.26 (s, C(CH3)3, 18 H), 1.17 (s, C(CH3)3, 18 H). 13C NMR
(CDCl3, 62.9 MHz): δ 34.9 (C(CH3)3), 34.7 (C(CH3)3), 31.3
(C(CH3)3), 31.3 (C(CH3)3). 31P NMR (CDCl3, 101.3 MHz): δ
-12.6 (s). MS (HiResMALDI): 688.4060 (M+, 100%).
Syn th esis of P d Br (p-CN-C6H4)(2b), 8b. To a mixture of
30 mg of PdBr(p-CN-C6H4)(TMEDA) (0.074 mmol) and 57.4
mg of 2b (0.074 mmol) was added 3 mL of THF. The solution
was stirred at 65°C for 18 h. After the solution was cooled to
room temperature, the solvent was evaporated and the residue
chromatographed on silica gel (CH2Cl2/acetone ) 100:1).
Recrystallization from CH2Cl2/pentane gave 59 mg (75%) of
the product as a white solid. Anal. Calcd for
C61H68N2-
Syn th esis of (R)-2-(Bis(3,5-d i-ter t-bu tylp h en yl)p h os-
p h in yl)-2′-(m eth oxy)-1,1′-bin a p h th yl. To a suspension of
(R)-2-(bis(3,5-di-tert-butylphenyl)phosphinyl)-2′-(hydroxy)-1,1′-
binaphthyl (1.56 g, 2.24 mmol) and potassium carbonate (1.23
g, 8.9 mmol) in acetone (15 mL) was added MeI (1.28 g, 9.0
mmol). The mixture was heated to 60 °C and stirred for 5 h at
which point another 0.68 g of MeI was added followed by
stirring for 16 h at 60 °C. After being cooled to room
temperature, the reaction mixture was filtrated over Celite
and the Celite washed with CH2Cl2. The solvents were
evaporated and the residue chromatographed on silica gel
(hexane/EtOAc ) 3:2) to give 1.45 g (91%) of the product as a
white solid. Anal. Calcd for C49H57O2P: C, 83.01; H, 8.10.
Found: C, 83.09; H, 8.10. 1H NMR (CD2Cl2, 400 MHz): δ 7.96-
OPBrPd: C, 68.96; H, 6.45; N, 2.64. Found: C, 68.69; H, 6.69;
3
N, 2.55. 1H NMR (CD2Cl2, 500 MHz): δ 4.01 (t, J HH ) 8.5,
1H, OCH2), 3.55 (m, 1H, NCH), 3.34 (t, 3J HH ) 9.5, 1H, OCH2),
2.74 (m, 1H, CH(CH3)2), 1.24 (s, 18H, C(CH3)3), 1.06 (d,
3
3J HH ) 7, 3H, CH(CH3)2), 0.87 (d, J HH ) 6.5, 3H, CH(CH3)2),
0.85 (s, 18H, C(CH3)3). 13C NMR (CD2Cl2, 125 MHz): δ 72.7
(NCH), 71.7 (CH2O), 35.4 (C(CH3)3), 34.8 (C(CH3)3), 31.5
(C(CH3)3), 31.2 (C(CH3)3), 29.6 (CH(CH3)2), 21.4 (CH(CH3)2),
16.6 (CH(CH3)2). 31P NMR (CDCl3, 202 MHz): δ 25.6 (s). MS
(FAB): 981.5 (M+ - Br, 40%). For a more detailed NMR
assignment see the Supporting Information.
Syn th esis of (C6H4CH2NMe2)P d (4a )Cl, 9a . To a mixture
of [Pd(µ-Cl)][(C6H4CH2NMe2)]2 (30 mg, 0.054 mmol) and 4a
(47.7 mg, 0.109 mmol) was added 3 mL of CH2Cl2. The solution
was stirred for 30 min at room temperature. After removal of
the solvent, the crude product was recrystallized from toluene/
pentane to give 114 mg (74%) of the product. Anal. Calcd for
3
7.91 (m, aromatic, 2 H), 7.80 (d, J HH ) 9.1 Hz, aromatic, 1
H), 7.72-7.66 (m, aromatic, 2 H), 7.54-7.44 (m, aromatic, 4
H), 7.33-7.12 (m, aromatic, 7 H), 6.94 (m, aromatic, 1 H), 6.73
(d, 3J HH ) 8.4 Hz, aromatic, 1 H), 1.27 (s, C(CH3)3, 18 H), 1.20
(s, C(CH3)3, 18 H). 13C NMR (CDCl3, 100 MHz): δ 57.0 (O-
CH3), 35.3 (C(CH3)3), 35.2 (C(CH3)3), 31.8 (C(CH3)3), 31.7
(C(CH3)3). 31P NMR (CDCl3, 162 MHz): δ 29.4 (s). MS (ESI):
709.1 (M+, 100%).
C
41H35NPClPd: C, 68.91; H, 4.94; N, 1.96. Found: C, 68.71;
H, 4.98; N, 2.03. 1H NMR (CD2Cl2, 500 MHz): δ 4.52 (d,
3J HH ) 13, 1H, NCH2), 3.48 (dd, J HH ) 13, J PH ) 3.5, 1H,
3
4
4
NCH2), 3.05 (d, J PH ) 2.5, 3H, NCH3), 3.05 (s, 3H, NCH3).
13C NMR (CD2Cl2, 125 MHz): δ 73.8 (NCH2), 52.4 (NCH3), 49.0
(NCH3). 31P NMR (CDCl3, 202 MHz): δ 39.1 (s). MS (HiRes-
MALDI): calcd 678.1550, found 678.1544 (M+ - Cl, 100%).
For a more detailed NMR assignment see the Supporting
Information.
Syn th esis of (R)-2-(Bis(3,5-d i-ter t-bu tylp h en yl)p h os-
p h in o)-2′-(m eth oxy)-1,1′-bin a p h th yl, 5b. To a mixture of
(R)-2-(bis(3,5-di-tert-butylphenyl)phosphinyl)-2′-(methoxy)-1,1′-
binaphthyl (1.45 g, 2.03 mmol) and triethylamine (5.8 mL, 41.3
mmol) in 40 mL of xylene was added HSiCl3 (1.1 mL, 11 mmol).
The mixture was heated to 130 °C for 6 h. After being cooled
to room temperature, the mixture was diluted with ether and
quenched with a small amount of saturated NaHCO3. The
resulting suspension was filtrated over Celite and the Celite
washed with copious amounts of ether. After removal of the
solvent, the crude product was purified by chromatography
on silica gel (hexane/EtOAc ) 25:1) to give 1.43 g (100%) of
the product as a white solid. Anal. Calcd for C49H57O2P: C,
84.93; H, 8.29. Found: C, 84.91; H, 8.22. 1H NMR (CDCl3, 250
Syn th esis of (C6H4CH2NMe2)P d (4b)Cl, 9b. To a mixture
of [Pd(µ-Cl)][(C6H4CH2NMe2)]2 (30 mg, 0.054 mmol) and 4b
(72.1 mg, 0.109 mmol) was added 3 mL of CH2Cl2. The solution
was stirred for 30 min at room temperature. After removal of
the solvent, the residue was dissolved in 2 mL of pentane. After
a few seconds, the product precipitated from the solution and
was removed by filtration. Yield: 76 mg (74%). Anal. Calcd
for C57H67NPClPd: C, 72.91; H, 7.19; N, 1.49. Found: C, 72.33;
1
H, 7.17; N, 1.59. H NMR (CD2Cl2, 500 MHz): δ 4.54 (b, 1H,
3
3
4
MHz): δ 8.05 (d, J HH ) 9.0, aromatic, 1H), 7.87-7.96 (m,
NCH2), 3.42 (dd, J HH ) 13, J PH ) 3, 1H, NCH2), 3.06 (s, 3H,

2304 Organometallics, Vol. 23, No. 10, 2004
Dotta et al.
NCH3), 2.46 (s, 3H, NCH3), 1.26 (s, 18H, C(CH3)3), 0.81 (br,
18H, C(CH3)3). 13C NMR (CD2Cl2, 125 MHz): δ 73.7 (NCH2),
52.1 (NCH3), 48.4 (NCH3), 35.6 (C(CH3)3), 34.8 (C(CH3)3), 31.5
(C(CH3)3), 30.8 (C(CH3)3). 31P NMR (CDCl3, 202 MHz): δ 40.4
(s). MS (HiResMALDI): 902.4031 (M+ - Cl, 100%). For a more
detailed NMR assignment see the Supporting Information.
Crystals suitable for X-ray diffraction were obtained from a
methanol solution of 9b by adding a few drops of water.
Syn th esis of P d Cl(C6H4CH2NMe2)(4c), 9c. To a mixture
of [Pd(µ-Cl)][(C6H4CH2NMe2)]2 (55.8 mg, 0.101 mmol) and 4c
(100 mg, 0.202 mmol) was added 3 mL of CH2Cl2. The solution
was stirred for 30 min at room temperature. After removal of
the solvent, the residue was recrystallized from toluene/
pentane and washed twice with pentane. Yield: 86 mg (56%).
Anal. Calcd for C45H43NPClPd: C, 70.13; H, 5.62; N, 1.82.
Found: C, 70.23; H, 5.68; N, 1.76. 1H NMR (CD2Cl2, 500
Allylic Alk yla tion . To 4 µmol of [Pd(η3-C3H5)( 2a or 2b)]-
(OTf) in 2 mL of CH2Cl2 were added 28 µL of cyclohexenyl
acetate (0.2 mmol), 68 µL of dimethylmalonate (0.6 mmol), 148
µL of BSA (0.6 mmol), and 1 mg of KOAc. The reaction mixture
was stirred at 40 °C, followed by addition of 50 mL of ether.
The organic phase was washed with water and brine and dried
over MgSO4. After evaporation of the solvent, the crude
product was purified by chromatography on silica gel (hexane/
EtOAc ) 9:1) to give the product as a colorless oil. The ee was
determined by HPLC with a Chiracel OB-H column (hexane/
iPrOH ) 90:10, 0.3 mL/min), tR ) 30.0 min (minor isomer),
tR ) 23.5 min (major isomer).
reaction
time (h)
yield
(%)
ee
(%)
catalyst
[Pd(2a )(η3-C3H5)](OTf)
[Pd(2b)(η3-C3H5)](OTf)
3
20
66
36
36
56
3
3
MHz): δ 4.66 (d, J HH ) 13, 1H, NCH2), 3.49 (d, J HH ) 13,
1H, NCH2), 3.09 (s, 3H, NCH3), 2.56 (s, 3H, NCH3), 2.34 (s,
6H, CH3), 1.62 (s, 6H, CH3). 13C NMR (CD2Cl2, 125 MHz): δ
73.8 (NCH2), 52.4 (NCH3), 48.6 (NCH3), 21.6 (CH3), 20.8 (CH3).
31P NMR (CDCl3, 202 MHz): δ 40.0 (s). MS (HiResMALDI):
calcd 734.2178, found 734.2204 (M+ - Cl, 64%). For a more
detailed NMR assignment see the Supporting Information.
Alk yla tin g Rin g Op en in g of Oxa ben zon or bor n a d ien e.
To a mixture of Pd(ligand)Cl2 (17 µmol) and 50 mg of
oxabenzonorbornadiene (0.35 mmol) were added 10 mL of
CH2Cl2 and a solution of dialkylzinc (0.26 mL of 2 M ZnMe2
in toluene or 0.52 mL of 1 M ZnEt2 in hexane, 0.52 mmol).
The resulting solution was stirred at room temperature. The
reaction was worked up by addition of a few drops of water,
stirring for half an hour, filtration over Celite, and evaporation
of the solvent. The crude product was purified by silica gel
chromatography (hexane/EtOAc ) 5:1). The ee was determined
by HPLC: (R ) Me) Chiracel OB-H, hexane/iPrOH ) 98:2,
0.5 mL/min, tR ) 21.5 min (major isomer for 2), tR ) 24.1 min
(major isomer (R)-1); (R ) Et) Chiracel OD-H, hexane/
iPrOH ) 98:2, 0.5 mL/min, tR ) 20.2 min (major isomer for
(R)-1), tR ) 18.7 min (minor isomer (R)-1).
Heck Ch em istr y. To a mixture of the catalyst (15 µmol of
Pd(OAc)2 and 30 µmol of ligand 4 or 15 µmol of Pd(dba)2 and
16.5 µmol of ligand 4) and 138.1 mg of 2-naphthyltriflat (0.5
mmol) were added 3 mL of toluene, 261 µL of NEtiPr2 (1.5
mmol) and 189 µL of 3,4-dihydrofuran (2.5 mmol). The solution
was stirred at 40 °C. Addition of 100 mL of pentane, washing
with 0.1 M HCl and saturated NaHCO3, drying over Na2SO4,
and chromatography on silica gel (hexane/EtOAc ) 19:1) gave
the product as a white solid. The ee was determined by HPLC
with a Chiracel OD-H column (hexane/iPrOH ) 99:1, 0.5 mL/
min), tR ) 19.6 min (minor isomer), tR ) 17.3 min (major
isomer).
Hyd r osilyla tion Ch em istr y. In a typical procedure, to a
mixture of 0.8 mg of [Pd(µ-Cl)(η3-C3H5)]2 (2.1 µmol) and 3.8
mg of ligand 4a (8.2 µmol) was added 0.5 mL of styrene (4.33
mmol). The solution was cooled to 5 °C and 0.53 mL of HSiCl3
(5.3 mmol) was added. The reaction solution was stirred at 5
°C for 20 h. NMR analysis confirmed complete disappearance
of the signals of styrene. The product was carefully poured
into a suspension of KF (4.3 g) in MeOH (40 mL) and stirred
for 30 min. The solvent was removed in vacuo, after which
DMF (50 mL) and H2O2 (35% water solution, 4.5 mL) were
added and the mixture was heated for 1 h at 60-70 °C. The
suspension was filtrated over Celite and the Celite washed
with 100 mL of CH2Cl2. The organic phase was washed with
water and dried over Na2SO4. Evaporation of the solvent and
chromatography on silica gel (hexane/EtOAc ) 4:1) gave 370
mg (70%) of 1-phenylethanol. The ee (92%) was determined
by HPLC: (1-phenylethanol) Chiracel OB-H, hexane/iPrOH )
90:10, 0.5 mL/min, tR ) 16.7 min ((S)-enantiomer), tR ) 12.5
min ((R)-enantiomer); (1-(4-MeO-phenyl)ethanol) Chiracel OB-
H, hexane/iPrOH ) 90:10, 0.5 mL/min, tR ) 31.9 min ((R)-
enantiomer), tR ) 23.8 min ((S)-enantiomer); (1-naphthyleth-
anol) Chiracel OD-H, hexane/iPrOH ) 90:10, 0.5 mL/min,
tR ) 20.7 min ((R)-enantiomer), tR ) 18.4 min ((S)-enantiomer).
Ack n ow led gm en t. P.S.P. thanks the Swiss Na-
tional Science Foundation, the “Bundesamt fu¨r Bildung
und Wissenschaft”, and the ETHZ for financial support.
A.A. thanks MURST for a grant (PRIN 2003). We also
thank J ohnson Matthey for the loan of precious metals.
Su p p or tin g In for m a tion Ava ila ble: Full listing of crys-
tallographic data for 8b‚CH2Cl2 and 9b, including tables of
positional and isotropic equivalent displacement parameters,
anisotropic displacement parameters, calculated positions of
the hydrogen atoms, bond distances, bond angles, and torsional
angles; figures showing the full numbering schemes; and NMR
details for 8b and 9a -c (Table S13). This material is available
free of charge via the Internet at http://pubs.acs.org.
reaction
time (h)
yield
(%)
ee
(%)
ligand
Pd source
2a
2b
2a
2b
Pd(OAc)2
Pd(OAc)2
Pd(dba)2
Pd(dba)2
96
300
71
71
14
87
80
79
97
79
98
89
OM034381B