trans-2,5-Dialkylpyrrolidinyl-containing phosphinamines. Synthetic and mechanistic studies in Pd-catalysed asymmetric allylic alkylation

Article abstract of DOI:10.1016/S0957-4166(99)00418-8

The preparation of new phosphinamine ligands possessing an enantiopure trans-2,5-dialkylpyrrolidinyl unit linked by a rigid o-phenylene bridge to a diphenylphosphine is described. Only that route forming the trans-2,5- dialkylpyrrolidine in the final step from (2-aminophenyl)diphenylphosphine proved successful. The cyclocondensation proceeded in 48% and 27% yields, respectively, for the dimethyl- and diethyl-analogues. Their palladium complexes were prepared and applied to the test of enantioselective alkylation of 1,3-diphenyl-2-propenyl acetate with dimethyl malonate in high chemical yields but with moderate enantioselectivities of up to 34% ee. ¹H NMR spectra of the η³-allyl Pd complexes of four trans-2,5- dialkylpyrrolidine-containing ligands were analysed in an attempt to explain the results obtained. In the cases of the 1,3-diphenylallyl complexes, two diastereomers were observed for all four ligands and their configurations were assigned with the aid of COSY and NOESY experiments. The catalytic results obtained are best interpreted by the reaction proceeding with nucleophilic attack on the allyl trans to the phosphorus donor atom of the major diastereomer.

Full text of DOI:10.1016/S0957-4166(99)00418-8

Pergamon
Tetrahedron: Asymmetry 10 (1999) 4157–4173
trans-2,5-Dialkylpyrrolidinyl-containing phosphinamines.
Synthetic and mechanistic studies in Pd-catalysed asymmetric
allylic alkylation
John P. Cahill, Deirdre Cunneen and Patrick J. Guiry ∗
Department of Chemistry, University College Dublin, Belfield, Dublin 4, Ireland
Received 14 September 1999; accepted 17 September 1999
Abstract
The preparation of new phosphinamine ligands possessing an enantiopure trans-2,5-dialkylpyrrolidinyl unit
linked by a rigid o-phenylene bridge to a diphenylphosphine is described. Only that route forming the trans-2,5-
dialkylpyrrolidine in the final step from (2-aminophenyl)diphenylphosphine proved successful. The cycloconden-
sation proceeded in 48% and 27% yields, respectively, for the dimethyl- and diethyl-analogues. Their palladium
complexes were prepared and applied to the test of enantioselective alkylation of 1,3-diphenyl-2-propenyl acetate
with dimethyl malonate in high chemical yields but with moderate enantioselectivities of up to 34% ee.
1H NMR spectra of the η3-allyl Pd complexes of four trans-2,5-dialkylpyrrolidine-containing ligands were
analysed in an attempt to explain the results obtained. In the cases of the 1,3-diphenylallyl complexes, two
diastereomers were observed for all four ligands and their configurations were assigned with the aid of COSY
and NOESY experiments. The catalytic results obtained are best interpreted by the reaction proceeding with
nucleophilic attack on the allyl trans to the phosphorus donor atom of the major diastereomer. © 1999 Elsevier
Science Ltd. All rights reserved.
1. Introduction
The ability of enantiopure, heterobidentate ligands to induce asymmetry by exerting a combination
of steric and electronic effects on reactions occurring within the co-ordination sphere of the transition
metal to which they are bound has led to the development of an active area of research in their design
and application in asymmetric catalysis. Of the possible mix of donor atoms the phosphinamine class
has received most attention and examples possessing different chiral elements and backbone scaffolding
have been designed and applied with success in catalytic asymmetric synthesis.1–4 The majority of
examples utilise an sp2 nitrogen and ligands possessing an sp3 nitrogen donor atom have only recently
∗
Corresponding author. E-mail: p.guiry@ucd.ie
0957-4166/99/$ - see front matter © 1999 Elsevier Science Ltd. All rights reserved.
PII: S0957-4166(99)00418-8

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been reported. Koga prepared diphenylphosphinopyrrolidines of type 1 which form five-membered
chelates but gave poor ees of 11–20% when applied to the palladium-catalysed reaction between sodium
dimethylmalonate and 1,3-diphenylpropenyl acetate.5
We have recently reported the preparation of phosphinamine ligands of type 2 and 3,6 bearing an
enantiopure trans-2,5-disubstituted pyrrolidine unit, and have described their application in iridium-
catalysed enantioselective imine reduction7 and in the palladium-catalysed asymmetric intermolecular
Heck reaction.8 Our optimum enantioselectivity in the test palladium-catalysed allylic substitution was
90% for ligand 3.9 This increased ee value, compared to those obtained with 1, can be attributed to
an increase in chelate ring size from five to six or to a more rigid backbone between the donor atoms.
Decreasing the chelate size again to five and having an o-phenylene backbone, present in the successful
DuPhos ligands of type 4,10 leads to the design of ligands 5 and 6, which would allow us to determine
whether chelate ring size or backbone rigidity was more important in the design of such ligand systems.
We now report the preparation of these new phosphinamine ligands 5–6, their application in palladium-
catalysed enantioselective allylic substitution and our mechanistic studies in this reaction using ligands
2–3 and 5–6.
2. Ligand preparation
The key step in our synthesis of phosphinamines 3 and 4 was the cyclocondensation of an amine with
enantiopure 2,5-dimethyl- or 2,5-diethyl-1,4-diol cyclic sulfate and similar, successful routes to trans-
2,5-disubstituted pyrrolidines have used appropriately substituted 1,4-dimesylates11 or 1,4-diacetates.12
We investigated a pathway in which the diphenylphosphino group was already in place prior to the
cyclocondensation, a strategy already successfully used in the synthesis of ligands of class 3 and 4.9 The
required (2-aminophenyl)diphenylphosphine 7 was prepared in 80% yield, according to the method of
Stetzer, by refluxing diphenylphosphine, 2-iodoaniline and triethylamine in acetonitrile for 34 h in the
presence of 1 mol% of tetrakis(triphenylphosphine)palladium, Scheme 1.13 Using the standard procedure
for pyrrolidine ring formation, 7 was reacted with (2S,5S)-hexanediol cyclic sulfate 8 to give (−)-
[2-((2R,5R)-2,5-dimethylpyrrolidinyl)phenyl]diphenylphosphine 5 in an optimised 43% yield.14 Each
proton associated with the pyrrolidine ring resonates at a different frequency in the 1H NMR spectrum,
implying restricted rotation about the aryl–nitrogen bond. The methyl groups at the 2,5-positions resonate
as doublets at 1.18 ppm and 0.70 ppm suggesting that the latter is shielded by ring current effects.
Similarly, that methine coupled to the methyl at 1.18 ppm appears at an unusually high field resonance
of 0.50 ppm. Using the optimised conditions for the preparation of 5, 7 was reacted with (3S,6S)-
octanediol cyclic sulfate 9 to give (−)-[2-((2R,5R)-2,5-diethylpyrrolidinyl)phenyl]diphenylphosphine 6
in 27% yield, Scheme 1. The moderate yields presumably reflect the steric congestion about the reacting
nitrogen.

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Scheme 1.
The enantioselective substitution of allylic acetates is an important asymmetric carbon–carbon bond
forming process1 catalysed by diphosphine complexes of palladium, and more recently with phosphin-
amine ligands.15 We wished to compare the enantiodifferentiating ability of ligands 5–6 with ligands 3–4
in this transformation and our results using in situ prepared palladium η3-allyl complexes are given in
Table 1.
Table 1
Application of pyrrolidine-containing ligands 3–6 to the asymmetric allylic alkylation of acetate 10a
The malonate nucleophile can be preformed as its sodium salt (NaMal) or prepared in situ by Trost’s

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procedure using N,O-bis(trimethylsilyl)acetamide (BSA) and catalytic quantities of potassium acetate.17
The highest enantioselectivity of 34% for the product malonate 11 was obtained by the malonate method
at room temperature using ligand 5 in DMF, entry 3. Other solvents tested using the same catalyst under
the same conditions gave lower ee values. The BSA method was also tested but this was found to be less
effective, giving slightly lower ee values of 28–32%, entries 5–8. When the ethyl-substituted complex 6
was tested a lower enantioselectivity of 26% was obtained compared to 34% using catalyst 5 under the
same conditions (compare entries 12 and 3). This was in contrast to the increase in enantioselectivity
observed in ligand class 3 going from the dimethyl- to the diethyl-substituted catalyst (55–90% ee,
respectively, entries 9 and 16). Varying the solvent to dichloromethane, acetonitrile and tetrahydrofuran
had an adverse effect on the ee, decreasing it to 10, 11 and 16% respectively, entries 9–11. The BSA
method was also tested for catalyst 6 and gave enantioselectivites of 18% in acetonitrile and 16%
in dichloromethane, entries 13 and 14. Even though the diethyl-substituted complex 6 contains larger
substituents at the stereogenic centres it is clear from the results that the ees obtained with it are lower.
Despite this it is worth noting that palladium complexes of our ligand system gave an ee of 34% compared
to the ees of 11–20% obtained by Koga with the related diphenylphosphinopyrrolidines 2. The groups at
the pyrrolidine stereocentres are similar in size, which suggests that rigidifying the backbone has only
a small overall effect and is thus not as important in ligand design as an increase in chelate ring size
from five to six. In related work, Widhalm has prepared ligands 12 and 13 and both ligands form a
five- and six-membered chelate, respectively.18 However, inspection of the enantioselectivities obtained
in palladium-catalysed allylic substitution reveals that they afforded 96 and 95% ee, respectively. In
this case the change in chelate ring size appears not to play as major a role as it does in our ligand
systems. Conversely, Tanner has found that the chelate size in bis-aziridines is similarly crucial in allylic
substitution as palladium complexes of ligand 14 give high yield and ee (89%, 99% ee) whilst ligand 15
gives only a 5% yield.19
3. Mechanistic studies
In an attempt to explain the stereoselectivities observed with ligands 2, 3, 5 and 6, we carried out
solution NMR studies on their cationic palladium(II) 1,3-diphenylallyl intermediates. The information
thus garnered could be useful for future rational ligand design in this area. For palladium complexes of
phosphinamine ligands the generally accepted mechanism1e of allylic alkylation involves the initial as-
sociation of a palladium(0) phosphinamine species to the olefinic fragment of racemic 1,3-diphenylprop-
2-enyl acetate 10 to give diastereomeric η2-palladium(0) species 12, which undergo oxidative addition to
give cationic palladium(II) η3-intermediates 13-endo and 13-exo, Scheme 2 [note: only two of the four
possible η2-palladium(0) species 12 are shown for clarity]. Intermediates 13 interconvert via a π–σ–π
mechanism, thus allowing racemic material the possibility to afford enantiomerically enriched product.
Carbon–carbon bond formation with soft nucleophiles then occurs outside the coordination sphere to
afford, after olefin dissociation from 14, the allylated product as either the (R)-11 or (S)-11 enantiomer.

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Scheme 2.
A considerable effort has been made to understand this critical enantiodifferentiating carbon–carbon
bond forming step from the initial investigations of Bosnich20 employing diphosphine ligands to the more
recent work of Brown, Pfaltz, Togni and Helmchen employing phosphinamine ligands.21–24 The key
findings from the latter studies suggest that the ground state of complex 13 contains an allyl which has
reoriented itself into a product-like geometry, thus facilitating nucleophilic attack on that allyl terminal
carbon trans to the phosphorus donor atom. The labilty of the diastereomeric 1,3-diphenylallyl complexes
is influenced by such electronic factors and also by intra-complex steric clashes between the ligand and
the allyl. Solution NMR studies on these key intermediates would allow us to determine the ratio of endo-
to exo-diastereomers and to gain some insight as to the influence of the alkyl groups at the stereogenic
centres of the pyrrolidine. [Nomenclature note: the endo-isomer is defined as that allyl configuration in
which the central allyl proton points in the same direction as the C-20 substituent; see Fig. 2a.] In the
present study it would allow a direct comparison between the solution behaviour of the 1,3-diphenylallyl
complexes of our four trans-2,5-dialkylpyrrolidinyl-containing phosphinamine ligands.
3.1. Solution NMR studies of palladium 1,3-diphenylallyl complexes of 2 and 3
Hence we prepared the η3-1,3-diphenylallyl palladium tetrafluoroborate salt 15 in 96% yield follo-
wing literature precedent by the reaction of 2 with di-µ-chloro-bis(1,3-diphenyl-π-allyl)dipalladium,
Scheme 3.25
1
In contrast to the corresponding unsubstituted π-allyl complex, which was broad,9 the H NMR of
this complex at room temperature gave sharp peaks, Fig. 1.
It can be seen that there are two diastereomeric intermediates present in a 5:2 ratio and the full
assignment is facilitated by observing the characteristic pattern (a double doublet) of that allyl proton
trans to phosphorus, and all other allyl protons are deduced from DQF–COSY experiments. In this
fashion the proton of the allyl trans to phosphorus of the major intermediate was assigned at 5.72 ppm
(J1=10.5, J2=3.0), the central proton appeared as a double doublet at 6.90 ppm (J1=10.5, J2=7.2) and the

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Scheme 3.
Figure 1. 1H NMR spectrum of the diphenylallyl complex 15
allyl proton trans to nitrogen is a doublet at 4.22 ppm with the required coupling constant of 7.2 Hz.
Using similar logic the allyl protons of the minor diastereomer occurred at 6.00, 6.53 and 5.16 ppm,
respectively. The ratio of diastereomeric intermediates was confirmed by 31P NMR spectroscopy with
resonances at 23.5 ppm (minor) and 21.2 ppm (major). Using COSY the protons of the pyrrolidine ring
of the major diastereomer could also be identified; one of the methyl groups of the pyrrolidine occurs as
a doublet (J 8.0) at 1.33 ppm and the other as a doublet (J 8.0) at 1.24 ppm but it is impossible to tell
which is Me-20 or Me-50. The benzylic protons resonate at 3.39 and 3.78 ppm. The correct assignment of
the doublet at 1.24 ppm, which leads to the correct assignment of the major diastereomer, was aided by
obtaining a 2D-NOESY spectrum. In the published X-ray structure of the palladium dichloride complex,
only Me-20 is close in space to one of the benzylic protons and therefore the peak at 1.24 ppm is assigned
to Me-20 as it is the only methyl doublet of the major diastereomer to show an NOE with the benzylic
proton at 3.39 ppm, Fig. 2a.7 The allyl proton trans to nitrogen at 4.20 ppm shows a strong cross-peak to
the allyl proton trans to phosphorus at 5.72 ppm, indicating these two protons are close together in space,
thereby verifying the syn–syn π-allyl orientation hinted at by the vicinal coupling constants obtained.
Me-50 shows a strong cross-peak to the allyl proton trans to phosphorus at 5.72 ppm and to allyl phenyl
protons which is only possible in the endo-diastereomer and thus confirms the structure of the major
diastereomer, which does not interconvert to the exo-diastereomer on the timescale of the NOE.26

J. P. Cahill et al. / Tetrahedron: Asymmetry 10 (1999) 4157–4173
4163
Figure 2. (a) Side view of X-ray structure of Pd dichloride complex of 2. (b) Important NOEs allowing assignment of the major
diastereomer
In a similar manner the trans-2,5-diethyl-substituted pyrrolidine 1,3-diphenyl allyl palladium com-
plexes 16 were prepared but with the opposite hand of ligand 3 used in catalysis, i.e. 2S,5S-3, but
the information obtained could be readily extrapolated to explain the allylic alkylation results. Thus,
a mixture of diastereomeric complexes 16-endo and 16-exo was prepared in 93% yield, Scheme 4.
Scheme 4.
The 1H NMR spectrum of this complex at room temperature was sharp and again showed that one of
the two possible diastereomeric intermediates was favoured, in this case in a 3:1 ratio. The key peaks
of both diastereomers, which were assigned using similar techniques as for complex 15, are given in
Table 2.
Table 2
1H NMR chemical shifts of allylic protons in complexes 16 in CDCl3. Peaks of the major diastereomer
are given above the minor

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There were two critical NOEs in the major diastereomer which allowed its unambiguous assignment.
Firstly between one of the benzylic protons at 3.38 ppm and an ethyl methylene proton at 1.42–1.48
ppm which specifies this methylene as CH2-60, thus allowing complete assignment of the two ethyl
substituents. The second key NOE was between the allyl proton trans to phosphorus at 6.02 ppm and an
ethyl methylene proton at 1.76–1.85 ppm, which specifies the major diastereomer as 16-endo, Fig. 3.
Figure 3.
3.2. Solution NMR studies of palladium 1,3-diphenylallyl complexes of 5 and 6
The 1,3-diphenylallyl palladium complexes 17 and 18 were prepared in an analogous manner from
ligands 5 and 6 in 86 and 87% yields, respectively.
The 1H NMR spectrum of 17 at room temperature was sharp and showed a slight preference (3:2 ratio)
for one of the two possible diastereomeric intermediates, Fig. 4.
The key peaks of both E,E-diastereomers, which were assigned using similar techniques as for
complexes 15–16, are given in Table 3. The four methyl peaks are well-separated and only one of the
peaks in the major diastereomer shows an NOE with a multiplet centred at 6.25 ppm assigned to H-3
on the aryl ring. Only Me-20 can show such an NOE and hence Me-20 and Me-50 can be distinguished.
Similarly for the minor diastereomer, Me-20 resonates at 0.78 ppm as it shows an NOE with a multiplet at
6.54 ppm due to H-3 of the minor aryl ring. One cross-peak exists between Me-50 of the minor pyrrolidine
and an allyl proton trans to phosphorus. As the two diastereomeric allyl protons trans to phosphorus
resonate at 6.02 ppm we cannot distinguish between the major and the minor allyl partners. In contrast to
complexes 15 and 16 the two species interconvert on the timescale of the NOE and specifically link the
allyl proton Ha in one diastereomer with the allyl proton Hc in the other, due to rotation about the Pd–C
bond in a σ-allyl intermediate.15a
[{(−)-[2-((2R,5R)-2,5-Diethylpyrrolidinyl)phenyl]diphenylphosphine}-[1,3-diphenyl-π-allyl]palladi-
um]tetrafluoroborate complexes 18 were obtained as a 1:1 mixture of diastereomers. The key allyl peaks
of both diastereomers, which were assigned using similar techniques as for complex 18, are given in

J. P. Cahill et al. / Tetrahedron: Asymmetry 10 (1999) 4157–4173
4165
Figure 4. 1H NMR spectrum of complex 17
Table 3
1H NMR chemical shifts of allylic protons in complexes 17 in CDCl3. Peaks of the major diastereomer
are given above the minor
Table 4. The complete assignment of the protons in the pyrrolidine ring of either diastereomers was
not possible due to the occurrence of a series of complicated multiplets in the aliphatic region from
0.40 to 2.20 ppm. However, a number of NOEs allowed structural assignment of the two diastereomeric
intermediates. The proton trans to phosphorus in one of the diastereomers appears at 5.93 ppm and
has an NOE with a methine proton of a pyrrolidine which appears at 4.41 ppm. The methine proton is
assigned as H-20 and hence the allyl must be endo. As with complex 17 the two species diastereomers
interconvert by a similar mechanism on the timescale of the NOE.
Table 4
1H NMR chemical shifts of allylic protons in complex 18 in CDCl3

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J. P. Cahill et al. / Tetrahedron: Asymmetry 10 (1999) 4157–4173
3.3. Mechanism of allylic alkylation catalysed by Pd complexes of ligands 2–3 and 5–6
In the case of the 1,3-diphenylallyl complexes of ligands 2 and 3, the implication of the NMR studies is
that either the nucleophile attacks trans to nitrogen27 in the minor diastereomer, or trans to phosphorus in
the major diastereomer. A considerable body of evidence now exists on related phosphinamine examples
to favour the latter possibility and in addition via a late transition-state.21–24 The later the transition-state
the greater are the steric interactions between ligand and allyl, which may explain why the asymmetric
induction obtained using ligand 2 (50% ee) is lower than that obtained with 3 (90% ee), despite the ground
state diastereomer ratio being so close (5:2 vs 3:1, respectively). Non-equilibration of these diastereomers
on the NMR timescale suggests that the rate of nucleophilic attack is slower than the rate of diastereomer
interconversion to achieve the ees observed. Using the X-ray structure of the palladium dichloride of 2 as
our basis, a model for the reaction transition-state can be envisaged in which attack trans to phosphorus
of the minor diastereomer engenders unwanted steric interactions between Me-50 and the phenyl group
of the diphenylallyl moiety as it rolls into a product-like geometry (Fig. 5a). Attack trans to phosphorus
of the major diastereomer is not as sterically disfavoured, thus leading to the preferred (R)-enantiomer of
11 (Fig. 5b). The larger bulk of the 2,5-diethylpyrrolidine unit increases the difference in energy between
the transition states, leading to an improved ee.
Figure 5. Model of: (a) the disfavoured diastereomer; and (b) the favoured diastereomer at a late transition-state for nucleophilic
attack trans to phosphorus
In the case of the 1,3-diphenylallyl complexes of ligands 5 and 6, there is little ground state discrimina-
tion between the diastereomeric allyls but, in the one case where unambiguous assignment can be made,
the favoured enantiomer can again arise from attack trans to phosphorus of the predominant diastereomer.
By virtue of having a five-membered chelate rather than a six-membered one as in the case of 2 and 3, the
pyrrolidine ring is pulled back from the allyl and the 2,5-dialkyl substituents play a less significant role
in intra-complex interactions. This is seen quite clearly as both complexes 17 and 18 readily interconvert
on the timescale of the NOE and in addition the ees are considerably lowered compared to ligands 2 and
3.
The lessons for future ligand design are clear: a six-membered chelate is preferred and bulkier
substituents than methyl and ethyl are necessary to give improved ees.
In conclusion, we have prepared new diphenylphosphinopyrrolidine ligands 4 and 5 and applied
their palladium complexes in the test allylic alkylation with high chemical yields but moderate
enantioselectivities.28 Higher ees are obtained using palladium complexes of ligands 5 and 6. Solution
NMR studies were useful in attempting to understand the catalytic results obtained. Further work will be
disclosed on related mechanistic studies in this area employing molecular modelling.29

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4. Experimental
4.1. General
NMR spectra were recorded on a Jeol 270 MHz or a Varian Unity 500 MHz spectrometer. 1H chemical
shifts are reported in δ ppm relative to CHCl3 (7.27 ppm), 13C chemical shifts are reported relative to
the central peak of CDCl3 (77.0 ppm), and 31P chemical shifts are reported relative to 85% aqueous
phosphoric acid (0.0 ppm). Elemental microanalyses were carried out in-house using a Carlo Erba
1106 elemental analyser. Electron impact mass spectra were determined on a VG Analytical 770 mass
spectrometer with attached INCOS 2400 data system in the EI mode unless otherwise stated. Electrospray
mass spectra were recorded on a VG (Micromass) Quattro with electrospray probe. IR spectra were
recorded on a Perkin–Elmer Paragon 1000 FT spectrometer. Optical rotations were recorded on a
Perkin–Elmer 241 polarimeter. Melting points were recorded on a Gallenkamp melting point apparatus
and are uncorrected.
Solvents were dried immediately before use by distillation from standard drying agents and sub-
jected to degassing by three freeze–thaw cycles at 0.1 mmHg. Tetrakis(triphenylphosphine)palladium,
diphenylphosphine, 2-iodoaniline, sodium hydride (60% disp. in mineral oil), silver tetrafluoroborate, di-
methyl malonate, tris[3-(heptafluoropropylhydroxymethylene)-(+)-camphorato]europium(III) and N,O-
bis(trimethylsilyl)acetamide (BSA) were commercially available (Aldrich Chemical Co.) and were
used as purchased. n-Butyllithium was used as a 1.6 M solution in hexane. (2S,5S)-Hexanediol cy-
clic sulfate and (3S,6S)-octanediol cyclic sulfate were purchased from Strem Chemicals. (E)-1,3-
Diphenylprop-2-enyl acetate,20 di-µ-chloro-bis(π-allyl)dipalladium30 and di-µ-chloro-bis(1,3-diphenyl-
π-allyl)dipalladium31 were prepared according to literature procedures. PdCl2 were obtained on loan
from Johnson–Matthey plc. Separations by column chromatography was performed using Merck Kiesel-
gel 60 (Art. 7734) and Merck aluminium oxide 90 (Art 1097).
4.2. (−)-[2-((2R,5R)-2,5-Dimethylpyrrolidinyl)phenyl]diphenylphosphine 4
(2-Aminophenyl)diphenylphosphine (0.34 g, 1.22 mmol) and (2S,5S)-hexanediol cyclic sulfate (0.22
g, 1.22 mmol) were placed in a Schlenk tube. To this mixture, tetrahydrofuran (3.0 ml) was added and the
reaction was refluxed for 48 h. A white precipitate formed and the reaction was cooled to 0°C. Sodium
hydride (54 mg, 1.34 mmol) was added slowly to the reaction which was allowed to warm slowly to
room temperature, stirred for 2 h and refluxed again for 24 h. The reaction mixture was transferred
to a round-bottom flask and the solvent removed in vacuo to yield a brown oil. The oil was dissolved
in ether (20 ml) and washed successively with a 10% ammonium chloride solution (20 ml), water (20
ml), and brine (15 ml). The organic layer was dried with anhydrous sodium sulfate and the solvent
was removed under reduced pressure. Purification by column chromatography (silica) afforded (−)-[2-
((2R,5R)-2,5-dimethylpyrrolidinyl)phenyl]diphenylphosphine (185 mg, 43%) as a colourless oil which
23
solidified overnight, m.p. 46–47°C; [α]D −60.4 (c 1, chloroform); (found C, 80.30; H, 7.29; N, 3.87;
P, 8.63. C24H26NP requires C, 80.22; H, 7.24; N, 3.90; P, 8.64%); νmax (Nujol)/cm−1 2922 (Ar-H), 1463
(P-Ar) and 1242 (N-Ar); δH (270 MHz, CDCl3) 0.50 (d, 3H, J 5.9, Me-50), 0.70 (d, 3H, J 5.9, Me-20),
1.06–1.24 (m, 1H, H-4a0), 1.25–1.41 (m, 1H, H-3b0), 1.76–1.93 (m, 1H, H-3a0), 1.95–2.12 (m, 1H, H-
4b0), 3.51–3.66 (m, 1H, H-20), 4.24–4.46 (m, 1H, H-50), 6.69–6.74 (m, 1H, H-3), 6.77–6.82 (m, 1H,
H-5), 6.89–6.93 (m, 1H, H-6), 7.12–7.19 (m, 6H, H-200, H-400, H-600) and 7.22–7.25 (m, 5H, H-4, H-300,
H-500); δC (67.8 MHz, CDCl3) 18.74 (Me-5), 18.93 (Me-2), 30.14 (C-40), 32.30 (C-30), 53.06 (C-20),
56.53 (C-50), 122.37 (C-3), 123.03 (C-5), 128.04 (d, JP-C 7.6, C-300), 128.43 (d, JP-C 6.4, C-500), 128.83

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(C-400), 133.81 (d, JP-C 19.3, C-6), 133.98 (d, JP-C 15.0, C-200), 134.06 (C-4), 134.28 (d, JP-C 15.0, C-600),
134.69, 137.84 (d, JP-C 12.9, C-100), 137.92 (d, JP-C 10.7, C-1) and 150.62 (d, JP-C 19.3, C-2); δP (109.3
MHz, CDCl3) −9.6; m/z (EIMS, 70 eV) 359 (M+, 68%), 316 (94), 282 (49), 172 (100), 158 (71) and 118
(42).
4.3. (−)-[2-((2R,5R)-2,5-Diethylpyrrolidinyl)phenyl]diphenylphosphine 5
(2-Aminophenyl)diphenylphosphine (0.25 g, 0.90 mmol) and (3S,6S)-octanediol cyclic sulfate (0.19
g, 0.90 mmol) were placed in a Schlenk tube. To this mixture, tetrahydrofuran (2.0 ml) was added and the
reaction was refluxed for 48 h. A white precipitate formed and the reaction was cooled to 0°C. Sodium
hydride (40 mg, 0.99 mmol) was added slowly to the reaction which was allowed to warm slowly to
room temperature, stirred for 2 h and refluxed again for 24 h. The reaction mixture was transferred
to a round-bottom flask and the solvent removed under reduced pressure to yield a brown oil. The oil
was dissolved in ether (20 ml) and washed successively with a 10% ammonium chloride solution (20
ml), water (20 ml), and brine (15 ml). The organic layer was dried with anhydrous sodium sulfate and
the solvent was removed in vacuo. Purification by column chromatography afforded (−)-[2-((2R,5R)-
2,5-diethylpyrrolidinyl)phenyl]diphenylphosphine (150 mg, 27%) as a colourless oil which solidified
23
overnight, m.p. 45–46°C; [α]D −48.9 (c 1, chloroform); (found C, 80.68; H, 7.81; N, 3.61. C26H30NP
requires C, 80.62; H, 7.75; N, 3.62%); νmax (Nujol)/cm−1 2925 (Ar-H), 1461 (P-Ar) and 1238 (N-Ar);
δH (270 MHz, CDCl3) 0.50 (t, 3H, J 7.3, Me-70), 0.67–0.73 (m, 2H, H-60), 0.93–1.11 (m, 2H, H-80), 1.21
(t, 3H, J 7.1, Me-90), 1.31–1.47 (m, 2H, H-4a0, H-3b0), 1.97–2.06 (m, 2H, H-4b0, H-3a0), 3.54–3.61 (m,
1H, H-20), 3.96–4.03 (m, 1H, H-50), 6.77–6.82 (m, 2H, H-3), 6.94–6.98 (m, 1H, H-6), 7.12–7.21 (m, 6H,
H-200, H-400, H-600) and 7.23–7.31 (m, 5H, H-4, H-300, H-500); δC (67.8 MHz, CDCl3) 10.72 (Me-70),
14.84 (C-60), 17.53 (C-80), 18.24 (Me-90), 26.94 (C-40), 31.37 (C-30), 52.46 (C-50), 57.64 (C-20), 121.87
(C-3), 122.79 (C-5), 128.54 (d, JP-C 7.7, C-300), 128.65 (d, JP-C 6.6, C-500), 128.82 (C-400), 133.57 (d,
JP-C 19.4, C-6), 134.17 (d, JP-C 14.8, C-200), 134.21 (C-4), 134.36 (d, JP-C 14.8, C-600), 134.87, 137.26
(d, JP-C 13.1, C-100), 137.81 (d, JP-C 10.7, C-1) and 151.02 (d, JP-C 19.3, C-2); δP (109.3 MHz, CDCl3)
−9.5; m/z (EIMS, 70 eV) 387 (M+, 20%), 358 (100), 277 (24), 172 (154), and 57 (53).
4.4. Allylic alkylation procedures
4.4.1. Malonate ion procedure
Sodium dimethyl malonate (0.042 g, 0.275 mmol) was placed in a dry Schlenk which had previously
been flushed with nitrogen and dry degassed acetonitrile (0.3 ml) was added to form a white suspension.
To this was added a solution of in situ prepared catalyst [di-µ-chloro-bis(π-allyl)dipalladium (0.0025
mmol) and diphenylphosphinopyrrolidine (0.005 mmol)] and (E)-1,3-diphenylprop-2-enyl acetate (0.063
g, 0.250 mmol) in dry degassed acetonitrile (0.1 ml) to form a pale orange suspension. Reaction progress
was monitored by TLC (petroleum ether 40–60°C:diethyl ether, 2:1, as the eluent). After stirring under
nitrogen at room temperature for 2 days, acetic acid (0.1 ml) was added and the solvent was removed in
vacuo. Water (25 ml) was added and the reaction was extracted into diethyl ether (25 ml), then washed
with water (25 ml) and brine (25 ml). The solution was dried with MgSO4, filtered and the solvent
removed in vacuo to give an an orange oil. This was purified on silica gel plates (eluent=petroleum
ether 40–60°C:diethyl ether, 2:1) to afford the product, (R)-methyl-2-carbomethoxy-3,5-diphenylpent-4-
enoate as a colourless oil, Rf=0.37; νmax (Nujol)/cm−1 1733 (C_O) and 1600 (C_C); δH (500 MHz,
CDCl3) 3.51 (s, 3H, -OMe), 3.70 (3H, s, -OMe), 3.95 (1H, d, J 11.2, CH(CO2Me)2), 4.26 (1H, dd, J 8.8,

J. P. Cahill et al. / Tetrahedron: Asymmetry 10 (1999) 4157–4173
4169
J 11, H-1), 6.33 (1H, dd, J 8.8, 5.6, H-2), 6.47 (1H, d, J 15.6, H-3) and 7.33–7.18 (10H, m, Ph); m/z
(EIMS, 70 eV) 324 (M+, 5%), 193 (20), 105 (100) and 91 (27).
4.4.2. BSA procedure
A solution of catalyst [di-µ-chloro-bis(π-allyl)dipalladium (0.0025 mmol) and diphenylphosphi-
nopyrrolidine (0.005 mmol)] in dry degassed acetonitrile (0.5 ml) was added to potassium ace-
tate (0.005 mmol), under a nitrogen atmosphere, to form a suspension. To this suspension was
then added 1,3-diphenylprop-2-enyl acetate (0.025 mmol), dimethylmalonate (0.275 mmol), and N,O-
bis(trimethylsilyl)acetamide (BSA) (0.275 mmol) by syringe. The yellow suspension was allowed to stir
under nitrogen at ambient temperature and the reaction rate was monitored by TLC and the reaction
mixture was purified as for the malonate ion procedure.
4.4.3. Determination of enantiomeric excess
1
The ee was found by H NMR spectroscopy from the spectrum obtained after adding 20–30 µl of a
0.2 M solution of tris[3-(heptafluoropropylhydroxymethylene)-(+)-camphorato]europium(III) to 10–15
mg of methyl-2-carbomethoxy-3,5-diphenylpent-4-enoate in CDCl3 (0.5 ml). The methoxy groups of
methyl-2-carbomethoxy-3,5-diphenylpent-4-enoate resonate at 3.51 ppm and 3.70 ppm. Following the
addition of the chiral shift reagent and subsequent formation of diastereomers four methoxy peaks are
1
present in the H spectrum. The methoxy peak originally at 3.70 ppm is changed to two peaks at 3.74
ppm and 3.76 ppm and the relative integration of these peaks gives the ee value. If the right-hand peak of
these two is larger then this is typical of the (S)-enantiomer in excess, which was confirmed by comparing
the specific rotation obtained with literature values.
4.5. [{(−)-{2-[((20R,50R)-2,5-Dimethylpyrrolidinyl)methyl]phenyl}diphenylphosphine}-[1,3-diphenyl-
π-allyl] palladium]tetrafluoroborate 15
Di-µ-chloro-bis(1,3-diphenyl-π-allyl)dipalladium (0.067 g, 0.100 mmol), (−)-{2-[((20R,50R)-
2,5-dimethylpyrrolidinyl)methyl]phenyl}diphenylphosphine (0.075 g, 0.20 mmol) and silver
tetrafluoroborate (0.078 g, 0.400 mmol) were placed in a Schlenk under nitrogen. Dried and
degassed dichloromethane (3.0 ml) was added via syringe to give an orange suspension which
was stirred for 16 h. The suspension was filtered, the solvent removed in vacuo and diethyl
ether added to precipitate a yellow solid. This solid was filtered and dried to give [{(−)-{2-
[((20R,50R)-2,5-dimethylpyrrolidinyl)methyl]phenyl}diphenylphosphine}-[1,3-diphenyl-π-allyl]palladi-
23
um]tetrafluoroborate, (0.146 g, 96%), as a mixture of two diastereomers, m.p. 115°C (dec.); [α]D
−57.4 (c 1, chloroform); (found: C, 63.47; H, 5.46; N, 2.02. C40H41NPPdBF4 requires C, 63.40; H,
5.41; N, 1.84%); νmax (KBr) 2965 (HC aliph.), 1436 (P-Ph), 1060 (B-F) cm−1; δH (500 MHz, CDCl3)
major diastereomer 1.02–1.06 (m, 2H,0H-3b , H-4a ), 1.24 (d, 3H, J 8.0, Me-20), 1.33 (d, 3H, J 8.0,
0
0
Me-50), 1.75–1.81 (m, 2H, H-3a , H-4b ), 2.95–3.03 (m, 1H, H-50), 3.05–3.13 (m, 1H, H-20), 3.26 (dd,
0
1H, J 13.2, 0.8, benzylic-Ha), 3.72 (dd, 1H, J 13.2, 3.8, benzylic-Hb), 4.22 (d, 1H, J 7.2, allyl trans-N),
5.72 (dd, 1H, J 10.5, JP-H 3.0, allyl trans-P), 6.90 (dd, 1H, J 10.5, J 7.2, central allyl H) and 6.68–7.82
(m, 24H, Ar-H), minor diastereomer 1.06 (d, 3H, J 6.05, Me-20), 1.43 (d, 3H, J 6.5, Me-50), 1.86–1.92
0
0
0
(m, 2H, H-3b , H-4a ), 2.26–2.34 (m, 2H, H-3a , H-4b ) 3.31–3.38 (m, 1H, H-50), 3.39 (dd, 1H, J 13.3,
0.7, benzylic-Ha), 3.42–3.51 (m, 1H, H-20), 3.78 (dd, 1H, J 13.3, 4.0, benzylic-Hb), 5.16 (d, 1H, J 6.5,
allyl trans-N), 6.00 (dd, 1H, J 10.0, JP-H 3.0, allyl trans-P), 6.53 (dd, 1H, J 7.0, J 4.5, central allyl
H) and 6.68–7.82 (m, 24H, Ar-H); δC (67.8 MHz, CDCl3) major diastereomer 16.12 (Me-20), 24.25
(Me-50), 29.58 (C-30), 30.22 (C-40), 56.05 (d, JP-C 12.9, benzylic-C), 62.17 (C-20), 63.20 (C-50), 72.14

4170
J. P. Cahill et al. / Tetrahedron: Asymmetry 10 (1999) 4157–4173
(d, JP-C 6.5, allyl trans-N), 103.73 (d, JP-C 22.6, allyl trans-P) 110.34 (d, JP-C 5.3, central allyl), minor
diastereomer 17.77 (Me-20), 23.10 (Me-50), 28.63 (C-30), 29.11 (C-40), 52.76 (d, JP-C 12.8, benzylic-C),
61.38 (C-20), 63.65 (C-50), 70.87 (d, JP-C 6.5, allyl trans-N), 101.26 (d, JP-C 22.5, allyl trans-P), 110.17
(d, JP-C 5.3, central allyl), major and minor diastereomers (Ar-C) 126.37, 127.10, 127.37, 127.40,
127.73, 127.78, 128.00, 128.54, 128.87, 128.90, 129.30, 129.46, 129.51, 129.55, 129.64, 129.69, 129.84,
129.93, 130.01, 130.19, 130.20, 131.23, 131.47, 131.72, 132.10, 132.84, 133.27, 133.60, 133.73, 134.63,
134.82, 135.01, 135.10, 135.15, 135.36, 136.29, 136.32, 138.57 and 138.81; δP (109.3 MHz, CDCl3)
minor diastereomer 23.5 and major diastereomer 21.2; m/z (ESI/pos in CH3OH) cation 672 (100%,
M−BF4).
4.6. [{(−)-{2-[((20S,50S)-2,5-Diethylpyrrolidinyl)methyl]phenyl}diphenylphosphine}-[1,3-diphenyl-p-
allyl]palladium]tetrafluoroborate 16
Di-µ-chloro-bis(1,3-diphenyl-π-allyl)dipalladium (0.034 g, 0.050 mmol), (−)-{2-[((20S,50S)-
2,5-diethylpyrrolidinyl)methyl]phenyl}diphenylphosphine (0.040 g, 0.100 mmol) and silver
tetrafluoroborate (0.039 g, 0.200 mmol) were placed in a Schlenk under nitrogen. Dried and
degassed dichloromethane (1.8 ml) was added to afford a yellow/orange suspension which was stirred
for 16 h. The silver chloride which formed was removed by filtration. The solution was concentrated
in vacuo and diethyl ether added to afford a yellow/orange solid which was filtered and dried to give
[{(−)-{2-[((20S,50S)-2,5-diethylpyrrolidinyl)methyl]phenyl}diphenylphosphine}-[1,3-diphenyl-π-allyl]-
23
palladium]tetrafluoroborate (0.075 g, 93%) as a mixture of two diastereomers, m.p. 113°C (dec.); [α]D
−74.8 (c 0.5, chloroform); (found: C, 64.82; H, 5.66; N, 1.69. C42H45NPPdBF4 requires C, 64.04;
H, 5.72; N, 1.78%); νmax (KBr) 2939 (HC aliph.), 1448 (P-Ph) and 1057 (B-F) cm−1; δH (500 MHz,
CDCl3) major diastereomer 0.71 (t, 3H, J 7.3, Me-90), 0.89 (t, 3H, J 7.3, Me-70), 1.28–1.34 (m, 2H,
0
0
0
0
0
0
H-3b , H-4a ), 1.36–1.410 (m, 1H, H-6b ), 1.42–1.48 (m, 1H, H-6a ), 1.62–1.69 (m, 2H, H-3a , H-4b ),
0
1.76–1.85 (m, 1H, H-8b ), 1.91–2.00 (m, 1H, H-8a ), 2.79–2.84 (m, 1H, H-20), 2.97–3.01 (m, 1H, H-50),
3.38 (dd, 1H, J 12.7, 3.4, benzylic-Hb), 3.72 (d, 1H, J 12.7, benzylic-Ha), 4.19 (d, 1H, J 11.2, allyl
trans-N), 6.02 (dd, 1H, J 13.7, JP-H 4.4, allyl trans-P), 6.78–6.82 (m, 1H, central allyl H), 6.67–7.78
(m, 24H, Ar-0H), minor diastereomer 0.55 (t, 3H, J 7.3, Me-90), 0.68 (t, 3H, J 7.3, Me-70), 1.08–1.15
0
0
0
0
(m, 1H, H-6b ), 0.82–0.086 (m, 1H, H-6a ), 1.16–1.22 (m, 2H, H-3a , H-4b ), 1.38–1.44 (m, 1H, H-8a ),
1.42–1.48 (m, 1H, H-8b ), 1.61–1.66 (m, 2H, H-3b , H-4a ), 2.52–2.58 (m, 1H, H-20), 2.63–2.66 (m, 1H,
H-50), 3.46 (dd, 1H, J 14.2, 7.3, benzylic-Hb), 3.95 (d, 1H, J 11.2, allyl trans-N), 4.26 (dd, 1H, J 14.2,
2.6, benzylic-Ha), 6.32 (dd, 1H, J 8.8, JP-H 6.8, allyl trans-P), 6.46–6.50 (m, 1H, central allyl H) and
6.67–7.78 (m, 24H, Ar-H); δP (109.3 MHz, CDCl3) 21.1 and 22.3; m/z (ESI/pos in CH3OH) cation 700
(100%, M−BF4).
0
0
4.7. [{(−)-[2-((2R,5R)-2,5-Dimethylpyrrolidinyl)phenyl]diphenylphosphine}-[1,3-diphenyl-π-allyl]-
palladium]tetrafluoroborate 17
Di-µ-chloro-bis(1,3-diphenyl-π-allyl)dipalladium (0.037 g, 0.056 mmol), (−)-[2-((2R,5R)-2,5-
dimethyl pyrrolidinyl)phenyl]diphenylphosphine (0.040 g, 0.110 mmol) and silver tetrafluoroborate
(0.044 g, 0.220 mmol) were placed in a Schlenk under nitrogen. Dichloromethane (3.2 ml) was added via
syringe to give an orange suspension which was stirred for 16 h. The solid was removed by filtration, the
filtrate was then concentrated in vacuo and diethyl ether added to precipitate a yellow solid. The solid was
filtered and dried to afford [{(−)-[2-((2R,5R)-2,5-dimethylpyrrolidinyl)phenyl]diphenylphosphine}-[1,3-
diphenyl-π-allyl]palladium]tetrafluoroborate (0.075 g, 86%) as a mixture of two diastereomers, m.p.

J. P. Cahill et al. / Tetrahedron: Asymmetry 10 (1999) 4157–4173
4171
23
118°C (dec.); [α]D −58.3 (c 0.5, chloroform); (found: C, 62.48; H, 5.64; N, 1.89. C39H39NPPdBF4
requires C, 62.82; H, 5.23; N, 1.88%); νmax (KBr)/cm−1 2965 and 1060 (B-F); δH (500 MHz, CDCl3)
diastereomer 1: 0.78 (d, 3H, J 6.8, Me-50), 1.12–1.15 (m, 1H, H-3a0), 1.16–1.20 (m, 1H, H-4b0),
1.43–1.47 (m, 1H, H-4a0), 1.51 (d, 3H, J 6.3, Me-20), 1.55–1.58 (m, 1H, H-3b0), 3.58–3.63 (m, 1H,
H-20), 4.52–4.60 (m, 1H, H-50), 4.99 (dd, 1H, J 11.5, 13, allyl trans-N), 6.02 (dd, 1H, J 10.2, JP-H 13.4,
allyl trans-P), 6.26 (m, 1H, H-3), 6.62 (app. tr., 1H, J 13.2, central allyl H), 7.05–7.76 (m, 23H, Ar-H);
diastereomer 2: 0.50 (m, 1H, H-4b0), 1.11 (d, 3H, J 6.8, Me-50), 1.18 (d, 3H, J 6.3, Me-20), 1.67–1.70 (m,
1H, H-3a0), 1.73–1.77 (m, 1H, H-4a0), 1.78–1.82 (m, 1H, H-3b0), 3.45–3.51 (m, 1H, H-20), 3.58–3.63
(m, 1H, H-50), 5.08 (dd, 1H, J 11.2, 13.7, allyl trans-N), 6.02 (dd, 1H, J 10.2, JP-H 13.4, allyl trans-P),
6.26 (m, 1H, H-3), 6.69 (dd, 1H, J 13.7, 11.3, central allyl H), 6.89 (t, 1H, J 7.3, H-5) and 7.05–7.76 (m,
22H, Ar-H); δC (67.8 MHz, CDCl3) diastereomer 1: 18.07 (Me-50), 21.61 (Me-20), 31.36 (C-40), 35.26
(C-30), 68.17 (C-50), 69.85 (C-20), 73.02 (d, JP-C 6.6, allyl trans-N), 105.27 (d, JP-C 22.5, allyl trans-P),
111.31 (d, JP-C 5.4, central allyl); diastereomer 2: 18.05 (Me-50), 21.86 (Me-20), 31.18 (C-40), 34.07
(C-30), 63.62 (C-20), 65.28 (C-50), 71.56 (d, JP-C 6.6, allyl trans-N), 103.46 (d, JP-C 22.5, allyl trans-P),
111.31 (d, JP-C 5.4, central allyl); diastereomer 1 and diastereomer 2: (Ar-C) 126.38, 126.93, 126.97,
127.35, 127.84, 128.64, 128.71, 128.90, 129.06, 129.13, 129.22, 129.65, 129.68, 129.82, 129.87, 130.42,
130.83, 131.50, 131.67, 131.89, 132.07, 132.18, 132.23, 133.92, 134.11, 134.31, 134.49, 134.66, 134.85,
135.07, 135.09, 135.19, 136.21, 136.47, 138.46 and 138.91; δP (109.3 MHz, CDCl3) 33.3 and 34.3; m/z
(ESI/pos in CH3OH) 669 (100%, M−BF4).
4.8. [{(−)-[2-((2R,5R)-2,5-Diethylpyrrolidinyl)phenyl]diphenylphosphine}-[1,3-diphenyl-π-allyl]-
palladium]tetrafluoroborate 18
Di-µ-chloro-bis(1,3-diphenyl-π-allyl)dipalladium (0.036 g, 0.055 mmol), (−)-[2-((2R, 5R)-2,5-diethyl
pyrrolidinyl)phenyl]diphenylphosphine (0.042 g, 0.110 mmol) and silver tetrafluoroborate (0.042 g,
0.220 mmol) were placed in a Schlenk under nitrogen. Dichloromethane (3.0 ml) was added via syringe
to give an orange suspension which was stirred for 16 h. The solid was removed by filtration, the
solvent was then reduced in vacuo and diethyl ether added to give a yellow solid. The solid was filtered
and dried to give [{(−)-[2-((2R, 5R)-2,5-diethylpyrrolidinyl)phenyl]diphenylphosphine}-[1,3-diphenyl-
π-allyl]palladium]tetrafluoroborate (0.074 g, 87%) as a mixture of two diastereomers, m.p. 114°C (dec.);
[α]D23 −44.2 (c 0.3, chloroform); (found: C, 63.52; H, 5.47; N, 1.76. C41H43NPPdBF4 requires C, 63.65;
H, 5.56; N, 1.81%); νmax (KBr)/cm−1 2965 and 1060 (B-F); δH (500 MHz, CDCl3) diastereomer 1: 0.50
(t, 2H, J 6.3, Me), 0.8–2.1 (m, 12H), 3.3–3.4 (m, 1H, H-20), 5.24 (d, 1H, J 11.2, allyl trans-N), 5.93 (dd,
1H, J 10.3, JP-H 13.7, allyl trans-P), 6.66 (dd, 1H, J 13.7, J 11.8, central allyl H) and 6.8–7.8 (m, 24H);
diastereomer 2: 1.21 (t, 3H, J 6.4, Me), 0.8–2.1 (m, 12H), 4.3–4.4 (m, 1H, H-20), 5.00 (d, 1H, J 9.8, allyl
trans-N), 6.09 (dd, 1H, J 10.8, JP-H 13.7, allyl trans-P), 6.61 (m, 1H, central allyl H) and 6.8–7.8 (m,
24H); δP (109.3 MHz, CDCl3) 33.6 and 34.5; m/z (ESI/pos in CH3OH) 697 (100%, M−BF4).16
Acknowledgements
We thank Forbairt for a Basic Research Award (SC/94/565) to support this work and a Forbairt
Research Scholarship (BR/94/158) to J.P.C. We acknowledge the Department of Chemistry for the
provision of high-field NMR facilities and Johnson–Matthey plc for the loan of PdCl2. Thanks to
Professor Per-Ola Norrby for helpful comments, and to Mr. Cormac Saunders for critical reading of
this manuscript.

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J. P. Cahill et al. / Tetrahedron: Asymmetry 10 (1999) 4157–4173
References
1. Allylic alkylation: (a) Noyori, R. In Asymmetric Catalysis in Organic Synthesis; Wiley: New York, 1994; pp. 82–85.
(b) Hayashi, T. In Catalytic Asymmetric Synthesis; Ojima, I., Ed.; VCH: Weinheim, 1993; p. 325. (c) Heumann, A. In
Transition Metals for Organic Synthesis; Beller, M.; Bolm, C., Eds.; Wiley-VCH: Weinheim, 1998; pp. 251–259. (d)
Frost, C. G.; Howarth, J.; Williams, J. M. J. Tetrahedron: Asymmetry 1992, 3, 1089. (e) Trost, B. M.; van Vranken, D. L.
Chem. Rev. 1996, 96, 395.
2. Hydrosilylations: selected papers: (a) Newman, L. M.; Williams, J. M. J.; McCague, R.; Potter, G. A. Tetrahedron:
Asymmetry 1996, 6, 1597. (b) Langer, T.; Janssen, J.; Helmchen, G. Tetrahedron: Asymmetry 1996, 6, 1599. (c) Uemura,
S.; Nishibayashi, Y.; Segawa, K.; Ohe, K. Organometallics 1995, 14, 5486.
3. Hydroborations: selected papers: (a) Brown, J. M.; Hulmes, D. I.; Layzell, T. P. J. Chem. Soc., Chem. Commun. 1993, 1673.
(b) Valk, J.-M.; Whitlock, G. A.; Layzell, T. P.; Brown, J. M. Tetrahedron: Asymmetry 1995, 6, 2593. (c) Schnyder, A.;
Hintermann, L.; Togni, A. Angew. Chem., Int. Ed. Engl. 1995, 34, 931. (d) Review: Beletskaya, I.; Pelter, A. Tetrahedron
1997, 57, 4957.
4. Hydrogenanation: [imines/olefins] (a) Pfaltz, A.; Schnider, P.; Koch, G.; Pretôt, R.; Wang, G.; Bohnen, F.; Krüger, C.
Chem. Eur. J. 1997, 3, 887. [Ketones] (b) Langer, T.; Helmchen, G. Tetrahedron Lett. 1996, 37, 1381.
5. Kubota, H.; Koga, K. Tetrahedron Lett. 1994, 35, 6689.
6. Cahill, J. P.; Bohnen, F.; Goddard, R.; Krüger, C.; Guiry, P. J. Tetrahedron: Asymmetry 1998, 9, 3831.
7. Cahill, J. P.; Lightfoot, A. P.; Goddard, R.; Rust, J.; Guiry, P. J. Tetrahedron: Asymmetry 1998, 9, 4307.
8. Guiry, P. J.; Hennessy, A. J.; Cahill, J. P. Topics in Catalysis 1997, 4, 311.
9. Cahill, J. P.; Guiry, P. J. Tetrahedron: Asymmetry 1998, 9, 4301.
10. Burk, M. J.; Bienewald, F.; Harris, M. Angew. Chem., Int. Ed. Engl. 1998, 37, 1931 and references cited therein.
11. (a) Short, R. P.; Kennedy, R. M.; Masamune, S. J. Org. Chem. 1989, 54, 1755. (b) Chong, J. M.; Clarke, I. S.; Koch, I.;
Olbach, P. C.; Taylor, N. J. Tetrahedron: Asymmetry 1995, 6, 409. (c) Sweet, J. A.; Cavallari, J. M.; Price, W. A.; Ziller, J.
W.; McGrath, D. V. Tetrahedron: Asymmetry 1997, 8, 207.
12. (a) Schwink, L.; Knochel, P.; Tetrahedron Lett. 1997, 38, 3711. (b) Woltersdorf, M.; Kranich, R.; Schmalz, H.-G.
Tetrahedron 1997, 53, 7219.
13. Herd, O.; Hebler, A.; Hingst, M.; Tepper, M.; Stelzer, O. J. Organomet. Chem. 1996, 522, 69.
14. The use of more concentrated solutions than those employed in Ref. 9 gave higher yields.
15. Selected recent phosphorous–nitrogen examples: (a) Brown, J. M.; Hulmes, D. I.; Guiry, P. J. Tetrahedron 1994, 50, 4493.
(b) Togni, A.; Bruckhardt, Gramlich, V.; Progosin, P. S.; Salzmann, R. J. Am. Chem. Soc. 1996, 118, 1031. (c) Chelucci,
G.; Cabras, M. A.; Botteghi, C.; Basoli, A.; Marchetti, M. Tetrahedron: Asymmetry 1996, 7, 885. (d) Koch, G.; Pfaltz,
A. Tetrahedron: Asymmetry 1996, 7, 2213. (e) Zhang, W.; Toshikazu, H.; Ikeda, I. Tetrahedron Lett. 1996, 37, 4545.
(f) Chelucci, G.; Medici, S.; Saba, A. Tetrahedron: Asymmetry 1997, 8, 3183. (g) Saitoh, A.; Morimoto, T.; Achiwa, K.
Tetrahedron: Asymmetry 1997, 8, 3567. (h) Imai, Y.; Zhang, W.; Kida, T.; Nakatsuji, Y.; Ikeda, I. Tetrahedron Lett. 1998,
39, 4343. (h) Ogasawara, M.; Yoshida, K.; Kamei, H.; Kato, K.; Uozumi, Y.; Hayashi, T. Tetrahedron: Asymmetry 1998,
9, 1779. (i) Saitoh, A.; Achiwa, K.; Morimoto, T. Tetrahedron: Asymmetry 1998, 9, 741. (j) Zhang, W.; Yoneda, Y.-I.;
Kida, T.; Nakatsuji, Y.; Ikeda, I. Tetrahedron: Asymmetry 1998, 9, 3371. (h) Widhalm, M.; Mereiter, K.; Bourghida, M.
Tetrahedron: Asymmetry 1998, 9, 2983.
16. von Matt, P.; Pfaltz, A. Angew. Chem., Int. Ed. Engl. 1993, 32, 566.
17. Trost, B. M.; Murphy, D. J. Organometallics 1985, 4, 1143.
18. (a) Bourghida, M.; Widhalm, M. Tetrahedron: Asymmetry 1998, 9, 1073. (b) Wimmer, P.; Widhalm, P. Tetrahedron:
Asymmetry 1995, 6, 657.
19. Tanner, D.; Harden, A.; Johansson, F.; Wyatt, P.; Andersson, P. G. Acta Chem. Scand. 1996, 50, 361.
20. (a) Auburn, P. R.; MacKenzie, P. B.; Bosnich, B. J. Am. Chem. Soc. 1985, 107, 2033; (b) MacKenzie, P. B.; Whelan, J.;
Bosnich, B. J. Am. Chem. Soc. 1985, 107, 2047.
21. Claridge, T. D. W.; Long, J. M.; Brown, J. M.; Hibbs, D.; Hursthouse, M. B. Tetrahedron 1997, 53, 4035.
22. von Matt, P.; Lloyd-Jones, G. C.; Pfaltz, A.; Macko, L.; Neuburger, M.; Zehnder, M.; Ruegger, H.; Pregosin, P. S. Helv.
Chim. Acta 1995, 78, 265.
23. Togni, A.; Bruckhardt, U.; Gramlich, V.; Pregosin, P. S.; Salzmann, R. J. Am. Chem. Soc. 1996, 118, 1031.
24. Sprinz, J.; Kiefer, M.; Helmchen, G.; Huttner, G.; Walter, O.; Zsolnai, L. Reggelin, M. Tetrahedron Lett. 1994, 35, 1523.
25. Togni, A.; Rihs, G.; Pregosin, P. S.; Ammann, C. Helv. Chim. Acta 1990, 73, 723.
26. (a) Granberg, K. L.; Backvall, J. E. J. Am. Chem. Soc. 1992, 114, 6858. (b) Gogoll, A.; Ornebro, J.; Grennberg, H.;
Backvall, J. E. J. Am. Chem. Soc. 1994, 116, 3631. (c) Breutel, C.; Pregosin, P. S.; Salzmann, R.; Togni, A. J. Am. Chem.
Soc. 1994, 116, 4067.

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27. For an example of nucleophiic attack trans to nitrogen, see: Trost, B. M.; Oslob, J. D. J. Am. Chem. Soc. 1999, 121, 3057.
28. Since the original submission of this manuscript we have noted that ligand 5 has also been prepared by the group of
Moberg, OMCOS 10 Poster Abstract No. 452; our initial work was outlined in OMCOS 8 Poster Abstract No. 54.
29. Malone, Y.; Norrby, P.-O.; Farrell, A.; Cahill, J. P.; Guiry, P. J. Unpublished results.
30. Dent, W. T.; Long, R.; Wilkinson, A. J. Am. Chem. Soc. 1964, 86, 1585.
31. Hayashi, T.; Yamamoto, A.; Ito, Y.; Nishioka, E.; Miura, H.; Yanagi, K. J. Am. Chem. Soc. 1989, 111, 6301.