Modular furanoside phosphite ligands for asymmetric Pd-catalyzed allylic substitution

Article abstract of DOI:10.1021/jo0159284

A series of diphosphite, phosphine-phosphite, and thioether-phosphite ligands 1-5 with a furanoside backbone have been used in the enantioselective palladium-catalyzed allylic substitution of rac-1,3-diphenyl-2-propenyl acetate giving low to high enantioselectivies (from close to 0% to 97% ee). The modular nature of these ligands enables systematic investigations of the effect of the ligand structure on the enantioselectivity. The enantioselectivity is mainly determined by the configuration of the stereogenic center C-3 of the furanose backbone. From this we conclude that the attack of the nucleophile takes place trans toward the donating group at the stereogenic C-5 atom. Systematic variation of the donor group attached to the carbon atom C-5 indicated that the presence of a bulky phosphite functionality has a positive effect on enantioselectivity. Thus, the highest ee's are obtained using the bulky diphosphite ligand 1b containing a xylofuranoside backbone.

Full text of DOI:10.1021/jo0159284

J . Org. Chem. 2001, 66, 8867-8871
8867
Mod u la r F u r a n osid e P h osp h ite Liga n d s for Asym m etr ic
P d -Ca ta lyzed Allylic Su bstitu tion
†
‡
†
‡
Oscar P a` mies, Gino P. F. van Strijdonck, Montserrat Di e´ guez, Sirik Deerenberg,
†
†
,†
‡
Gemma Net, Aurora Ruiz, Carmen Claver,* Paul C. J . Kamer, and
Piet W. N. M. van Leeuwen*,
‡
Departament de Qu ı´ mica F ı´ sica i Inorg a` nica, Universitat Rovira i Virgili. Pl. Imperial Tarraco,
1
. 43005 Tarragona, Spain, and Institute of Molecular Chemistry, University of Amsterdam,
Nieuwe Achtergracht 166, 1018 WV Amsterdam, The Netherlands
claver@quimica.urv.es
Received J uly 15, 2001
A series of diphosphite, phosphine-phosphite, and thioether-phosphite ligands 1-5 with a
furanoside backbone have been used in the enantioselective palladium-catalyzed allylic substitution
of rac-1,3-diphenyl-2-propenyl acetate giving low to high enantioselectivies (from close to 0% to
9
7% ee). The modular nature of these ligands enables systematic investigations of the effect of the
ligand structure on the enantioselectivity. The enantioselectivity is mainly determined by the
configuration of the stereogenic center C-3 of the furanose backbone. From this we conclude that
the attack of the nucleophile takes place trans toward the donating group at the stereogenic C-5
atom. Systematic variation of the donor group attached to the carbon atom C-5 indicated that the
presence of a bulky phosphite functionality has a positive effect on enantioselectivity. Thus, the
highest ee’s are obtained using the bulky diphosphite ligand 1b containing a xylofuranoside
backbone.
In tr od u ction
For that purpose, carbohydrates are particularly ad-
vantageous. They are readily available and highly func-
tionalized compounds with several stereogenic centers.
This allows a systematic regio- and stereoselective in-
troduction of different functionalitites in the synthesis
of series of chiral ligands that can be screened in the
The palladium-mediated allylic substitution reaction
is known as an efficient synthetic tool for the formation
of carbon-carbon and carbon-heteroatom bonds.1
A
large number of chiral ligands, mainly P- and N-contain-
ing ligands, possessing either C - or C -symmetry have
5,6
2
1
search for high activities and enantioselectivities. At
been successfully applied to the asymmetric palladium-
catalyzed allylic substitution.1 Among the P-ligands,
diphosphines have played a dominant role in the success
of allylic substitution, although recent reports have also
shown the potential utility of chiral phosphite-oxazo-
the same time, they can provide useful information about
the origin of the stereoselectivity of the reaction.
In previous studies, several types of ligands derived
from carbohydrates have been applied in asymmetric Pd-
allylic substitution with varying degrees of success.
b,d
6n
2
3
4
line, phosphite-thioether, phosphite-phosphine, and
Pregosin et al. reported good enantioselectivities (up to
5
more recently diphosphite ligands in asymmetric allylic
7
9
7%) with thioglucose-based mixed ligands. Widhalm et
alkylation. However, a systematic evaluation of the
effectiveness of these phosphite ligands is hampered by
the lack of a systematic design of series of ligands having
a similar backbone. More research needs to be done to
understand the role of the phosphite moiety in the origin
of the stereochemistry of the allylic substitution reaction.
al. reported moderate (up to 79%) enantiomeric excesses
at room temperature with a new diphosphine, xylophos.
8
(6) For some recent applications, see: (a) Beller, M.; Kraute, J . G.
E.; Zapf, A. Angew. Chem., Int. Ed. Engl. 1997, 36, 772. (b) Yonehara,
K.; Hashizume, T.; Mori, K.; Ohe, K.; Uemura, S. Chem. Commun.
1999, 415. (c) Ayers, T. A.; RajanBabu, T. V. Process Chem. Pharm.
Ind. 1999, 327. (d) Reetz, M. T.; Neugebauer, T. Angew. Chem., Int.
Ed. 1999, 38, 179. (e) P a` mies, O.; Di e´ guez, M.; Net, G.; Ruiz, A.; Claver,
C. Organometallics 2000, 19, 1488. (f) P a` mies, O.; Net, G.; Ruiz, A.;
Claver, Eur. J . Inorg. Chem. 2000, 2011. (g) P a` mies, O.; Di e´ guez, M.;
Net, G.; Ruiz, A.; Claver, C. Chem. Commun. 2000, 1607; (h) Li, W.;
Zhang, Z.; Xiao, D.; Zhang, X. J . Org. Chem. 2000, 65, 3489. (i) P a` mies,
O.; Di e´ guez, M.; Net, G.; Ruiz, A.; Claver, C. Tetrahedron: Asymmetry
2000, 11, 4377. (j) Di e´ guez, M.; P a` mies, O.; Ruiz, A.; Castill o´ n, S.;
Claver, C. Tetrahedron: Asymmetry 2000, 11, 4701. (k) Reetz, M. T.;
Mehler, G. Angew. Chem., Int. Ed. 2000, 39, 3889. (l) P a` mies, O.;
Di e´ guez, M.; Net, G.; Ruiz, A.; Claver, C. Chem Commun. 2000, 2383.
(m) Di e´ guez, M.; P a` mies, O.; Net, G.; Ruiz, A.; Claver, C. Tetrahe-
dron: Asymmetry 2001, 12, 651. (n) Di e´ guez, M.; P a` mies, O.; Ruiz,
A.; Castill o´ n, S.; Claver, C. Chem. Eur. J . 2001, 7, 3086.
*
To whom correspondence should be addressed. claver@
quimica.urv.es and pwnm@anorg.chem.uva.nl.
†
Universitat Rovira i Virgili.
University of Amsterdam.
‡
(
1) For recent reviews, see: (a) Tsuji, J . Palladium Reagents and
Catalysis, Innovations in Organic Synthesis; Wiley: New York, 1995.
b) Trost, B. M.; van Vranken, D. L. Chem. Rev. 1996, 96, 395. (c)
(
J ohannsen, M.; J orgensen, K. A. Chem. Rev. 1998, 98, 1869. (d) Pfaltz,
A.; Lautens, M. In Comprehensive Asymmetric Catalysis; J acobsen, E.
N.; Pfaltz, A.; Yamamoto, H., Eds.; Springer-Verlag: Berlin, 1999; Vol.
2
, Chapter 24.
(2) Pr e´ t oˆ t, R.; Pfaltz, A. Angew. Chem., Int. Ed. 1998, 37, 323.
(
3) Selvakumar, K.; Valentini, M.; Pregosin, P. S.; Albinati, A.
(7) (a) Barbaro, P.; Currao, A.; Herrmann, J .; Nesper, R.; Pregosin,
P. S.; Salzmann, R. Organometallics 1996, 15, 1879. (b) Albinati, A.;
Pregosin, P. S.; Wick, K. Organometallics 1996, 15, 2419. (c) Boog-
Wick, K.; Pregosin, P. S.; Trabesinger, G. Organometallics 1998, 17,
3254.
(8) P a` mies, O.; Ruiz, A.; Net, G.; Claver, C.; Kalchhauser, H.;
Widhalm, M. Monats. Chem. 2000, 131, 1173.
Organometallics 1999, 18, 4591.
4) Deerenberg, S.; Schrekker, H. S.; van Strijdonck, G. P. F.; Kamer,
P. C. J .; van Leeuwen, P. W. N. M.; Goubitz, K. J . Org. Chem. 2000,
5, 4810.
5) Di e´ guez, M.; J ansat, S.; Gomez, M.; Ruiz, A.; Muller, G.; Claver,
C. Chem. Commun. 2001, 1132.
(
6
(
1
0.1021/jo0159284 CCC: $20.00 © 2001 American Chemical Society
Published on Web 11/29/2001

8
868 J . Org. Chem., Vol. 66, No. 26, 2001
P a` mies et al.
Sch em e 1
substituents in ortho positions of the biphenol moieties
were investigated using ligands 1.
We also investigated the electronic effects on the
catalyst performance by varying the substituents in para
positions of the biphenol moiety using ligands 2.
Next, we extended the study to the influence of other
ligand functionalities at carbon atom C-5 on the catalytic
performance using ligands 3, 4, and 5. In these mixed
ligands, the phosphite moiety at C-5 has either been
substituted for different thioether moieties (ligands 3) or
a phosphine moiety (ligand 4). In the latter ligand, we
also substituted the phosphite moiety with an atropiso-
merically pure binaphthol group to obtain ligands 5.
Asym m etr ic Allylic Alk yla tion . In a first set of
experiments, we used the palladium-catalyzed allylic
alkylation of 1,3-diphenyl-2-propenyl acetate 6 with
dimethyl malonate to assess the potential of ligands 1-5
for asymmetric catalysis. The reactions were carried out
in dichloromethane at room temperature in the presence
Kunz et al. and Uemura et al.6b,10 reported moderate to
good enantiomeric excesses (up to 96%) at low temper-
ature (0 °C) using phosphorus-oxazoline ligands derived
from D-glucosamine. RajanBabu et al. reported moderate
enantioselectivities (up to 59%) using diphosphinite
9
1
1
ligands with a glucopyranoside backbone. More re-
cently, Di e´ guez et al. have reported good enantioselec-
tivities (up to 95%) with diphosphites derived from D-(+)-
glucose at room temperature.5
Following our interest in phosphite ligands, and having
in mind the modular nature of carbohydrates, we report
here the use of a series of diphosphite, phosphine-
phosphite, and thioether-phosphite furanoside ligands
in the Pd-catalyzed allylic substitution reaction. The
furanoside backbone in these ligands allows the system-
atic variation of the configuration at the stereogenic
center C-3 and the introduction of different functional-
ities at the nonstereogenic center C-5 in the ligand
Scheme 1). These structural variations may provide
information about the role of the phosphite moiety in the
origin of the stereochemistry of the reaction.
We also investigate the effect of different substituents
in the ortho and para positions of the biphenol-phosphite
moiety on the catalyst performance (Scheme 1), since
they have shown to have a significant effect on the
product outcome in many other catalytic reactions.6
of a catalyst generated in situ from 0.5 mol % of π-allyl-
3
palladium chloride dimer [PdCl(η -C
3
H
5
)]
2
, 1 mol % of the
corresponding ligand, and a catalytic amount of KOAc.
The nucleophile was generated from dimethyl malonate
in the presence of N,O-bis(trimethylsilyl)acetamide (BSA).
The results are summarized in Table 1.
The reaction using xylofuranoside diphosphite ligand
1
a , containing two unsubstituted biphenol moieties,
provided (S)-7 in good yield but with low ee (entry 1).
The introduction of bulky tert-butyl substituents in the
ortho and para positions of both biphenol moieties (ligand
1
(
9
b) had an extremely positive effect on enantioselectivity
entry 2). Thus, the selectivity improved from 20% ee to
0% ee. Furthermore, the presence of tert-butyl groups
(
also had a positive effect in activity (entry 1 vs entry 2).
Using ribofuranoside diphosphite ligands 2, in which
the configuration of the carbon atom C-3 is opposite to
the configuration of this atom in ligands 1, resulted in
very low enantioselectivities, even though these ligands
d,l,n,12
possess bulky tert-butyl groups in ortho position (entries
5
3
and 4). In line with the results of Di e´ guez et al.,
Resu lts a n d Discu ssion
comparison of ligands 2a and 2b showed that the activity
and enantioselectivity of the reaction was also affected
by the para substituents on the biphenol moieties (entries
Liga n d Design . To study the role of the phosphite
moiety in the determination of the stereoselectivity in
the Pd-catalyzed allylic substitution reactions, we de-
signed a series of modular furanoside ligands 1-5.
Initially, we investigated the effect of stereogenic
carbon atom C-3 in the sugar backbone and the effects
of the different substitution in the bisphenol moiety using
diphosphite ligands 1 and 2. Thus, the influence of the
configuration of the stereogenic carbon atom C-3 (see
Scheme 1) on the enantioselectivity was studied using
diphosphite ligands 1 and 2, which have the opposite
configuration on C-3. The different configuration on C-3
will lead to a different geometry around the palladium
center.
3
and 4). As compared to tert-butyl groups (ligand 2a ),
the presence of methoxy groups at the para positions (2b)
slowed the reaction down dramatically, whereas the
enantioselectivity was slightly higher (ligand 2b).
Replacing the phosphite functionality at C-5 for a
thioether moiety resulted in the mixed xylofuranoside
thioether-phosphite ligands 3. The resulting Pd-com-
plexes are less enantioselective than their diphosphite
counterparts 1 (entries 5 and 6 vs 1 and 2). Different
substituents in the thioether moiety largely affect the
activity, but they have no significant influence on the
enantiodiscrimination (entries 5 and 6). From this we
conclude that the enantioselectivity is controlled mainly
by the phosphite moiety. This is confirmed by the use of
ligand 3c containing the smaller unsubstituted biphenol
moiety, which resulted in a drop in ee from 58% (3a ,
entry 5) to 3% (3c, entry 7).
To explore the effect of the steric bulk on the product
outcome (conversion and enantioselectivity), different
(
(
9) Gl a¨ ser, B.; Kunz, H. Synlett 1998, 53.
10) Yonehara, K.; Hashizume, T.; Mori, K.; Ohe, K.; Uemura, S. J .
Org. Chem. 1999, 64, 9374.
11) (a) Nomura, N.; Mermet-Bouvier, Y. C.; RajanBabu, T. V.
Synlett 1996, 745. (b) Clyne, D. S.; Mermet-Bouvier, Y. C.; Nomura,
N.; RajanBabu, T. V. J . Org. Chem. 1999, 64, 7601.
Substitution of the phosphite moiety attached to C-5
in ligand 1b for a diphenylphosphine moiety (4) results
in a much lower activity and enantioselectivity (entries
(
(
12) For more examples, see: (a) Buisman, G. J . H.; van der Veen,
2
and 8). The influence of the phosphite moiety in this
L.; Klootwijk, A.; de Lange, W. G. J .; Kamer, P. C. J .; van Leeuwen, P.
W. N. M.; Vogt, D. Organometallics 1997, 16, 2929. (b) P a` mies, O.;
Net, G.; Ruiz, A.; Claver, C. Tetrahedron: Asymmetry 1999, 10, 2007.
type of ligand was studied using ligands 5 possessing
enantiomerically pure binaphthol groups. The use of

Modular Furanoside Phosphite Ligands
J . Org. Chem., Vol. 66, No. 26, 2001 8869
Ch a r t 1
1
Ta ble 1. P a lla d iu m -Ca ta lyzed Asym m etr ic Allylic
catalyzed allylation is the nucleophilic attack. Usually,
nucleophilic attack occurs predominantly at the allyl
Alk yla tion w ith Ch ir a l Liga n d s 1-5a
terminus located trans to the ligand that is the better
π-acceptor.1
d,13
However, recently, Deerenberg et al. have
shown that, when a phosphine-phosphite ligand is used,
4
the attack takes place trans to the phosphine moiety.
entry
L*
time (h)
% convb
% eec
Although the phosphite is a better π-acceptor, the
σ-donating capacity of the phosphine has a larger influ-
ence. Thus, for phosphine-phosphite ligands 4 and 5, we
also expect the nucleophilic attack trans to the phosphine
moiety. This is confirmed by our catalysis results that
show that the enantioselectivity is mainly controlled by
the phosphite moiety at C-3. Since the alkylated product
(S)-7 was obtained as the major enantiomer using ligands
1
2
3
4
5
6
7
8
9
1a
1b
2a
2b
3a
3b
3c
4
22
95
83
100
11
58
23
100
100
100
100
20 (S)
90 (S)
1 (R)
1.5
1.5
22
1.5
1.5
22
22
22
22
5 (R)
58 (S)
54 (S)
3 (S)
42 (S)
20 (S)
6 (R)
5a
5b
4
and 5a in the reaction of 6 with dimethyl malonate,
1
0
the reaction probably proceeds through an exo-diastere-
oisomer B rather than a endo-diastereoisomer A inter-
mediate in the equilibrium as shown in Figure 1.
a
All reactions were run at room temperature. Diphenylallyl
acetate-to-palladium ratio is 100. Malonate-to-palladium ratio is
3
00. Ligand-to-palladium ratio is 1. Catalyst preparation time is
0 min. Conversion percentage of acetate 7 determined by GC.
Enantiomeric excesses determined by HPLC on a Chiralcel-OD
column. Absolute configuration drawn in parentheses.
b
In the case of phosphite-thioether ligands 3, the two
3
c
3
functionalities have similar donor properties and it is
difficult to predict where the nucleophilic attack will take
place. Our results in catalysis (entries 5-7) clearly
indicate that the thioether moiety hardly affects the
enantioselectivity. The enantioselectivity is mainly con-
trolled by the phosphite moiety. Therefore, we assume
that the attack of the nucleophile takes place trans
toward the thioether moiety. Similarly to phosphine-
ligands 5a and 5b in the allylic alkylation result in 20%
and 6% ee, respectively. Interestingly, the sense of the
asymmetric induction is reversed indicating that the
absolute stereochemistry of the binaphthyl in the phos-
phite moiety also plays an important role in the asym-
metric induction. Comparing these results with the
results obtained using ligand 4, we can assume that the
atropisomeric biphenol moiety in ligand 4 probably
adopts an atropoisomeric (S)-configuration in the allyl-
palladium complex responsible for the catalytic activity.
Or igin of th e En a n tioselectivity. It has been gener-
ally accepted that the enantioselective step in the Pd-
(13) Steric and electronic effects on the ligand can affect the
regioselectivity; see for instance: (a) Pretot, R.; Lloyd-J ones, G. C.;
Pfaltz, A. Pure Appl. Chem. 1998, 70, 1035. (b) van Haaren, R. J .;
Druijven, C. J . M.; van Strijdonck, G. P. F.; Oevering, H.; Reek, J . N.
H.; Kamer, P. C. J .; van Leeuwen, P. W. N. M. J . Chem. Soc., Dalton
Trans. 2000, 1549. (c) Loiseleur, O.; Elliot, M. C.; von Matt, P.; Pfaltz,
A. Helv. Chim. Acta 2000, 83, 2287.

8
870 J . Org. Chem., Vol. 66, No. 26, 2001
P a` mies et al.
Ta ble 2. P a lla d iu m -Ca ta lyzed Asym m etr ic Allylic
a
Am in a tion w ith Ch ir a l Liga n d s 1-5
entry
L*
% convb
% eec
1
2
3
4
5
1b
2a
2b
3a
4
60
14
3
7
100
97 (R)
32 (S)
nd
67 (R)
66 (R)
d
a
All reactions were run at room temperature during 22 h.
Acetate-to-palladium ratio is 100. Benzylamine-to-palladium ratio
is 120. Ligand-to-palladium is 1. Catalyst preparation time is 30
b
min. Conversion percentage of acetate 7 determined by GC.
c
Enantiomeric excesses determined by HPLC on a Chiralcel-OJ
d
column. Absolute configuration drawn in parentheses. Not de-
termined.
F igu r e 1.
reactivity of the nucleophile versus the different π-allyl
intermediates, since the results indicate that in all cases
the nucleophile predominantly attacks on the exo-dias-
tereoisomer B of allyl-palladium intermediate. A plau-
sible explanation can be found either in the enhancement
of the steric interaction upon attack of the nucleophile
as the result of the formation of a more bulky chiral
pocket or a late transition state. Nucleophilic substitution
3
of the (η -allyl)Pd cationic complex to form the Pd olefin
1
4
complex must be accompanied by rotation. A late
transition state therefore results in larger ligand-allyl
interaction.
Asym m etr ic Allylic Am in a tion . As a model reaction
of the allylic amination, we investigated the palladium-
catalyzed reaction of 1,3-diphenyl-2-propenyl acetate 6
with benzylamine as the nucleophile. The amination
reaction was performed in dichloromethane at room
temperature in the presence of a catalyst generated in
situ as described for the alkylation experiments. The
results are shown in Table 2.
F igu r e 2.
phosphite ligands 4 and 5a , the reaction may proceed
through a diasteriomer B (Figure 1).
For the homo-donor diphosphite ligands 1 and 2, we
assume that the nucleophilic attack predominantly occurs
trans to the phosphite moiety attached to C-5. This
hypothesis is based on the following:
In general, the results follow the same trend as that
observed for the allylic alkylation, which is not unex-
(i) The configuration of the stereocenter C-3 strongly
influences the enantioselectivity. Thus, using ligands
with xylofuranoside backbone, with (R)-configuration at
C-3, give ee’s up to 90%, while with ribofuranoside
ligands, with opposite configuration at C-3, very low
enantioselectivity is obtained.
1c
pected because the reactions have a similar mechanism.
However, the enantiomeric excesses obtained are higher,
and the reaction rates are much lower. The higher ee’s
in the allylic amination can be explained by a later
transition state, which results in larger ligand-allyl
(
ii) The sense of the asymmetric induction obtained
14
interaction. The catalyst precursor containing diphos-
with ligands 1 is the same as that obtained with hetero-
donor ligands 3 and 4, having the same configuration at
C-3, for which the nucleophilic attack occurs cis to the
phosphite moiety at C-3.
Further proof for this hypothesis can be found in the
recent work of Di e´ guez et al. using related gluco-, allo-,
and talo-furanoside diphosphites which showed that the
configuration of carbon atom C-5 had little influence on
the outcome of the reaction.5
phite ligand 1b gave an excellent compromise between
activity and enantioselectivity (entry 1). The steroselec-
tivity of the amination is the same as for the alkylation
reaction, though the CIP descriptor is inverted due to the
change of priority of the groups. These results support a
mechanism via a exo-allyl-palladium intermediate B for
the allylic substitution reactions described in this paper
(see Figure 2).
In addition, ligands 1 have a strong preference for the
nucleophilic attack on the exo-diastereoisomer B of allyl-
palladium intermediate as the predominant formation of
Con clu sion s
A series of diphosphite, thioether-phosphite and phos-
(S)-7 suggests (Figure 2), while for ligands 2 the attack
phine-phosphite ligands 1-5 with furanoside backbone
of the malonate is not selective.
has been successfully applied to the Pd-catalyzed allylic
The higher enantiodiscrimination obtained for the
bulky xylofuranoside diphosphite 1b compared with those
obtained with thioether-phosphite and phosphine-phos-
phite ligands, containing the same phosphite moiety at
stereogenic carbon atom C-3, cannot be explained by the
(14) (a) Dierkes, P.; Ramdeehul, S.; Barloy, L.; de Cian, A.; Fischer,
J .; Kamer, P. C. J .; van Leeuwen, P. W. N. M.; Osborn, J . A. Angew.
Chem., Int. Ed. Engl. 1993, 32, 566. (b) Ramdeehul, S.; Dierkes, P.;
Aguado, R.; Kamer, P. C. J .; van Leeuwen, P. W. N. M.; Osborn, J . A.
Angew. Chem., Int. Ed. 1998, 37, 3118.

Modular Furanoside Phosphite Ligands
J . Org. Chem., Vol. 66, No. 26, 2001 8871
substitution reactions. Low to good enantioselectivities
chromatographic analyses were conducted with a DB-1 J &W
3
0 m column (split/splitless injector, film thickness 3.0 µm,
(up to 97%) were obtained in the reaction of rac-1,3-
carrier gas 70 kPa He, FID detector). Enantiomeric excesses
were determined by HPLC using a Daicel OD column.
diphenyl-2-propenyl acetate with dimethyl malonate and
benzylamine. The modular nature of these ligands en-
ables systematic investigations of the effect of the ligand
structure on enantioselectivity. From the results in
catalysis we can conclude that the nucleophilic attack
takes place trans toward the carbon atom C-5. Thus, the
configuration of stereogenic carbon atom C-3 strongly
effects the enantioselectivity. However, comparing the
experiments with ligands having different functionalities
at C-5, we can conclude that the presence of bulky
phosphite moiety improves the enantioselectivity, due
either to the formation of a more effective chiral pocket
or a late transition state. Thus, the best enantioselec-
tivities have been obtained using bulky diphosphite
ligand 1b.
Allylic Alk yla tion Exp er im en ts. A degassed solution of
3
0
0
3
2
.005 mmol of [PdCl(η -C
3
H
5
)]
2
in dichloromethane (1.5 mL),
.01 mmol of ligand, and 0.5 mmol of decane was stirred for
0 min. Subsequently, a solution of 1 mmol of rac-1,3-diphenyl-
-propenyl acetate in dichloromethane (0.736 mL, 1.31 M), 3
mmol of dimethyl malonate, 3 mmol of N,O-bis(trimethylsilyl)-
acetamide (BSA), and a pinch of KOAc were added. The
reaction mixture was stirred at room temperature. To deter-
mine the conversion by GC, a sample was quenched with a
dibenzylideneacetone (DBA) solution. To determine the ee by
HPLC (Daicel OD, 0.5% 2-propanol/hexane, flow ) 0.5 mL/
min, t
R
) 35.4 min (R), t ) 38.7 min (S), λ ) 254 nm), a sample
R
was filtered over basic alumina using dichloromethane as the
eluent.
Allylic Am in a tion Exp er im en ts. A degassed solution of
3
0
0
3
.005 mmol of [PdCl(η -C
3
H
5
)]
2
in dichloromethane (1.5 mL),
.01 mmol of ligand, and 0.5 mmol of decane was stirred for
0 min. Subsequently, a solution of 1 mmol of rac-1,3-diphenyl-
Exp er im en ta l Section
Gen er a l Con sid er a tion s. All reactions were carried out
in flame-dried glasswork using standard Schlenk techniques
under an atmosphere of argon. Solvents were purified by
2-propenyl acetate in dichloromethane (0.736 mL, 1.31 M) and
benzylamine (1.2 mmol) were added. The reaction mixture was
stirred at room temperature. To determine the conversion by
GC, a sample was quenched with a dibenzylideneacetone
(DBA) solution. To determine the ee by HPLC (Daicel OJ , 13%
1
5
16
standard procedures. Diphosphites 1 and 2, thioether-
6
e
6l
6l
phosphites 3, and phosphine-phosphite ligands 4 and 5
were prepared by previously described methods. Racemic (E)-
2-propanol/hexane, flow ) 0.5 mL/min, t
17.5 min (R), λ ) 254 nm), a sample was filtered over silica
gel eluted with 10% Et O/hexane.
R
) 14.2 min (S), t )
R
1
,3-diphenyl-2-propenyl acetate was prepared as previously
1
7
1
13
1
31
1
reported.
H, C{ H}, and P{ H} NMR spectra were
2
recorded on a Varian Gemini 300 MHz spectrometer. Gas
Ack n ow led gm en t. We thank the Spanish Ministe-
rio de Educaci o´ n y Cultura and the Generalitat de
Catalunya (CIRIT) for financial support (PB97-0407-
CO5-01). Financial support from CW/STW is also grate-
fully acknowledged (project no. 349-3590).
(
15) Buisman, G. J . H.; Martin, M. E.; Vos, E. J .; Klootwijk, A.;
Kamer, P. C. J .; van Leeuwen, P. W. N. M. Tetrahedron: Asymmetry
995, 6, 719.
16) P a` mies, O.; Net, G.; Ruiz, A.; Claver, C. Tetrahedron: Asym-
metry 2000, 11, 1097.
17) Auburn, P. R.; Mackenzie, P. B.; Bosnich B. J . Am. Chem. Soc.
985, 107, 2033.
1
(
(
1
J O0159284