Sugar-based diphosphoroamidite as a promising new class of ligands in Pd-catalyzed asymmetric allylic alkylation reactions

Article abstract of DOI:10.1021/jo062311j

(Chemical Equation Presented) We have designed a new family of readily available modular diphosphoroamidite ligands from D-xylose for Pd-catalyzed asymmetric allylic alkylation reactions. This constitutes the first example of diphosphoroamidite ligands ap

Full text of DOI:10.1021/jo062311j

Sugar-Based Diphosphoroamidite as a Promising New Class of
Ligands in Pd-Catalyzed Asymmetric Allylic Alkylation Reactions
Eva Raluy, Montserrat Di e´ guez,* and Oscar P a` mies*
Departament de Qu ´ı mica F ´ı sica i Inorg a` nica, UniVersitat RoVira i Virgili, Campus Sescelades, C/
Marcel‚l ´ı Domingo, s/n, 43007 Tarragona, Spain
montserrat.dieguez@urV.cat; oscar.pamies@urV.cat
ReceiVed NoVember 9, 2006
We have designed a new family of readily available modular diphosphoroamidite ligands from D-xylose
for Pd-catalyzed asymmetric allylic alkylation reactions. This constitutes the first example of diphos-
phoroamidite ligands applied to this process. Good-to-excellent activities (TOFs up to 850 mol substrate
-
1
×
(mol Pd × h) ) and enantioselectivities (ee’s up to 95%) have been obtained for several substrates
with different electronic and steric properties. The results indicate that catalytic performance is highly
affected by the substituents and the axial chirality of the biaryl moieties of the ligand. We also discuss
the synthesis and characterization of the Pd-π-allyl intermediates to get more insight into the origin of
enantioselectivity using these catalytic systems.
Introduction
compoundssbiaryl diphosphite ligandsshave also demonstrated
their potential utility by overcoming the most common limita-
tions of this process, such as low reaction rates and high
The development of methods for enantioselective carbon-
carbon bond formation is one of the key issues in organic
synthesis. A versatile method for achieving this is the palladium-
catalyzed asymmetric allylic substitution with carbon nucleo-
6
substrate specificity. Therefore, these ligand systems have
provided excellent enantioselectivities and activities in different
6
substrate types. The use of biaryl phosphites was beneficial
1
philes. A large number of chiral ligands, mainly P- and N-
because (1) the reaction rates increased due to the larger
ligands, which possess either C2 or C1 symmetry, have provided
1
high enantiomeric excesses. Most of the chiral ligands devel-
(3) See, for example: (a) Trost, B. M.; Oslob, J. D. J. Am. Chem. Soc.
oped for asymmetric allylic substitution are mixed bidentate
1999, 121, 3057. (b) Trost, B. M.; Bunt, R. C. J. Am. Chem. Soc. 1994,
116, 4089. (c) Trost, B. M.; Krueger, A. C.; Bunt, R. C.; Zambrano, J. J.
Am. Chem. Soc. 1996, 118, 6520. (d) Dierkes, P.; Randechul, 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. 1998, 37, 3116.
(4) See, for example: (a) Fern a´ ndez, F.; G o´ mez, M.; Jansat, S.; Muller,
G.; Mart ´ı n, E.; Flores-Santos, L.; Garcia, P. X.; Acosta, A.; Aghmiz, A.;
Gimen e´ z-Pedros, M.; Masdeu-Bult o´ , A. M.; Di e´ guez, M.; Claver, C.;
Maesro, M. A. Organometallics 2005, 24, 3946. (b) Khiar, N.; Araujo, C.
S.; Su a´ rez, B.; Fern a´ ndez, I. Eur. J. Org. Chem. 2006, 1685. (c) Jansat, S.;
G o´ mez, M.; Muller, G.; Di e´ guez, M.; Aghmiz, A.; Claver, C.; Masdeu-
Bulto, A. M.; Flores-Santos, L.; Mart ´ı n, E.; Maestro, M. A.; Mah ´ı a, J.
Tetrahedron: Asymmetry 2001, 12, 1469.
donor ligands (such as P-N, P-S, and S-N).1,2 The efficiency
of this type of hard-soft heterodonor ligands has been mainly
attributed to the different electronic effects of the donor atoms.
3
4
However, homodonor ligands (e.g., diphosphine, dithioether,
5
and bisoxazoline ligands) have, though to a lesser extent, also
demonstrated their potential usefulness in this process mainly
based on the chiral discrimination induced by C2 or C1 backbone
symmetry. Recently, a group of less electron-rich phosphorus
(
1) For recent reviews, see: (a) Tsuji, J. Palladium Reagents and
(5) See, for instance: (a) Ghosh, A. K.; Mathivanan, P.; Cappiello, J.
Tetrahedron: Asymmetry 1998, 9, 1. (b) Pfaltz, A. Acc. Chem. Res. 1993,
26, 339. (c) Peric a` s, M. A.; Puigjaner, C.; Riera, A.; Vidal-Ferran, A.;
G o´ mez, M.; Jim e´ nez, F.; Muller, G.; Rocamora, M. Chem. Eur. J. 2002, 8,
4164.
(6) (a) Di e´ guez, M.; Jansat, S.; Gomez, M.; Ruiz, A.; Muller, G.; Claver,
C. Chem. Commun. 2001, 1132. (b) Di e´ guez, M.; P a` mies, O.; Claver, C.
AdV. Synth. Catal. 2005, 347, 1257. (c) Di e´ guez, M.; P a` mies, O.; Claver,
C. J. Org. Chem. 2005, 70, 3363.
Catalysis. InnoVations in Organic Synthesis; Wiley: New York, 1995. (b)
Trost, B. M.; van Vranken, D. L. Chem. ReV. 1996, 96, 395. (c) Johannsen,
M.; Jorgensen, K. A. Chem. ReV. 1998, 98, 1689. (d) Pfaltz, A.; Lautens,
M. In ComprehensiVe Asymmetric Catalysis; Jacobsen, E. N., Pfaltz, A.,
Yamamoto, H., Eds.; Springer-Verlag: Berlin, 1999; Vol. 2, Chapter 24.
(
e) Trost, B. M.; Crawley, M. L. Chem. ReV. 2003, 103, 2921.
2) Masdeu-Bult o´ , A. M.; Di e´ guez, M.; Martin, E.; G o´ mez, M. Coord.
Chem. ReV. 2003, 242, 159.
(
10.1021/jo062311j CCC: $37.00 © 2007 American Chemical Society
2
842
J. Org. Chem. 2007, 72, 2842-2850
Published on Web 03/20/2007

Sugar-Based Diphosphoroamidite Ligands
Results and Discussion
Ligand Synthesis. The new diphosphoroamidite ligands 1-6
were synthesized very efficiently from diamine 8 by reacting 2
equiv of the desired in-situ-formed phosphorochloridite11 in the
presence of pyridine. 3,5-Dideoxy-3,5-diamino-1,2-O-isopro-
pylidene-ribofuranose 8 was easily prepared on a large scale
from inexpensive D-(+)-xylose. All the ligands were stable
during purification on neutral alumina under an atmosphere of
1
argon and isolated in moderate yields as white solids. The H,
P, and C NMR spectra were as expected for these C1 ligands
FIGURE 1. Diphosphoroamidite ligands 1-6.
31
13
(
see the Experimental Section and Scheme 1).
Asymmetric Allylic Alkylation Reactions. We first inves-
7
π-acceptor ability of the phosphite moiety and (2) enantiose-
lectivity increased because the chiral pocket (the chiral cavity
where the allyl is embedded) created is flexible enough to allow
the perfect coordination of hindered and unhindered substrates
tigated the Pd-catalyzed allylic substitution of rac-1,3-diphenyl-
-acetoxyprop-1-ene S1, which is widely used as a model
3
substrate, with dimethyl malonate using the chiral diphospho-
roamidite ligands 1-6 (eq 1).
(
which decreases the substrate specificity).8
Following our interest in highly modular, versatile π-acceptor
ligands, and encouraged by the success of the phosphoroamidite
9
ligands in asymmetric catalysis, we report here the synthesis
of a new family of furanoside diphosphoroamidite ligands (1-
6
, Figure 1) for the enantioselective Pd-catalyzed allylic
alkylation reactions. We also discuss the synthesis and charac-
terization of the Pd-π-allyl intermediates to get more insight
into the origin of the enantioselectivity using these catalytic
systems.
These diphosphoroamidite ligands are derived from natural
D-(+)-xylose, so they also have the advantage of carbohydrates,
such as availability at a low price and facile modular construc-
The catalysts were generated in situ from 0.5 mol % of π-allyl-
3
palladium chloride dimer [PdCl(η -C3H5)]2, 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).
We determined the optimal reaction conditions by conducting
a series of experiments in which the solvent and the ligand-to-
palladium ratio were varied. We first studied the effect of four
solvents with ligand 1 (Table 1, entries 1-4). The best activity
and enantioselectivity was achieved with dichloromethane as
solvent (entry 1). We next studied the effect of varying the
ligand-to-palladium ratio (Table 1, entries 1, 5, and 6). The
results show that an excess of ligand is not needed for good
activities and enantioselectivities.
tion, which makes the tedious optical resolution procedure
unnecessary.10 The modular construction of these ligands allows
sufficient flexibility to fine tune the steric and electronic
properties of the biaryl moieties to explore how they affect
catalytic performance (activity and selectivity). In this way, we
studied how attaching different groups to the ortho and para
positions of the biphenyl moieties affects the catalytic perfor-
mance with ligands 1-4. To further investigate how enanti-
oselectivity was influenced by the configuration of the biaryl
moieties, ligands 5 and 6 containing different enantiomerically
pure binapthyl moieties were also tested. As a result, the optimal
combination for maximum activity and selectivity for different
substrates types were reached.
For comparative purposes, the rest of the ligands were tested
under conditions that provided the optimum tradeoff between
enantioselectivities and reaction rates, i.e., a ligand-to-palladium
ratio of 1.1 and dichloromethane as a solvent. The results, shown
in Table 2, indicate that catalytic performance (activities and
enantioselectivities) is highly affected by the substituents and
the axial chirality of the biaryl moieties. In general, good activity
To the best of our knowledge this is the first example of
diphosphoroamidite ligands applied to the enantioselective Pd-
catalyzed allylic substitution reactions.
-
1 13
(
TOFs up to 850 mol S1 × (mol Pd × h) ) and enantiose-
lectivity (ee’s up to 75%) were obtained in the alkylation of
S1.
(
7) (a) van Strijdonck, G. P. F.; Boele, M. D. K.; Kamer, P. C. J.; de
Vries, J. G.; van Leeuwen, P. W. N. M. Eur. J. Inorg. Chem. 1999, 1073.
b) P a` mies, O.; Di e´ guez, M.; Claver, C. J. Am. Chem. Soc. 2005, 127, 3646.
8) The flexibility that offers the biphenyl moiety can be used to fine
The effect of the biphenyl substituents was investigated with
ligands 1-4 (Table 2, entries 1-4). We found that these
moieties affect both activity and enantioselectivity. Substituents
in the para positions of the biphenyl moieties are required for
good enantioselectivity (Table 2, entries 1, 2, and 4 vs 3). Thus,
ligands 1, 2, and 4 with substituents at para positions of the
biphenyl moieties provided higher enantioselectivities than
ligand 3, without substituents in these positions. However, the
type of substituents in the para positions is also important.
Therefore, the presence of the methoxy group in the biphenyl
(
(
tune the chiral pocket formed upon complexation. See: (a) ref 7b. (b) Mata,
Y.; Di e´ guez, M.; P a` mies, O.; Claver, C. AdV. Synth. Catal. 2005, 347, 1943.
(
9) See, for instance: (a) Feringa, B. L. Acc. Chem. Res. 2000, 33, 346.
(
b) Jagt, R. B. C.; Toullec, P. Y.; Geerdink, D.; de Vries, J. G.; Feringa, B.
L.; Minnaard, A. J. Angew. Chem., Int. Ed. 2006, 45, 2789. (c) Tissot-
Croset, K.; Polet, D.; Alexakis, A. Angew. Chem., Int. Ed. 2004, 43, 2426.
(
d) Polet, D.; Alexakis, A.; Tissot-Croset, K.; Corminboeuf, C.; Ditrich, K.
Angew. Chem., Int. Ed. 2006, 12, 3596. (e) Boele, M. D. K.; Kamer, P. C.
J.; Lutz, M.; Spek, A. L.; de Vries, J. G.; van Leeuwen, P. W. N. M.; van
Strijdonck, G. P. F. Chem. Eur. J. 2004, 10, 6232. (f) Biswas, K.; Prieto,
O.; Goldsmith, P. J.; Woodward, S. Angew. Chem., Int. Ed. 2005, 44, 2232.
(
g) Alejakis, A.; Benhaim, C.; Rosset, S.; Humam, M. J. Am. Chem. Soc.
(11) (a) Buisman, G. J. H.; Kamer, P. C. J.; van Leeuwen, P. W. N. M.
Tetrahedron: Asymmetry 1993, 4, 1625. (b) 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.
(12) (a) P a` mies, O.; Di e´ guez, M.; Net, G.; Ruiz, A.; Claver, C. J. Chem.
Soc., Dalton Trans. 1999, 3439. (b) Seio, K.; Miyashita, T.; Sato, K.; Sekine,
M. Eur. J. Org. Chem. 2005, 5163.
2
2
2
002, 124, 5262. (h) Di e´ guez, M.; Ruiz, A.; Claver, C. Chem. Commun.
001, 2702. (i) Raluy, E.; Claver, C.; P a` mies, O.; Di e´ guez, M. Org. Lett.
007, 9, 49.
(10) (a) Di e´ guez, M.; P a` mies, O.; Claver, C. Chem. ReV. 2004, 104, 3189.
(b) Di e´ guez, M.; P a` mies, O.; Ruiz, A.; D ´ı az, Y.; Castill o´ n, S.; Claver, C.
Coord. Chem. ReV. 2004, 248, 2165. (c) Di e´ guez, M.; Ruiz, A.; Claver, C.
Dalton Trans. 2003, 2957.
(13) TOF measured at around 30% conversion.
J. Org. Chem, Vol. 72, No. 8, 2007 2843

Raluy et al.
SCHEME 1. Synthesis of the New Diphosphoroamidite Ligands 1-6a
a
(a) Ref 12. (b) PPh3, THF/H2O. (c) ClP(OR)2, Py, toluene.
TABLE 1. Pd-Catalyzed Allylic Alkylation of S1 Using Ligand 1:
TABLE 3. Pd-Catalyzed Allylic Alkylation of S2 Using Ligand 1:
Effect of the Solvent and Ligand-to-Palladium Ratioa
a
Effect of the Solvent and Ligand-to-Palladium Ratio
%
conversion
(min)
% conversion
b
% eec
(min)b
% eec
entry
solvent
ratio of 1/Pd
entry
solvent
ratio of 1/Pd
1
2
3
4
5
6
CH2Cl2
DMF
toluene
THF
CH2Cl2
CH2Cl2
1.1
1.1
1.1
1.1
0.8
2
100 (15)
90 (15)
10 (15)
20 (15)
62 (15)
100 (15)
66 (R)
53 (R)
58 (R)
54 (R)
67 (R)
62 (R)
1
2
3
4
5
6
CH2Cl2
DMF
toluene
THF
THF
THF
1.1
1.1
1.1
1.1
0.8
2
100 (120)
100 (120)
56 (120)
100 (120)
95 (120)
100 (120)
82 (S)
75 (S)
79 (S)
88 (S)
88 (S)
86 (S)
a
a
Conditions: 0.5 mol % [Pd(π-C3H5)Cl]2, 30 min; 3 equiv of
CH2(COOMe)2 and N,O-bis(trimethylsilyl)acetamide (BSA), a pinch of
Conditions: 0.5 mol % [Pd(π-C3H5)Cl]2, 30 min; 3 equiv of
CH2(COOMe)2 and N,O-bis(trimethylsilyl)acetamide (BSA), a pinch of
b
1
b
KOAc, room temperature. Measured by H NMR. Reaction time in minutes
shown in parentheses. Determined by HPLC (Chiralcel-OD). Absolute
configuration shown in parentheses.
KOAc, room temperature. Measured by GC. Reaction time in minutes
c
shown in parentheses. c Determined by GC. Absolute configuration shown
in parentheses.
TABLE 2. Pd-Catalyzed Allylic Alkylation of S1 with Ligands
enantioselectivity (ee’s up to 74% (R)) and high activity (TOFs
a
1
-6
-
1
up to >560 mol S1 × (mol Pd × h) ) were obtained.
We next tested this new family of ligands in the Pd-catalyzed
asymmetric allylic alkylation of cyclic substrates (eq 2).
%
conversion
(min)
b
% eec
entry
ligand
1
2
3
4
5
6
1
2
3
4
5
6
1
5
100 (15)
33 (15)
11 (15)
87 (15)
78 (30)
85 (30)
98 (60)
24 (150)
66 (R)
59 (R)
13 (S)
63 (R)
75 (R)
30 (R)
66 (R)
74 (R)
d
7
d
8
a
Conditions: 0.5 mol % [Pd(π-C3H5)Cl]2, 1.1 mol % ligand, room
b
1
Enantioselectivity in cyclic substrates is usually more difficult
to control, mainly because of the presence of less sterically
demanding syn substituents, which play a crucial role in the
enantioselection observed with acyclic substrates in the corre-
temperature. Measured by H NMR. Reaction time in minutes shown in
parentheses. Determined by HPLC (Chiralcel-OD). Absolute configuration
shown in parentheses. Reaction carried out at 0.1 mol % of [Pd(π-
C3H5)Cl]2.
c
d
1
sponding Pd-allyl intermediate. Therefore, few catalytic
moieties has a negative effect on both activity and enantiose-
lectivity (Table 2, entry 1 vs 2). Moreover, the substituents in
the ortho positions of the biphenyl moieties have a slight but
important effect on both activity and enantioselectivity (Table
3b,d,7b,14
systems have provided good enantioselectivities.
We first tested the efficiency of the chiral diphosphoroamidite
ligands 1-6 in the Pd-catalyzed allylic alkylation of rac-3-
acetoxycyclohexene S2 (eq 2), which is usually used as a model
cyclic substrate.
The preliminary investigations into the solvent effect and the
ligand-to-palladium ratio using ligand 1 provided a different
trend for the solvent effect than those into the previously tested
substrate S1. Therefore, the best enantioselectivities and reaction
rates were obtained when THF was used as solvent and the
ligand-to-palladium ratio was 1.1 (Table 3).
The results of using ligands 1-6 under the optimized
conditions are shown in Table 4. In general, high enantiose-
lectivity (ee’s up to 88%) with good activity were obtained in
the alkylation of S2. Again, enantioselectivity was affected by
the substituents at the biaryl moieties and the cooperative effect
between stereocenters. However, the effect of these parameters
was different from those observed in the alkylation of S1.
2, entries 1 vs 4). Activities and enantioselectitivies are therefore
highest when tert-butyl groups are present at both ortho and
para positions of the biphenyl moieties.
To further investigate how enantioselectivity was influenced
by the groups attached to the biaryl moieties, ligands 5 and 6
containing different enantiomerically pure binapthyl moieties
were also tested (Table 2, entries 5 and 6). Ligand 5 containing
R-binaphtyl moieties produced the R-9 product in 75% ee, while
ligand 6 containing S-binaphtyls produced the R-9 product in
lower enantioselectivity (30% ee). These results indicate that
there is a cooperative effect between the configuration of the
biaryl moieties and the configurations of the ligand backbone
that results in a matched combination for ligand 5. Note that
this cooperative effect is highly advantageous, allowing us to
increase enantioselectivity up to 75% ee (entry 5).
We also performed the reaction at a low catalyst concentration
(14) Evans, D. A.; Campos, K. R.; Tedrow, J.; Michael, F. E.; Gagn e´ ,
(S1/Pd ) 500) using ligands 1 and 5 (entries 7 and 8). Good
M. R. J. Am. Chem. Soc. 2000, 122, 7905.
2844 J. Org. Chem., Vol. 72, No. 8, 2007

Sugar-Based Diphosphoroamidite Ligands
TABLE 4. Pd-Catalyzed Allylic Alkylation of S2 and S3 with
TABLE 5. Selected Results for the Pd-Catalyzed Allylic Alkylation
of S5a
a
Ligands 1-6
%
conversion
(min)
% conversion
b
% eec
(min)b
12/13c
% eed
entry
ligand
substrate
entry
ligand
1
2
3
4
5
6
7
1
2
3
4
5
6
1
S2
S2
S2
S2
S2
S2
S3
100 (120)
100 (120)
90 (120)
32 (120)
19 (120)
42 (120)
51 (360)
88 (S)
76 (S)
17 (S)
5 (S)
56 (R)
72 (S)
95 (S)
1
2
3
4
5
6
1
2
3
4
5
6
1
100 (30)
100 (30)
100 (30)
100 (30)
100 (30)
100 (30)
100 (120)
65/35
65/35
60/40
40/60
65/35
80/20
65/35
76 (S)
22 (R)
13 (S)
72 (S)
33 (R)
20 (S)
83 (S)
e
7
a
a
Conditions: 0.5 mol % [Pd(π-C3H5)Cl]2, 1.1 mol % ligand, room
Conditions: 0.5 mol % [Pd(π-C3H5)Cl]2, 1.1 mol % ligand, room
b
temperature. b Conversion percentage measured by H NMR. Reaction time
1
temperature. Conversion percentage of acetates 10 and 11 determined by
GC. Reaction time in minutes shown in parentheses. Enantiomeric excesses
determined by GC. Absolute configuration shown in parentheses.
c
c
in minutes shown in parentheses. Branched to linear ratio determined by
1
H NMR. d Enantiomeric excesses determined by HPLC. Absolute config-
e
uration shown in parentheses. T ) 0 °C.
Therefore, enantioselectivity was best with ligand 1 (88% (S)
ee). These results clearly show the importance of using modular
scaffolds in the ligand design.
in Table 5. Interestingly, under nonoptimized conditions, the
catalytic system containing ligand 1 produced the desired
branched isomer as the major product with high activity and
enantioselectivity (ee’s up to 83% (S)). The results indicate that
enantioselectivities are highly affected by the substituents in
the para position of the biphenyl moieties (Table 5, entries 1-4).
However, regioselectivity is mainly governed by the substituents
at the ortho positions (Table 5, entries 1-4). It should be note
that the cooperative effect previously observed with substrates
S1 and S2 has the main effect on regioselectivity (Table 5,
entries 5 and 6). These results are among the best reported so
Regarding the effect of the substituents in the biphenyl
moieties, again substituents in the para position are necessary
for high ee’s (entries 1 and 2 vs 3). However, in contrast to the
alkylation of S1, the effect of the type of substituent in ortho
positions is more significant. Therefore, enantioselectivities and
activities are higher when more sterically demanding substituents
t
are present (i.e., Bu > Me).
Concerning the effect of the configuration of the biaryl
moieties, the cooperative effect previously reported with
substrate S1 also showed a different tendency and the matched
combination was therefore observed for ligand 6 (entries 5 and
15
far, and it is clear that they represent a major improvement
16
over other Pd-homodonor bidentate catalytic systems that
6
).
Encouraged by the excellent results obtained in the alkylation
predominantly provide the linear achiral product as the major
one.
of cyclic substrate S2, we examined the stereoselective allylic
alkylation of the seven-membered cyclic substrate S3 using
ligand 1 (Table 4, entry 7). Interestingly, for this sterically
undemanding substrate, high enantioselectivities (ee’s up to
To sum up, these diphosphoroamidite ligands have provided
good results in different substrates types. The high activities
and enantioselectivities (ee’s up to 95%) obtained for cyclic
substrates are particularly noteworthy as is the combination of
high regio- and enantioselectivitities (regioselectivities up to
9
5%) were also obtained.
In summary the results obtained with cyclic substrates are
65% and ee’s up 83%) for monosubstituted substrate S4. These
3b,d,7b,14
among the best reported so far.
facts, along with the promising results obtained for substrate
S1, open up the Pd-catalyzed allylic alkylation reactions to a
new class of ligandssthe diphosphoroamidites. The efficiency
of the ligand design is also corroborated by the fact that these
Pd-diphosphoroamidite catalysts provide higher activities,
regio-, and enantioselectivities than their Pd-diphosphite
To further study the potential of these readily available
ligands, we also tested them in the allylic alkylation of the
monosubstituted linear substrate 1-(1-naphthyl)allyl acetate S4
(eq 3).
6
b
analogues (Scheme 2). In addition, these ligands provide
comparable results to those with related heterodonor phosphite-
phosphoroamidite ligands recently described for this process.9i
Origin of Enantioselectivity: Study of the Pd-π-allyl
Intermediates. In order to get more insight into the effect of
the ligand parameters on catalytic performance, we performed
a study of the Pd-π-allyl compounds 14-17, [Pd(π-allyl)(L)]-
BF4 (L ) diphosphoroamidite ligands), since they are key
intermediates in the studied allylic alkylation reactions (Scheme
For this substrate, as well as controlling the enantioselectivity
of the process, the regioselectivity is also a problem, because a
mixture of regioisomers may be obtained. Most Pd catalysts
developed to date favor the formation of the achiral linear
1
3
). These ionic palladium complexes containing 1,3-diphenyl
and cyclohexenyl groups were prepared from the corresponding
palladium allyl dimer and the appropriate ligand in the presence
of silver tetrafluoroborate, following the previously described
1
product 13 rather than the desired branched isomer 12.
Therefore, the development of highly regio- and enantioselective
Pd catalysts is still a challenge.15 The results are summarized
(16) See, for example: (a) Laurenti, D.; Feuerstein, M.; P e` pe, G.; Doucet,
H.; Santelli, M. J. Org. Chem. 2001, 66, 1633. (b) Canal, J. M.; G o´ mez,
M.; Jim e´ nez, F.; Rocamora, M.; Muller, G.; Du n˜ ach, E.; Franco, D.;
Jim e´ nez, A.; Cano, F. H. Organometallics 2000, 19, 966. (c) Godleski, S.
A. In ComprehensiVe Organic Synthesis; Trost, B. M., Fleming, I.,
Semmelhack, M. F., Eds.; Pergamon Press: Oxford, U.K., 1991; Vol. 4,
pp 585-662.
(
15) For successful applications of Pd catalysts, see: (a) Pr e´ t oˆ t, R.; Pfaltz,
A. Angew. Chem., Int. Ed. 1998, 37, 323. (b) Hilgraf, R.; Pfaltz, A. Synlett
999, 1814. (c) You, S. L.; Zhu, X. Z.; Luo, Y. M.; Hou, X. L.; Dai, L. X.
J. Am. Chem. Soc. 2001, 123, 7471.
1
J. Org. Chem, Vol. 72, No. 8, 2007 2845

Raluy et al.
SCHEME 2
SCHEME 3. Preparation of Pd-Allyl Intermediates 14-17
SCHEME 4. Diastereoisomer Pd-Allyl Intermediates 14a
methodology (Scheme 3).17 The complexes were characterized
in solution using H, 13C, and P NMR spectroscopy. The
1
31
spectral assignments (see the Experimental Section) were based
1
1
31
1
13
1
on information from H- H, P- H, and C- H correlation
1
1
measurements in combination with H- H NOESY experi-
ments.
A. 1,3-Diphenyl Allyl Palladium Complexes. To understand
the differences in catalytic performance observed in the alky-
lation of S1 using ligands 1-6, we decided to study the 1,3-
diphenylallyl palladium complexes containing ligand 2 (which
provided product (R)-9 in good enantioselectivity) and ligand
a
P1: Phosphorus atom next to C-3. P2: Phosphorus atom next to C-5
(assigned by 31P- H HMBC correlation experiment).
1
and the fact that enantiomeric excess of 9 is higher than the
diastereoisomeric excess of the Pd intermediates, the B isomer
must react faster than the A isomer. This is consistent with the
fact that for both isomers, the most electrophilic allylic terminal
carbon atom is the one trans to the phosphorus at C-5 (P2) in
the B isomer.
The NMR study of the Pd-allyl intermediate containing
ligand 3, [Pd(η -1,3-diphenylallyl)(3)]BF4 (15), showed a
mixture of two isomers in a ratio of 1:1 (see the Experimental
Section). One of the isomers could be unambiguously assigned
by NOE experiment to a syn/syn isomer A (Scheme 5).
However, for the other isomer and in contrast to 14, the VT-
3
without substituents on the para positions of the biphenyl
moieties (which provided low enantioselectivity in the reversed
enantiomer). In addition, this study allowed us to explain the
important effect of the para substituents of the biphenyl groups
on catalytic performance (see above).
The NMR study of the Pd-allyl intermediate containing
3
ligand 2, [Pd(η -1,3-diphenylallyl)(2)]BF4 (14), showed a
3
mixture of two isomers in a ratio of 1:1 (see the Experimental
Section). No changes were observed down to -80 °C. Both
isomers could be unambiguously assigned by NOE to the two
syn/syn isomers (Scheme 4). The carbon NMR chemical shifts
indicate for both isomers that the most electrophilic allyl carbon
terminus is trans to the phosphorus at the C-5 position (P2).
Assuming that the nucleophilic attack takes place at the more
electrophilic carbon terminus18 and based on the observed
stereochemical outcome of the reaction, 59% (R) in product 9,
3
1
P NMR spectra indicated a fluxional behavior for the
phosphorus next to C-3 (P1) in isomer B (assigned by 31P- H
1
HMBC correlation experiment) that could not be frozen out until
-
80 C. This fluxionability can be attributed to an equilibrium
between syn/syn and syn/anti isomers (Scheme 5) or to the
fluxional behavior of the biphenyl moieties. However, the study
of the models suggested that the absence of the para substituents
in the biphenyl moieties in ligand 3 caused a different orientation
of the biphenyl moieties in the Pd-π-allyl intermediate than
for complex 14 which resulted in a new steric repulsion between
one of the biphenyl moieties and one of the phenyl substituents
(
17) Deerenberg, S.; Schrekker, H. S.; van Strijdonck, G. P. F.; Kamer,
P. C. J.; van Leeuwen, P. W. N. M.; Fraanje, J.; Goubitz, K. J. Org. Chem.
000, 65, 4810.
18) It is well-known that the enantioselectivity in the palladium-catalyzed
2
(
allylic alkylation with soft reagents is controlled by the nucleophilic attack
to the more electrophilic terminal carbon of the allyl ligand in the Pd(II)
intermediates such as 14. See ref 1.
2846 J. Org. Chem., Vol. 72, No. 8, 2007

Sugar-Based Diphosphoroamidite Ligands
SCHEME 5. Diastereoisomer Pd-Allyl Intermediates 15a
SCHEME 6. Diastereoisomer Pd-Allyl Intermediates 16a
a
P1: Phosphorus atom next to C-3. P2: Phosphorus atom next to C-5
a
P1: Phosphorus atom next to C-3. P2: Phosphorus atom next to C-5
3
1
1
(
assigned by P- H HMBC correlation experiment).
31
1
(
assigned by P- H HMBC correlation experiment).
SCHEME 7. Diastereoisomer Pd-Allyl Intermediates 17a
of S1 in this isomer (Scheme 5). The formation of the anti
isomer minimized this new steric repulsion. It should be noted
that this syn/anti isomerism is observed at the most electrophilic
1
3
allylic terminal carbon (the one exhibiting the highest
C
chemical shifts). Assuming that the nucleophilic attack takes
place at the most electrophilic carbon atom, the attack at syn/
syn isomer B will lead to the formation of (R)-9, while the attack
in syn/anti isomer B′ will lead to the formation of the opposite
enantiomer of product 9.
Another important difference between complexes 14 and 15
was found in the 13C NMR spectra. For each isomer of complex
1
5 the electronic differences between both allylic terminal
1
3
carbons (∆(δ C) ≈ 1 ppm) decreased considerably compared
13
to those of isomers of 14 (∆(δ C) ≈ 8 ppm). Therefore, the
electrophilicity of the allylic terminal carbons for 15 decreased.
In summary, the notable decrease in enantioselectivity
observed using the Pd/3 catalyst in comparison with the Pd/2
catalyst system may be due to either the presence of a syn/syn
and syn/anti equilibrium or the possibility that the nucleophile
attacks at both allylic terminal carbons in each isomer, due to
a
P1: Phosphorus atom next to C-3. P2: Phosphorus atom next to C-5
31
1
(
assigned by P- H HMBC correlation experiment).
stereochemical outcome of the reaction, 88% (S) in product 10,
and the fact that enantiomeric excess of 10 is higher than the
diastereoisomeric excesses of the Pd intermediates, the B isomer
must react faster than the A isomer. This is consistent with the
fact that for both isomers the most electrophilic allylic carbon
atom is the one trans to the phosphorus at C-5 in the B isomer.
13
their low electronic differentiation (∆(δ C) ≈ 1 ppm), or a
combination of both. However, the fact that the allylic terminal
carbons in complex 14 are more electrophilic may explain the
higher activities obtained with the Pd/2 catalytic system (Table
2
, entries 2 vs 3).
B. Cyclohexenyl Allyl Palladium Complexes. In order to
In contrast to complex 16, the NMR study of the Pd-allyl
intermediate containing ligand 4, [Pd(η -cyclo-C3H9)(4)]BF4
3
elucidate the difference in catalytic performance observed with
ligands 1-6 in the alkylation of cyclic substrates (S2 and S3),
we next studied the ionic palladium complexes containing the
cyclohexenyl groups. In contrast to the alkylation of S1, the
substituents in the ortho positions of the biaryl moieties also
have a considerable effect on catalytic performance. For this
reason, we decided to study the cyclohexenyl allyl-palladium
complexes containing ligand 1 (which provided the best
enantioselectivity) and ligand 4 (which provided the lowest
enantioselectivity).
(17), revealed the presence of one isomer in excess 1.8:1 (see
the Experimental Section). Both isomers could be assigned by
NOE to the two syn/syn isomers (Scheme 7). Another important
difference between complexes 16 and 17 is the lower electronic
differentiation between the more electrophilic allylic terminus
carbon atoms of both isomers (A and B) in complex 17
1
3
13
(
∆(δ C) ≈ 0.6 ppm) than in complex 16 (∆(δ C) ≈ 4 ppm).
This low electronic differentiation suggests that the nucleophile
can attack both isomers at a similar rate. However, the difference
between the diastereoisomeric ratio and enantioselectivity
observed in the alkylation of S2 (de ) 28% vs ee ) 5%)
indicates that the nucleophile reacts faster with the minor isomer,
but the relative reaction rates between both isomers is much
lower than in complex 16. The lower activity observed with
Pd/4 catalytic system may be due to fact that the allylic terminal
carbons in complex 17 are less electrophilic than with complex
16 (Table 4, entries 1 vs 4).
The NMR study of the Pd-allyl intermediate containing
3
ligand 1, [Pd(η -cyclo-C6H9)(2)]BF4 (16), showed a mixture of
two isomers in a ratio of 1:1 (see the Experimental Section).
Both isomers could be assigned by NOE to the two syn/syn
isomers (Scheme 6). The carbon NMR chemical shifts indicated
for both isomers that the most electrophilic allylic terminus
carbon is trans to the phosphorus at the C-5 position (P2).
Assuming that the nucleophilic attack takes place at the most
electrophilic allylic carbon terminus and based on the observed
J. Org. Chem, Vol. 72, No. 8, 2007 2847

Raluy et al.
Conclusion
3,5-Bis[(3,3′,5,5′-tetra-t-butyl-1,1′-biphenyl-2,2′-diyl)phosphite]-
,5-diamine-3,5-dideoxy-1,2-O-isopropylidene-ribofuranose (1).
3
In summary, we have described the first application of
diphosphoroamidite ligands for the Pd-catalyzed asymmetric
allylic substitution reactions of several substrate types. These
ligands have the advantage of being easily prepared in a few
steps from commercial D-xylose, an inexpensive natural chiral
feedstock. In addition, they can be easily tuned so the effect of
different substituents and configurations of the biaryl moieties
on catalytic performance can be explored. By carefully selecting
the ligand components, we obtained good results in different
substrate types. Particularly, for the hindered disubstituted linear
substrate S1, we found that substituents in the para positions of
the biphenyl moieties are needed for good enantioselectivity.
However, for cyclic substrates S2 and S3, in addition to the
presence of para substituents, the presence of bulky substituents
in the ortho positions are necessary for high enantioselectivity.
For the monosubstituted linear substrate S5, the results indicate
that enantioselectivities are highly affected by the substituents
in the para position of the biphenyl moieties. However,
regioselectivity is mainly governed by the substituents at the
ortho positions. Therefore, the presence of substituents in the
para positions combined with bulky substituents in the ortho
positions of the biaryl moieties are necessary to obtain the
optimum tradeoff between regio- and enantioselectivities. The
study of the 1,3-diphenyl and cyclohexenyl Pd-π-allyl inter-
mediates by NMR spectroscopy allows the understanding of
the catalytic behavior observed. This study indicates that the
nucleophilic attack takes place predominantly at the allylic
terminal carbon atom located trans to the phosphoroamidite
moiety attached to C-5.
Phosphorochloridite (2.2 mmol) produced in situ was dissolved in
toluene (5 mL), and pyridine (0.36 mL, 4.6 mmol) was added. 8
(189 mg, 1 mmol) was azeotropically dried with toluene (3 × 2
mL) and then dissolved in toluene (10 mL), to which pyridine (0.36
mL, 4.6 mmol) was added. The phosphorochloridite solution was
transferred slowly over 5 min at room temperature to the solution
of 8. The reaction mixture was stirred overnight at 80 °C, and the
pyridine salts were removed by filtration. Evaporation of the solvent
gave a white foam, which was purified by flash chromatography
over neutral alumina (toluene/NEt
3
) 100/2) to produce a white
powder. Yield: 0.55 g, 52%. P NMR, δ (C ): 149.4 (d, 1P,
-P ) 4 Hz). H NMR, δ (C ):
, Bu),
31
6 6
D
1
J
P
-P ) 4 Hz), 150.7 (d, 1P, J
.12 (s, 3H, CH ), 1.24 (s, 9H, CH
1.32 (s, 18H, CH , Bu), 1.48 (s, 3H, CH ), 1.58 (s, 9H, CH , Bu),
P
6 6
D
t
t
1
3
3 3
, Bu), 1.25 (s, 9H, CH
t
t
3
t
3
3
t
1.62 (s, 9H, CH
3.26 (m, 1H, NH-C-3), 3.35 (m, 1H, H-3), 3.40 (m, 1H, NH-C-
), 3.56 (m, 1H, H-5), 3.62 (m, 1H, H-4), 3.68 (m, 1H, H-2), 5.33
3 3
, Bu), 1.63 (s, 18H, CH , Bu), 3.04 (m, 1H, H-5′),
5
3
13
(
(
d, 1H, H-1, J
1
-2 ) 4 Hz), 7.0-7.6 (m, 8H, CHd). C NMR, δ
t
t
C
6
D
6
): 26.7 (CH
3
), 27.0 (CH
3
), 31.9 (CH
3
t
, Bu), 32.0 (CH
3
, Bu),
t
t
t
32.1 (CH
3
, Bu), 32.3 (CH
C, Bu), 42.6 (d, CH , J -P ) 24.2 Hz), 55.7 (d, CH
Hz), 80.8 (C-2), 81.9 (C-4), 104.3 (C-1), 112.2 (CMe ), 124.4 (CHd
, 124.5 (CHd), 124.7 (CHd), 124.9 (CHd), 126.9 (CHd), 127.1
CHd), 127.2 (CHd), 127.3 (CHd), 127.6 (CHd), 134.2 (C),
3
, Bu), 35.0 (C, Bu), 36.0 (C, Bu), 36.1
t
(
2
C
2 C
, J -P ) 15.9
2
)
(
134.4 (C), 134.5 (C), 134.7 (C), 141.2 (C), 141.3 (C), 146.6
(C), 146.7 (C), 146.8 (C), 147.0 (C). Anal. Calcd (%) for
C H N O P : C, 72.15; H, 8.89; N, 2.63. Found: C, 72.45; H,
64 94 2 7 2
8.59; N, 2.49.
3
,5-Bis[(3,3′-bis-t-butyl-5,5′-bis-methoxy-1,1′-biphenyl-2,2′-
diyl)phosphite]-3,5-diamine-3,5-dideoxy-1,2-O-isopropylidene-
ribofuranose (2). Treatment of the corresponding phosphrochlo-
ridite (2.2 mmol) produced in situ and 8 (189 mg, 1 mmol), as
described for compound 1, afforded diphosphoroamidite 2, which
The high activities and enantioselectivities (ee’s up to 95%)
obtained for cyclic substrates S2 and S3 are particularly
noteworthy as is the combination of high regio- and enantiose-
lectivitities (regioselectivities up to 65% and ee’s up 83%) for
monosubstituted substrate S4. These facts together with the
promising results obtained for substrate S1 open up the Pd-
catalyzed allylic alkylation reactions to a new class of ligandss
the diphosphoroamidites.
was purified by flash chromatography (toluene/NEt
produce a white powder. Yield: 0.41 g, 43%. P NMR, δ (C
3
) 100/2) to
):
),
31
6
D
6
1
1
48.5 (s, 1P), 151.4 (s, 1P). H NMR, δ (C
6
D
6
): 1.10 (s, 3H, CH
3
t
t
1.29 (s, 3H, CH ), 1.52 (s, 9H, CH , Bu), 1.54 (s, 9H, CH , Bu),
3
3
3
t
t
1.55 (s, 9H, CH
3.26 (s, 3H; OCH
s, 3H; OCH ), 3.39 (s, 3H; OCH
H, H-5), 3.63 (m, 1H, H-4), 3.86 (m, 1H, H-2), 5.39 (d, 1H, H-1,
3
, Bu), 1.58 (s, 9H, CH
), 3.31 (s, 3H; OCH
), 3.40 (m, 1H, H-3), 3.50 (m,
3
, Bu), 3.15 (m, 1H, H-5′),
3
3
), 3.32 (b, 2H, NH), 3.34
(
3
3
1
J
CH
3
13
1
-2 ) 4 Hz), 6.6-7.2 (m, 8H, CHd). C NMR, δ (C
6
D
6
): 26.7
, Bu), 32.0 (CH
-P ) 22 Hz), 55.1 (d, C-3, J -P
), 80.2 (C-2), 82.1 (C-4), 104.4 (C-1),
), 113.3 (CHd), 113.4 (CHd), 113.8 (CHd), 114.8
Experimental Section
t
t
(
3
), 27.0 (CH
3
), 31.7 (CH
Bu), 35.9 (C, Bu), 41.8 (d, C-5, J
) 15 Hz), 55.4, 55.5 (OCH
112.3 (CMe
3
, Bu), 31.9 (CH
3
3
,
t
t
General Considerations. All reactions were carried out using
standard Schlenk techniques under an atmosphere of argon. Solvents
were purified and dried by standard procedures. 3,5-Dideoxy-3,5-
C
C
3
2
1
2
diazido-1,2-O-isopropylidene-ribofuranose 7 and phosphorochlo-
(CHd), 114.9 (CHd),115.2 (CHd),128.8 (CHd),129.6 (CHd),
134.9 (C), 135.1 (C), 135.3 (C), 156.3 (C), 156.4 (C), 156.5 (C),
11
1
13
1
ridite were prepared as previously described. H, C{ H}, and
31
1
P{ H} NMR spectra were recorded using a 400 MHz spectrom-
70 2 11 2
156.7 (C). Anal. Calcd (%) for C52H N O P : C, 64.99; H, 7.34;
1
13
eter. Chemical shifts are relative to that of SiMe
4
( H and C) as
( P) as external standard.
,5-Dideoxy-3,5-diamino-1,2-O-isopropylidene-ribofuranose
8). 3,5-Dideoxy-3,5-diazido-1,2-O-isopropylidene-ribofuranose 7
2.0 g, 4.1 mmol) was dissolved in a THF/H O (90 mL, 4:1), and
N, 2.91. Found: C, 65.01; H, 7.41; N, 2.79.
3
1
internal standard or H
3
(
(
3
PO
4
3,5-Bis[(3,3′-bis-trimethylsilyl-1,1′-biphenyl-2,2′-diyl)phosphite]-
3,5-diamine-3,5-dideoxy-1,2-O-isopropylidene-ribofuranose (3).
Treatment of the corresponding phosphrochloridite (2.2 mmol)
produced in situ and 8 (189 mg, 1 mmol), as described for
compound 1, afforded diphosphoroamidite 3, which was purified
2
triphenylphosphine (5.0 g, 19.1 mmol) was added. The reaction
mixture was stirred overnight at room temperature, and the THF
was evaporated under vacuum. The residue was extracted with ether
by flash chromatography (toluene/NEt
3
) 100/2) to produce a white
powder. Yield: 0.46 g, 51%. P NMR, δ (C ): 148.0 (s, 1P),
): -0.32 (s, 9H, CH -Si), 0.38
-Si), 0.4 (s, 18H, CH -Si), 1.13 (s, 3H, CH ), 1.36
), 2.92 (m, 1H, H-5′), 3.06 (m, 1H, H-3), 3.14 (m, 1H,
NH-C-5), 3.29 (s, 1H, NH-C-3), 3.45 (m, 1H, H-5), 3.56 (m,
31
6 6
D
1
(
3 × 20 mL). Evaporation of the aqueous solution gave the product
154.3 (s, 1P). H NMR, δ (C
(s, 9H, CH
(s, 3H, CH
D
6 6
3
1
as a yellow oil. Yield: 1.2 g, 77%. H NMR, δ: 1.34 (s, 3H; CH
1
3
),
3
3
3
2
.53 (s, 3H; CH
3
), 1.62 (b, 4H, NH
2
), 2.83 (dd, 1H, H-5′, J5′-5 )
3
3
1
3.6 Hz, J5′-4 ) 6 Hz), 3.02 (m, 1H, H-3), 3.07 (dd, 1H, H-5,
2
3
3
J
5
-5′ ) 13.6 Hz, J
5
-4 ) 3.2 Hz), 3.66 (m, 1H, H-4), 4.46 (t, 1H,
1H, H-4), 3.79 (m, 1H, H-2), 5.47 (d, 1H, H-1, J
1
-2 ) 4 Hz),
3
3
3
13
13
H-2, J
NMR, δ: 26.6 (CH
), 82.4 (C-4), 104.3 (C-1), 112.1 (CMe
: C, 51.05; H, 8.57; N, 14.88. Found: C, 51.12; H, 8.64;
2
-1 ) J
2
-3 ) 4 Hz), 5.77 (d, 1H, H-1, J
), 26.8 (CH ), 42.9 (C-5), 56.4 (C-3), 81.0 (C-
). Anal. Calcd (%) for
1
-2 ) 4 Hz).
C
6.9-7.4 (m, 12H, CHd). C NMR, δ (C
0.59 (CH -Si), 0.63 (CH -Si), 0.68 (CH
0.86 (CH -Si), 26.8 (CH ), 27.1 (CH ), 42.6 (d, C-5, J
Hz), 54.4 (C-3), 80.7 (C-2), 82.1 (C-4), 104.3 (C-1), 112.1 (CMe
124.8 (CHd), 125.2 (CHd), 125.4 (CHd), 126.0 (CHd), 132.2
D
6 6
): 0.56 (CH
3
-Si),
-Si),
3
3
3
3
3
-Si), 0.82 (CH
3
2
C
2
3
3
3
C
-P ) 20
H N O
8 16 2 3
2
),
N, 14.97.
2848 J. Org. Chem., Vol. 72, No. 8, 2007

Sugar-Based Diphosphoroamidite Ligands
(
(
C), 132.3 (C), 132.4 (CHd), 132.5 (CHd), 132.6 (CHd), 132.5
CHd), 135.7 (CHd), 138.1 (C), 156.4 (C), 155.5 (C), 156.0 (C).
137.0 (CHd), 137.2 (CHd), 137.7 (CHd), 137.9 (CHd), 151.8
(C), 151.9 (C), 154.3 (C), 154.4 (C). Anal. Calcd (%) for
Anal. Calcd (%) for C44
Found: C, 58.31; H, 6.84 N, 3.01.
,5-Bis[(3,3′,5,5′-tetramethyl-1,1′-biphenyl-2,2′-diyl)phosphite]-
,5-diamine-3,5-dideoxy-1,2-O-isopropylidene-ribofuranose (4).
Treatment of the corresponding phosphrochloridite (2.2 mmol)
produced in situ and 8 (189 mg, 1 mmol), as described for
compound 1, afforded diphosphoroamidite 4, which was purified
H
62
N
2
O
7
P
2
Si
4
: C, 58.38; H, 6.90; N, 3.09.
C
60
H
70
N
2
O
7
P
2
Si
4
: C, 65.19; H, 6.38; N, 2.53. Found: C, 65.07;
H, 6.42; N, 2.58.
3
3
Preparation of [Pd((η -1,3-diphenylallyl)(2)]BF
4
. Ligand 2
3
3
(48.1 mg, 0.05 mmol) and the complex of [Pd(µ-Cl)(η -1,3-
diphenylallyl)] (17.3 mg, 0.025 mmol) were dissolved in CD Cl
(1.5 mL) at room temperature under argon. AgBF (9.8 mg, 0.5
mmol) was added after 30 min, and the mixture was stirred for 30
min. The mixture was then filtered over Celite under argon, and
2
2
2
4
by flash chromatography (toluene/NEt
3
) 100/2) to produce a white
powder. Yield: 0.23 g, 32%. P NMR, δ (C ): 141.8 (s, 1P),
): 1.29 (s, 3H, CH ), 1.48 (s, 3H,
), 2.30 (s, 3H, CH ), 2.31 (s, 3H, CH ),
), 2.40 (s, 3H, CH ), 2.47 (s, 3H, CH ), 2.49 (s,
), 2.50 (s, 3H, CH ), 3.14 (m, 1H, H-5′), 3.28 (m, 2H,
31
D
6
the resulting solution was analyzed by NMR.
6
1
31
1
48.0 (s, 1P). H NMR, δ (C
CH ), 2.18 (s, 3H, CH
.36 (s, 3H, CH
H, CH
6
D
6
3
Isomer 14B: P NMR (CD
2
Cl
2
), δ: 145.0 (d, 1P, P next to
-P ) 116 Hz).
, CH t-Bu), 2.81
(m, 1H, NH), 3.52 (m, 2H, H-5, H-5′), 3.71 (m, 1H, H-4), 3.8-4.0
(m, 14H, H-3, N-H, OCH ), 4.57 (m, 1H, H-2), 5.20 (m, 1H, CH
terminal), 5.26 (m, 1H, CH terminal), 5.66 (d, 1H, H-1, J
3.2 Hz), 6.24 (m, 2H, CHd), 6.44 (m, 1H, CH central), 6.5-7.2
(m, 16 H, CHd). 13C NMR (CD
Cl ), δ: 26.3 (CH ), 26.6 (CH ),
31-33 (m, CH , t-Bu), 35-36 (m, C, t-Bu), 38.7 (m, C-5), 53.4
(m, C-3), 56.0 (OCH ), 56.2 (OCH ), 56.4 (OCH ), 78.4 (m, C-2),
79.9 (m, C-4), 92.8 (m, CH terminal), 100.0 (m, CH terminal),
3
3
3
3
C-3, J
P
-P ) 116 Hz), 148.1 (d, 1P, P next to C-5, J
P
1
2
3
3
3
3
H NMR (CD Cl ), δ: 1.2-1.7 (m, 42H, CH
2
2
3
3
3
3
NH), 3.37 (m, 1H, H-3), 3.42 (m, 2H, H-5, H-4), 4.16 (m, 1H,
3
3
3
H-2), 5.52 (d, 1H, H-1, J
1
-2 ) 4 Hz), 6.9-7.4 (m, 8H, CHd).
): 16.9 (CH ), 17.1 (CH ), 17.3 (CH ), 17.5
), 21.2 (CH ), 21.3 (CH ), 26.7 (CH ), 27.0 (CH ),
-P ) 20 Hz), 54.0 (d, C-3, J -P ) 12 Hz), 81.1
C-2), 81.6 (C-4), 104.6 (C-1), 112.2 (CMe ), 128.5 (CHd), 128.6
CHd), 128.8 (CHd), 129.6 (CHd), 130.2 (C), 131.4 (CHd),
1
-2 )
13
C NMR, δ (C
CH ), 20.9 (CH
0.3 (d, C-5, J
6
D
6
3
3
3
(
4
3
3
3
3
3
3
2
2
3
3
C
C
3
(
(
2
3
3
3
1
1
1
31.5 (CHd), 131.6 (CHd), 131.7 (CHd), 132.3 (C), 132.7 (C),
33.4 (C), 133.6 (C), 134.0 (C), 147.0 (C), 147.1 (C), 147.8 (C),
104.9 (C-1), 113.3 (m, CH central), 114.3 (CMe
(aromatic carbons).
2
), 114.5-157.0
Isomer 14A: 31P NMR (CD
Cl
-P ) 115 Hz), 148.0 (d, 1P, P next to C-5, J
H NMR (CD Cl ), δ: 1.2-1.7 (m, 42H, CH , CH
(m, 1H, NH), 3.52 (m, 2H, H-5, H-5′), 3.71 (m, 1H, H-4), 3.8-4.0
(m, 14H, H-3, N-H, OCH ), 4.66 (m, 1H, H-2), 5.18 (m, 1H, CH
terminal), 5.24 (m, 1H, CH terminal), 5.72 (d, 1H, H-1, J
3.6 Hz), 6.24 (m, 2H, CHd), 6.44 (m, 1H, CH central), 6.5-7.2
(m, 16 H, CHd). 13C NMR (CD
Cl ), δ: 26.3 (CH ), 26.6 (CH ),
31-33 (m, CH , t-Bu), 35-36 (m, C, t-Bu), 38.7 (m, C-5), 53.4
(m, C-3), 56.0 (OCH ), 56.2 (OCH ), 56.4 (OCH ), 78.4 (m, C-2),
79.9 (m, C-4), 92.8 (m, CH terminal), 99.3 (m, CH terminal), 104.9
), δ: 144.7 (d, 1P, P next to
-P ) 115 Hz).
t-Bu), 2.81
46 2 7 2
47.98 (C). Anal. Calcd (%) for C40H N O P : C, 65.92; H, 6.36;
2
2
N, 3.84. Found: C, 65.99; H, 6.42; N, 3.89.
C-3, J
P
P
1
3,5-Bis[((R)-3,3′-bis-trimethylsilyl-1,1′-binaphthyl-2,2′-diyl)-
2
2
3
3
phosphite]-3,5-diamine-3,5-dideoxy-1,2-O-isopropylidene-ribo-
furanose (5). Treatment of the corresponding phosphrochloridite
3
3
(
2.2 mmol) produced in situ and 8 (189 mg, 1 mmol), as described
for compound 1, afforded diphosphoroamidite 5, which was purified
by flash chromatography (toluene/NEt ) 100/2) to produce a white
powder. Yield: 0.33 g, 30%. P NMR, δ (C ): 147.2 (s, 1P),
): 0.43 (s, 9H, CH -Si), 0.45 (s,
-Si), 0.57 (s, 9H, CH -Si), 1.12
), 2.79 (m, 2H, H-5′, NH-C-3),
.08 (m, 1H, H-3), 3.23 (m, 1H, NH-C-5), 3.38 (m, 1H, H-2),
1
-2 )
3
2
2
3
3
31
6
D
6
3
1
1
9
51.2 (s, 1P). H NMR, δ (C
H, CH -Si), 0.52 (s, 9H, CH
), 1.38 (s, 3H, CH
6
D
3
6
3
3
3
3
3
3
(s, 3H, CH
3
3
(C-1), 113.3 (m, CH central), 114.3 (CMe
2
), 114.5-157.0 (aromatic
3
4
2
1
4
1
carbons).
3
3
.41 (m, 1H, H-4), 5.03 (d, 1H, H-1, J
0H, CHd). 13C NMR, δ (C
): 0.6 (CH
.0 (CH -Si), 1.1 (CH -Si), 1.1 (CH -Si), 26.5 (CH
2.7 (d, C-5, J -P ) 16 Hz), 54.4 (C-3), 80.5 (C-2), 81.5 (C-4),
04.1 (C-1), 111.9 (CMe ), 125.0 (CHd), 125.1 (CHd), 125.4
1
-2 ) 4 Hz), 6.8-8.2 (m,
-Si), 0.7 (CH -Si),
), 27.1 (CH ),
Preparation of [Pd((η -1,3-diphenylallyl)(3)]BF
4
. Ligand 3
3
6
D
6
3
3
(45.2 mg, 0.05 mmol) and the complex of [Pd(µ-Cl)(η -1,3-
diphenylallyl)] (17.3 mg, 0.025 mmol) were dissolved in CD Cl
(1.5 mL) at room temperature under argon. AgBF (9.8 mg, 0.5
3
3
3
3
3
2
2
2
C
4
2
mmol) was added after 30 min, and the mixture was stirred for 30
min. The mixture was then filtered over Celite under argon, and
the resulting solution was analyzed by NMR.
(
1
(
CHd), 127.1 (CHd), 127.4 (CHd), 127.5 (CHd), 127.6 (CHd),
27.8 (CHd), 128.2 (CHd), 128.6 (CHd), 128.8 (CHd), 129.1
CHd), 129.2 (CHd), 129.6 (CHd), 131.2 (CHd), 131.8 (CHd),
Isomer 15B: 31P NMR (CD
C-3, J
Cl
-P ) 97 Hz), 148.5 (d, 1P, P next to C-5, J
H NMR (CD Cl ), δ: 0.3-0.7 (m, 36H, CH -Si), 1.2-1.3 (m,
6H, CH ), 2.9 (m, 1H, NH), 3.4-3.9 (m, 5H, H-3, H-4, H-5, H-5′,
NH), 4.63 (m, 1H, H-2), 5.48 (m, 1H, CH terminal), 5.52 (m, 1H,
), δ: 145.2 (d, 1P, P next to
2
2
1
1
32.7 (C), 133.0 (C), 133.4 (C), 133.6 (C), 134.7 (C), 135.0 (C),
36.6 (CHd), 136.9 (CHd), 137.7 (CHd), 137.9 (CHd), 153.0
P
P
-P ) 97 Hz).
1
2
2
3
(
C), 153.9 (C), 154.5 (C). Anal. Calcd (%) for C60
C, 65.19; H, 6.38; N, 2.53. Found: C, 65.25; H, 6.29; N, 2.39.
,5-Bis[((S)-3,3′-bis-trimethylsilyl-1,1′-binaphthyl-2,2′-diyl)-
H
70
N O P
2 7 2
Si
4
:
3
3
3
CH terminal), 5.66 (d, 1H, H-1, J -2 ) 3.6 Hz), 6.52 (m, 1H, CH
1
13
phosphite]-3,5-diamine-3,5-dideoxy-1,2-O-isopropylidene-ribo-
furanose (6). Treatment of the corresponding phosphrochloridite
central), 6.7-7.7 (m, 22 H, CHd). C NMR (CD
(CH -Si), 26.3 (CH ), 39.1 (m, C-5), 53.1 (m, C-3), 78.6 (m, C-2),
79.5 (b, C-4), 95.4 (m, CH terminal), 97.1 (m, CH terminal), 104.3
2 2
Cl ), δ: 0-2.2
3
3
(
2.2 mmol) produced in situ and 8 (189 mg, 1 mmol), as described
for compound 1, afforded diphosphoroamidite 6, which was purified
by flash chromatography (toluene/NEt ) 100/2) to produce a white
powder. Yield: 0.24 g, 22%. P NMR, δ (C ): 153.5 (s, 1P),
): 0.54 (s, 9H, CH -Si), 0.56 (s,
-Si), 0.67 (s, 9H, CH -Si), 1.00
(C-1), 112.2 (m, CH central), 114.1 (CMe
carbons).
2
), 125-155 (aromatic
3
31
Isomer 15A: 31P NMR (CD
6
D
6
2
Cl
-P ) 97 Hz), 149.7 (d, 1P, P next to C-5, J
H NMR (CD Cl ), δ: 0.3-0.7 (m, 36H, CH -Si), 1.2-1.3 (m,
6H, CH ), 2.9 (m, 1H, NH), 3.4-3.9 (m, 5H, H-3, H-4, H-5, H-5′,
NH), 4.70 (m, 1H, H-2), 5.40 (m, 1H, CH terminal), 5.44 (m, 1H,
2
), δ: 145.8 (d, 1P, P next to
1
1
9
54.6 (s, 1P). H NMR, δ (C
H, CH -Si), 0.62 (s, 9H, CH
), 1.05 (s, 3H, CH
6
D
3
6
3
C-3, J
P
P
-P ) 97 Hz).
1
3
3
2
2
3
(s, 3H, CH
3
3
), 3.32 (m, 3H, H-3, H-5′, NH),
3
3
1
.48 (m, 1H, NH), 3.60 (m, 1H, H-5), 3.67 (m, 1H, H-4), 4.32 (m,
3
3
H, H-2), 5.05 (d, 1H, H-1, J
1
-2 ) 3.6 Hz), 6.8-8.2 (m, 20H,
CH terminal), 5.71 (d, 1H, H-1, J -2 ) 4.0 Hz), 6.52 (m, 1H, CH
1
13
13
CHd). C NMR, δ (C
CH -Si), 1.1 (CH -Si), 1.2 (CH
3.0 (d, C-5, J -P ) 28 Hz), 56.3 (d, C-3, J
C-2, J -P ) 5.2 Hz), 82.2 (d, C-4, J -P ) 6.4 Hz), 104.4 (C-1),
12.3 (CMe ), 125.1 (CHd), 125.3 (CHd), 126.0 (CHd), 127.1
CHd), 127.2 (CHd), 127.4 (CHd), 127.5 (CHd), 127.7 (CHd),
28.2 (CHd), 128.6 (CHd), 128.8 (CHd), 129.0 (CHd), 131.4
CHd), 131.8 (CHd), 132.4 (C), 132.7 (C), 132.9 (C), 133.1 (C),
D
6 6
): 0.7 (CH
-Si), 26.7 (CH
-P ) 22 Hz), 80.5 (d,
3
-Si), 0.8 (CH
3
-Si), 0.9
central), 6.7-7.7 (m, 22 H, CHd). C NMR (CD
(CH -Si), 26.3 (CH ), 39.1 (m, C-5), 53.1 (m, C-3), 78.6 (m, C-2),
79.5 (b, C-4), 95.9 (m, CH terminal), 96.9 (m, CH terminal), 104.3
2 2
Cl ), δ: 0-2.2
(
4
3
3
3
3
), 26.9 (CH
3
),
3
3
C
C
(C-1), 112.2 (m, CH central), 114.1 (CMe
carbons).
2
), 125-155 (aromatic
C
C
1
(
1
(
2
Preparation of [Pd(cyclo-C
0.05 mmol) and the complex of [Pd(µ-Cl)(cyclo-C
0.025 mmol) were dissolved in CD Cl (1.5 mL) at room temper-
6
H
9
)(1)]BF
4
. Ligand 1 (53.2 mg,
6 9 2
H )] (11.0 mg,
2
2
J. Org. Chem, Vol. 72, No. 8, 2007 2849

Raluy et al.
ature under argon. AgBF
4
(9.8 mg, 0.5 mmol) was added after 30
16.9-17.3 (CH
(CH ), 28.8 (CH
79.5 (m, C-2), 80.2 (b, C-4), 91.8 (dd, CH terminal, J
Hz, J -P ) 8 Hz), 97.3 (m, CH terminal), 104.8 (C-1), 113.7 (m,
CH central), 114.1 (CMe ), 128.9-138.0 (aromatic carbons).
Allylic Alkylation of rac-1,3-Diphenyl-3-acetoxyprop-1-ene
3
-Ar), 18.7 (CH
2
2
), 21.2 (CH
-P ) 16 Hz), 53.5 (m, C-3),
-P ) 31.6
3
3
-Ar), 26.6 (CH ), 28.2
min, and the mixture was stirred for 30 min. The mixture was then
filtered over Celite under argon, and the resulting solution was
analyzed by NMR.
2
), 37.1 (d, C-5, J
C
C
C
Isomer 16A: 31P NMR (CD
C-3, J
), δ: 144.5 (d, 1P, P next to
-P ) 75.8
t-Bu, CH ),
), 3.49 (m, 1H, H-5′), 3.70 (m, 2H, NH), 3.78
m, 2H, H-4, H-5), 4.07 (m, 1H, H-3), 4.38 (m, 1H, CH terminal),
.72 (m, 1H, H-2), 5.02 (m, 1H, CH central), 5.83 (d, 1H, H-1,
2
Cl
2
2
P
-P ) 75.8 Hz), 145.7 (d, 1P, P next to C-5, J
P
1
Hz). H NMR (CD
.83 (m, 2H, CH
2
Cl
2
), δ: 1.2-1.6 (m, 82H, CH
3
, CH
3
2
3
3 5 2
(S1). A degassed solution of [PdCl(η -C H )] (0.9 mg, 0.0025
1
(
2
mmol) and the diphosphoroamidite ligand (0.0055 mmol) in
dichloromethane (0.5 mL) was stirred for 30 min. Subsequently, a
solution of rac-S1 (126 mg, 0.5 mmol) in dichloromethane (1.5
mL), dimethyl malonate (171 µL, 1.5 mmol), N,O-bis(trimethyl-
silyl)-acetamide (370 µL, 1.5 mmol), and a pinch of KOAc were
added. The reaction mixture was stirred at room temperature. After
4
3
J -2 ) 4.0 Hz), 5.93 (m, 1H, CH terminal), 7.1-7.6 (m, 8 H,
1
13
CHd). C NMR (CD
Cl
2 2
), δ: 18.7 (CH
2
), 26.0 (CH
2 3
), 26.4 (CH ),
2
3
4
1
6.7 (CH
3
), 28.0 (CH
2
), 31.6-32.6 (CH
3
, t-Bu), 35.2 (C, t-Bu),
5.9 (C, t-Bu), 38.2 (m, C-5), 53.8 (m, C-3), 78.6 (C-2), 79.9 (C-
), 91.2 (m, CH terminal), 97.9 (m, CH terminal), 104.9 (C-1),
5
min the reaction mixture was diluted with Et
saturated NH Cl(aq) (25 mL) was added. The mixture was extracted
with Et
O (3 × 10 mL), and the extract was dried over MgSO
The solvent was removed, and the conversion was measured by
2
O (5 mL), and
4
13.6 (m, CH central), 114.2 (CMe
Isomer 16B: 31P NMR (CD
Cl
-P ) 75.8 Hz), 148.6 (d, 1P, P next to C-5, J
2
), 125-150 (aromatic carbons).
), δ: 140.9 (bd, 1P, P next to
-P ) 75.8
t-Bu, CH ),
.49 (m, 2H, H-5, H-5′), 3.78 (m, 2H, H-4, H-3), 4.21 (m, 1H,
N-H), 4.37 (m, 1H, N-H), 4.54 (m, 1H, CH terminal), 4.62 (m,
2
4
.
2
2
C-3, J
Hz). H NMR (CD
3
P
P
1
H NMR. To determine the ee by HPLC (Chiralcel-OD, 0.5%
-propanol/hexane, flow 0.5 mL/min), a sample was filtered over
1
2 2
Cl ), δ: 1.2-1.6 (m, 82H, CH
3
, CH
3
2
2
basic alumina using dichloromethane as the eluent.
Allylic Alkylation of rac-3-Acetoxycyclohexene (S2) and rac-
3
1
H, H-2), 5.02 (m, 1H, CH central), 5.81 (d, 1H, H-1, J -2 ) 4.0
1
13
3
3
-Acetoxycycloheptene (S3). A degassed solution of [PdCl(η -
Hz), 5.83 (m, 1H, CH terminal), 7.1-7.6 (m, 8 H, CHd). C NMR
3 5 2
C H (0.9 mg, 0.0025 mmol) and the diphosphoroamidite ligand
)]
(
(
(
CD
CH
2
Cl
2
), δ: 18.8 (CH
2
), 26.4 (CH
3 3 2
), 26.7 (CH ), 28.2 (CH ), 28.3
(0.0055 mmol) in THF (0.5 mL) was stirred for 30 min. Subse-
2
), 31.6-32.6 (CH
3
, t-Bu), 35.2 (C, t-Bu), 35.9 (C, t-Bu), 38.2
quently, a solution of substrate (0.5 mmol) in THF (1.5 mL),
dimethyl malonate (171 µL, 1.5 mmol), N,O-bis(trimethylsilyl)-
acetamide (370 µL, 1.5 mmol), and a pinch of KOAc were added.
The reaction mixture was stirred at room temperature. After 30
m, C-5), 53.8 (m, C-3), 78.7 (C-2), 80.2 (C-4), 90.8 (m, CH
terminal), 101.9 (m, CH terminal), 104.9 (C-1), 113.6 (m, CH
central), 114.2 (CMe ), 125-150 (aromatic carbons).
Preparation of [Pd(cyclo-C )(4)]BF . Ligand 4 (36.5 mg,
.05 mmol) and the complex of [Pd(µ-Cl)(cyclo-C )] (11.0 mg,
.025 mmol) were dissolved in CD Cl (1.5 mL) at room temper-
(9.8 mg, 0.5 mmol) was added after 30
2
6
H
9
4
min the reaction mixture was diluted with Et
saturated NH Cl(aq) (25 mL) was added. The mixture was extracted
with Et
2
O (5 mL), and
0
0
6 9 2
H
4
2
2
2
O (3 × 10 mL), and the extract was dried over MgSO
4
.
ature under argon. AgBF
4
Conversion and enantiomeric excess were determined by GC using
an FS-â-Cyclodex 25 m column ( i.d. 0.2 mm, film thickness 0.33
mm, carrier gas, 100 kPa He, FID detector).
min, and the mixture was stirred for 30 min. The mixture was then
filtered over Celite under argon, and the resulting solution was
analyzed by NMR.
Isomer 17A: 31P NMR (CD
Allylic Alkylation of 1-(1-Naphthyl)allyl Acetate (S4). A
2
Cl
2
), δ: 148.0 (d, 1P, P next to
-P ) 78 Hz).
), 1.59 (s, 3H, CH ),
), 2.40 (s, 3H, CH -Ar),
-Ar), 3.61 (m, 2H, H-5,
3
degassed solution of [PdCl(η -C
H
3 5
)]
2
(1.8 mg, 0.005 mmol) and
C-3, J
P
-P ) 78 Hz), 149.2 (d, 1P, P next to C-5, J
H NMR (CD Cl ), δ: 0.9-1.2 (m, 2H, CH
.65 (s, 3H, CH ), 1.6-2.2 (m, 4H, CH
.60 (m, 18H, CH -Ar), 2.78 (s, 3H, CH
P
1
the diphosphoroamidite ligand (0.011 mmol) in dichloromethane
0.5 mL) was stirred for 30 min. Subsequently, a solution of rac-
2
2
2
3
(
1
2
3
2
3
S4 (113 mg, 0.5 mmol) in dichloromethane (1.5 mL), dimethyl
malonate (171 µL, 1.5 mmol), N,O-bis(trimethylsilyl)-acetamide
3
3
H-5′), 3.83 (m, 1H, H-4), 4.18 (m, 2H, H-3, N-H), 4.36 (m, 1H,
NH), 4.75 (m, 1H, H-2), 5.14 (m, 1H, CH terminal), 5.24 (m, 1H,
CH central), 5.83 (d, 1H, H-1, J
(370 µL, 1.5 mmol), and a pinch of KOAc were added. The reaction
3
mixture was stirred at room temperature. After 2 h the reaction
mixture was diluted with Et O (5 mL), and saturated NH Cl(aq)
1
-2 ) 3.6 Hz), 6.02 (m, 1H, CH
13
terminal), 7.2-7.5 (m, 8 H, CHd). C NMR (CD
7.3 (CH ), 21.1 (CH
CH ), 28.8 (CH ), 39.2 (d, C-5, J -P ) 19.2 Hz), 52.6 (d, C-3,
-P ) 19.7 Hz), 79.5 (m, C-2), 80.2 (b, C-4), 93.2 (dd, CH
-P ) 31.4 Hz, J -P ) 5.2 Hz), 96.7 (dd, CH terminal,
-P ) 33.9 Hz, J -P ) 5.4 Hz), 104.7 (C-1), 113.7 (m, CH central),
14.1 (CMe ), 128.9-138.0 (aromatic carbons).
Isomer 17B: 3 P NMR (CD
-P ) 79 Hz), 151.3 (d, 1P, P next to C-5, J
H NMR (CD Cl ), δ: 0.9-1.2 (m, 2H, CH ), 1,45 (s, 3H, CH
.65 (s, 3H, CH ), 1.6-2.2 (m, 4H, CH ), 2.42 (s, 3H, CH -Ar),
.60 (m, 18H, CH -Ar), 2.76 (s, 3H, CH -Ar), 3.61 (m, 1H, H-5′),
2
Cl
2
), δ: 16.9-
2
4
(
25 mL) was added. The mixture was extracted with Et
2
O (3 × 10
1
(
3
-Ar), 18.6 (CH
2
3
-Ar), 26.6 (CH
3
), 28.2
4
mL), and the extract was dried over MgSO . The solvent was
2
2
C
removed, and the conversion and regioselectivity were measured
J
C
1
by H NMR. To determine the ee by HPLC (Chiralcel-OJ, 3%
terminal, J
C
C
2-propanol/hexane, flow 0.7 mL/min), a sample was filtered over
J
C
C
basic alumina using dichloromethane as the eluent.
1
2
1
2
Cl
2
), δ: 146.3 (d, 1P, P next to
-P ) 79 Hz).
),
C-3, J
P
P
Acknowledgment. We are indebted to Professor P. W. N.
M. van Leeuwen, University of Amsterdam, for his comments
and suggestions. We thank the Spanish Government (Consolider
Ingenio CSD2006-0003, CTQ2004-04412/BQU, and the Ramon
y Cajal Fellowship to O.P.) and the Generalitat de Catalunya
1
2
2
2
3
1
2
3
2
1
3
2
3
3
3
.76 (m, 1H, H-3), 3.83 (m, 1H, H-4), 3.97 (m, 1H, H-5), 4.18 (m,
H, N-H), 4.75 (m, 1H, H-2), 5.24 (m, 1H, CH central), 5.33 (m,
H, CH terminal), 5.83 (d, 1H, H-1, J
(2005SGR007777 and Distinction to M.D.) for financial support.
3
1
-2 ) 3.6 Hz), 5.88 (m, 1H,
13
2 2
CH terminal), 7.2-7.5 (m, 8 H, CHd). C NMR (CD Cl ), δ:
JO062311J
2850 J. Org. Chem., Vol. 72, No. 8, 2007