Highly modular P-OP ligands in asymmetric allylic substitution

Article abstract of DOI:10.1016/j.tetasy.2010.08.004

A library of highly modular P-OP ligands have been evaluated in Pd-catalysed allylic substitutions with C- and N-nucleophiles. Catalyst optimisation via a variation of the phosphino and phosphite substituents led to a 'lead' catalyst, which efficiently me

Full text of DOI:10.1016/j.tetasy.2010.08.004

Tetrahedron: Asymmetry 21 (2010) 2281–2288
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Tetrahedron: Asymmetry
journal homepage: www.elsevier.com/locate/tetasy
Highly modular P-OP ligands in asymmetric allylic substitution
Armen Panossian a, Héctor Fernández-Pérez a, Dana Popa a, Anton Vidal-Ferran a,b,
⇑
a Institute of Chemical Research of Catalonia (ICIQ), Av. Països Catalans 16, 43007 Tarragona, Spain
b Catalan Institute for Research and Advanced Studies (ICREA), Pg. Lluis Companys 23, 08010 Barcelona, Spain
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 7 July 2010
Accepted 9 August 2010
Available online 9 September 2010
A library of highly modular P-OP ligands have been evaluated in Pd-catalysed allylic substitutions with C-
and N-nucleophiles. Catalyst optimisation via a variation of the phosphino and phosphite substituents led
to a ‘lead’ catalyst, which efficiently mediated the allylic substitutions when various combinations of sub-
strates and nucleophiles were tested. Ground-state calculations were carried out and these allowed a
clearer understanding of the stereochemical outcome of the reaction.
Ó 2010 Elsevier Ltd. All rights reserved.
R1
R1
R2
R2
1. Introduction
L
[M]
S
R1
R2
Nu
Allylic alkylation is amongst the most important methodologies
for the stereoselective formation of C–C bonds, enabling the crea-
tion of diverse carbon frameworks for targets ranging from natural
products to non-natural organic compounds. Enantiomerically en-
riched alkylation products are formed from racemic substrates by
differentiation of the reactivity of the two allyl termini in the inter-
G1
X
Y
G2
+
or
Nu
M= Metal centre
X, Y= Donor binding groups
S= Spacer
L
L = Leaving
group
G= Substituents
mediate
p-allyl complexes. Desymmetrisation of the allyl system
depends on the electronic and/or steric effects induced by the li-
gand bound to the metal centre.1
Nu
Nu
For C2-symmetric ligands (e.g., bisoxazolines), desymmetrisa-
tion arises solely from steric interactions between the substituents
of the ligand and the substrate.1,2 On the other hand, non-steric
factors may become preponderant in C1-symmetric ligands, as for
example in those containing two distinct donor groups, X and Y,
that differ in their coordination to the metal centre (e.g., P,N-li-
gands). In this case, desymmetrisation may chiefly occur due to
the different trans-influences of X or Y, as these may preferentially
lengthen one of the two distal metal-Callyl bonds (Scheme 1).1,3
We recently reported on the preparation of a library of highly
modular P-OP (phosphine-phosphinite and phosphine-phosphite)
ligands and their use in asymmetric hydrogenation,4 and we felt
that studying their application in allylic substitutions was the next
logical step forward in assessing the utility of these ligands in
asymmetric catalysis. We found that the literature precedent on
the use of P-OP ligands in allylic substitution was scarce.5 We rea-
soned that the different coordinating properties of the phosphino
group and of the phosphite/phosphinite group could be efficient
tools for desymmetrisation of the terminal allyl carbons. Further-
more, we envisioned that modular ligand design should enable cat-
alyst optimisation via systematic variation of the different
R1
R1
R2
G2
R2
G2
M
M
S
G1
X
Y
G1
X
Y
S
steric
desymmetrisation
electronic
desymmetrisation
or
Scheme 1. Metal-mediated nucleophilic allylic substitutions.
components of the catalytic system (G1, G2, X, Y or S) as differenti-
ating tools (electronic, steric or a combination of both) for the ter-
minal allyl carbons. Herein, we report our efforts to evaluate
structurally diverse P-OP ligands in palladium-mediated asymmet-
ric allylic substitutions.
2. Results and discussion
Our initial set of ligands comprised phosphine-phosphinites 1
and phosphine-phosphites 2–5 (Fig. 1),6 which we chose in order
to evaluate the effect of sterically and/or electronically diverse
phosphorus functionalities on the catalytic performance of their
corresponding palladium complexes.
⇑
Corresponding author. Tel.: +34 977 920 210; fax: +34 977 920 228.
E-mail address: avidal@iciq.es (A. Vidal-Ferran).
0957-4166/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2010.08.004

2282
Ph2P
Ph
A. Panossian et al. / Tetrahedron: Asymmetry 21 (2010) 2281–2288
Ph2P
Ph
BH3
LiBH4 (1.1 equiv.)
Et2O, 0 ºC
X
P
Cl
X
P
OR
OPPh2
OR
O
2
2
H
O
P
O
8a; X= CF3
8b; X= OMe
9a; X= CF3, 85%
9b; X= OMe, 50%
1a; R= Me
2a; R= Me
1b; R= CPh3
2b; R= CPh3
X
Ph2P
Ph
Ph2P
Ph
X
n-BuLi (1.1 equiv.)
1)
OMe
O
OMe
THF, -70 ºC - r.t., 5 min
BH3
P
O
O
O
P
O
P
O
2) Ph
OMe
THF,
Ph
OMe
OH
O
10 (1 equiv.)
-70 ºC - r.t., o/n
3
4; (Sa)-BINOL
5; (Ra)-BINOL
11a; X= CF3, 45%
11b; X= OMe, 69%
Figure 1. P-OP ligands.
X
X
DABCO (2.2 equiv.) Toluene,
60 ºC, 2 h
1)
The in situ-generated Pd-complexes between 1a or 1b and
[Pd(
3-C3H5)Cl]2 mediated the allylic substitution of 6a with di-
P
g
methyl malonate (DMM) with high activities but poor selectivities
(Table 1, entries 1 and 2). Better ee’s were obtained when the diph-
enylphosphinite fragment was replaced with a biphenol-derived
phosphite moiety (Table 1, entries 3 and 4). In this case, the size
of the alkoxy group had a greater impact on enantioselectivity:7
the smaller group (the OMe in 2a) gave the higher ee (40%) (Table 1,
entry 3). Thus, we performed all subsequent optimisation studies
using the OMe group at the R-oxy position. Disappointingly, the
Pd-complex derived from the dioxaphospholane-containing ligand
3 afforded drastically lower conversion and ee (Table 1, entry 5). As
biaryl-based phosphites provided the best enantioselectivity, the
(S)- and (R)-BINOL-derived ligands 4 and 5 were selected. Although
the catalytic precursor-bearing ligand 4 showed only modest activ-
ity and selectivity (Table 1, entry 6), the one based on 5 achieved
high conversion and the highest ee (80%, Table 1, entry 7). The
incorporation of a less-coordinating counteranion into the catalytic
Ph
OMe
O
O
P
O
O
2) Cl
P
O
12 (1.1-1.5 equiv.)
4 Å MS, Toluene, -5 ºC, o/n
13a; X= CF3, 77%
13b; X= OMe, 63%
Scheme 2. Synthesis of electronically tuned P-OP ligands.
ꢀ
ꢀ
species (PF6 instead of Cl ), did not lead to an improvement of the
enantioselectivity either at room temperature or at 0 °C (Table 1,
entries 8 and 9).
Our results underscore an interesting match/mismatch effect.
Indeed, Pd-complexes of ligands 4 and 5 behaved rather distinctly:
the former yielded the product with lower ee, whereas the latter
gave the opposite enantiomer with higher ee. Thus, the (S)-BI-
NOL-derived substituent on the phosphite group overrides the
asymmetric induction generated by the ligand backbone, whereas
the (R)-BINOL one enhances it.
Table 1
Evaluation of 1–5 in Pd-catalysed allylic substitutions
CH2(CO2Me)2 (3 equiv.)
[Pd(η3-C3H5)Cl]2 (1.25 mol %)
We reasoned that a more pronounced differentiation between
the two phosphorus functionalities could enhance the enantiose-
lectivity. Thus, we wished to modulate the donor ability of the
phosphino moiety in 5, by introducing electron-withdrawing
(13a, X = CF3) or -donating (13b, X = OMe) substituents (Scheme 2).
Similar variations had already been studied theoretically by Gold-
fuss et al.8 on P,N-derived allylpalladium complexes and they pre-
dicted that a more electron-rich phosphine unit led to a longer
bond between palladium and the allyl carbon trans to the phospho-
rus (a more pronounced trans-influence). Based on their results,
and considering that for other phosphine-phosphites, the phos-
phino groups have been reported to induce a stronger trans-influ-
ence than the phosphite ones,5a we anticipated higher ee’s when
passing from the ligand containing the (p-CF3–C6H4)2P substituent
13a, to the one with the Ph2P moiety 5, and lastly, to the one with
the (p-MeO–C6H4)2P group 13b.
Ligands 1-5 (2.5 mol %)
Ph
Ph
Ph
Ph
BSA (3 equiv.), KOAc (5 mol %)
DCM
OAc
6a
CH(CO2Me)2
7a
Entry
Ligand
ta (h)
Temp (°C)
Conv.b (%)
eec (%) (configuration)
1
2
3
4
5
6
7
8
9
1a
1b
2a
2b
3
2.5
2.5
5
rt
rt
rt
rt
rt
rt
rt
rt
0
>95
>95
>95
>95
37
16 (R)
21 (R)
40 (R)
27 (R)
14 (R)
56 (S)
80 (R)
78 (R)
79 (R)
5
24
24
1
2
2
4
56
5
>95
>95
>95
5d
5d
a
b
c
Reaction time.
Conversion was determined by 1H NMR.
Enantiomeric excess was measured by chiral HPLC and absolute configuration
We therefore prepared the borane complexes of secondary
phosphines 9a and 9b, with which to open the epoxy ether 10
was assigned by comparison with published data.
9
d
(Scheme 2), in a single step using LiBH4 as the reducing agent.
Preformed [Pd(
g
3-C3H5)(5)]PF6 was used as the catalyst instead of the usual
3-C3H5)(5)]Cl).
catalyst (in situ-generated [Pd(
g
The borane adducts of the phosphino-alcohols, 11a and 11b, were

A. Panossian et al. / Tetrahedron: Asymmetry 21 (2010) 2281–2288
2283
Table 2
Comparative study of ligands 5, 13a and 13b in Pd-catalysed allylic substitutions with C- and N-nucleophiles
Nu (3 equiv.)
[Pd(η3-C3H5)Cl]2 (1.25 mol %)
Ligands 5, 13a or 13b (2.5 mol %)
R1
R2
R1
R2
OAc R3
Nu R3
BSA (3 equiv.), KOAc (5 mol %)
DCM, rt
6a; R1 = R2 = Ph, R3 = H
6b; R1 = Me, R2 = R3 = Ph
6c; R1 = R2 = p-Cl-C6H4, R3 = H
7a-d
Entry
Subs.
Nua
Prod.
Ligand
tb (h)
Conv.c (%)
eed (%) (configuration)
1
2
3
4
5
6
7
8
9
6a
6a
6a
6b
6c
6a
6a
6a
6a
DMM
DMM
DMM
DMM
DMM
BZA
BZA
BZA
BZA
7a
7a
7a
7b
7c
7d
7d
7d
7d
13a
13b
13be
13bf
13b
13a
5
1
1
1
90
2
24
72
24
17
>95
>95
>95
92
>95
3
3
9
67
64 (R)
80 (R)
78 (R)
34 (R)
67 (R)
46 (S)
61 (S)
81 (S)
81 (S)
13b
13be
a
b
c
d
e
f
Nucleophile: DMM (dimethyl malonate); BZA (PhCH2NH2).
Reaction time.
Conversion was determined by 1H NMR.
Enantiomeric excess was measured by chiral HPLC and absolute configuration was assigned by specific rotation measurement or comparison with published data.
Preformed [Pd(
3-C3H5)(13b)]PF6 was used as the catalyst instead of the usual catalyst (in situ-generated [Pd( 3-C3H5)(13b)]Cl).
5 mol % of catalyst were used instead of 2.5 mol %.
g
g
obtained by stereospecific and regioselective epoxide ring-open-
ing.4,10 Ligands 13a–b were finally obtained in 77% and 63% yield,
respectively (Scheme 2) after borane cleavage and O-phosphoryla-
tion using DABCO as the nucleophile/base for both transforma-
tions, thereby markedly simplifying our previous4 experimental
procedure.
Table 3
Selected geometrical parameters for complexes 14
Entry
Complex
Distancesa (Å)
Pd–CtPO
Pd–CtP
PPdP–CtP
PPdP–CtPO
1
2
3
4
5
6
14-endo-syn-syn
14-endo-syn-anti
14-exo-syn-anti
14-exo-syn-syn
14-endo-anti-syn
14-exo-anti-syn
2.27
2.24
2.26
2.32
2.32
2.43
2.33
2.39
2.33
2.29
2.26
2.23
0.58
0.13
ꢀ0.04
ꢀ0.26
0.45
ꢀ0.02
0.11
ꢀ0.08
ꢀ0.36
ꢀ0.22
0.11
We then studied the Pd-complexes derived from 13 in allylic
substitutions, comparing their catalytic performance to that of 5.
All of them performed similarly in the allylic alkylation of 6 with
DMM, providing near total conversion of the substrate within 1 h
(Table 2). As anticipated, 13a (CF3-substituted) gave the lowest
ee, whereas 13b (OMe-substituted) gave the same enantiomeric
excess as 5 (compare Table 1, entry 7 with Table 2, entry 2).11
We used benzylamine (BZA) as a model nitrogen nucleophile to
study the allylic substitution of 6 mediated by the Pd-complexes of
5, 13a and 13b (Table 2, entries 6–9). We clearly observed the ex-
pected trend of increasing enantioselectivity with 13a (X = CF3;
46% ee), 5 (X = H; 61% ee), and 13b (X = OMe; 81% ee). Conversions
ꢀ0.26
a
Pd–CtP = Pd–(Callyl trans to P) bond distance; Pd–CtPO = Pd–(Callyl trans to PO)
bond distance; PPdPO–CtP = distance between the P–Pd–PO mean plane and the
Callyl trans to P; PPdPO–CtPO = distance between the P–Pd–PO mean plane and the
Callyl trans to PO.
Fig. 4). Assuming that the trans-influence governs the enantioselec-
tivity by directing the nucleophile to the allyl terminus that is fur-
thest from the palladium centre, only complexes 14-endo-syn-syn
and 14-exo-syn-syn led to the experimentally observed stereoiso-
mer of 7. In contrast, all of the remaining complexes led to substi-
tuted products with a Z-configuration, which we did not observe.
Thus, analysis of the stereochemical outcome of the reaction based
merely on the differentiation of the allyl unit due to trans-influ-
ences leads in our case to an incongruence: none of the possible
were low when in situ-generated [Pd(
as the catalyst. Conversely, they were dramatically higher when
g
3-C3H5)(13b)]Cl was used
preformed [Pd(g
3-C3H5)(13b)]PF6 was used instead (Table 2, entry
9) and the enantioselectivity remained unchanged.12 This is the
highest ee reported in the rare examples of allylic aminations with
P-OP-based palladium complexes.
To gain further insight into the basis of the stereodirecting
mechanisms,13 the geometries of the [Pd( 3-PhCHCHCHPh)(5)]+
g
[Pd(g
3-PhCHCHCHPh)(5)]+ complexes gives the minor enantiomer
complexes 14 were optimised at the full DFT level.14 Selected geo-
metrical parameters are summarised in Figure 4 and Table 3. Our
calculations predicted that the phosphino group was responsible
for the strongest trans-influence on the allyl group in three of the
six diastereoisomers, thus preferentially elongating the bond be-
tween the palladium and the terminal allyl carbon trans to the
phosphino group (Pd-CtP, Fig. 4) in 14-endo-syn-syn, 14-endo-syn-
of 7. Apparently, the electronic effects are not the only source of
enantiodiscrimination in the reaction. This was confirmed by a
Hammett analysis of the enantiomeric ratio (er) with respect to
rp (Fig. 2). Indeed, the log(er) data did not perfectly fit rp and
moreover the low absolute value of the slopes, that is, of the
15
constant
q (<1 for DMM and BZA as nucleophiles), also suggests
that the electronic effects are not the only influence on
anti and 14-exo-syn-anti. In the remaining [Pd(g
3-PhCHCH
enantioselectivity.15a
CHPh)(5)]+ complexes considered 14-exo-syn-syn, 14-endo-anti-
syn and 14-exo-anti-syn, the bond between the palladium atom
It has been reported for analogous systems16 that nucleophilic
attack may be determined by steric effects, more precisely by the
orientation of the allyl group with respect to the X-Pd-Y plane
and the allyl carbon trans to the phosphite was longer (Pd-CtPO
,

2284
A. Panossian et al. / Tetrahedron: Asymmetry 21 (2010) 2281–2288
for DMM and (S)-7d for BZA as nucleophiles] from 14-endo-syn-
syn. The formation of the electronically disfavoured stereoisomer
[(S)-7a for DMM and (R)-7d for BZA as nucleophiles], which is
observed in a minor amount, could be rationalised by nucleophilic
attack onto 14-endo-anti-syn.
3. Conclusions
In conclusion, we have described an efficient synthesis of new
phosphine-phosphite ligands that incorporate substituents with
different electronic properties on the phosphino group. We evalu-
ated a library of highly modular P-OP ligands in palladium-cata-
lysed allylic substitutions. The first phosphine-phosphinite
ligands to be tested in this reaction gave poor enantioselectivities,
while catalyst optimisation via variation of the phosphine and
phosphite substituents led to the development of a lead catalyst
derived from 13b, which afforded enantioselectivities ranging from
low to acceptable for all combinations of substrates and nucleo-
philes. Lastly, a rationalisation of the stereochemical outcome of
the reaction solely based on trans-influences on Pd-complexes 14
was unable to provide a complete picture of the stereochemical
outcome of the reaction. A subtle interplay between electronic
Figure 2. Hammett plot of the enantiomeric ratio of products 7a and 7d when
using ligands 13a, 5 and 13b.
(X, Y = donor binding groups). When two vicinal allylic carbons
tend to be aligned with that plane in the starting Pd–allyl complex,
the energy barrier for allylic substitution is reduced and nucleo-
philic attack takes place at the allylic terminus which is furthest
out of the plane (Fig. 3).16
In complexes 14-endo-syn-syn and 14-endo-anti-syn, the allyl
groups present the highest degree of rotation with respect to the
plane (Table 3, entries 1 and 5). Thus, attack of the nucleophile
at these positionally activated allyl carbons would lead to the for-
mation of the electronically favoured substitution product [(R)-7a
and steric effects in the [Pd(g
3-PhCHCHCHPh)(5)]+ complexes 14
was shown to be determinant for stereochemical induction. Struc-
ture optimisation and evaluation in other transformations of
Sharpless epoxide-derived P-OP ligands are currently underway.
4. Experimental
4.1. General
All syntheses were carried out using chemicals as purchased
from commercial sources unless otherwise noted. Solvents were
dried and deoxygenated prior to use. Air- and moisture-sensitive
compounds were prepared under an argon atmosphere using stan-
dard Schlenk techniques. NMR spectra were recorded in CDCl3 un-
less otherwise noted using a 400 MHz spectrometer. Chemical
shifts (d) are reported relative to residual solvent signals or tetra-
methylsilane as an internal reference (0.00 ppm). IR spectra were
recorded using the Attenuated Total Reflection technique. Mass
spectra were obtained by matrix-assisted laser desorption/ionisa-
tion time of flight (MALDI-TOF) or electrospray ionisation (ESI,
HRMS). Optical rotations were measured in chloroform, dichloro-
methane or ethanol. Melting points were uncorrected.
X
Y
Pd
Nu
Nu
X
Y
Geometry A of the
starting Pd-allyl
intermediate
Pd
X
Y
Pd
Nu
Pd-alkene complex (C)
4.2. Synthetic route for the preparation of P-OP ligands 13a and
13b
Geometry B of the
starting Pd-allyl
intermediate
4.2.1. Bis(4-trifluoromethylphenyl)phosphine–boranecomplex9a
This compound was prepared according to the procedure of
Manners et al.9 Lithium borohydride (42 mg, 1.92 mmol, 1.1 equiv)
was introduced in a dry Schlenk flask equipped with a stirring bar.
The flask was purged with argon three times, then diethyl ether
(4.5 mL) was added. The mixture was cooled to 0 °C, then chlor-
obis[4-(trifluoromethyl)phenyl]phosphine 8a (621 mg, 1.74 mmol)
was added in one portion. The mixture turned cloudy white at
once, and was stirred for 1.5 h at 0 °C. After evaporation of the vol-
atiles, the residue was taken up in hexanes, filtered through Celite
and concentrated, to give 9a as an air-sensitive colourless oil
(537 mg, containing ca. 4% of the corresponding phosphine oxide;
85% yield of 9a). Due to the lability of the phosphorus–boron bond
in 9a, this compound was used shortly after preparation. 1H NMR
(CDCl3, 400 MHz): d (ppm) 7.89–7.71 (m, 8H), 6.43 (dq, J = 382.9,
7.2 Hz, 1H), 1.7–0.4 (m, 3H). 13C{1H} NMR (CDCl3, 100 MHz): d
ΔG
TSA
TSB
A,B
C
r.c.
Figure 3. Influence of the geometry of the Pd-allyl intermediate on the activation
barrier of the nucleophilic attack.
2
4
2
(ppm) 134.2 (qd, JC–F = 32.5, JC–P = 2.3 Hz, C), 133.6 (d, JC–P
=

A. Panossian et al. / Tetrahedron: Asymmetry 21 (2010) 2281–2288
2285
Figure 4. Calculated geometries for the diastereomeric Pd(g
3-PhCHCHCHPh) complexes derived from ligand 5. Positions in the allyl units, whose attack by the nucleophile is
favoured due to bond elongation, have been marked with a yellow sphere. aAttack at the ‘trans-influence’-favoured Callyl leads to (R)-7a with DMM. bAttacks at the Callyl which
are furthest out of the plane with DMM lead to (R)-7a or (S)-7a as indicated.
1
3
10.0 Hz, CH), 130.3 (d, JC–P = 54.1 Hz, C), 126.3 (dq, JC–P = 10.6,
After the addition of 10 mL of water and 10 mL of ethyl acetate,
the layers were separated and the aqueous phase was extracted
with ethyl acetate (3 ꢁ 10 mL). The combined organic layers were
washed with brine, dried over MgSO4, concentrated, and purified
by silica gel chromatography (hexanes/ethyl acetate 80:20) to give
11a as a white sticky foam (175 mg, 45% yield). Due to the lability of
the phosphorus–boron bond in 11a, this compound was further
derivatised shortly after preparation. 1H NMR (CDCl3, 400 MHz): d
(ppm) 8.13–8.05 (m, 2H), 7.83–7.76 (m, 2H), 7.51–7.41 (m, 4H),
7.34–7.27 (m, 2H), 7.20–7.13 (m, 3H), 4.50 (tdd, 3J = 7.2, 4.8,
3JC–F = 3.3 Hz, CH), 123.5 (q, JC–F = 272.7 Hz, C). 31P{1H} NMR
1
(CDCl3, 162 MHz): d (ppm) 6.2–4.3 (m). 11B{1H} NMR (CDCl3,
128 MHz): d (ppm) (ꢀ)40.4 (br s).
4.2.2. Bis(4-methoxyphenyl)phosphine–borane complex 9b
This compound17 was prepared using a procedure similar to the
one used for 9a. Lithium borohydride (55 mg, 2.53 mmol,
1.26 equiv) was introduced in a dry Schlenk flask equipped with
a stirring bar. The flask was purged with argon three times, then
diethyl ether (8 mL) was added. The mixture was cooled to 0 °C,
then chlorobis(4-methoxyphenyl)phosphine 8b (561 mg, 2.00
mmol) was added in one portion. After stirring at 0 °C to rt for
4 h, the reaction mixture was filtered through Celite using diethyl
ether as the washing eluent, and concentrated to give 9b as an
air-stable white solid (263 mg, 50% yield). 1H NMR (CDCl3,
400 MHz): d (ppm) 7.62–7.53 (m, 4H), 7.00–6.92 (m, 4H), 6.26
(dq, J = 377.8, 6.8 Hz, 1H), 3.82 (s, 6H), 1.7–0.4 (m, 3H). 13C{1H}
2
3
4.0 Hz, 1H), 4.21 (dd, JH–P = 17.0, JH–H = 4.0 Hz, 1H), 3.23 (ddd,
3
4
2JH–H = 9.6, JH–H = 4.8, JH–P = 1.6 Hz, 1H), 3.16 (s, 3H), 3.13 (dd,
3
2JH–H = 9.6, JH–H = 7.2 Hz, 1H), 2.70 (br s, 1H), 1.9–0.7 (m, 3H).
13C{1H} NMR (CDCl3, 100 MHz): d (ppm) 133.9 (qd, JC–F = 32.8,
2
4JC–P = 2.7 Hz, C), 133.56 (d, JC–P = 8.9 Hz, CH), 133.53 (d,
2
2JC–P = 9.1 Hz, CH), 133.1 (qd, JC–F = 32.9, JC–P = 2.9 Hz, C), 132.6
2
4
1
1
(d, JC–P = 38.1 Hz, C), 132.1 (d, JC–P = 41.1 Hz, C), 132.0 (d,
2JC–P = 1.1 Hz, C), 131.2 (d, JC–P = 5.0 Hz, CH), 128.5 (d, JC–P
=
4
3
5
3
1.1 Hz, CH), 128.1 (d, JC–P = 1.9 Hz, CH), 125.9 (dq, JC–P = 9.9,
4
NMR (CDCl3, 100 MHz): d (ppm) 162.4 (d, JC–P = 2.2 Hz, C), 134.7
3JC–F = 3.5 Hz, CH), 125.1 (dq, JC–P = 10.3, JC–F = 3.5 Hz, CH), 123.6
3
3
2
1
(d, JC–P = 10.6 Hz, CH), 117.4 (d, JC–P = 62.2 Hz, C), 114.8 (d,
3JC–P = 11.2 Hz, CH), 55.5 (s, CH3). 31P{1H} NMR (CDCl3, 162 MHz):
d (ppm) 3.4–(ꢀ)2.4 (m). 11B{1H} NMR (CDCl3, 128 MHz): d (ppm)
(ꢀ)37–(ꢀ)43 (m). IR: mmax (cmꢀ1) 3201, 2932, 2837, 2381, 2343,
1593, 1569, 1499, 1459, 1440, 1407, 1292, 1250, 1178, 1110,
1060, 1024, 903, 824, 799. HRMS (ESI): [M+Na]+, calculated for
1
1
(q, JC–F = 272.7 Hz, CF3), 123.5 (q, JC–F = 273.2 Hz, CF3), 73.0 (d,
3JC–P = 8.8 Hz, CH2), 69.2 (d, JC–P = 5.9 Hz, CH), 58.9 (s, CH3), 44.7
3
(d, JC–P = 30.8 Hz, CH). 31P{1H} NMR (CDCl3, 162 MHz): d (ppm)
1
23.2 (br s). 11B{1H} NMR (CDCl3, 128 MHz): d (ppm) (ꢀ)39.0
(br s). 19F{1H} NMR (CDCl3, 376 MHz): d (ppm) (ꢀ)63.4 (s, 3F),
(ꢀ)63.5 (s, 3F). IR: mmax (cmꢀ1) 2928, 2395, 1609, 1494, 1454,
1398, 1320, 1169, 1125, 1060, 1016, 966, 833, 700. HRMS (ESI):
[M+Na]+, calculated for C24H24BO2F6NaP: 523.1409, found:
C
14H18BO2NaP: 282.1072, found: 282.1071. Mp = 68–72 °C.
523.1401. ½a 2D7
¼ ꢀ116:8 (c 1.11, CHCl3).
ꢂ
4.2.3. ((1R,2S)-2-Hydroxy-3-methoxy-1-phenyl-propyl)bis(4-
trifluoromethylphenyl)phosphine–borane complex 11a
n-Butyllithium (2.5 M in hexanes; 0.34 mL, 0.85 mmol,
1.1 equiv) was added dropwise to a ꢀ70 °C solution of phos-
phine–borane complex 9a (259 mg, 0.77 mmol) in THF (3 mL) un-
der argon. The mixture was stirred at ꢀ70 °C for 2 min, removed
from the cooling bath and was allowed to warm up for 5 min, and
then cooled back to ꢀ70 °C. To this red solution was added drop-
wise a ꢀ70 °C solution of (2S,3S)-2-(methoxymethyl)-3-phenyloxi-
rane 10 (127 mg, 0.77 mmol, 1 equiv) in THF (4 mL). Next, 2 ꢁ 1 mL
of THF were used to rinse the equipment. The resulting yellow mix-
ture was stirred at ꢀ70 °C for 1 h. The cryostat was then switched
off, and the mixture was allowed to warm slowly to rt overnight.
4.2.4. ((1R,2S)-2-Hydroxy-3-methoxy-1-phenylpropyl)bis(4-
methoxyphenyl)phosphine–borane complex 11b
n-Butyllithium (2.5 M in hexanes; 0.34 mL, 0.85 mmol,
1.1 equiv) was added dropwise to a ꢀ70 °C solution of phos-
phine–borane complex 9b (200 mg, 0.77 mmol) in THF (3 mL) un-
der argon. The mixture was stirred at ꢀ70 °C for 2 min, removed
from the cooling bath and allowed to warm up for 5 min, and
cooled back to ꢀ70 °C. To this yellow-orange solution was added
dropwise
a
ꢀ70 °C solution of (2S,3S)-2-(methoxymethyl)-3-
phenyloxirane 10 (128 mg, 0.77 mmol, 1 equiv) in THF (4 mL).
Next, 2 ꢁ 1 mL of THF were used to rinse the equipment. The

2286
A. Panossian et al. / Tetrahedron: Asymmetry 21 (2010) 2281–2288
2
resulting yellow mixture was stirred at ꢀ70 °C for 1 h. The cryostat
was then switched off, and the mixture was allowed to warm
slowly to rt overnight. After the addition of 10 mL of water and
10 mL of ethyl acetate, the layers were separated and the aqueous
phase was extracted with ethyl acetate (3 ꢁ 10 mL). The combined
organic layers were washed with brine, dried over MgSO4, concen-
trated, and purified by silica gel chromatography (hexanes/ethyl
acetate 65:35) to give 11b as a white sticky foam (224 mg, 69%
yield). 1H NMR (CDCl3, 400 MHz): d (ppm) 7.93–7.84 (m, 2H),
7.39–7.31 (m, 2H), 7.31–7.22 (m, 2H), 7.19–7.17 (m, 3H), 7.07–
6.99 (m, 2H), 6.70–6.63 (m, 2H), 4.43 (tdd, 3J = 6.8, 5.2, 3.6 Hz,
CH), 133.0 (s, C), 132.8 (s, C), 132.3 (q, JC–F = 32.5 Hz, C), 131.7
4
2
(s, C), 131.4 (s, C), 130.84 (d, JC–P = 8.5 Hz, CH), 130.76 (q, JC–F
=
32.4 Hz, C), 130.4 (s, CH), 129.6 (s, CH), 128.54 (s, CH), 128.46 (d,
3JC–P = 6.1 Hz, CH), 127.5 (d, JC–P = 1.3 Hz, CH), 127.2 (s, CH),
5
2
3
126.4 (s, CH), 126.3 (s, CH), 125.9 (dq, JC–P = 7.6, JC–F = 3.7 Hz,
2
3
CH), 125.2 (s, CH), 125.0 (s, CH), 124.9 (dq, JC–P = 6.0, JC–F
3.7 Hz, CH), 124.5 (d, JC–P = 5.0 Hz, C), 124.5 (q, JC–F = 272.2 Hz,
C), 123.5 (q, JC–F = 272.2 Hz, C), 123.2 (d, JC–P = 2.5 Hz, C), 123.0
(d, JC–P = 6.6 Hz, CH), 121.9 (s, CH), 74.5 (dd, JC–P = 16.4, 12.0 Hz,
=
3
1
1
3
4
3
CH), 74.1 (d, JC–P = 3.4 Hz, CH2), 58.9 (s, CH3), 48.0 (dd, JC–P
=
14.5, 6.4 Hz, CH). 31P{1H} NMR (CDCl3, 162 MHz): d (ppm) 155.2
(br s, P–O), (ꢀ)5.7 (br s, P–C). 19F{1H} NMR (CDCl3, 376 MHz):
2
3
1H), 4.03 (dd, JH–P = 16.8, JH–H = 3.6 Hz, 1H), 3.85 (s, 3H), 3.70 (s,
2
3
4
3H), 3.19 (ddd, JH–H = 9.5, JH–H = 5.2, JH–P = 1.6 Hz, 1H), 3.15 (s,
d
(ppm) ꢀ63.0 (s, 6F). HRMS (ESI): [M+H]+, calculated for
2
3
3H), 3.09 (dd, JH–H = 9.5, JH–H = 6.8 Hz, 1H), 2.90 (br s, 1H), 1.9–
C44H33O4F6P2: 801.1758, found: 801.1761. ½a D24
¼ ꢀ180:5 (c 0.5,
ꢂ
0.7 (m, 3H). 13C{1H} NMR (CDCl3, 100 MHz): d (ppm) 162.2 (d,
CH2Cl2).
4JC–P = 2.5 Hz, C), 161.6 (d, JC–P = 2.5 Hz, C), 134.6 (d, JC–P
=
4
2
2
9.9 Hz, CH), 134.5 (d, JC–P = 10.1 Hz, CH), 133.3 (s, C), 131.4 (d,
4JC–P = 4.8 Hz, CH), 128.1 (s, CH), 127.4 (d, JC–P = 2.0 Hz, CH),
5
4.2.6. ((1R,2S)-1-(Bis(4-methoxyphenyl)phosphino)-3-methoxy-
1-phenylpropan-2-yl) ((R)-1,10-binaphthalen-2,20-yl) phosphite
13b
1
1
119.4 (d, JC–P = 17.9 Hz, C), 118.8 (d, JC–P = 21.5 Hz, C), 114.7 (d,
3JC–P = 10.8 Hz, CH), 113.8 (d, JC–P = 11.1 Hz, CH), 73.3 (d, JC–P
=
3
3
2
Hydroxyalkylphosphine-borane 11b (106 mg, 0.25 mmol) was
introduced as a toluene solution into a dry Schlenk flask under ar-
gon. The toluene was removed in vacuo, after which the residue
was then dried azeotropically twice with toluene and the flask
placed under argon. DABCO (62 mg, 0.55 mmol, 2.2 equiv) was
added and the flask quickly purged by doing quite fast vacuum/ar-
gon cycles, in order to avoid sublimation of DABCO. Toluene (4 mL)
was added, and the septum was swapped for a greased glass stop-
per while under a strong stream of argon. The flask was purged
again with quite fast vacuum/argon cycles and dipped into a
60 °C oil bath. After 2 h, it was allowed to cool down to rt. The glass
stopper was swapped back for a septum, after which the reaction
mixture was cooled to ꢀ5 °C and was added dropwise via cannula
8.4 Hz, CH2), 69.0 (d, JC–P = 5.7 Hz, CH), 58.9 (s, CH3), 55.5 (s,
CH3), 55.3 (s, CH3), 45.7 (d, JC–P = 33.2 Hz, CH). 31P{1H} NMR
1
(CDCl3, 162 MHz): d (ppm) 19.1–16.2 (m). 11B{1H} NMR (CDCl3,
128 MHz): d (ppm) (ꢀ)38.9 (br s). IR: mmax (cmꢀ1) 2897, 2377,
1595, 1569, 1501, 1455, 1291, 1255, 1181, 1106, 1062,
1027, 968, 828, 803, 703. HRMS (ESI): [M+Na]+, calculated for
C
24H30BO4NaP: 447.1872, found: 447.1864.
½
a 2D8
ꢂ
¼ ꢀ145:9 (c
1.06, CHCl3).
4.2.5. ((1R,2S)-1-(Bis(4-(trifluoromethyl)phenyl)phosphino)-3-
methoxy-1-phenylpropan-2-yl) ((R)-1,10-binaphthalen-2,20-yl)
phosphite 13a
Hydroxyalkylphosphine-borane 11a (175 mg, 0.35 mmol) was
introduced as a toluene solution into a dry Schlenk flask under ar-
gon. The toluene was removed in vacuo, after which the residue
was then dried azeotropically twice with toluene and the flask
placed under argon. Next, DABCO (86 mg, 0.77 mmol, 2.2 equiv)
was added and the flask quickly purged by doing quite fast vac-
uum/argon cycles, in order to avoid sublimation of DABCO. Toluene
(5 mL) was added, and the septum was swapped for a greased glass
stopper while under a strong stream of argon. The flask was purged
again with quite fast vacuum/argon cycles and dipped into a 60 °C
oil bath. After 2 h, it was allowed to cool down to rt. The glass stop-
per was swapped back for a septum, after which the reaction mix-
ture was cooled to ꢀ5 °C and was added dropwise via cannula onto
a ꢀ5 °C solution of (R)-(binaphthalene-2,20-diyl)chlorophosphite
12 (184 mg, 0.52 mmol, 1.5 equiv) in toluene (5 mL) to which
had been added a few 4 Å molecular sieves. Next, 2 ꢁ 1 mL of tol-
uene were used to rinse the equipment. The resulting cloudy mix-
ture was stirred overnight at ꢀ5 °C. The cryostat was then
switched off and the cooling bath was allowed to warm slowly to
rt. After stirring at rt for another 2 h, the mixture was introduced
in the glovebox and filtered through a very short pad of previously
dried and deoxygenated silica (ca. 1 mL). The pad was washed with
4 ꢁ 5 mL of toluene. The filtrate was concentrated in vacuo, then
purified by a short silica gel chromatography in the glovebox (n-
hexane/THF 80:20) to give phosphine-phosphite 13a as a white so-
lid (217 mg, 77% yield). 1H NMR (CDCl3, 400 MHz): d (ppm) 8.11–
8.05 (m, 1H), 8.02–7.96 (m, 2H), 7.95–7.87 (m, 4H), 7.70–7.64
(m, 2H), 7.48–7.35 (m, 7H), 7.33–7.22 (m, 6H), 7.15–7.02 (m,
onto
a
ꢀ5 °C solution of (R)-(binaphthalene-2,20-diyl)chloro-
phosphite 12 (97 mg, 0.27 mmol, 1.1 equiv) in toluene (4 mL) to
which had been added
a few 4 Å molecular sieves. Then,
2 ꢁ 1 mL of toluene were used to rinse the equipment. The result-
ing cloudy mixture was stirred overnight at ꢀ5 °C. The cryostat
was then switched off and the cooling bath was allowed to warm
slowly to rt. After stirring at rt for another 2 h, the mixture was
introduced in the glovebox and filtered through a very short pad
of previously dried and deoxygenated silica (ca. 1 mL). The pad
was washed with 4 ꢁ 5 mL of toluene. The filtrate was concen-
trated in vacuo to give phosphine-phosphite 13b as a white solid
(114 mg, 63% yield). 1H NMR (CDCl3, 500 MHz): d (ppm) 8.13–
8.03 (m, 2H), 8.01–7.96 (m, 1H), 7.93–7.88 (m, 2H), 7.81–7.73
(m, 2H), 7.49–7.36 (m, 5H), 7.31–7.23 (m, 4H), 7.21–7.14 (m,
2H), 7.10–6.99 (m, 3H), 6.97–6.92 (m, 2H), 6.74–6.68 (m, 2H),
4.52–4.42 (m, 1H), 3.79 (s, 3H), 3.74–3.68 (m, 4H), 3.25 (dd,
2JH–H = 9.9, JH–H = 4.4 Hz, 1H), 3.22 (s, 3H), 2.92 (dd, JH–H = 9.8,
3
2
3JH–H = 7.9 Hz, 1H). 13C{1H} NMR (CDCl3, 125 MHz):
d (ppm)
2
161.1 (s, C), 159.9 (s, C), 148.9 (d, JC–P = 4.2 Hz, C), 148.0 (d,
2JC–P = 2.1 Hz, C), 137.2 (d, JC–P = 11.4 Hz, C), 136.5 (s, CH), 136.3
2
(s, CH), 134.5 (s, CH), 134.3 (s, CH), 133.1 (s, C), 132.8 (s, C),
131.6 (s, C), 131.5 (s, C), 130.9 (d, JC–P = 8.0 Hz, CH), 130.1 (s,
CH), 129.6 (s, C), 128.4 (s, C), 128.2 (s, C), 128.0 (d, JC–P
13.8 Hz, C), 127.3 (s, C), 127.2 (s, C), 127.0 (d, JC–P = 15.2 Hz, C),
4
1
=
1
126.8 (s, C), 126.3 (s, C), 126.0 (s, C), 125.0 (s, C), 124.8 (s, C),
3
4
124.7 (d, JC–P = 4.7 Hz, C), 123.5 (d, JC–P = 7.9 Hz, CH), 123.1 (d,
3
3JC–P = 1.8 Hz, C), 122.1 (s, C), 114.7 (d, JC–P = 8.7 Hz, CH), 113.8
3
3
2
(d, JC–P = 7.3 Hz, CH), 75.2 (dd, JC–P = 18.1, 12.5 Hz, CH), 74.8 (d,
3H), 4.44–4.34 (m, 1H), 3.82 (dd, JH–H = 5.2, JH–P = 3.2 Hz, 1H),
3JC–P = 2.9 Hz, CH2), 58.9 (s, CH3), 55.3 (s, CH3), 55.2 (s, CH3), 48.8
2
3
3.20 (s, 3H), 3.19 (dd, JH–H = 9.6, JH–H = 5.2 Hz, 1H), 2.95 (dd,
(dd, JC–P = 14.7, JC–P = 6.6 Hz, CH). 31P{1H} NMR (CDCl3, 202
MHz): d (ppm) 157.0 (br s, P–O), (ꢀ)7.5 (br s, P–C). HRMS (ESI):
[M+H]+, calculated for C44H39O6P2: 725.2222, found: 725.2232.
1
3
2JH–H = 9.6, JH–H = 7.6 Hz, 1H). 13C{1H} NMR (CDCl3, 100 MHz): d
3
2
2
(ppm) 148.6 (d, JC–P = 4.8 Hz, C), 147.6 (d, JC–P = 2.5 Hz), 141.8
(d, JC–P = 18.4 Hz, C), 140.3 (d, JC–P = 21.0 Hz, C), 135.8 (d, JC–P
1
1
2
=
½
a 2D5
ꢂ
¼ ꢀ248:4 (c 0.5, CH2Cl2).
11.6 Hz, C), 135.4 (s, CH), 135.3 (s, CH), 133.3 (s, CH), 133.1 (s,

A. Panossian et al. / Tetrahedron: Asymmetry 21 (2010) 2281–2288
2287
4.3. Preparation of [allylpalladium(P-OP)]PF6 complexes
added to a solution of P-OP ligand (0.0025 mmol, 2.5 mol %) in
DCM (0.15 mL) under argon. The resulting solution was stirred at
rt for 20 min, then added to ( )-1,3-diphenylallyl acetate
(25.2 mg, 0.1 mmol). The nucleophile (0.3 mmol, 3 equiv), N,O-
In a typical procedure, a solution of P-OP ligand in DCM was
added to a suspension of allylpalladium chloride dimer (0.5 equiv)
in DCM under nitrogen. The pale yellow solution was stirred at rt
for 30 min, then added to a suspension of NH4PF6 in DCM. The mix-
ture was stirred overnight at rt then filtered through an HPLC filter
to eliminate solid residues. The final product was obtained as a 1:1
mixture of two isomers by precipitation from DCM/hexane 25:75
bis(trimethylsilyl)acetamide (73 lL, 0.3 mmol, 3 equiv), and finally
potassium acetate (0.5 mg, 0.005 mmol, 5 mol %) were added. The
reaction mixture was stirred at rt and conversion followed by
TLC. The reaction medium was quenched by the addition of 1 mL
of water and the aqueous layer was extracted with 3 ꢁ 1 mL of
DCM. The combined organic layers were passed through a plug
of MgSO4 and concentrated. The conversion and identity of the
product were determined by 1H NMR spectroscopy. The crude
sample was purified if necessary, and the enantiomeric excess of
the product was evaluated by chiral HPLC, or 1H NMR using
Eu(hfc)3 as a chiral lanthanide NMR shift reagent. The absolute
configuration of the major enantiomer of the product was assigned
according to the literature.
in 42% yield for [Pd(g
3-C3H5)(5)]PF6, and subsequently used in
catalysis. In an alternative procedure, after being stirred overnight,
the mixture was allowed to stand still at ꢀ20 °C for several hours.
It was allowed to reach rt again, then filtered through a plug of Cel-
ite and concentrated to give the desired [Pd(g
3-C3H5)(13b)]PF6
complex (94% yield) as a 1:1 mixture of two isomers, which was
subsequently used in catalysis.
4.3.1. [Pd(g
3-C3H5)(5)]PF6
1H NMR (CDCl3, 400 MHz): d (ppm) 8.34–8.23 (m, 2H), 8.15–6.91
(m, 52H), 5.91–5.75 (m, 1H), 5.75–5.58 (m, 1H), 4.95–4.83 (m, 1H),
4.83–4.63 (m, 2H), 4.51–4.34 (m, 3H), 4.20 (br s, 1H), 3.82 (br t,
J = 15.1 Hz, 1H), 3.69 (br s, 1H), 3.36–2.96 (m, 13H). 13C{1H} NMR
(CDCl3, 125 MHz), selected signals: d (ppm) 125.7 (br s, CH), 124.3
(br s, CH), 78.3 (br d, J = 43.9 Hz, CH2), 76.0 (br s, CH), 75.0 (br d,
J = 44.2 Hz, CH2), 72.4 (br dd, J = 22.9, 6.0 Hz, CH2), 71.9 (br d,
J = 28.6 Hz, CH2), 71.2 (br s, CH2), 59.2 (CH3), 42.2 (d, J = 27.4 Hz,
CH), 41.0 (d, J = 27.7 Hz, CH). 31P{1H} NMR (CDCl3, 162 MHz): d
4.4.1. (E)-Dimethyl 2-(1,3-diphenylallyl)malonate 7a18
The enantiomeric excess of this product was determined by chi-
ral HPLC on a Chiralcel OD-H column (n-hexane/i-propanol 99:1,
0.4 mL/min, 216 nm): tR = 28.9 min [major (R)], 31.5 min [minor
(S)].
4.4.2. Dimethyl 2-(4,4-diphenylbut-3-en-2-yl)malonate 7b19
The enantiomeric excess of the product was determined by
NMR spectroscopy using Eu(hfc)3 (6 equiv) as a chiral shift reagent
by integrating suitable signals of the diastereomeric complexes, or
by chiral HPLC on a Chiralcel OD-H column (n-hexane/i-propanol
99:1, 1 mL/min, 216 nm): tR = 10.0 min [major (R)], 12.5 min [min-
or (S)]. The absolute configuration of the major enantiomer of this
product was ascertained to be (R) by specific rotation measure-
2
2
(ppm) 141.9 (d, JP–P = 97.3 Hz, P–O), 140.7 (d, JP–P = 98.5 Hz, P–
2
2
O), 21.3 (d, JP–P = 97.3 Hz, P–C), 19.8 (d, JP–P = 98.5 Hz, P–C),
(ꢀ)141.1 (sept., 1JP–F = 713.0 Hz, PF6ꢀ). IR:
m
max (cmꢀ1) 3059, 1588,
1389, 1257, 1028, 871, 654. HRMS (ESI): [M ꢀ PF6ꢀ+MeOH]+, calcu-
lated for C46H43O5P2Pd+: 843.1621, found: 843.1639.
ment:20
½
a 2D6
ꢂ
¼ þ41:0 (c 0.5, EtOH) for a 34% ee sample.
4.3.2. [Pd(g
3-C3H5)(13b)]PF6
1H NMR (CDCl3, 400 MHz): d (ppm) 8.37–8.28 (m, 2H), 8.12–8.02
(m, 2H), 7.96–7.81 (m, 6H), 7.75–7.66 (m, 2H), 7.64–7.15 (m, 22H),
6.96–6.84 (m, 4H), 6.70–6.61 (m, 4H), 5.93–5.79 (m, 1H), 5.68–
5.54 (m, 1H), 4.88–4.77 (m, 1H), 4.76–4.60 (m, 2H), 4.36 (br t,
J = 8.1 Hz, 1H), 4.28 (dd, J = 16.7, 13.7 Hz, 2H), 4.19–4.12 (m, 1H),
3.94 (s, 6H), 3.84 (br t, J = 15.7 Hz, 1H), 3.72 (s, 3H), 3.71 (s, 3H),
3.69–3.61 (m, 1H), 3.23–3.08 (m, 12H), 2.97 (br t, J = 12.1 Hz, 1H).
13C{1H} NMR (CDCl3, 100 MHz), selected signals: d (ppm) 114.3 (d,
3JC–P = 12.6 Hz, CH), 75.8 (br s, CH), 71.1 (br s, CH2), 59.2 (s, CH3),
55.9 (s, CH3), 55.5 (s, CH3). 31P{1H} NMR (CDCl3, 162 MHz): d
4.4.3. (E)-Dimethyl 2-(1,3-bis(4-chlorophenyl)-allyl)malonate
7c14b
The enantiomeric excess of this product was determined by chi-
ral HPLC on a Chiralcel AD-H column (n-hexane/i-propanol 85:15,
0.8 mL/min, 254 nm): tR = 19.1 min [major (R)], 28.6 min [minor
(S)].
4.4.4. (E)-N-Benzyl-1,3-diphenylprop-2-en-1-amine 7d21
The enantiomeric excess of this product was determined by chi-
ral HPLC on
a Chiralcel OD-H column (n-hexane/i-propanol
2
2
(ppm) 142.1 (d, JP–P = 97.9 Hz, P–O), 141.0 (d, JP–P = 98.8 Hz,
99.5:0.5, 0.3 mL/min, 254 nm): tR = 64.8 min [minor (R)], 68.8 min
[major (S)].
2
2
P–O), 18.5 (d, JP–P = 97.9 Hz, P–C), 17.1 (d, JP–P = 98.8 Hz, P–C),
(ꢀ)141.1 (sept., 1JP–F = 713.0 Hz, PF6ꢀ). HRMS (ESI): [M ꢀ PF6ꢀ]+, cal-
culated for C47H43O6P2Pd+: 871.1570, found: 871.1548.
4.5. Computational data
4.4. (P-OP)Pd-catalysed allylic substitution reactions
The geometries of complexes [Pd(g
3-PhCHCHCHPh)(5)]+ 14
were calculated with a GAUSSIAN 03, Revision C.02,22 using the
B3LYP23 functional. 6-31g(d) Basis set24 was used for phosphorus,
oxygen, carbon and hydrogen atoms, whereas the Stuttgart-Dresden
In a typical procedure, 0.25 mL of a 0.005 M solution of allylpal-
ladium chloride dimer (i.e., 0.0025 mmol of Pd, 2.5 mol %) were
Table 4
Calculated bond distances of complexes 14 with B3LYP/6-31g(d) and PBE1PBE/6-31g(d) functionals
Entry
Complex
Bond distances (Å) calculated with B3LYP/6-31g(d)
Bond distances (Å) calculated with PBE1PBE/6-31g(d)
Pd–CtP
Pd–CtPO
Pd–P
Pd–PO
Pd–CtP
Pd–CtPO
Pd–P
Pd–PO
1
2
3
4
5
6
14-endo-syn-syn
14-endo-syn-anti
14-exo-syn-anti
14-exo-syn-syn
14-endo-anti-syn
14-exo-anti-syn
2.332
2.392
2.331
2.288
2.261
2.232
2.266
2.235
2.260
2.324
2.321
2.425
2.391
2.388
2.381
2.400
2.392
2.406
2.316
2.319
2.317
2.312
2.307
2.303
2.263
2.304
2.262
2.235
2.213
2.199
2.220
2.199
2.215
2.259
2.266
2.320
2.349
2.348
2.343
2.355
2.348
2.358
2.278
2.280
2.280
2.276
2.268
2.271
Pd–CtP = Pd–(Callyl trans to P) bond distance; Pd–CtPO = Pd–(Callyl trans to PO) bond distance; Pd–P = palladium to phosphine phosphorus bond distance; Pd–PO = palladium to
phosphite phosphorus bond distance.

2288
A. Panossian et al. / Tetrahedron: Asymmetry 21 (2010) 2281–2288
ECP25 as implemented in GAUSSIAN 03, Rev. C.02 was used for
palladium.
For the sake of comparison (Table 4), calculations were carried
out using the PBE1PBE26 functional, 6-31g(d) basis set for P, O, C
and H and the Stuttgart-Dresden ECP for palladium. Similar conclu-
sions could be extracted from the geometries calculated with
PBE1PBE with respect to the ones calculated with B3LYP.
10. (a) Brunner, H.; Sicheneder, A. Angew. Chem., Int. Ed. Engl. 1988, 27, 718–719;
(b) Gorla, F.; Togni, A.; Venanzi, L. M.; Albinati, A.; Lianza, F. Organometallics
1994, 13, 1607–1616.
11. In conditions identical to those of entry 2 in Table 2, 3-methyl-1-phenylbut-2-
en-1-yl acetate was converted to (E)-dimethyl 2-(2-methyl-4-phenylbut-3-en-
2-yl)malonate; and cyclohex-2-en-1-yl acetate gave the racemic substitution
product.
12. In the case of DMM as the nucleophile, variation of the counteranion of the
palladium precatalyst [Pd(g
3-C3H5)(13b)]X had little influence on the activity
and enantioselectivity; all reactions proceeded with >95% conversion and with
ee’s of 80%, 78% and 74% for Xꢀ = Clꢀ, PF6 and BArFꢀ, respectively, indicating a
ꢀ
Acknowledgements
tenuous counteranion effect.
13. 31P NMR analysis of [Pd( 3-PhCHCHCHPh)(5)]Cl revealed that only two
g
diastereoisomers were present in solution. Heavy signal overlapping did not
allow us to unequivocally establish the structure of the two complexes 14
present in solution.
We thank the MICINN (Grant CTQ2008-00950/BQU), DURSI
(Grant 2009GR623), Consolider Ingenio 2010 (Grant CSD2006-
0003) and the ICIQ Foundation for the financial support. H.F.-P.
gratefully acknowledges the ‘Programa Torres y Quevedo’ for the
financial support.
14. Energetic and geometrical analysis at the full DFT-level of the transition
structures for all possible reaction pathways is, even today, extremely time-
consuming in systems of such complexity. Calculations on the geometries of
the intermediate
p-allyl complexes are much quicker and has allowed
rationalisation of the stereochemical outcome of asymmetric allylic
substitutions (see for example: (a) Kollmar, M.; Goldfuss, B.; Reggelin, M.;
Rominger, F.; Helmchen, G. Chem. Eur. J. 2001, 7, 4913–4927; (b) Popa, D.;
Puigjaner, C.; Gomez, M.; Benet-Buchholz, J.; Vidal-Ferran, A.; Pericàs, M. A.
Adv. Synth. Catal. 2007, 349, 2265–2278). See Experimental for details on the
geometry optimisation of complexes 14 at the DFT level. We did not consider
the diastereoisomers 14-exo-anti-anti and 14-endo-anti-anti in the calculations,
as nucleophilic attack on these substrates by DMM or BZA would lead to (Z)-
alkenes 7a or 7d, respectively, neither of which we observed.
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