Optically active C3-symmetric triarylphosphines in asymmetric allylations

Article abstract of DOI:10.1016/S0040-4020(01)00346-5

A new class of optically active, monodentate, C³-symmetric ligands for asymmetric catalysis, 1-3, were prepared via routes involving asymmetric reduction of aryl ketones (Schemes 1-3). Single crystal X-ray structures of trans-PdCl₂(phosphine)₂ complexes of ligands 1a, 2a and 3a showed that the ligands do not adopt perfect C³-symmetric conformations in the solid state; in fact, all three have one aromatic ring lying 'face-on' to the metal. Circular dichroism studies of the same complexes provided some evidence for an aromatic ordering effect for complex 22, but none for 21 and 23. Palladium catalyzed allylation reactions using ligands 1-3 showed that encouraging enantioselectivities could be obtained, particularly for cyclic, allylic substrates.

Full text of DOI:10.1016/S0040-4020(01)00346-5

TETRAHEDRON
Pergamon
Tetrahedron 57 .2001) 5027±5038
Optically active C3-symmetric triarylphosphines in
asymmetric allylations
Mark T. Powell, Alexander M. Porte, Joe Reibenspies and Kevin Burgessp
Department of Chemistry, Texas A & M University, P.O. Box 30012, College Station, TX 77842, USA
Dedicated to Professor BarryM. Trost on the occasion of his 60th birthday
Received 30 November 2000; revised 7 March 2001; accepted 12 March 2001
AbstractÐA new class of opticallyactive, monodentate, C3-symmetric ligands for asymmetric catalysis, 1±3, were prepared via routes
involving asymmetric reduction of aryl ketones .Schemes 1±3). Single crystal X-ray structures of trans-PdCl2.phosphine)2 complexes of
ligands 1a, 2a and 3a showed that the ligands do not adopt perfect C3-symmetric conformations in the solid state; in fact, all three have one
aromatic ring lying `face-on' to the metal. Circular dichroism studies of the same complexes provided some evidence for an aromatic
ordering effect for complex 22, but none for 21 and 23. Palladium catalyzed allylation reactions using ligands 1±3 showed that encouraging
enantioselectivities could be obtained, particularly for cyclic, allylic substrates. q 2001 Elsevier Science Ltd. All rights reserved.
1. Introduction
phines that had been prepared previously.6,7 The C3-
symmetric phosphines that were known prior to these
studies were not particularlysuitable for asmymetric
catalysis,8±12 or simplycould not be resolved into their
enantiomers.13,14 This paper discusses synthesis, structure,
conformations of ligands 1±3, and their performance in
asymmetric allylation reactions involving ®ve different
p-allyl complex precursors.
A decade ago, ligand design for asymmetric catalysis
focused on bidentate, C2-symmetric systems.1 Recent
developments, however, have shown ligands that are not
C2-symmetric can also give high enantioselectivities. For
instance, opticallyactive phosphine oxazolines with low
overall symmetry have been shown to be valuable for
several asymmetric transformations.2 In fact, chiral
ligands do not even have to be bidentate for good enantio-
selectivities to be obtained. Some opticallyactive mono-
dentate ligands, like the 20-alkoxy-2-.diphenylphosphino)-
1,10-binaphthyl .MOP) systems,4 can induce excellent
enantioselectivities.3 The MOP ligands are relatively
unsymmetrical molecules proving that a high degree of
symmetry is not essential for monodentate ligands to be
successful in asymmetric catalysis. However, the inverse
of this situation has not been investigated thoroughly, i.e.
the potential of highlysymmetrical monodentate ligands in
asymmetric syntheses.
The research described in this paper was designed to explore
the importance of symmetry in monodentate ligands for
enantioselective catalysis. Speci®cally, could C3-symmetric
monodentate phosphine ligands be prepared easily, and, if
so, how would their structures and solution phase conforma-
tions correlate with their performance in asymmetric
catalysis? Ligands 1±3 were conceived to test this issue.5
These are fundamentallydifferent to C3-symmetric phos-
Keywords: C3-symmetric ligands; asymmetric allylations; palladium cata-
lysis.
p
Corresponding author. Tel.: 11-979-8454345; fax: 11-979-845-8839;
e-mail: burgess@tamu.edu
0040±4020/01/$ - see front matter q 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020.01)00346-5

5028
M. T. Powell et al. / Tetrahedron 57 ,2001) 5027±5038
Scheme 1. Syntheses of ligands 1.
Scheme 2. Syntheses of ligands 2.
2. Results and discussion
The synthesis was easily manipulated so that the alcohol 5
could be converted into other phosphine precursors. Thus a
Mitsunobu reaction17,18 was used to introduce aryl ether
functionalities in the routes outlined in Scheme 1b and c.
The stereochemistryof the benzylic position is not inverted
in Scheme 1a, but it is in Scheme 1b and c; this becomes
important when comparing induction that results from
ligands 1a and from 1b/1c.
2.1. Syntheses of ligands 1±3
A commerciallyavailable aryl ketone was reduced using the
CBS reagent .tetrahydro-1-methyl-3,3-diphenyl-1H,3H-
pyrrolo-[1,2-c]-[1,3,2]-oxazaborole-borane) to give the
benzylic alcohol 5 .Scheme 1a).15,16 This was methylated
to the ether 6, metalated with tert-butyl lithium, and the
corresponding aryl lithium species was quenched with
PCl3. Throughout this work, temperature control .internal
thermometer) and slow addition of the reagents was
crucial to obtaining good yields in the metalation/quench
procedures .see Section 4).
The synthetic approaches used to obtain ligands 2 were
similar to those described above except that the requisite
starting material, ketone 9, was prepared via methylation
of a commerciallyavailable ketone .Scheme 2). The
syntheses shown in Scheme 3 began with the known aryl

M. T. Powell et al. / Tetrahedron 57 ,2001) 5027±5038
5029
bromide 15; we found this easier to prepare via the bromi-
nation route shown19 than via an alternative route that has
been published.20 Asymmetric reduction of the diketone 16
using Ipc2BCl .B-chlorodiisopinocamphenylborane)21,22
gave better enantioselectivities than the CBS reagent did
for this particular substrate. Overall, ligands 3 were
more dif®cult to obtain than 1 and 2 mainlybecause the
yields in the ®nal metalation step were inferior in the former
case.
2.2. Solid state structures of ligand 1±3 derivatives
Three palladium complexes of the general formula trans-
PdCl2.PAr3)2 .21, from ligand 1a; 22, from 2a; and 23,
from 3a) were prepared, crystallized, and examined via
single crystal X-ray diffraction. Fig. 1 shows representations
of all three with one of the two phosphines omitted, and
viewed opposite a Pd±P bond .colloquiallyreferred to
here as `end-on'), and along the Cl±Pd±Cl axis .`side-on').
The design of ligand types 1±3 was based on the following
considerations. Ligands 1 were conceived as an easywayto
potentiallyinduce a C3-propeller-like conformation of the
aromatic rings. Data collected in asymmetric allylation
reactions using complexes of ligands 1 were encouraging,
but in absolute terms the enantioselectivities obtained were
moderate .see below). A 4-methoxysubstituent was incor-
porated into the second generation of phosphines, ligands 2,
to provide some restriction to the free rotation about the
aryl-.3-alkoxyethyl) bond, in an attempt to increase the
enantioselectivities that could be obtained using these
ligands. This change must also perturb the electronic char-
acteristics of the phosphorus center, but the electronic
change was not anticipated to be as signi®cant. These modi-
®cations did indeed alter the enantioselectivities of the
corresponding catalysts .see below), but further optimiza-
tion was desirable. A strategyfor further improvements to
the ligand design became apparent from crystallographic
studies. Triarylphosphines like 1 and 2 can crystallize
with the meta-substituent oriented exo with respect to the
metal phosphine bond, or endo to it. In the solid state, ligand
1a crystallized with two substituents that were clearly endo
and one that marginallytilts towards an exo orientation, but
that aryl ring rests in a conformation that is almost `face-on'
with respect to the metal. The more crowded ligand 2a
crystallized with one aryl-substituent endo, one exo, and
again one less clearly exo because the aryl ring also adopted
a near face-on conformation.
The third generation ligands 3 were designed to avoid
ambiguities caused by exo/endo conformations. A 3,5-
disubstituted aryl group with an edge pointing towards the
metal must have one endo-substituent and one exo. Fig. 1c
shows crystal structure of a complex formed from a ligand
of this type. Like the others in this series, it crystallized with
one aryl group in an edge-on orientation, another face-on,
and with one aryl unit with its face to the rest of the
complex.
Scheme 3. Syntheses of ligands 3.
2.3. Circular dichroism studies of ligand 1±3 derivatives
Rotational energybarriers about the P±arly bond in
complexes of ligands 1±3 are likelyto be small enough to

5030
M. T. Powell et al. / Tetrahedron 57 ,2001) 5027±5038
Figure 1. chem3d representations of data from solid state single crystal studies of the trans-.Ar3P)2PdCl2 complexes, shown with one ligand removed for
clarity. End-on and side-on views are shown in each case to illustrate the orientation of the aryl rings for clarity: .a) complex 21 from ligand 1a; .b) complex 22
from ligand 2a; and .c) complex 23 from ligand 3a.
permit the aryl groups to turn through 3608, though, par-
ticularlyfor ligands 3, rotation of the three aryl rings might
be somewhat concerted in a cog-like mechanism. The latter
point would be dif®cult to prove, but circular dichroism
experiments provided a convenient wayto search for
general trends in conformational rigidity. The hypothesis
followed was that complexes of the ligands might have
preferred conformations that could be detected byincreased
ellipticities in the aromatic region, relative to the free phos-
phines and the chiral aryl bromides .e.g. compound 5) that

M. T. Powell et al. / Tetrahedron 57 ,2001) 5027±5038
5031
Figure 2. CD spectra recorded in CH3CN for: .a) the aryl bromide 6; .b) complex 22 .from ligand 2a); and .c) complex 23 .from ligand 3a). Ligand 1a showed
no signi®cant ellipticityin the aromatic absorption region at anyof the temperatures indicated .data not shown).
theywere prepared from. Moreover, these ellipticity
differences should be temperature dependent.
bromide 6, complex 22 .from ligand 2a), and complex 23
.from ligand 3a), respectively. The CD spectrum of the aryl
bromide is a negative control; aromatic ellipticitywould not
be expected for this compound, and none was seen.
Complex 21 .from ligand 1a) also gave no signi®cant
ellipticityin this region. For 22, however, an appreciable
Fig. 2a±c show molar ellipticities per aromatic ring .a
correction to enable direct comparison of an aryl bromide
with one aromatic ring with triarylphosphines), for the aryl

5032
M. T. Powell et al. / Tetrahedron 57 ,2001) 5027±5038
Figure 3. Overall yield .yellow) and enantiomeric purity .blue), for the allylation shown.
ellipticitywas observed, and it was shown to be inversely
proportional to temperature. Surprisingly, the same effect is
not observed for complex 23. This leads to the conclusion
that the ellipticityin this region is not due to some confor-
mational preference in the ordering of the aromatic rings, or
that ligand 2a in 22 adopts a preferred conformation that
imparts a chiral ordering of the aromaticity. It is curious that
1a and 3a do not show the same effect if the aromatic groups
are ordered, but it could be that the complexed form of
ligand 1a undergoes conformational averaging between
several states, and ligand 3a in complex 23 populates two
conformers for which the ellipticities cancel.
substrate category. Cyclic carboxylates, like the one shown
in Fig. 3a, are relativelydif®cult to transform with high
enantioselectivities, but ligands from Helmchen23 and
from Trost24 have been used to give approximately95%
ee in such relations.
1,3-Diphenylpropenyl acetate has been studied in asym-
metric allylation reactions by many groups, and enantio-
selectivities of 99% or more have been reported in several
cases.25 Surprisingly, ligands 1±3 gave onlymodest
enantioselection in these processes .up to 32% for ligand
1c). Similarly, the analogous aliphatic substrates shown in
Fig. 3d gave enantioselectivities of 20% .ligand 3a) or less.
It is dif®cult to rationalize whythese two substrates should
give inferior results to the cyclic systems.
2.4. Asymmetric allylation reactions using ligands 1±3
The data illustrated in Fig. 3 for the four allylation reactions
shown in parts a±d illustrate that ligands 1±3 give the high-
est enantioselectivities for cyclic substrates. The enantio-
selectivities observed .up to 82% in Fig. 2a, and 75% in
Fig. 2b) compare favorablywith those reported for many
other ligands, but do not match the best obtained for either
Ligands 1±3, particularlythe ones with bulkysubstituents at
the benzylic position .i.e. in the series b and c), could be
anticipated to be so large that coordination of two cis-
phosphines and a p-allyl fragment around palladium is
disfavored. Hayashi and co-workers have used similarly

M. T. Powell et al. / Tetrahedron 57 ,2001) 5027±5038
5033
Figure 4. Overall yield .yellow), yield of the internal isomer .red), and enantiomeric purity of that isomer .blue), for the allylation shown.
hindered phosphines to favor formation of .p-allyl)PdCl-
.phosphine) complexes in a catalytic cycle over inter-
mediates of the type [.p-allyl)Pd.phosphine)2]1. The
trans-directing effect of the phosphine then controls the
regioselectivityof the alllyation leading to high regio-
selectivities for the branched .or internal) allylation product.
In some cases, high enantioselectivities were also obtained
for the branched products.4,26,27 Fig. 4 shows data from an
investigation designed to test if the larger ligands prepared
in this work, 2 and 3, could be used in a similar way. An
identical reaction was tested using triphenylphosphine as
the ligands as a control, and it gave a total yield of 92%
of the internal/terminal isomers in a ratio of 27:73. Each of
the ligands 2 and 3 gave better regioselection for the internal
isomer, the best being 3c, which gave an internal:terminal
ratio of 47:53. The maximum ee of the internal isomer was
obtained using ligand 3a, but this was only26% whereas
Hayashi and co-workers have obtained selectivities of more
than 90%.
show the aryl ligands do not adopt perfect propeller-shaped
conformations in the solid state. Moreover, the 3-substituted
derivatives 1 and 2 can align their meta-substituents in
endo and exo orientations relative to the metal. Ligands 3,
having two meta-substituents, were designed to nullify
that effect but, in solution, all the ligands must have a
considerable degree of conformational freedom.
Evidence was obtained for structural ordering of the
aromatic groups in compound 22 .a ligand 2a complex),
but similar trends were not observed for complexes of
ligands 1a and 3a.
Overall, these studies indicate that C3-symmetric triaryl-
phosphines do have the potential to be useful ligands in
asymmetric catalysis. Improved enantioselectivities could
probablybe obtained byintroducing more stringent
conformational restraints than are present in ligands
1±3.
4. Experimental
4.1. General procedures
3. Conclusions
Ligands 1±3 were prepared via relativelydirect routes
that involve asymmetric reduction of appropriately
functionalized aryl methyl ketones. This type of approach
gives a convenient entryinto the desired ligands. Free
rotation about the aryl±P bonds enables these ligands to
populate conformations that are not perfectly C3-symmetric;
this is evident from X-raycrsytallographic studies that
High ®eld NMR spectra were recorded on a Varian Unity
1
Plus spectrometer. Chemical shifts of H and 13C spectra
were referenced to the NMR solvents; 31P spectra are refer-
enced to H3PO4 .85%) external standard .0 ppm). IR spectra
were recorded on an FTIR instrument. Melting points are
uncorrected. Optical rotations were measured on a Jasco

5034
M. T. Powell et al. / Tetrahedron 57 ,2001) 5027±5038
DIP-360 digital polarimeter. Flash chromatographywas
performed using silica gel .230±600 mesh). Thin layer
chromatographywas performed on glass plates coated
with silica gel 60 F254 .E. Merck, Darmstadt, Germany).
Micro analyses were performed by Atlantic Microlab,
Norcross, GA. The CD spectra were recorded in quartz cells
of 0.1 mm path length using metal complex concentrations of
0.125 mM in CH3CN. CH2Cl2 was distilled over CaH2, Et2O
and THF over Na/benzophenone, and acetone over CaSO4.
Other solvents and reagents were used as received.
4.1.4. )S)-1-Bromo-3-)10-)200, 600-dimethylphenoxy)ethyl)-
benzene 8. Neat DEAD .0.92 mL, 7.5 mmol) was added
dropwise over 5 min to a solution of 5 .1.0 g, 4.9 mmol),
triphenylphosphine .2.0 g, 7.5 mmol), and 2,6-dimethyl-
phenol .0.92 g, 7.5 mmol) in dryEt O .25 mL) at 08C.
2
The reaction was allowed to warm to 258C and stirred for
12 h. The reaction was quenched with 1 mL of 30% H2O2,
washed with 1 M NaOH .20 mL), brine .20 mL), and dried
over Na2SO4. The mixture was ®ltered and concentrated in
vacuo. The crude oil was puri®ed via ¯ash chromatography,
using 2% EtOAc/hexanes as the eluting solvent, yielding the
title compound .0.89 g, 55% yield). [a]Dˆ254.38 .c 1.32,
4.1.1. )R)-1-)30-Bromophenyl)-ethanol 5. A solution of 4
.Aldrich; 10.8 g, 64.96 mmol) in CH2Cl2 .50 mL) was
added dropwise over 2 h to a solution of .S)-4,5,6,7-
tetrahydro-1-methyl-3,3-diphenyl-1H,3H-pyrrolo-[1,2-c]-
[1,3,2]-oxazaborole-borane .i.e. CBS, 0.9 g, 3.2 mmol) and
BH3´Me2S .5.1 mL, 51 mmol) in CH2Cl2 .30 mL) at 2208C.
The solution was allowed to stand at 2238C for 8 h. The
cold solution was added slowlyto methanol .50 mL) at
2208C. Rapid gas evolution occurred. The solution was
concentrated in vacuo, and the oilyresidue was puri®ed
bybulb-to-bulb distillation .94 8C, 0.5 mmHg) to yield the
title compound as a colorless oil .96%, 98.6% ee). The ee
was determined bychiral GC on a column prepared in
CCl4, 258C); IR .®lm) 2977, 2925, 1757, 1374, 1253 cm21
;
1H NMR .CDCl3) d 7.59 .t, Jˆ1.5 Hz, 1H), 7.43 .ddd,
Jˆ7.8, 2.1, 1.2 Hz, 1H), 7.32 .dt, Jˆ7.5, 1.2 Hz, 1H),
7.21 .t, Jˆ8.1 Hz, 1H), 6.99±6.87 .m, 3H), 4.90 .q,
Jˆ6.6 Hz, 1H), 2.16 .s, 6H), 1.56 .d, Jˆ6.6 Hz, 3H); 13C
NMR .CDCl3) d 154.6, 145.4, 131.1, 130.7, 129.8, 129.4,
125.0, 123.5, 122.4, 79.4, 22.4, 17.2.
4.1.5. Tris [)R)-3-)10-methoxyethyl)phenyl)]-phosphine
1a. Compound 6 .1.0 g, 4.7 mmol) was placed in a dry
round bottom ¯ask under nitrogen atmosphere. Et2O
.20 mL) was added and the clear solution was stirred and
house.28 [a]25 ˆ134.78 .c 1.35, CCl4, 258C); IR .®lm)
cooled to 2788C. A solution of BuLi .2.75 ml, 1.68 M) in
t
D
1
3350, 2978, 2870, 1677 cm21; H NMR .CDCl3) d 7.52±
pentane was added dropwise over 10 min using a syringe
pump. The reaction was stirred for 1 h at 2788C, then
warmed to 2308C. A solution of phosphorus trichloride
.0.13 mL, 1.5 mmol) in 2 mL of Et2O was added dropwise
over 10 min using a syringe pump. The reaction was
warmed to 258C, stirred for 12 h, concentrated in vacuo,
and puri®ed via ¯ash chromatographyto iyeld the title
7.18 .m, 4H), 4.80 .q, Jˆ6.3 Hz, 1H), 2.95 .s, 1H), 1.45 .d,
Jˆ6.3 Hz, 3H); 13C NMR .CDCl3) d 148.2, 130.5, 130.2,
128.6, 124.1, 122.6, 69.7, 25.3.
4.1.2. )R)-1-Bromo-3-)10-methoxyethyl)benzene 6. Neat 5
.1.0 g, 4.9 mmol) was added dropwise to a suspension of
NaH .0.18 g, 7.35 mmol) in DMF .4 mL) at 08C. Gas evolu-
tion occurred. The cold suspension was stirred for 30 min
whereupon it was treated with neat MeI .0.7 mL, 11.4 mmol
added in one portion) and allowed to warm to 258C and
stirred for 12 h. The reaction was quenched with water
.25 mL) and diluted with ether .100 mL). The organics
were washed with H2O .2£25 mL), with brine .25 mL),
dried .Na2SO4), and concentrated to dryness in vacuo.
[a]Dˆ181.88 .c 1.33, CCl4, 258C); IR .®lm) 2976, 2932,
2820 cm21; 1H NMR .CDCl3) d 7.47 .m,1H), 7.39 .m, 1H),
4.24 .q, Jˆ6.3 Hz, 1H), 3.22 .s, 3H), 1.40 .d, Jˆ6.3 Hz,
3H); 13C NMR .CDCl3) d 146.0, 130.5, 130.0, 129.2,
124.7, 122.6, 79.0, 56.6, 23.8.
1
compound .1.2 g, 59% yield). H NMR .CDCl3) d 7.48
.m, 3H), 7.43 .m, 2H), 7.27 .m, 9H), 4.30 .q, Jˆ10.5 Hz,
3H), 3.27 .s, 9H), 1.44 .d, Jˆ10.5 Hz, 9H); 13C NMR
.CDCl3) d 143.7 .d, Jˆ6.9 Hz), 137.5 .d, Jˆ10.8 Hz),
132.8, .d, Jˆ17 Hz), 128.7 .d, Jˆ6.5 Hz), 126.7, 79.5,
56.5, 23.9; 31P NMR .CDCl3) d 24.3.
4.1.6. Tris [)S)-3-)10-phenoxyethyl)phenyl)]-phosphine
1b. Compound 7 .1.0 g, 3.4 mmol) was placed in a dry
round bottom ¯ask under nitrogen atmosphere. THF
.20 mL) was added and the clear solution was stirred and
t
cooled to 2788C. A solution of BuLi .2.75 ml, 1.68 M) in
pentane was added dropwise over 10 min using a syringe
pump. The reaction was then stirred for 1 h at 2788C, then
warmed to 2308C. A solution of phosphorus trichloride
.0.13 mL, 1.5 mmol) in 2 mL THF was added dropwise
over 10 min using a syringe pump. The reaction was
warmed to 258C, stirred for 12 h, concentrated in vacuo,
and puri®ed via ¯ash chromatographyto iyeld the title
compound .0.36 g, 48% yield). [a]Dˆ2146.78 .c 1.02,
4.1.3. )S)-1-Bromo-3-)10-phenoxyethyl)benzene 7. Neat
DEAD .0.92 mL, 7.5 mmol) was added dropwise over
5 min to a solution of 5, triphenylphosphine .2.0 g,
7.5 mmol) and phenol .0.71 g, 7.5 mmol) in dryEt 2O
.25 mL) at 08C. The reaction was allowed to warm to
258C and stirred for 12 h. The reaction was quenched with
1 mL 30% H2O2, washed with 1 M NaOH .20 mL), brine
.20 mL), and dried .Na2SO4). The mixture was ®ltered and
concentrated in vacuo. The crude oil was puri®ed via ¯ash
chromatography, using 2% EtOAc/hexanes as the eluting
solvent, yielding the title compound .1.18 g, 80% yield).
1
CHCl3, 258C); H NMR .CDCl3) d 7.50 .s, 3H), 7.38±
7.15 .m, 15H), 6.90±6.78 .m, 9H), 5.25 .q, Jˆ6.5 Hz,
3H), 1.60 .d, Jˆ6.3 Hz, 9H); 13C NMR .CDCl3) d 157.8,
143.4 .d, Jˆ7.1 Hz), 137.3 .d, Jˆ11.0 Hz), 132.5 .d,
Jˆ17.0 Hz), 131.1 .d, Jˆ22.0 Hz), 129.3, 128.8 .d,
Jˆ6.8 Hz), 126.1, 120.7, 116.0, 75.7, 24.3; 31P NMR
.CDCl3) d 24.2.
1
IR .®lm) 3063, 2982, 2924, 1601, 1493, 1237 cm21; H
NMR .CDCl3) d 7.55 .t, Jˆ1.5 Hz, 1H), 7.39 .dt, Jˆ7.8,
1.5 Hz, 1H), 7.31 .dt, Jˆ7.8, 1.2 Hz, 1H), 6.94±6.85 .m,
3H), 5.26 .q, Jˆ6.6 Hz, 1H), 1.62 .d, Jˆ6.6 Hz, 3H); 13C
NMR .CDCl3) d 157.6, 145.7, 130.5, 130.2, 129.4, 128.6,
124.1, 122.7, 120.9, 115.8, 75.1, 24.4.
4.1.7. Tris [)S)-3-)10-)200,600-dimethylphenoxyethyl)-
phenyl)]-phosphine 1c. Compound 8 .1.0 g, 3.4 mmol)
was placed in a dryround bottom ¯ask under nitrogen

M. T. Powell et al. / Tetrahedron 57 ,2001) 5027±5038
5035
atmosphere. THF .20 mL) was added and the clear solution
was stirred and cooled to 2788C. A solution of BuLi
.2£25 mL), with brine .25 mL), dried .Na2SO4), ®ltered,
and concentrated to dryness in vacuo. The crude oil was
puri®ed bybulb-to-bulb distillation to give 2.1 g .90%) of
the ether as a clear oil. [a]Dˆ1105.58 .c 1, MeOH, 258C);
IR .®lm) 3050, 2976, 2929, 2837 cm21; 1H NMR .CDCl3) d
7.47 .d, Jˆ2.4 Hz, 1H), 7.31 .dd, Jˆ8.5 Hz, Jˆ2.4 Hz, 1H),
6.72 .d, Jˆ8.5 Hz, 1H), 4.66 .q, Jˆ6.0 Hz, 1H), 3.79 .s,
3H), 3.25 .s, 3H), 1.34 .d, Jˆ6.0 Hz, 3H); 13C NMR
.CDCl3) d 155.6, 134.2, 130.5, 128.7, 113.3, 112.0, 72.9,
56.7, 55.4, 22.3; HRMS .EI) m/z calcd for [M1H]
244.0098, found 244.0088.
t
.2.75 ml, 1.68 M) in pentane was added dropwise over
10 min using a syringe pump. The reaction was then stirred
for 1 h at 2788C, then warmed to 2308C. A solution of
phosphorus trichloride .0.13 mL, 1.5 mmol) in 2 mL THF
was added dropwise over 10 min using a syringe pump. The
reaction was warmed to 258C, stirred for 12 h, concentrated
in vacuo and puri®ed via ¯ash chromatographyto yield the
title compound .0.31 g, 44% yield). [a]Dˆ2208.48 .c 1.0,
1
CHCl3, 258C); H NMR .CDCl3) d 7.42±7.38 .m, 6H),
7.35±7.30 .m, 3H), 7.23±7.18 .m, 3H), 6.98±6.90 .m,
9H), 4.92 .q, Jˆ6.3 Hz, 3H), 2.10 .s, 18H), 1.55 .d,
Jˆ6.3 Hz, 9H); 31P NMR .CDCl3) d 23.9.
4.1.11. )S)-1-Bromo-3-methoxy-5-)10-phenoxyethyl)ben-
zene 12. Neat DEAD .1.0 mL, 6.5 mmol) was added drop-
wise over 5 min to a solution of 10 .1 g, 4.35 mmol),
triphenylphosphine .1.7 g, 6.5 mmol), and phenol .0.61 g,
4.1.8. 3-Bromo-6-methoxyphenyl-ethanone 9. A solution
of 3-bromo-6-hydroxyphenyl-methyl ketone .Aldrich;
2.0 g, 9.3 mmol) in 20 mL acetone was treated with
K2CO3 .2.6 g, 19 mmol) under a nitrogen atmosphere. The
yellow solution was stirred for 1 h, then neat MeI .1.5 g,
10 mmol, 0.64 mL) was added in one portion. The reaction
was stirred for 2 h. The reaction was concentrated in vacuo
6.5 mmol) in dryEt O .40 mL) at 08C. The reaction was
2
allowed to warm to 258C and stirred for 12 h. The reaction
was quenched with 1 mL 30% H2O2, washed with 1 M
NaOH .20 mL), brine .20 mL), and dried over Na2SO4.
The mixture was ®ltered and concentrated in vacuo. The
crude oil was puri®ed via ¯ash chromatography, using
0.5% EtOAc/hexanes as the eluting solvent, yielding the
title compound .1.06 g, 80% yield). [a]Dˆ232.48 .c 0.5,
and the oilyresidue was partitioned between Et O .6 mL)
2
and water .20 mL). The organics were separated and the
aqueous fraction was washed with Et2O .2£6 mL). The
organic layers were combined and washed with brine
.10 mL), dried over Na2SO4, and concentrated in vacuo to
yield the title compound as a white solid .2.0 g, 95%). Mp
36±378C; 1H NMR .CDCl3) d 7.82 .d, Jˆ2.7 Hz, 1H), 7.53
.dd, Jˆ8.8, 2.7 Hz, 1H), 6.86 .d, Jˆ8.8 Hz, 1H), 3.89 .s,
3H), 2.58 .s, 3H); 13C NMR .CDCl3) d 197.9, 157.8, 135.9,
132.6, 129.2, 113.4, 112.8, 55.6, 31.6; Anal. calcd for
C9H9BrO2: C, 47.37; H, 3.98. Found: C, 47.20; H, 3.97.
1
CDCl3, 258C); IR .®lm) 3444, 2978, 2933 cm21; H NMR
.CDCl3) d 7.51 .d, Jˆ2.4 Hz, 1H), 7.30 .dd, Jˆ7.5, 2.4 Hz,
1H), 7.24±7.17 .m, 2H), 6.90 .t, Jˆ1 Hz, 1H), 6.88 .d, Jˆ
2.0 Hz, 1H), 6.75 .d, Jˆ7.5 Hz, 1H), 5.63 .q, Jˆ9.4 Hz,
1H), 3.87 .s, 3H), 1.55 .d, Jˆ9.4 Hz, 3H); 13C NMR
.CDCl3) d 157.7, 154.8, 133.8, 130.9, 129.3, 128.9, 120.6,
115.5, 113.5, 112.0, 69.3, 55.6, 22.6; Anal. calcd for
C15H15BrO2: C, 58.65; H, 4.92. Found: C, 58.82; H, 4.86.
4.1.12. )S)-1-Bromo-3-methoxy-5-)10-)200,600-dimethyl-
phenoxy)ethyl)benzene 13. Neat DEAD .5.08 mL,
32.4 mmol) was added dropwise over 5 min to a solution
of 10 .5.0 g, 22 mmol), triphenylphosphine .8.50 g, 32.5
mmol), and phenol .3.96 g, 32.4 mmol) in drydiethly
ether .200 mL) at 08C. The reaction was allowed to warm
to 258C and stirred for 18 h. The reaction was quenched with
5 mL 30% H2O2, washed with 1N NaOH .80 mL), brine
.80 mL), and dried over Na2SO4. The mixture was ®ltered
and concentrated in vacuo. The crude oil was puri®ed via
¯ash chromatography, using hexanes as the eluting solvent,
yielding the title compound .3.1 g, 42% yield). Mp 45±
4.1.9. )R)-1-)30-Bromo-60-methoxyphenyl)-ethanol 10. A
solution of 9 .15 g, 65 mmol) in CH2Cl2 .50 mL) was added
dropwise over 5 h to a solution of .S)-4,5,6,7-tetrahydro-1-
methyl-3,3-diphenyl-1H,3H-pyrrolo-[1,2-c]-[1,3,2]-oxa-
zaborole-borane .0.90 g, 3.2 mmol) and BH3´Me2S .6.5 mL,
65 mmol) in CH2Cl2 .50 mL) at 2258C. The solution was
allowed to stand at 2238C for 12 h. The cold solution was
added slowlyto methanol .50 mL) at 2208C. Rapid gas
evolution occurred. The solution was concentrated in
vacuo and the oilyresidue was recrystallized from hexanes
to yield 10.5 g .70%) of the alcohol in .99% ee .GC) as
1
white needles. [a]25 ˆ171.68 .c 0.5, CHCl3); IR .®lm)
468C; IR .®lm) 3006, 1487, 1261 cm21; H NMR .CDCl3)
D
1
3600±3150, 2967, 2935, 2846 cm21; H NMR .CDCl3) d
d 7.82 .d, Jˆ2.7 Hz, 1H), 7.35 .dd, Jˆ8.6, 2.7 Hz, 1H),
6.99±6.86 .m, 3H), 6.73 .d, Jˆ8.6 Hz, 1H), 5.31 .q, Jˆ
6.3 Hz, 1H), 3.72 .s, 3H), 2.20 .s, 6H), 1.45 .d, Jˆ6.3 Hz,
3H); 13C NMR .CDCl3) d 155.1, 154.6, 134.5, 131.1, 130.8,
129.7, 128.8, 123.3, 113.2, 112.0, 74.0, 55.6, 21.7, 17.2;
Anal. calcd for C17H19BrO2: C, 61.07; H, 5.73. Found: C,
60.88; H, 5.68.
7.47 .d, Jˆ2.4 Hz, 1H), 7.31 .dd, Jˆ8.5, 2.4 Hz, 1H), 6.72
.d, Jˆ8.5 Hz, 1H), 4.66 .q, Jˆ6.0 Hz, 1H), 3.79 .s, 3H),
1.34 .d, Jˆ6.0 Hz, 3H); 13C NMR .CDCl3) d 157.8,
138.0, 130.7, 128.9, 112.1, 65.6, 55.5, 22.9 Anal. calcd for
C9H11BrO2: C, 47.37; H, 3.98; Br, 34.62. Found: C, 47.24;
H, 3.96; Br, 34.75.
4.1.10. )R)-1-Bromo-3-methoxy-5-)10-methoxyethyl)ben-
zene 11. A solution of 10 .2.2 g, 9.5 mmol) in THF .5 mL)
was added dropwise over 5 min to a suspension of NaH
.0.27 g, 11.4 mmol) in THF .15 mL) at 08C. Gas evolution
occurred. The cold suspension was stirred for 30 min where-
upon neat MeI .0.7 mL, 11.4 mmol) was added in one
portion. The reaction was allowed to warm to 258C. The
reaction was quenched with water .25 mL) and diluted
with ether .100 mL). The organics were washed with H2O
4.1.13. Tris [)R)-3-methoxy-5-)10-methoxyethyl)phenyl)]-
phosphine 2a. Compound 11 .1.0 g, 4.1 mmol) was placed
in a dryround bottom ¯ask under nitrogen atmosphere. THF
.5 mL) was added and the clear solution was stirred and
cooled to 2788C using a dryice/acetone bath. A solution
t
of BuLi .2.42 ml, 1.68 M) in pentane was added dropwise
over 10 min using a syringe pump. The reaction was
then stirred for 30 min more at 2788C. A solution of phos-
phorus trichloride .0.19 g, 0.118 mL, 1.4 mmol) in 5 mL

5036
M. T. Powell et al. / Tetrahedron 57 ,2001) 5027±5038
dryTHF was then added dropwise over 10 min using a
syringe pump. The reaction was warmed to room tempera-
ture and stirred for 12 h. The reaction was quenched with
1 mL of a degassed solution of 0.5 M HCl. The reaction was
concentrated in vacuo and puri®ed via ¯ash chroma-
tographyusing a column of silica that was 4 cm high and
4 cm in diameter and 20% EtOAc/hexanes as the eluent to
yield the title compound .439 mg, 62% yield). [a]Dˆ138.08
.c 1.5, CHCl3, 258C); IR .®lm) 3001, 2956, 2834,
.CDCl3) d 156.7, 155.5, 134.1 .d, 18 Hz), 133.0 .d, 23 Hz),
132.2 .d, 8.0 Hz), 131.5, 129.4, 128.8, 123.2, 110.9, 74.3,
55.8, 21.8, 17.4; 31P NMR d 23.9; Anal. calcd for
C51H57O6P: C, 75.75; H, 7.55. Found: C, 75.82; H, 7.48.
4.1.16. 1-)3-Acetyl-5-bromo-phenyl)ethanone 16. 5-Bromo-
isophthalic acid .Aldrich; 5 g, 21 mmol) was suspended in
100 mL CH2Cl2 and stirred. The white suspension was
treated with DMF .0.1 mL), then neat oxalyl chloride
.8.8 g, 6 mL, 57 mmol) was added dropwise over 1 h.
Then the reaction was stirred for 1 h until it became clear.
The clear yellow solution was concentrated in vacuo and the
oilyresidue was distilled .110 8C, 0.27 mmHg) to yield a
yellow solid which was dissolved in Et2O and treated with
a solution of LiMe2Cu .7.68 g, 32.8 mmol) in 100 mL Et2O
at 21008C. The reaction was stirred for 30 min and then
quenched with a saturated solution of NH4Cl .50 mL) in
water, warmed to 258C, ®ltered, and extracted with Et2O
.3£30 mL). The organics were combined and dried over
Na2SO4, ®ltered, and concentrated in vacuo. The crude
residue was recrystallized from n-pentane to yield the
title compound29 .2.8 g, 58%), mp 80±828C; 1H NMR
.CDCl3) d 8.39 .s, 1H), 8.24 .s, 2H), 2.63 .s, 6H); 13C
NMR .CDCl3) d 195.8, 138.9, 135.3, 126.4, 123.5, 26.7;
Anal. calcd for C10H9O2: C, 49.82; H, 3.76. Found: C,
50.22; H, 3.90; HRMS .FAB) calcd for [M1H] 240.9864,
found 240.9886.
1
1597 cm21; H NMR .CDCl3) d 7.40 .d, Jˆ2.5 Hz, 3H),
7.27±7.25 .m, 3H), 6.83 .d, Jˆ7.25 Hz, 3H), 4.71 .q, Jˆ
6.8 Hz, 3H), 3.83 .s, 9H), 3.19 .s, 9H), 1.32 .d, Jˆ6.8 Hz,
9H); 13C NMR .CDCl3) d 157.4, 133.7 .d, Jˆ10.1 Hz), 131.8
.d, Jˆ3.6 Hz), 131.4, 110.4 .d, Jˆ4.1 Hz), 73.3, 56.5, 55.3,
22.4; 31P NMR .CDCl3) d 27.3; HRMS .MALDI) calcd for
[M1H] 526.2438, found [M1H]ˆ526.2439.
4.1.14. Tris [)S)-3-methoxy-5-)10-phenoxyethyl)phenyl)]-
phosphine 2b. Compound 12 .0.48 g, 1.6 mmol) was
placed in a dryround bottom ¯ask under nitrogen atmos-
phere. THF .5 mL) was added and the clear solution was
stirred and cooled to 2788C using a dryice/acetone bath. A
t
solution of BuLi .0.94 ml, 1.68 M) in pentane was added
dropwise over 10 min using a syringe pump. The reaction
was then stirred for 30 min more at 2788C. The reaction
was warmed to 2508C and phosphorus trichloride .0.07 g,
0.04 mL, 0.52 mmol) was added dropwise. The reaction was
warmed to room temperature. The reaction was quenched
with 1 mL of a solution of 0.5 M HCl, which had been
previouslydegassed. The reaction was concentrated in
vacuo and puri®ed via ¯ash chromatographyusing a column
of silica that was 15 cm high and 4 cm in diameter, and
using 3% EtOAc/hexanes as the eluent to yield the title
compound .200 mg, 54% yield). [a]Dˆ2122.08 .c 1.5,
4.1.17. 1-Bromo-3,5-bis-))R)-10-hydroxyethyl)benzene 17.
.1)-Ipc2BCl .Aldrich; 1.61 g, 4.98 mmol) was dissolved in
THF .10 mL) and cooled to 2308C. A solution of 16 .0.5 g,
2.1 mmol) in THF .2 mL) was added dropwise over 15 min.
The yellow solution was allowed to stand at 2228C for 12 h.
The reaction was concentrated in vacuo, then treated with
16 mL of saturated aqueous NaHCO3 and 30% aqueous
hydrogen peroxide .3:1) at 508C for 12 h. The reaction
was cooled to 258C and diluted with water .10 mL). The
product was extracted with CH2Cl2 .3£50 mL). The
organics were washed with brine .100 mL) and dried with
Na2SO4, ®ltered, and concentrated. The title compound was
puri®ed via recrystallization from Et2O/pentane .1:1) .75%
yield, .99% ee, GC). Mp 77±788C; [a]Dˆ150.28 .c 1.0,
1
CHCl3, 258C); IR .®lm) 2939, 1475, 1014 cm21; H NMR
.CDCl3) d 7.32 .dd, Jˆ6.6, 1.7 Hz, 2H), 7.16±7.08 .m, 6H),
6.85±6.57 .m, 16H); 5.61 .q, Jˆ6.3 Hz, 3H), 3.86 .s, 9H),
1.51 .d, Jˆ6.3 Hz, 9H); 13C NMR .CDCl3); d 157.6, 133.0
.d, 6 Hz), 131.3 .d, 22 Hz), 130.2 .d, 16 Hz), 129.5, 129.1,
120.3, 115.7, 115.5, 110.5, 69.6, 55.5, 22.5; 31P NMR
.CDCl3) d 23.8.
1
4.1.15. Tris [)S)-3-methoxy-5-)10-)200, 600-dimethylphenoxy-
ethyl)phenyl)]-phosphine 2c. Compound 13 .0.60 g,
1.9 mmol) was placed in a dryround bottom ¯ask under
nitrogen atmosphere. THF .6 mL) was added and the clear
solution was stirred and cooled to 2788C using a dryice/
MeOH, 258C); IR .®lm) 3351, 2973, 1573 cm21; H NMR
.CDCl3) d 7.34 .s, 2H), 7.25 .s, 1H), 4.82 .q, Jˆ6.6 Hz,
2H), 2.09 .s, 2H), 1.45 .d, Jˆ6.6 Hz, 6H); 13C NMR
.CDCl3) d 148.1, 127.3, 122.4, 121.0, 69.5, 25.1; HRMS
.EI) calcd for [M1H]ˆ244.0098, found 244.0099.
t
acetone bath. A solution of BuLi .1.11 ml, 1.68 M) in
pentane was added dropwise over 10 min using a syringe
pump. The reaction was then stirred for 30 min more at
2788C. The reaction was warmed to 2508C and phosphorus
trichloride .0.082 g, 0.052 mL, 0.62 mmol) was added drop-
wise. The reaction was warmed to room temperature. The
reaction was quenched with 1 mL of degassed 0.5 M HCl.
The reaction was concentrated in vacuo and puri®ed via
¯ash chromatographyusing a column of silica that was
15 cm high and 4 cm in diameter using 3% EtOAc/hexanes
as the eluent to yield the title compound .281 mg, 57%
yield). Mp 57±628C; [a]Dˆ2149.08 .c 1.75, CHCl3,
4.1.18. 1-Bromo-3,5-bis-))R)-10-methoxyethyl)benzene 18.
A solution of 17 .0.31 g, 1.2 mmol) in THF .5 mL) was
added dropwise over 5 min to a suspension of NaH
.0.67 g, 2.7 mmol) in THF .5 mL) at 08C. Gas evolution
occurred. The cold suspension was stirred for 30 min where-
upon it was treated with neat MeI .0.17 mL, 2.7 mmol) in
one portion and allowed to warm to 258C. The reaction was
quenched with water .25 mL) and diluted with ether
.100 mL). The organics were washed with water .3£
25 mL), with brine .25 mL), dried .Na2SO4), and concen-
trated to dryness in vacuo. The crude oil was puri®ed by
¯ash chromatographyusing 5% EtOAc/hexane as the eluent
to give 0.27 g .80%) of the ether as a clear oil.
[a]Dˆ1119.18 .c 1.0, CDCl3, 238C); IR .®lm) 2976,
1
258C); IR .®lm) 2954, 2852, 1496, 1245 cm21; H NMR
.CDCl3) d 7.72 .dd, Jˆ7.1, 2.0 Hz, 2H), 7.20 .td, Jˆ7.8,
2.2 Hz), 6.94±6.79 .m, 14H), 5.37 .q, Jˆ6.3 Hz, 3H), 3.71
.s, 9.0 Hz), 2.1 .s, 18H), 1.46 .d, Jˆ 9.0 Hz, 9H); 13C NMR
1
2929, 2854, 1117 cm21; H NMR .CDCl3) d 7.36 .s, 2H),

M. T. Powell et al. / Tetrahedron 57 ,2001) 5027±5038
5037
7.15 .s, 1H), 4.25 .q, Jˆ6.4 Hz, 2H), 3.23 .s, 6H), 1.40 .d,
Jˆ 6.4 Hz, 6H); 13C NMR .CDCl3) d 146.2, 128.3, 122.6,
79.0, 56.7, 23.8; HRMS .EI) calcd for [M1H] 272.0411,
found 272.0412.
.CDCl3) d 23.7; HRMS m/z calcd for [M1H] 611.343,
found 611.344.
4.1.22. Tris [3,5-bis-))S)-10-phenoxyethyl)phenyl]-phos-
phine 3b. Compound 19 .0.28 g, 0.71 mmol) was placed
in a drySchlenk ¯ask under nitrogen atmosphere. THF
.3 mL) was added and the clear solution was stirred and
4.1.19. 1-Bromo-3,5-bis-)S-10-phenoxyethyl)benzene 19.
Neat DEAD .0.92 mL, 5.82 mmol) was added dropwise
over 5 min to a solution of 17, triphenylphosphine .1.5 g,
t
cooled to 2788C. A solution of BuLi .0.49 ml, 1.6 M)
5.82 mmol), and phenol .0.55 g, 5.82 mmol) in dryEt O
2
in pentane was added dropwise using a syringe pump. A
solution of phosphorus trichloride .0.03 g, 0.02 mL,
0.24 mmol) in THF .2 mL) was added dropwise using a
syringe pump. The reaction was warmed to 258C and stirred
for 12 h. The reaction was quenched with 1 mL of a solution
of 0.5 M HCl. The reaction was concentrated in vacuo and
puri®ed via ¯ash chromatographyusing 10% EtOAc/
hexanes as the eluent to yield the title compound .83 mg,
35% yield). [a]Dˆ2270.78 .c 1.0, CHCl3, 258C); IR .®lm)
.10 mL) at 08C. The reaction was allowed to warm to
258C and stirred for 12 h. The reaction was quenched with
1 mL 30% H2O2, washed with 1 M NaOH .5 mL), brine
.5 mL), and dried over Na2SO4. The mixture was ®ltered
and concentrated in vacuo. The crude oil was puri®ed via
¯ash chromatography, using hexanes as the eluent, yielding
the title compound .0.62 g, 80% yield). IR .®lm) 2979,
1
1574, 1236 cm21; H NMR .CDCl3) d 7.53 .s, 2H), 7.41
1
.s,1H), 7.29 .t, Jˆ7.5 Hz, 4H), 7.01 .t, Jˆ7.5 Hz, 2H), 7.01
.t, Jˆ 7.6 Hz, 2H), 6.91 .d, Jˆ7.8 Hz, 4H), 5.32 .q,
Jˆ6.6 Hz, 2H), 1.70 .d, Jˆ6.6 Hz, 6H); 13C NMR
.CDCl3) d 157.5, 145.9, 129.3, 127.7, 123.0, 121.6, 121.0,
115.8, 75.1, 24.2; HRMS .FAB) m/z calcd for [M1H]
396.0725, found 396.0725.
2973, 2834, 1592, 1245; H NMR .CDCl3) d 7.49 .s, 8H),
7.22±7.17 .m, 12H), 6.88±6.85 .m, 18H), 5.50 .q, Jˆ
6.3 Hz, 6H), 1.51 .d, Jˆ6.3 Hz, 18H); 13C NMR .CDCl3)
d 156.8, 143.9 .d, Jˆ7 Hz), 137.6 .d, Jˆ11 Hz), 131.4,
130.8 .d, Jˆ18 Hz), 128.8, 125.4, 123.4, 81.4, 17.2.
4.1.23. Tris [3,5-bis-)S-10-)200, 600-dimethyl)-phenoxyethyl)-
phenyl]-phosphine 3c. Compound 20 was placed in a dry
Schlenk ¯ask under nitrogen atmosphere. THF .2.5 mL)
was added and the clear solution was stirred and cooled to
2788C. A solution of tBuLi .0.53 ml, 1.7 M) in pentane was
added dropwise using a syringe pump. The reaction was
warmed to 2608C and stirred for 20 min. A solution of
phosphoros trichloride .0.04 g, 0.02 mL, 0.27 mmol) in
THF .2 mL) was added dropwise using a syringe pump.
The reaction was warmed to 258C and stirred for 12 h.
The reaction was quenched with 1 mL of a solution of
0.5 M HCl, concentrated in vacuo, then puri®ed via ¯ash
chromatographyusing 5% EtOAc/hexanes as the eluent to
yield the title compound .0.131 g, 49% yield). [a]Dˆ22668
.c 1.24, CHCl3, 258C); IR .®lm) 2974, 2835, 1593,
4.1.20. 1-Bromo-3,5-bis-))S)-10-)200,600-dimethyl)-phenoxy-
ethyl)benzene 20. Neat DEAD .4.6 mL, 29.4 mmol) was
added dropwise over 5 min to a solution of 16 .2.4 g,
9.8 mmol), triphenylphosphine .7.7 g, 29.4 mmol), and
2,6-dimethylphenol .3.6 g, 29.4 mmol) in dry THF
.20 mL) at 08C. The reaction was allowed to warm to
258C and stirred for 24 h. The reaction was quenched with
5 mL 30% H2O2, washed with 1N NaOH .10 mL), brine
.10 mL), and dried over Na2SO4. The mixture was ®ltered
and concentrated in vacuo. The crude oil was puri®ed via
¯ash chromatography, using hexanes as the eluting solvent,
yielding the title compound .1.9 g, 42% yield). Mp 75±
1
768C; IR .®lm) 2977, 1475, 1199 cm21; H NMR .CDCl3)
d 7.67 .s, 2H), 7.47 .s, 1H), 7.10±6.98 .m, 6H), 5.01 .q,
Jˆ6.3 Hz, 2H), 7.01 .t, Jˆ7.6 Hz, 2H), 6.91 .d, Jˆ7.8 Hz,
4H), 2.28 .s, 12H), 1.68 .d, Jˆ6.6 Hz, 6H); 13C NMR
.CDCl3) d 154.6, 145.3, 131.0, 128.5, 123.5, 123.2, 122.2,
79.4, 22.5, 17.2; HRMS .FAB) m/z calcd for [M1H]
453.1298, found 453.1256.
1246 cm21 1H NMR .CDCl3) d 7.46±7.42 .m, 9H),
;
6.98±6.86 .m, 18H), 4.91 .q, Jˆ8.5 Hz, 6H), 2.11 .s,
36H), 1.45 .d, Jˆ8.5 Hz, 18H); 13C NMR .CDCl3) d
154.9, 143.5 .d, Jˆ7 Hz), 137.7 .d, Jˆ10 Hz), 131.1,
130.8 .d, Jˆ20 Hz), 128.8, 125.4, 123.4, 80.0, 22.7, 17.2;
31P NMR .CDCl3) d 23.0; HRMS .MALDI) calcd
[M1H]ˆ1151.6219, found 1151.6090.
4.1.21. Tris [3,5-bis-))R)-10-methoxyethyl)phenyl]-phos-
phine 3a. Compound 18 .0.19 g, 0.68 mmol) was placed
in a drySchlenk ¯ask under nitrogen atmosphere. THF
.3 mL) was added and the clear solution was stirred and
4.1.24. Allylic alkylation reactions. Fig. 3a. Allylpalla-
dium chloride dimer .Strem; 2.5 mg, 0.0069 mmol), the
ligand .0.0138 mmol), and CH2Cl2 .0.5 mL) were placed
in a half-dram vial. A glass bead was added to agitate the
yellow mixture and the vial was shaken at 08C for 30 min.
Neat carbonic acid cyclopent-2-enyl ester benzyl ester
.30 mg, 0.14 mmol) and phthalimide .61 mg, 0.41 mmol)
were added and the reaction was shaken for 24 h. Each
reaction was passed through a silica plug and analyzed by
chiral HPLC using a Chiralcel OD column .ligand, yield, ee,
con®guration): 1a 72% yield, 17% ee, R; 1b 45% yield, 54%
ee, S; 1c 54% yield, 81% ee, S; 2a 50% yield, 82% ee, R; 2b
51% yield, 67% ee, S; 2c 47% yield, 74% ee, S; 3a 68%
yield, 27% ee, R; 3b 20% yield, 65% ee, S; 3c 47% yield,
19% ee, S. Fig. 3b. Was performed in a similar manner to
reaction 1 using allylpalladium chloride dimer .3.5 mg,
0.0096 mmol), the ligand .0.0194 mmol), CH2Cl2
t
cooled to 2608C. A solution of BuLi .0.40 ml, 1.7 M) in
pentane was added dropwise using a syringe pump. The
reaction was then warmed to 2508C. A solution of phos-
phorus trichloride .0.03 g, 0.02 mL, 0.23 mmol) in THF
.2 mL) was added dropwise using a syringe pump. The
reaction was warmed to room temperature and stirred for
12 h. The reaction was quenched with 1 mL of a solution of
0.5 M HCl. The reaction was concentrated in vacuo and
puri®ed via ¯ash chromatographyusing 20% EtOAc/
hexanes as the eluent to yield the title compound .56 mg,
40% yield). [a]Dˆ261.38 .c 1.0, CHCl3, 258C); IR .®lm)
1
2976, 2819, 1115 cm21; H NMR .CDCl3) d 7.32±7.17
.m, 9H), 4.30±4.19 .m, 6H), 1.32 .d, Jˆ6.3 Hz, 18H); 13C
NMR .CDCl3) d 143.9 .d, Jˆ7 Hz), 137.9 .d, Jˆ13 Hz),
130.6 .d, Jˆ19 Hz), 124.6, 79.4, 56.3, 23.6; 31P NMR

5038
M. T. Powell et al. / Tetrahedron 57 ,2001) 5027±5038
.0.5 mL), carbonic acid cyclohex-2-enyl ester methyl ester
.30 mg, 0.19 mmol), and dimethyl malonate .84 mg, 0.58
mmol). Each reaction was passed through a silica plug and
analyzed by chiral GC28 .ligand, yield, ee, con®guration):
1a 61% yield, 23% ee, R; 1b 64% yield, 55% ee, S; 1c 79%
yield, 72% ee, S; 2a 80% yield, 75% ee, R; 2b 60% yield,
54% ee, S; 2c 74% yield, 61% ee, S; 3a 85% yield, 25% ee,
R; 3b 83% yield, 21% ee, S; 3c 76% yield, 22% ee, S. Fig.
3c. Was performed in a similar manner to reaction 1, but
at 108C. Allylpalladium chloride dimer .3.5 mg, 0.0096
mmol), the ligand .0.0194 mmol), and CH2Cl2 .0.5 mL)
were mixed ®rst, then 1,3-diphenylpropenyl acetate
.48 mg, 0.19 mmol), dimethyl malonate .84 mg, 0.58
mmol), and N,O-bis.trimethylsilyl)acetamide .0.38 mmol)
were added. Each reaction was passed through a silica
plug and analyzed by chiral HPLC using a Chiralpak AD
column .ligand, yield, ee, con®guration): 1a 88% yield,
12% ee, S; 1b 87% yield, 15% ee, R; 1c 90% yield, 32%
ee, R; 2a 86% yield, 22% ee, S; 2b 84% yield, 20% ee, R; 2c
80% yield, 24% ee, R; 3a 80% yield, 21% ee, S; 3b 82%
yield, 24% ee, R; 3c 76% yield, 26% ee, R. Fig. 3d. Was
performed in a similar manner to reaction 1 but at 108C
using allylpalladium chloride dimer .3.5 mg, 0.0096
mmol), the ligand .0.0194 mmol), and CH2Cl2 .0.5 mL)
®rst, then trans-4-pivaloxy-2-pentene .31 mg, 0.19 mmol),
dimethyl malonate .84 mg, 0.58 mmol), and N,O-bis.tri-
methylsilyl)acetamide .0.38 mmol) were added and the
reaction was shaken for 24 h. The reaction was passed
through a silica plug and analyzed by chiral GC .ligand,
yield, ee, con®guration): 1a 87% yield, 8% ee, R; 1b 87%
yield, 9% ee, S; 1c 85% yield, 12% ee, S; 2a 89% yield, 10%
ee, R; 2b 80% yield, 15% ee, S; 2c 82% yield, 19% ee, S; 3a
83% yield, 20% ee, R; 3b 82% yield, 19% ee, S; 3c 82%
yield, 19% ee, S. Fig. 4. A mixture of allylpalladium
chloride dimer .1.1 mg, 0.006 mmol), the ligand .0.0066
mmol), and THF .0.5 mL) was shaken at 2308C for
30 min and then treated with 3-acetoxy-3-.4-methoxy-
phenyl)-1-propene .41 mg, 0.20 mmol) and sodium
dimethylmethyl malonate .58 mg, 0.40 mmol), and the
reaction was shaken for 24 h. The reaction was passed
through a silica plug and analyzed by chiral HPLC using a
Chiralpak AD column .ligand, yield, % internal, ee, con-
®guration): 2a 99% yield, 30%, 19% ee, R; 2b 99% yield,
41%, 24% ee, S; 2c 99% yield, 40%, 22% ee, S; 3a 99%
yield, 33%, 26% ee, R; 3b 76% yield, 44%, 22% ee, S; 3c
69% yield, 47%, 21% ee, S.
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