Synthesis and post-resolution modification of new axially chiral ligands for asymmetric catalysis

Article abstract of DOI:10.1002/ejoc.201000794

The synthesis of four new members of the Quinazolinap series of ligands is described. Three of these ligands were prepared by post-resolution modification of the known ligand (R)-7-chloro-2-isopropyl-Quinazolinap, a new approach which offers an expedient route to a range of enantiopure ligands as it precludes the need for resolution of each ligand prepared. The remaining ligand, 7-chloro-2-methyl-Quinazolinap, was prepared in a seven-step synthetic sequence incorporating palladium- and nickel-catalyzed transformations as the key steps. A diastereomerically pure palladacycle of this ligand was characterised by X-ray crystallography. (R)-7-Chloro-2-isopropyl-Quinazolinap was applied to the rhodium-catalyzed hydroboration of vinylarenes with regioselectivities of up to > 99:1 and ee values of up to 68%. Each of the Quinazolinap ligands prepared were applied to the palladium-catalyzed allylic alkylation of 1,3-diphenylprop-2-enyl acetate resulting in conversions of up to 100% and ee values of up to 85%. Solution-phase NMR studies on a palladium complex of one of the ligands provided a rationale for the sense of asymmetric induction. Foue new members of the Quinazolinap series of ligands are prepared, three by post-resolution modification. They were applied to the rhodium-catalyzed hydroboration of vinylarenes with regioselectivities of catalyzed allylic of up to >99:1 and ee values of up to 68%. Each of the Quinazolinap ligands prepared were applied to the palladium-catalyzed allylic alkylation of 1,3-diphenylprop-2-enyl acetate in a synthetic and mechanistic study which helped to rationalize the sense of asymmetric induction observed.

Full text of DOI:10.1002/ejoc.201000794

FULL PAPER
DOI: 10.1002/ejoc.201000794
Synthesis and Post-Resolution Modification of New Axially Chiral Ligands for
Asymmetric Catalysis
William J. Fleming,[a] Helge Müller-Bunz,[a][‡] and Patrick J. Guiry*[a]
Keywords: Ligand design / Chiral resolution / Chirality / Atropisomerism / Asymmetric synthesis / Palladium /
Hydroboration
The synthesis of four new members of the Quinazolinap
series of ligands is described. Three of these ligands were
prepared by post-resolution modification of the known li-
dacycle of this ligand was characterised by X-ray crystal-
lography. (R)-7-Chloro-2-isopropyl-Quinazolinap was ap-
plied to the rhodium-catalyzed hydroboration of vinylarenes
gand (R)-7-chloro-2-isopropyl-Quinazolinap,
a new ap- with regioselectivities of up to Ͼ 99:1 and ee values of up to
proach which offers an expedient route to a range of enantio-
pure ligands as it precludes the need for resolution of each
ligand prepared. The remaining ligand, 7-chloro-2-methyl-
Quinazolinap, was prepared in a seven-step synthetic se-
quence incorporating palladium- and nickel-catalyzed trans-
formations as the key steps. A diastereomerically pure palla-
68%. Each of the Quinazolinap ligands prepared were ap-
plied to the palladium-catalyzed allylic alkylation of 1,3-di-
phenylprop-2-enyl acetate resulting in conversions of up to
100% and ee values of up to 85%. Solution-phase NMR
studies on a palladium complex of one of the ligands pro-
vided a rationale for the sense of asymmetric induction.
azolinap ligands (exemplified by 2a–j).[7] This allowed for
studies on the effects of altering the basicity of the donor
nitrogen and for the facile introduction of steric bulk at the
2-position, which is believed to be important in the transfer
of chiral information from catalyst to reaction product. Re-
lated atropisomeric axially chiral phosphinamine ligands
from the groups of Knochel and Chan include PINAP 3
and Pyphos 4, respectively, both of which have been suc-
cessfully applied to rhodium-catalyzed hydroboration of
vinylarenes.[8]
Introduction
The theme of chirality has become central to contempo-
rary organic synthesis due to its relevance in areas ranging
from material to medical science. However, the synthesis of
chiral molecules in one enantiomeric form is one of the
most difficult challenges.[1] Since the outstanding success of
Noyori’s BINAP ligand,[2] and its subsequent applications
in asymmetric transition metal catalysis,[3] the development
of new atropisomeric ligands has become an area of intense
interest.[4] Of particular relevance to our work is the devel-
opment of chiral heterobidentate systems due to their abil-
ity to induce asymmetry in a variety of reactions. Of these
the phosphinamine ligand class has received the most inter-
est due to the combination of steric and electronic effects
exerted on substrates at the coordination sphere of the tran-
sition metal to which they are bound.[5]
The first successful axially chiral phosphinamine ligand,
Quinap 1, was developed by Brown and incorporated a
naphthalene-isoquinoline backbone with the necessary ste-
ric requirements to prevent free rotation about the biaryl
linkage.[6] We subsequently developed the related Quin-
[a] Centre for Synthesis and Chemical Biology, School of
Chemistry and Chemical Biology, UCD Conway Institute,
University College Dublin,
Belfield, Dublin 4, Ireland
Fax: +353-1-716-2127
E-mail: p.guiry@ucd.ie
[‡] Correspondance concerning single-crystal X-ray data should be
directed to this author (helge.muellerbunz@ucd.ie)
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201000794.
Figure 1. Quinap, Quinazolinap and related axially chiral P,N li-
gands.
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New Axially Chiral Ligands for Asymmetric Catalysis
Recently we reported the synthesis and resolution of the selectivities were decreased by the inclusion of the 7-substit-
Quinazolinap ligand 5a which possesses a chlorine at the 7- uent, while the regioselectivities remained in the same
position, which was incorporated to facilitate potential range.
post-resolution modification at this position.[9] Ligand 5a
Table 1. Rhodium-catalyzed hydroboration of vinylarenes 9–16.
has previously been shown to be efficacious in the copper-
catalyzed β-borylation of α, β-unsaturated esters[9] and we
now wish to report the application of this ligand to the
rhodium-catalyzed hydroboration of vinylarenes. We also
wish to report the synthesis of ligands 5b–d, via one step
post-resolution modifications of 5a, and the synthesis and
resolution of 7-chloro-2-methyl-Quinazolinap (6) from
commercially available starting materials (Figure 1).
Results and Discussion
Rhodium-Catalyzed Hydroboration
The rhodium-catalyzed enantioselective hydroboration
of olefins is a valuable synthetic transformation, typically
employing a chiral catalyst and an achiral borane source.
The ease of transformation of the organoboranes produced
into various functional groups has made hydroboration a
valuable synthetic technique in organic chemistry.[10] Pre-
viously, members of the Quinazolinap series of ligands have
been shown to be effective for this transformation[7c,7f,7h,7i]
and we now wish to report the application of the Quinazol-
inap ligand 5a to this transformation.
Vinylarene derivatives 9–16 were tested as hydroboration
substrates using in situ-prepared rhodium-Quinazolinap
complex (S)-8 as the active catalyst (Scheme 1). Reactions
were carried out both at room temperature and at 0 °C and
it was found that for all but one of the substrates the higher
temperature gave superior results (Table 1). Styrene 9 was
quantitatively converted to product, with an α: β ratio of
80:20 and an ee value of 65% (Table 1, entry 1). p-Meth-
oxystyrene performed similarly, albeit with a lower regiose-
lectivity of 68:32 (entry 2). The regioselectivity was in-
creased when various β-methylstyrenes were used as sub-
strates (entries 2–6) and cis-β-methylstyrene 12 was hydro-
borated with an α: β ratio of Ͼ 99:1. The presence of elec-
[a] T = 20 °C. [b] T = 0 °C. [c] Conversion and α/β ratio determined
tron-donating substituents on the aryl ring was detrimental
to conversion, regio- and enantioselectivity (entries 5 and
6). The cyclic substrates 15 and 16 gave excellent regioselec-
tivities (entries 7 and 8) with moderate ee values of 55%
and 64%, respectively. The effect of the 7-chloro substituent
can be evaluated by comparison with the analogous unsub-
by 1H NMR spectroscopy. [d] ee determined by chiral HPLC or
GC.[7c]
Post-Resolution Modification of (R)-5a
In the standard synthesis of previous members of the
stituted ligand 2c.[7c] As a general trend, the enantio- Quinazolinap ligand series, each ligand was prepared by a
Scheme 1. Formation of rhodium-Quinazolinap catalyst.
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W. J. Fleming, H. Müller-Bunz, P. J. Guiry
FULL PAPER
Scheme 2. Post-resolution modification of (R)-5a.
multi-step synthetic sequence from commercially available Synthesis and Resolution of 6
starting materials. As part of our ongoing investigations it
was proposed that modification of resolved ligands could
Racemic Quinazolinap 6 was prepared using the syn-
give access to a variety of enantiopure ligands. In contrast thetic route previously employed for the synthesis of other
to BINAP and its analogues which are typically prepared members of this class of ligand.[7] Acylation of the commer-
from enantiopure BINOL, axially chiral P,N ligands are cially available 7-chloroanthranilamide 17 followed by a cy-
prepared racemically and then resolved.[4a] An important clocondensation furnished the quinazoline 18 in almost
design feature of the ligands 5a and 6 was the incorporation quantitative yield over the 2 steps. POCl3-mediated chlori-
of a chlorine atom at the 7-position, as it was envisaged nation of 18 yielded the chloro-quinazoline 19 in 67% yield
that this chlorine would not only act as an electronic modi- after column chromatography. The Suzuki–Miyaura cross-
fier for the donor nitrogen but also as a functional handle coupling of 19 with aryl boronic acid 20 gave the biaryl 21
for the diversification of these ligands at a late stage. Due in moderate yield (73%). Removal of the methyl ether with
to the availability of sufficient quantities of (R)-5a in our BBr3 and triflation of the resulting naphthol led to the for-
laboratory, this ligand was chosen for the post-resolution mation of 22 in a 62% yield over the 2 steps. The final
modifications in this study (Scheme 2).
step in the ligand synthesis was the nickel-catalyzed cross-
We previously observed that oxidative addition occurred coupling between the triflate 22 and diphenylphosphane in
at the 7-position under the conditions of the Ni-catalyzed the presence of NiCl2(dppe)/DABCO following the proto-
phosphanylation employed in the synthesis of 5a.[9] With col of Cai[11] which gave the desired phosphne 6 in a low
this in mind it was decided to subject (R)-5a to the same yield of 33% (Scheme 3).[12]
conditions which resulted in the formation of (R)-5d in a
The resolution of atropisomeric P-N ligands is typically
62% yield. (R)-5b and (R)-5c were prepared in yields of carried out by the formation of diastereomers using
33% and 70%, respectively, by a Pd-dppf [dppf = 1,1Ј- enantiopure palladacycles derived from palladium amine
bis(diphenylphosphanyl)ferrocene] mediated aryl amination complexes, followed by fractional crystallisation to yield a
under microwave conditions (initial power 300 W).
diastereomerically pure complex (Scheme 4). The palladium
Scheme 3. Synthesis of racemic ligand 6.
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New Axially Chiral Ligands for Asymmetric Catalysis
Scheme 4. Resolution of ligand 6.
complex (R,R)-cis-23 was used in the resolution of Quinap bonds.[14] The reaction involves the nucleophilic displace-
1 and previously prepared members of the Quinazolinap ment of an allylic leaving group and is catalyzed by a vari-
family. This method was employed in the present study via ety of transition metal catalysts, although palladium re-
the formation of the diastereomeric palladacycles (Sa,R)-24 mains the most widely used. Quinazolinaps (S)-5a and 6
and (Ra,R)-24. The racemic phosphane 6 was stirred in and (R)-5b–d were applied to the palladium-catalyzed
MeOH with the chloro-bridged resolving agent (R,R)-cis- asymmetric allylic alkylation involving the reaction of 1,3-
23 and subsequent addition of KPF6 in water formed the diphenylprop-2-enyl acetate 25 and dimethyl malonate 26,
diastereomeric palladacycles in a 1:1 ratio. Crystallisation Table 2. In the present study conditions were optimised for
from hot butanone/Et2O precipitated (Sa,R)-24 whose pu- ligand (S)-5a and these conditions were employed for reac-
rity was determined to be Ͼ 99% by 1H and 31P NMR tions involving each of the remaining ligands 5b–e.[15]
spectroscopy. The absolute configuration of the precipitated
Table 2. Palladium-catalyzed allylic alkylation.
diastereomer was determined by single-crystal X-ray analy-
sis, Figure 2. Decomplexation of the enantiopure ligand
from palladium was achieved in a 95% yield by stirring the
palladacycle (Sa,R)-24 with dppe in dichloromethane.
Entry[a]
Ligand
Conversion (%)
ee (%)[b]
1
2
3
4
5
(S)-5a
(R)-5b
(R)-5c
(R)-5d
(S)-6
100
100
100
100
100
78 (R)
51 (S)
64 (S)
58 (S)
85 (R)
1
[a] Conversion determined by H NMR spectroscopy. [b] ee values
determined by chiral HPLC [OD, 99:1 hexane/2-propanol, 0.2 mL/
min, RT (R) = 46.2 min, RT (S) 49.1 min].
Figure 2. Single crystal X-ray structure of (Sa,R)-24,[13] counterion
and hydrogens omitted for clarity. Selected bond lengths (Å): N1–
Pd1 2.177(2), P1–C1 1.822(2), Cl–C 1.722(4) and P–Pd 2.2422(9).
Selected bond angles: P1–Pd1–N1 81.27(8)°, C1–P1–Pd1 91.7(1)°
and N1–Pd–N2 100.5(1)°.
Complete conversions were obtained with all the Quin-
azolinap ligands tested using the optimised conditions
(Table 2, entries 1–5). Each of the ligands derived from (R)-
5a gave a lower ee value than the parent 7-chloro analogue,
entries 1–4. For each of these ligands there is a possibility
of some monodentate binding to palladium through the
phosphorus at the 7-position of 5d and the nitrogen at the
7-position of 5b and 5c, although it appears that this is not
Palladium-Catalyzed Allylic Alkylation
Allylic alkylation is an important reaction for forming the case as this would most likely have led to much lower
different types of carbon-carbon and carbon-heteroatom ee values. It is clear that substitution at the 7-position has
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W. J. Fleming, H. Müller-Bunz, P. J. Guiry
FULL PAPER
an effect on the enantioselectivity, although it is difficult to 2D NOESY spectrum, a cross-peak between the isopropyl
make a correlation between the nature of the substituent unit, specifically one of the two diastereotopic methyl
and the enantioselectivity induced. The nitrogen and phos- groups of the Quinazolinap ligand, and the major allyl pro-
phorus containing substituents are both electron-donating ton trans to phosphorus indicates that under these condi-
by resonance, although chlorine is net electron-with- tions the major diastereomer formed was endo-29,
drawing. Increasing the pKa of nitrogen may decrease the Scheme 6.
effect of the trans-influence of phosphorus, which could be
deleterious to enantioinduction. Ligand 6 was the best per-
forming ligand in the present study (entry 5), with complete
conversion with a good ee of 85%.
1
Solution-Phase H NMR Studies on the Palladium Allyl
Complex of 7-Chloro-2-isopropyl-Quinazolinap (Sa)-5a
A detailed solution-phase 1H NMR study on the cationic
palladium(II) 1,3-diphenyl-η3-allyl intermediate 29 derived
from ligand (S)-5a was carried out to gain insight in the
Scheme 6. NOE interactions.
enantioselection process. The procedure involved identi-
Experimentally, the use of ligand (S)-5a gives the (R)-
fying the diastereomeric complexes formed by 1H NMR
enantiomer of 27 as the major product (78% ee). This can
spectroscopy and measuring the ratio of diastereomers by
be explained by considering nucleophilic attack occurring
integration. The coupling between the allyl protons was
trans to phosphorus in a late transition state model,
1
confirmed by H-1H correlation spectroscopy (COSY), and
Scheme 6. In this model, as the nucleophile approaches, the
insight into the relative positions of the allyl and ligand
allyl phenyl group is free to roll upwards without any steric
protons was gained by 2-D nuclear Overhauser effect spec-
interaction with the quinazoline moiety to give the η2-palla-
troscopy (NOESY). The Quinazolinap-allyl complexes were
dium olefin complex, leading to the (R)-product. In con-
prepared by the reaction of the Quinazolinap ligand (S)-5a
trast, attack trans to the phosphorus of the exo-dia-
with the palladium allyl dimer 28 in the presence of an ex-
stereomer is disfavoured as the allylphenyl group would be
cess of sodium tetrafluoroborate. The two possible dia-
required to roll downwards causing an unwanted (and high
stereomeric complexes exo- and endo-29 are shown,
energy) steric clash with the isopropyl unit.[18] This suggests
Scheme 5.[16]
that ligands possessing (S)-chirality favour the formation of
In the 1H NMR spectrum taken at –20 °C both dia-
the (R)-product.
stereomeric complexes were present in a ratio of 87:13,
which was confirmed by the 31P NMR spectrum which
showed two peaks at δ = 29.4 ppm (most abundant) and
Conclusions
32.1 ppm.[17] In the major diastereomeric intermediate the
central allyl proton showed up as a triplet at δ = 6.42 ppm
The synthesis of four new enantiopure Quinazolinap li-
with a coupling constant of 11.2 Hz. The other allyl protons gands is presented; three of these ligands 5b–d were pre-
1
of the major diastereomer were identified by H-1H COSY pared by post-resolution modification of (R)-7-chloro-2-
and appeared at 5.58 (dd, J = 11.2, 9.9 Hz, trans to phos- isopropyl-Quinazolinap 5a and the remaining ligand 6 was
phorus) and 3.86 (d, J = 11.2 Hz, trans to nitrogen). In the prepared by a 7-step synthetic sequence followed by resolu-
Scheme 5. Quinazolinap-allyl complex formation.
6000
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New Axially Chiral Ligands for Asymmetric Catalysis
Preparation of Ligands 5b–d
tion. Post-resolution modification is a new approach which
offers an expedient route to a range of enantiopure ligands
as it precludes the need for resolution of each ligand pre-
pared. Ligand 5a was applied to the rhodium-catalyzed hy-
droboration of a range of vinylarenes with ee values of up
to 68% and regioselectivities of up to Ͼ 99:1. Each of the
ligands were applied to the palladium-catalyzed allylic alky-
lation of 1,3-diphenylprop-2-enyl acetate with complete
Post-Resolution Modification of 5a
(Ra)-N,N-Dibutyl-4-[2-(diphenylphosphanyl)naphthalen-1-yl]-2-iso-
propylquinazolin-7-amine (5b):
with tris(dibenzylideneacetone)dipalladium(0) (Pd2dba3, 5.5 mg,
0.006 mmol), (diphenylphosphanyl)ferrocene (dppf, 6.7 mg,
0.012 mmol) and dry, degassed toluene (1.5 mL) and stirred at
room temperature for 30 min. The resulting dark solution was
A Schlenk tube was charged
conversions and ee values of up to 85%. Solution phase transferred via syringe to a 10 mL microwave vial containing (Ra)-
7-chloro-4-[2-(diphenylphosphanyl)naphthalen-1-yl]-2-isopropyl-
quinazoline (30 mg, 0.06 mmol) and sodium tert-butoxide (7.0 mg,
0.072 mmol) and to this was added dibutylamine (9.3 mg, 12.2 µL,
0.072 mmol). The vial was placed in a CEM Discoverer microwave
with an initial power setting of 300 W and heated to 125 °C for 2
h. The toluene was removed in vacuo to yield a brown oil. Column
chromatography (silica gel, pentane/EtOAc, 2:1) yielded the title
compound (13 mg, 33% yield) as a yellow oil, [α]2D0 = +15 (c = 0.25,
CDCl3). 1H NMR (400 MHz, CDCl3): δ = 7.99–7.79 (m, 3 H),
7.65–7.54 (m, 2 H), 7.48 (t, J = 7.6 Hz, 2 H), 7.40–7.10 (m, 7 H),
7.02 (d, J = 9.3 Hz, 1 H), 6.97 (dd, J = 8.3, 1.6 Hz, 2 H), 6.83 (dd,
J = 9.5, 2.3 Hz, 1 H), 6.69 (dd, J = 9.3, 2.3 Hz, 1 H), 3.47–3.29
(m, 4 H), 3.15 (sept, J = 6.5 Hz, 1 H), 1.71–1.50 (m, 4 H), 1.54–
1.11 (m, 8 H), 1.02–0.90 (m, 6 H), 0.88 (t, J = 7.0 Hz, 2 H) ppm.
13C NMR (101 MHz CDCl3): δ = 152.8, 151.8, 133.8, 133.5, 133.5,
133.3, 130.1, 129.1, 128.6, 128.3, 128.2, 128.1, 128.1, 127.9, 127.9,
127.5, 126.8, 126.6, 126.5, 126.3, 126.1, 126.0, 126.0, 125.0, 50.9,
38.2, 38.0, 21.8, 21.2, 20.3, 13.5 ppm, C-P couplings not assigned
(2 peaks obscured). 31P NMR (121 MHz, CDCl3): δ = –13.7 ppm.
NMR studies on the 1,3-diphenylallyl palladium complex
of ligand (S)-5a provided a rationale for the sense of asym-
metric induction.
Experimental Section
General: All reactions were performed under anhydrous conditions
and an inert atmosphere of nitrogen in oven-dried glassware with
magnetic stirring. Yields refer to chromatographically and spectro-
scopically (1H NMR) homogeneous materials, unless otherwise
indicated. Reagents were used as obtained from commercial
sources or purified according to the guidelines of Perrin and Arma-
rego.[19] Evaporation in vacuo refers to the removal of volatiles on
a Büchi rotary evaporator with an integrated vacuum pump. Flash
chromatography was carried out using Merck Kiesegel 60 F254
(230–400 mesh) silica gel following the method of Still et al.[20]
Thin-layer chromatography (TLC) was performed on Merck DC-
Alufolien plates pre-coated with silica gel 60 F254. They were visu-
alised either by quenching of ultraviolet fluorescence, or by char-
ring with an acidic vanillin solution (vanillin, H2SO4 and acetic
acid in MeOH). The Microanalytical Laboratory, University Col-
lege Dublin, performed elemental analyses. Electrospray mass spec-
tra were recorded on a Micromass Quattro with electrospray probe.
Exact mass ESI mass spectra (HRMS) were measured on a micro-
mass LCT orthogonal time of flight mass spectrometer with leucine
IR (NaCl): ν
= 2957, 1612, 1550, 1497, 1368 cm–1. HRMS
˜
max
C41H45N3P calcd. 610.3351, found 610.3334.
(Ra)-4-[2-(Diphenylphosphanyl)naphthalen-1-yl]-2-isopropyl-N-phen-
ylquinazolin-7-amine (3c): A Schlenk tube was charged with tris(di-
benzylideneacetone)dipalladium(0) (Pd2dba3, 5.5 mg, 0.006 mmol),
diphenylphosphanylferrocene (dppf, 6.7 mg, 0.012 mmol) and dry,
degassed toluene (1.5 mL) and stirred at room temperature for
30 min. The resulting dark solution was transferred via syringe to
a 10 mL microwave vile containing (Ra)-7-chloro-4-[2-(diphen-
1
enkephalin (Tyr-Gly-Phe-Leu) as an internal lock mass. H NMR
spectra were recorded on a 300 MHz Varian-Inova spectrometer,
a 400 MHz Varian-Inova spectrometer, a 500 MHz Varian-Inova
spectrometer or a 600 MHz Varian-Inova spectrometer. Chemical
shifts are quoted in ppm relative to tetramethylsilane and coupling
constants (J) are quoted in Hz and are uncorrected. CDCl3 was
used as the solvent for all NMR spectra unless otherwise stated.
75.4 MHz 13C NMR spectra were recorded on a 300 MHz Varian-
Inova spectrometer, 101 MHz 13C NMR spectra on a 400 MHz
Varian-Inova spectrometer and 125 13C NMR spectra on a
500 MHz Varian-Inova spectrometer. Tetramethylsilane was used
as the internal standard in all 13C NMR spectra recorded. All 13C
NMR spectra are 1H decoupled unless otherwise stated.
121.4 MHz 31P NMR spectra were recorded on a 300 MHz Varian-
Inova spectrometer and 162 MHz 31P NMR spectra on a 400 MHz
Varian-Inova spectrometer. 31P Chemical shifts are reported rela-
tive to 85% aqueous phosphoric acid (δ =0.0 ppm). All 31P NMR
ylphosphanyl)naphthalen-1-yl]-2-isopropylquinazoline
(30 mg,
0.06 mmol) and sodium tert-butoxide (7.0 mg, 0.072 mmol) and to
this was added aniline (6.5 mg, 6.5 µL, 0.072 mmol). The vial was
placed in a CEM Discoverer microwave with an initial power set-
ting of 300 W and heated to 125 °C for 2 h. The toluene was re-
moved in vacuo to yield the title compound as a brown oil. Prepar-
ative TLC (silica gel, pentane/EtOAc, 2:1) yielded the title com-
pound (24 mg, 70% yield) as an orange powder, m.p. 150–152 °C,
[α]2D0 = +30 (c = 0.2, CDCl3). 1H NMR (400 MHz, CDCl3): δ =
8.71 (br. s, 1 H), 7.99–7.78 (m, 4 H), 7.46 (t, J = 6.5 Hz, 2 H),
7.35–7.02 (m, 15 H), 7.01–6.88 (m, 3 H), 3.55 (sept., J = 6.1 Hz, 1
H), 1.17 (d, J = 6.1 Hz, 6 H) ppm. 13C{31P} NMR (101 MHz
CDCl3): δ = 138.5, 136.0 (d, J = 11.2 Hz), 133.6 (d, J = 20.2 Hz),
133.3, 133.2 (d, J = 18.8 Hz), 131.3 (d, J = 7.7 Hz), 130.0, 129.8,
129.4, 129.0, 128.9, 128.5 (d, J = 6.6 Hz), 128.5, 128.3 (d, J =
11.2 Hz), 128.3, 127.4, 127.3, 125.5 (d, J = 6.9 Hz), 125.2, 122.4,
34.9, 20.9, 20.6 ppm, 3 C signals obscured. 31P NMR (121 MHz,
1
spectra are H decoupled unless otherwise stated. All reaction sol-
vents were obtained from a PureSolv-300–3-MD dry solvent dis-
penser and used without further purification unless otherwise
stated. Melting points (m.p.) are quoted to the nearest 0.5 °C.
HPLC analysis was carried out on a Shimadzu LC 2010A using a
Supelco 2-4304 β-Dex® 120 column (30 mϫ0.25 mm, 0.25 mm
film). GC analysis was carried out on a Shimadzu GC 2010 using
CDCl ): δ = –13.6 ppm. IR (NaCl): ν
= 3055, 2087, 1265, 909,
˜
3
max
735 cm–1. HRMS C39H33N3P calcd. 574.2412, found 574.2414.
(R)-7-(Diphenylphosphanyl)-4-[2-(diphenylphosphanyl)naphthalen-1-
yl]-2-isopropylquinazoline (3d): To
a solution of NiCl2(dppe)
[5.2 mg, 0.01 mmol; dppe: 1,2-bis(diphenylphosphane)ethane] in
a Chiralcel OD column (0.46 cm I.D. ϫ25 cm). Optical rotation DMF (1 mL) was added Ph2PH (14 mg, 0.075 mmol), and the mix-
values were measured on a Perkin–Elmer 241 Polarimeter. [α]D val-
ture was stirred at 100 °C for 30 min. A solution of (Ra)-7-chloro-
4-[2-(diphenylphosphanyl)naphthalen-1-yl]-2-isopropylquinazoline
ues are given in 10–1 degcm2 g–1.
Eur. J. Org. Chem. 2010, 5996–6004
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
6001

W. J. Fleming, H. Müller-Bunz, P. J. Guiry
(51.7 mg, 0.1 mmol) and DABCO (44 mg, 0.4 mmol) in DMF anhydrous dimethoxyethane (DME, 100 mL) and stirred at room
FULL PAPER
(1 mL) was added via syringe to form a dark brown solution. After
1 h a second portion of Ph2PH (14 mg, 0.075 mmol) was added
and stirring continued for 24 h, after which the solution was cooled
to room temperature and filtered through Celite®. The residue was
reduced in vacuo and taken up in dichloromethane (10 mL) and
washed with water (10 mL) and brine (10 mL). The organic layer
was dried (MgSO4), and concentrated in vacuo to give a brown oil.
Flash column chromatography (silica gel, pentane/EtOAc, 4:1) gave
the title compound as a white solid (41 mg, 62%). [α]2D0 = +20 (c =
0.25, CDCl3), identical physical data to previously prepared race-
mic sample.
temperature for 10 min. 2-(Methoxynaphthalen-1-yl)boronic acid
(3.3 g, 16.4 mmol) and caesium fluoride (4.98 g, 32.8 mmol) were
added under a flow of nitrogen. The yellow solution was stirred at
85 °C for 16 h (TLC). After cooling to room temperature water
(60 mL) and dichloromethane (60 mL) were added and the layers
separated. Extraction was completed with further portions of
dichloromethane (3ϫ50 mL). The organic layers were combined,
dried (MgSO4) and reduced in vacuo to give the crude product as
a yellow solid. Purification by column chromatography (silica gel,
pentane/EtOAc, 3:1) gave 7 (4.0 g, 73%) as a white solid, m.p. 140–
1
141 °C. H NMR (400 MHz, CDCl3): δ = 8.4 (dd, J = 9.2, 2.0 Hz,
2 H), 7.87 (dd, J = 7.2, 3.2 Hz, 1 H), 7.41 (app t, J = 9.2 Hz, 2 H),
7.35–7.36 (m, 1 H), 7.32–7.33 (m, 1 H), 7.29–7.31 (m, 1 H), 7.06–
7.08 (m, 1 H), 3.80 (s, 3 H), 2.99 (s, 3 H) ppm. 13C NMR
(101 MHz, CDCl3): δ = 167.7, 165.7, 154.8, 151.6, 140.2, 133.1,
131.7, 129.2, 128.7, 128.3, 128.1, 127.6, 127.3, 124.3, 124.2, 122.0,
Procedures for the Synthesis and Resolution of Ligand 3e
7-Chloro-2-methylquinazolin-4(3H)-one (15): 2-Amino-4-chloro-
benzamide 14 (25.0 g, 147 mmol) was suspended in dichlorometh-
ane (250 mL) and to this pyridine (13.0 mL, 161 mmol) was added.
Acetyl chloride (11.4 mL, 161 mmol) was added slowly and the pre-
cipitate dissolved. Stirring was continued at room temperature for
2 h during which time a precipitate formed. The solvent was re-
duced in vacuo and a small sample of the acylated product was
purified by column chromatography (pentane/ethyl acetate, 1:1),
119.1, 113.2, 56.6, 27.0 ppm. IR (KBr): ν
= 3061, 1601, 6504,
˜
max
800 cm–1. C20H15ClN2O (338.58): calcd. C 71.75, H 4.52, N 8.37,
Cl 10.59; found C 71.64, H 4.45, N 8.26, Cl 10.55.
1-(7-Chloro-2-methylquinazolin-4-yl)naphthalen-2-yl Trifluorometh-
anesulfonate (18): 7-Chloro-4-(2-methoxynaphthalen-1-yl)-2-meth-
ylquinazoline (8.0 g, 23.9 mmol) was dissolved in dry dichloro-
methane (120 mL). Boron tribromide (1  in DCM, 47.8 mL,
47.8 mmol) was added carefully and the dark red/black solution
was stirred for 18 h.[6a] Water (100 mL) was added carefully and
stirring continued for 1 h, after which time an orange precipitate
formed, which was filtered and thoroughly dried under vacuum.
The orange solid was taken up in dichloromethane (120 mL) and
to this was added N,N-dimethylaminopyridine (8.8 g, 71.7 mmol).
Trifluoromethanesulfonic anhydride (7.4 g, 4.45 mL, 26.3 mmol)
was added and the resulting black solution stirred at room tem-
perature for 4 h. The solution was washed with HCl (1 , 100 mL)
and extraction completed with further portions of dichloromethane
(3ϫ50 mL). The organic layers were combined, dried (MgSO4) and
solvent removed in vacuo. Purification by column chromatography
(silica gel, pentane/EtOAc, 3:1) yielded the title compound (6.4 g,
1
m.p. 205.5–208.0 °C. H NMR (400 MHz, DMSO [D6]): δ = 11.73
(s, 1 H), 8.52 (d, J = 2.1 Hz, 1 H), 8.30 (br. s, 1 H), 7.79 (d, J =
8.4 Hz, 2 H), 7.16 (dd, J = 8.4, 2.1 Hz, 1 H), 2.06 (s, 3 H) ppm.
13C (101 MHz, DMSO [D6]): δ = 170.6, 169.4, 141.6, 137.3, 131.0,
122.7, 120.0, 118.7, 25.7 ppm. IR (KBr): ν
= 1764, 1642, 1599,
˜
max
1049, 779 cm–1. To the remaining residue was added to 5% aque-
ous NaOH (350 mL) and the solution was heated at reflux until all
solid had dissolved (ca. 15 mins). 1  HCl was added until the pH
was about 7, the white precipitate which formed was filtered,
washed with water (200 mL) and dried by applying pump vaccum.
5 (27.1 g, 98%) was isolated as white fibrous crystals, m.p. 264–
1
266 °C. H NMR (300 MHz, DMSO): δ = 12.30 (br. s, 1 H), 8.05
(d, J = 8.5 Hz, 1 H), 7.60 (d, J = 1.5 Hz, 1 H), 7.46 (dd, J = 6.5,
2 Hz, 1 H), 2.34 (s, 3 H) ppm. 13C NMR (75 MHz, DMSO): δ =
161.8, 156.8, 150.8, 139.5, 128.5, 126.8, 126.4, 120.2, 22.2 ppm. IR
(KBr): ν
= 3023, 1679, 1600 and 1340 cm–1. m/z (EIMS 70 eV)
˜
max
1
62% over 2 steps) as a white solid, m.p. 133.0–135.0 °C. H NMR
193 (M+ 100%), 195 (36%). C9H7ClN2O (194.62): calcd. C 55.54,
H 3.63, N 14.39, Cl 18.22; found C 55.35, H 3.49, N 14.17, Cl
18.47.
(400 MHz, CDCl3): δ = 8.14 (d, J = 9.1 Hz, 1 H), 8.09 (d, J =
1.7 Hz, 1 H), 8.01 (d, J = 8.3 Hz, 1 H), 7.62–7.59 (m, 2 H), 7.46
(t, J = 7.2 Hz, 1 H), 7.39–7.31 (m, 2 H), 7.24 (m, 1 H), 2.99 (s, 3
H) ppm. 13C NMR (101 MHz, CDCl3): δ = 265.8, 163.4, 151.8,
144.9, 141.0, 132.6, 132.4, 132.4, 128.8, 128.7, 128.7, 128.0, 127.8,
4,7-Dichloro-2-methyl-3,4-dihydroquinazoline (16): A solution of 7-
chloro-2-methylquinazolin-4(3H)-one 15 (5.0 g, 25.7 mmol) and
N,N-diethylanailine (5.6 mL, 38.5 mmol) in benzene (60 mL) was
azeotropically dried using a Dean–Stark trap. Phosphorus oxychlo-
ride (1.56 mL, 16.9 mmol) was added and refluxed for 16 h giving
a brick-red solution. The mixture was cooled to room temperature,
diluted with ethyl acetate (40 mL) and washed sequentially with
water (2ϫ40 mL), HCl (1 , 2ϫ40 mL), water (40 mL), NaHCO3
(40 mL), water (40 mL) and brine (40 mL). The solution was dried
(MgSO4) and volatiles reduced in vacuo to give a yellow solid. This
was purified by column chromatography (silica gel, pentane/
EtOAc, 4:1) to yield 6 (3.67 g, 67%) as a white solid, m.p. 95–96 °C.
1H NMR (300 MHz, CDCl3): δ = 8.16 (d, J = 9.0 Hz, 1 H), 7.96
(d, J = 2.1 Hz, 1 H), 7.60 (dd, J = 9.0, 2.1 Hz, 1 H), 2.85 (s, 3 H)
ppm. 13C NMR (101 MHz, CDCl3): δ = 165.0, 162.2, 152.2, 141.6,
127.7, 126.9, 126.1, 121.4, 119.8, 119.8, 26.7 ppm. IR (KBr): ν
˜
max
= 3063, 1557, 1415, 1215 cm–1. LRMS 453.0, 455.0 (2:1).
C20H12ClF3N2O3S (452.61): calcd. C 53.05, H 2.67, N 6.19, Cl 7.83,
S 7.08; found C 53.00, H 2.70, N 6.06, Cl 8.21, S 7.58.
7-Chloro-4-[2-(diphenylphosphanyl)naphthalen-1-yl]-2-methylquinaz-
oline (3e): To a solution of NiCl2(dppe) [116 mg, 0.22 mmol; dppe:
1,2-bis(diphenylphosphane)-ethane] in DMF (4 mL) was added
Ph2PH (305 mg, 3.3 mmol), and the mixture was stirred at 100 °C
for 30 min. A solution of 8 (1.0 g, 2.2 mmol) and DABCO (1.6 g,
8.8 mmol) in DMF (4 mL) was added via cannula to give initially
a pale green transparent solution which over the course of 1 h
became a dark brown solution. After 1 h a second portion of
Ph2PH (305 mg, 3.3 mmol) was added. After 24 h at 100 °C the
solution was cooled to room temperature and filtered through Ce-
lite® the residue was reduced in vacuo and taken up in dichloro-
methane (10 mL) and washed with water (10 mL) and brine
(10 mL). The organic layer was dried (MgSO4) and concentrated
129.4, 127.4, 127.3, 120.5, 26.3 ppm. IR (KBr): ν
= 760, 1463,
˜
max
1583, 1360 cm–1. m/z (EIMS 70 eV) 212.9 [(M – H)+ 100%], 215.0
[(M+ – H) 68%], 216.0 [(M+ – H) 10%]. C9H6Cl2N2 (213.92): calcd.
C 50.73, H 2.84, N 13.15; found C 50.75, H 2.93, N 13.04.
7-Chloro-4-(2-methoxynaphthalen-1-yl)-2-methylquinazoline
4,7-Dichloro-2-methyl-3,4-dihydroquinazoline (16)
16.4 mmol) and Pd(PPh3)4 (0.57 g, 0.05 mmol) were dissolved in
(17): in vacuo to give a brown oil. 3e (355 mg, 33%) was isolated by
(3.5 g,
column chromatography (silica gel, pentane/EtOAc, 20:1 to 9:1) as
a white solid, m.p. 94–96 °C. 1H NMR (400 MHz, CDCl3): δ =
6002
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© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2010, 5996–6004

New Axially Chiral Ligands for Asymmetric Catalysis
8.03 (d, J = 8.5 Hz, 1 H), 7.90, (t, J = 8.3 Hz, 2 H), 7.80 (ddd, J
= 8.4, 6.8, 1.5 Hz, 1 H), 7.50 (t, J = 7.5 Hz, 1 H), 7.40 (dd, J =
8.5, 3.2 Hz, 1 H), 7.36–7.19 (m, 10 H), 7.16 (dd, J = 10.7, 4.4 Hz,
Asymmetric Allylic Alkylation Procedure: Ligand 3a–e (9.1µmol,
6.0 mol-%) and [Pd(C3H5)Cl]2 (1,4 mg, 3.8 µmol, 2.5 mol-%) were
stirred in dichloromethane (1.5 mL) for 20 min to give a pale yellow
2 H), 7.10 (d, J = 8.5 Hz, 1 H), 2.79 (s, 3 H) ppm. 13C NMR solution. To this was added (E)-1,3-diphenylallyl acetate (37.8 mg,
(101 MHz, CDCl3): δ = 169.2 (d, Jcp = 6.7 Hz), 163.9, 150.6, 136.8 0.15 mmol) and the resulting solution stirred for an additional
(d, Jcp = 11.4 Hz), 136.7 (d, Jcp = 10.7 Hz), 134.7 (d, Jcp = 15.5 Hz),
133.8 (d, Jcp = 4.2 Hz), 133.7 (d, Jcp = 12.5 Hz), 133.5 (d, Jcp
5 min. Dimethyl malonate (51 µL, 0.45 mmol), N,O-bis(trimethyl-
silyl)acetamide (BSA, 111 µL, 0.45 mmol) and base (ca. 1 mg) were
=
7.2 Hz), 131.8 (d, Jcp = 7.4 Hz), 129.8, 129.1, 128.6, 128.6, 128.4, added. The resulting mixture was stirred at room temperature for
128.3, 128.0, 128.0, 127.0, 126.9, 126.9, 126.6, 126.1, 26.4 ppm. (2
24 h. The solvent was reduced in vacuo to give a yellow oil which
was purified by column chromatography (pentane/ethyl acetate,
10:1) to give the product as a clear oil. 1H NMR (300 MHz,
CDCl3): δ = 7.34–7.20 (m, 10 H), 6.47 (d, J = 15.8 Hz, 1 H), 6.34
(dd, J = 15.8, 8.4 Hz, 1 H), 4.27 (dd, J = 10.8, 8.5 Hz, 1 H), 3.95
(d, J = 10.8 Hz 1 H), 3.70 (s, 3 H), 3.52 (s, 3 H) ppm. The% conver-
peaks obscured). 31P NMR (121 MHz, CDCl3): δ = –13.4 ppm.
IR (KBr): ν
= 2360, 1555, 1478, 1461 cm–1. HRMS calcd. for
˜
max
C31H22ClN2P 489.1287, found 489.1273.
Resolution of 3e: (+)-Di-µ-chlorobis{(R)-dimethyl[1-(1-naphthyl)-
ethyl]aminato-C2,N}dipalladium(II) (41.6 mg, 0.065 mmol) and
(R,S)-7-chloro-4-[2-(diphenylphosphanyl)naphthalen-1-yl]-2-meth-
ylquinazoline (60 mg, 0.12 mmol) were dissolved in MeOH (5 mL)
and stirred for 16 h to give a yellow solution. To this was added
KPF6 (22 mg, 0.12 mmol) in water (1 mL), upon which a yellow
precipitate formed. Stirring was continued for 10 min and filtered
to yield a yellow powder which was shown to be a 1:1 mixture of
the (Ra,R) and (Sa,R) bidentate complexes (31P NMR showed two
peaks of equal intensity at δ = 37.6 and 40.8 ppm). Fractional
crystallisation from butanone/diethyl ether gave a single dia-
stereomer (Sa, R)-3e (35 mg, 31%), m.p. 226–227 °C. [α]2D0 = –201
(c = 0.5, CHCl3). 1H NMR (400 MHz, CDCl3): δ = 8.16 (d, J =
8.3 Hz, 1 H), 8.08 (d, J = 8.3 Hz, 1 H), 7.89–7.13 (m, 11 H), 7.09
(d, J = 8.7 Hz, 1 H), 6.97–6.74 (m, 9 H), 6.70 (t, J = 6.2 Hz, 1 H),
6.61 (dd, J = 8.3, 6.5 Hz, 1 H), 4.26 (t, J = 7.9 Hz, 1 H), 3.55 (s, 3
H), 2.75 (s, 3 H), 2.52 (d, J = 3.3 Hz, 3 H), 1.29 (d, J = 6.3 Hz, 3
H) ppm. 31P NMR (121 MHz, CDCl3): δ = 37.6, 143.5 (sept, J =
712 Hz) ppm. HRMS calcd. for C45H38ClN3PPd 792.1527, found
792.1498. Absolute configuration was determined by X-ray crystal-
lography, crystals were grown by slow diffusion of pentane into a
solution of the complex in CDCl3.
1
sion was determined by H NMR spectroscopy of the crude reac-
tion mixture. The ee values were determined by chiral HPLC Di-
acel’s Chiralpak® OD, 1 cm ϫ25 cm; hexanes/isopropyl alcohol
(99:1), 0.2 mLmin–1; 25 °C; 254 nm; RT 46.2 min (R), 49.1 min (S).
Absolute configuration was assigned by comparison of the optical
rotation of enantio-enriched product with the literature data.[21]
Supporting Information (see also the footnote on the first page of
1
this article): Relevant H, 13C, NMR spectra for compounds 5b–d,
6, 21–22, and spectra relating to the NMR studies of allylic alkyl-
ation.
[1] B. M. Trost, Proc. Natl. Acad. Sci. USA 2004, 101, 5348–5355.
[2] A. Miyashita, A. Yasuda, H. Takaya, K. Toriumi, T. Ito, T.
Souchi, R. Noyori, J. Am. Chem. Soc. 1980, 102, 7932–7934.
[3] a) I. Ojima, Catalytic Asymmetric Synthesis, 2nd ed.; VCH:
Weinheim, 2000; b) R. Noyori, Asymmetric Catalysis in Or-
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Rosini, L. Franzini, A. Raffaelli, P. Salvadori, Synthesis 1992,
503–517.
[4] a) M. McCarthy, P. J. Guiry, Tetrahedron 2001, 57, 3809–3844;
b) P. J. Guiry, M. McCarthy, P. M. Lacey, C. P. Saunders, S.
Kelly, D. J. Connolly, Curr. Org. Chem. 2000, 4, 835–850; c) Y.-
M. Li, F.-Y. Kwong, W.-Y. Yu, A. S. C. Chan, Coord. Chem.
Rev. 2007, 251, 2119–2144.
Decomplexation: The (Sa,R)-palladium complex (30 mg,
0.03 mmol) was dissolved in dichloromethane (2 mL) and to this
was added 1,2-bis(diphenylphosphane)ethane (11 mg, 0.03 mmol)
and the resulting solution was stirred for 3 h at room temperature.
Solvent was removed in vacuo and the resulting solid was purified
by column chromatography (silica gel, CH2Cl2) to give (Sa)-7-
chloro-4-[2-(diphenylphosphanyl)naphthalen-1-yl]-2-methylquinaz-
oline as a white solid (95%). [α]2D0 = –61 (c = 1, CHCl3). Identical
physical data to a previously prepared racemic sample.
[5] C. P. Saunders, P. J. Guiry, Adv. Synth. Catal. 2004, 346, 497–
537.
[6] a) N. W. Alcock, J. M. Brown, D. I. Hulmes, Tetrahedron:
Asymmetry 1993, 4, 743–756; b) H. Doucet, E. Fernandez, T. P.
Layzell, J. M. Brown, Chem. Eur. J. 1999, 5, 1320–1330; c) J. M.
Brown, D. I. Hulmes, P. J. Guiry, Tetrahedron 1994, 50, 4493–
4506; d) C. Chen, X. Li, S. L. Schreiber, J. Am. Chem. Soc.
2003, 125, 10174–10175; e) N. Gommermann, C. Koradin, P.
Knochel, Angew. Chem. Int. Ed. 2003, 42, 5763–5944.
[7] a) M. McCarthy, R. Goddard, P. J. Guiry, Tetrahedron: Asym-
metry 1999, 10, 2797–2807; b) P. M. Lacey, C. McDonnell, P. J.
Guiry, Tetrahedron Lett. 2000, 41, 2457–2478; c) D. J. Con-
nolly, P. M. Lacey, M. McCarthy, C. P. Saunders, A. M. Car-
roll, R. Goddard, P. J. Guiry, J. Org. Chem. 2004, 69, 6572–
6589; d) S. P. Flanagan, R. Goddard, P. J. Guiry, Tetrahedron
2005, 61, 9808–9821; e) T. Fekner, H. Müller-Bunz, P. J. Guiry,
Org. Lett. 2006, 8, 5109–5112; f) A. C. Maxwell, C. Franc, L.
Pouchain, H. Müller-Bunz, P. J. Guiry, Org. Biomol. Chem.
2008, 6, 3848–3853; g) T. Fekner, H. Müller-Bunz, P. J. Guiry,
Eur. J. Org. Chem. 2008, 5055–5066; h) M. McCarthy, M. W.
Hooper, P. J. Guiry, Chem. Commun. 2000, 1333–1334; i) A. C.
Maxwell, S. P. Flanagan, R. Goddard, P. J. Guiry, Tetrahedron:
Asymmetry 2010, 21, 1458–1473.
Asymmetric Hydroboration Procedure: The required Quinazolinap-
rhodium(1,5-cyclooctadiene)trifluoromethanesulfonate catalyst (5
µmol) in THF (2 mL) was placed under nitrogen in a Schlenk tube.
Freshly distilled catecholborane (53 µL, 0.5 mmol) was added via
microlitre syringe and the light brown solution was allowed to stir
for five minutes at the required temperature. The substrate olefin
(0.5 mmol) was injected and the reaction mixture was stirred for
either two hours or twenty-four hours at room temperature or at
0 °C. The reaction was then cooled to 0 °C; ethanol (1 mL) was
added; followed by 1  NaOH (3 mL) and H2O2 (3 mL). The ice
bath was removed and the solution was stirred for one h at room
temperature. The reaction mixture was transferred to a separatory
funnel and diethyl ether (10 mL) was added. The organic layer was
washed with 1  NaOH (10 mL), brine (10 mL) and dried with
MgSO4. The solution was filtered and the solvent was removed in
vacuo to give the hydroborated product as an oil. Conversion and
[8] a) T. F. Knöpfel, P. Aschwanden, T. Ichikawa, T. Watanabe,
E. M. Carreira, Angew. Chem. Int. Ed. 2004, 43, 5971–5973; b)
F. Y. Kwong, Q. Yang, T. C. W. Mak, A. S. C. Chan, K. S.
Chan, J. Org. Chem. 2002, 67, 2769–2777.
[9] W. J. Fleming, H. Müller-Bunz, V. Lillo, E. Fernández, P. J.
Guiry, Org. Biomol. Chem. 2009, 7, 2520–2524.
1
regioselectivity were determined by H NMR spectroscopy. The ee
value was calculated by chiral GC or HPLC analysis as previously
reported.[7c]
Eur. J. Org. Chem. 2010, 5996–6004
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
6003

W. J. Fleming, H. Müller-Bunz, P. J. Guiry
FULL PAPER
[10] a) P. J. Guiry, A. M. Carroll, T. P. O’Sullivan, Adv. Synth. Ca-
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J. Org. Chem. 2003, 4695–4712; c) A. G. Coyne, P. J. Guiry,
[16] The endo-isomer is defined as the allyl configuration in which
the central allyl proton points in the same direction as the
naphthyl–phosphorus bond.
Modern Reduction Methods (Ed.: P. G. Andersson), I. [17] Relevant spectra can be found in the Supporting Information.
Munslow, Wiley-VCH, 2008, chapter 3, pp. 65–84; d) P. J.
[18] For selected references for mechanistic studies on Pd-catalysed
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T. J. Fullerton, T. Dietsche, J. Am. Chem. Soc. 1978, 100, 3435–
3443; b) T. Hayashi, T. Hagihara, M. Konishi, M. Kumada,
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Chem. Soc. 2001, 123, 6508–6510; f) J. M. Canal, M. Gómez,
F. Jiménez, M. Rocamora, G. Muller, E. Duñach, D. Franco,
A. Jiménez, F. H. Cano, Organometallics 2000, 19, 966–978; g)
P. R. Auburn, P. B. MacKenzie, B. Bosnich, J. Am. Chem. Soc.
1985, 107, 2033–2046; h) P. S. Pregosin, R. Salzmann, Coord.
Chem. Rev. 1996, 155, 35–68; i) A. Togni, U. Burckhardt, V.
Gramlich, P. S. Pregosin, R. Salzmann, J. Am. Chem. Soc.
1997, 118, 1031–1037; j) J. Sprintz, M. Kiefer, G. Helmchen,
M. Reggelin, G. Huttner, O. Walter, L. Zsolnai, Tetrahedron
Lett. 1994, 35, 1523–1526; k) C. P. Butts, E. Filali, G. C. Lloyd-
Jones, P.-O. Norrby, D. A. Sale, Y. Schramm, J. Am. Chem.
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Guiry, ChemCatChem 2009, 1, 233–235.
[11] D. Cai, J. F. Payack, D. R. Bender, D. L. Hughes, T. R. Verho-
even, P. J. Reider, J. Org. Chem. 1994, 59, 7180.
[12] Trace quantities (Ͻ 3% by 31P NMR spectroscopy) of the bis-
phospanylated product were observed.
[13] Crystal data and structure refinement for (Sa,R)-24: empirical
formula C91H78N6F12P4Cl4Pd2, formula weight 1962.07, T =
100(2) K, crystal system: triclinic, space group P1(#1), unit
cell dimensions: a = 9.4963(7) Å, α = 103.099(2)°, b =
15.2678(11) Å,
β = 94.973(2)°, c = 15.3460(11) Å, γ =
99.163(2)°, volume 2121.9(3) Å3, Z = 1, density (calcd.): 1.535
Mg/m3, reflections collected: 43701, independent reflections:
20950 [R(int) = 0.0338]. CCDC-745826 contains the supple-
mentary crystallographic data for this paper. These data can be
obtained free of charge from: The Cambridge Crystallographic
Data Centre via www.ccdc.cam.ac.uk/data_request/cif.
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Received: June 2, 2010
[15] For optimisation studies see Supporting Information.
Published Online: September 14, 2010
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