Allene synthesis by an asymmetric Baylis-Hillman style reaction on vinylphosphine oxides

Article abstract of DOI:10.1039/b104436m

A novel reaction has been discovered with a mechanism similar to the Baylis-Hillman reaction. Reaction of a vinylic phosphine oxide with (R)-N-lithio-α-methylbenzylbenzylamine 2 in the presence of an aldehyde gave hydroxyphosphine oxides in good to moderate yields and moderate to poor enantioselectivities. The hydroxyphosphine oxides undergo the Horner-Wittig elimination reaction to produce allenes. Baylis-Hillman reactions of vinylic phosphine oxides with tertiary amines were also investigated.

Full text of DOI:10.1039/b104436m

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Allene synthesis by an asymmetric Baylis–Hillman style reaction
on vinylphosphine oxides
David J. Fox, Jonathan A. Medlock, Richard Vosser and Stuart Warren*
1
University Chemical Laboratory, Lensfield Road, Cambridge, UK CB2 1EW.
E-mail: sw134@cam.ac.uk
Received (in Cambridge, UK) 21st May 2001, Accepted 18th July 2001
First published as an Advance Article on the web 15th August 2001
A novel reaction has been discovered with a mechanism similar to the Baylis–Hillman reaction. Reaction of
a vinylic phosphine oxide with (R)-N-lithio-α-methylbenzylbenzylamine 2 in the presence of an aldehyde
gave hydroxyphosphine oxides in good to moderate yields and moderate to poor enantioselectivities. The
hydroxyphosphine oxides undergo the Horner–Wittig elimination reaction to produce allenes. Baylis–Hillman
reactions of vinylic phosphine oxides with tertiary amines were also investigated.
(Scheme 1), we found that the use of other internal electrophiles
resulted in Baylis–Hillman like products. Reaction of 1
(Ar = Ph) with methyl iodide gave a 76% yield of the phosphine
oxide 4 and reaction with cyclobutanone, which we have used
previously as an internal quench,11 gave a 50% yield of the
hydroxyphosphine oxide 5.
Introduction
The Baylis–Hillman reaction is a method for the α-alkylation of
an α,β-unsaturated carbonyl compound. The reaction is cat-
alysed by a nucleophilic catalyst, usually a tertiary amine; the
accepted mechanism is conjugate addition of the nucleophilic
catalyst, quenching of the enolate with an electrophile and then
elimination of the catalyst.1,2 The standard Baylis–Hillman
reaction suffers from very slow reaction rates and much recent
attention has focused on improving the rate using a wide variety
of nucleophilic catalysts and Lewis acids,3,4 high pressure5 and
microwave irradiation.6 Asymmetric Baylis–Hillman reactions
have been reported using a variety of strategies, and enantio-
meric excesses of up to 99% have been reported for the use of a
chiral catalyst.7
Reaction with a prochiral electrophile, pivalaldehyde, gave
enantiomerically enriched products, albeit with poor selectivity.
A range of aldehydes was investigated (Scheme 2, Table 1,
We have recently reported the synthesis of enantiomerically
enriched aminophosphine oxides 3 by the application of the
asymmetric conjugate addition reaction developed by Davies8
to vinylic phosphine oxides 1 (Scheme 1).9,10 The reaction
Scheme 2 Reagents and conditions: i, R2CHO, THF, Ϫ78 ЊC; ii, 2;
iii, H2O.
entries 1–5), and all the products were (E)-vinyl phosphine
oxides. An α-quaternary centre is required on the aldehyde for
any enantioselectivity to be observed. Yields were decreased for
aldehydes bearing an α-secondary centre (entry 5), presumably
due to competing deprotonation of the aldehyde by the lithium
amide. No reaction was observed with benzaldehyde (entry 6);
benzaldehyde may have been reduced by the lithium amide. No
reaction was observed with acetone or diisopropyl ketone. The
former is presumably rapidly deprotonated and the latter is
probably too hindered to react. Other vinylic phosphine oxides
were investigated (Table 1, entries 7–9). The highest enantio-
meric excess was observed for the vinylic phosphine oxide 6b
bearing a tert-butyl substituent (entry 7).
When the reaction was performed on the vinylic phosphine
oxide 6e, the hydroxyphosphine oxide 9 was isolated as a
mixture of diastereoisomers, as well as the expected product
8d (Scheme 3). This suggests that the reaction is proceeding
by an addition–elimination mechanism (Scheme 4), similar
to the Baylis–Hillman reaction, rather than by an α-lithiation
Scheme 1 Reagents and conditions: i, Me3SiCl, THF, Ϫ78 ЊC; ii, 2;
iii, H2O; iv, TBAF, THF.
proceeded only in the presence of trimethylsilyl chloride as
an internal quench. We now report a modestly asymmetric
Baylis–Hillman style reaction which has been used to synthesise
enantiomerically enriched allenes.
Results and discussion
During further investigation of the conjugate addition reaction
2240
J. Chem. Soc., Perkin Trans. 1, 2001, 2240–2249
This journal is © The Royal Society of Chemistry 2001
DOI: 10.1039/b104436m

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Table 1 Synthesis of compounds 7 and 8 from 6a–d
Entry
Starting material
R1
R2
Product
Yield (%)
Ee (%)
1
2
3
4
5
6
7
8
9
6a
6a
6a
6a
6a
6a
6b
6c
6d
Ph
Ph
Ph
Ph
Ph
Ph
tBu
iPr
Me
tBu
7a
7b
7c
7d
7e
7f
8a
8b
8c
87
55
67
62
33
0
58
53
47
28
13
23
0
1-SPhcyHexa
CMe2CH2CH᎐CH2
᎐
iPr
(CH2)6Me
Ph
0
—
51
12
11
tBu
tBu
tBu
a 1-Phenylsulfanylcyclohexyl.
6a was treated with the lithium amide 2 in the absence of an
electrophile and quenched with deuterated methanol after 30
minutes. The recovered starting material showed no deuteration
of the α-position. The analogous reaction involving the deuter-
ated vinyl phosphine oxide 10 (prepared with 80% deuterium
incorporation at the α-position in an analogous way to the
preparation14 of 6a), and quenching with methanol, showed no
loss of deuteration. Although this suggests that deprotonation
is not occurring, Seebach and co-workers have shown that the
deprotonation of carbonyl compounds with lithium amides
and quenching with D2O or deuterated alcohols do not always
result in deuteration at the α-position.15,16 Seebach achieved
deuteration by treatment of the enolate–amine complex with
n-butyllithium after deprotonation by the lithium amide and
then quenching with a deuterium source. Repeating this with the
vinylphosphine oxide 6a resulted in complete deuteration of the
α-position. Although this suggests that deprotonation may be
occurring, it is far from conclusive as deprotonation may be due
to the n-butyllithium rather than the lithium amide.
t
Scheme 3 Reagents and conditions: i, BuCHO, THF, Ϫ78 ЊC; ii, 2;
iii, H2O.
Evidence for the Baylis–Hillman style reaction also comes
from reaction of the (Z)-vinylic phosphine oxide 11. The
phosphine oxide 11 was synthesised in three steps from benz-
aldehyde (Scheme 6), using literature methods.17–19 Reaction
Scheme 4
Scheme 6 Reagents and conditions: i, PPh3, CBr4, CH2Cl2, 84%; ii,
Pd(PPh3)4, Bu3SnH, PhH, 29%; iii, Pd(PPh3)4, Et3N, Ph2P(O)H, PhMe,
90 ЊC, 77%.
of 11 under the standard reaction conditions gave the (E)-
hydroxyphosphine oxide 7a with an enantiomeric excess of 31%
in exactly the same sense as observed previously (Scheme 7). In
Scheme 5
mechanism (Scheme 5). Nagaoka and Tomioka have reported
a similar reaction of vinylic phosphonates catalysed by LDA
and suggest a Baylis–Hillman style reaction.12 Such a mechan-
ism has also been reported by Harrowven and Poon13 for the
reaction of lithium tetramethylpiperidine with diethyl maleate
and a range of ketones.
t
Scheme 7 Reagents and conditions: i, BuCHO, THF, Ϫ78 ЊC; ii, 2;
iii, H2O.
the absence of an electrophile, complete isomerisation of the
(Z)-phosphine oxide 11 to the (E)-isomer 6a is observed with
either 1 or 0.2 equivalents of the lithium amide 2. Thus, in
the reaction illustrated in Scheme 7, the (Z)-phosphine oxide 11
Mechanistic investigations
In order to determine the mechanism of formation of the
hydroxyphosphine oxides 7 and 8, the vinylic phosphine oxide
J. Chem. Soc., Perkin Trans. 1, 2001, 2240–2249
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is presumably isomerising to the (E)-isomer 6a, which sub-
sequently reacts. We believe that the results above and the
isolation of the aminophosphine oxide 9 show that this novel
reaction has an addition–elimination mechanism (Scheme 4),
that is, a Baylis–Hillman style reaction.
The Baylis–Hillman style reaction has also been performed
with the sulfonamide imine 12, producing the aminophosphine
oxide 13 in moderate yield but poor enantioselectivity (Scheme
8). Various reaction conditions were investigated to attempt
Scheme 10 Reagents and conditions: i, 16, THF, Ϫ78 ЊC; ii, 2; iii, H2O;
iv, LiOH, MeOH.
Scheme 8 Reagents and conditions: i, 12, THF, Ϫ78 ЊC; ii, 2; iii, H2O.
to improve the enantioselectivity. Use of the lithium amide
derived from the C2 symmetric amine20 14 resulted in a lower
yield (53%) of the hydroxyphosphine oxide 7a and only a 12%
enantiomeric excess. If external quench conditions were used
(addition of the aldehyde after the addition of the lithium
amide), the resulting hydroxyphosphine oxides were racemic.
Quenching the reaction at Ϫ78 ЊC gave the hydroxyphosphine
oxide 7a in 19% ee. Changing the order of addition of the
reagents had a slight effect. Addition of a solution of the
hydroxyphosphine oxide and aldehyde to the solution of
lithium amide 2 gave the hydroxyphosphine oxide 7a in 35% ee
and the hydroxyphosphine oxide 8a in 43% ee.
Scheme 11 Reagents and conditions: i, NaH, DMF, 60 ЊC.
Horner–Wittig elimination,23 we can assign the stereochemistry
of the major enantiomer of the hydroxyphosphine oxides as the
24,25
(R)-enantiomer 21. Wang and co-workers
have previously
reported the synthesis of allenes by addition of a lithiated
vinyl phosphine oxide (generated by iodide–lithium exchange)
to aldehydes and ketones and spontaneous Horner–Wittig
elimination on warming to room temperature.
Determination of the stereochemistry
Origins of the selectivity
In the above discussion, the major isomer of product has
not been indicated. Attempts were made to derivatise the
hydroxyphosphine oxides 7a and 8a with enantiomerically
pure derivatising groups without success, presumably due to
the bulky tert-butyl and diphenylphosphinoyl groups. In order
to derivatise hydroxyphosphine oxides such as 7 and 8, we
envisaged synthesising a hydroxyphosphine oxide such as 17.
The protected aldehyde 16 was synthesised in excellent yield
from the known mono-protected diol21 15 (Scheme 9). The
To account for the observed selectivity, two stereochemical
defining steps have to be considered. The first, the asymmetric
conjugate addition of the lithium amide, is accounted for by an
extension of the model proposed by Davies and co-workers,26
where the lithium amide approaches the top face of the double
bond, as drawn (Scheme 12), with the methyl group pointing
Scheme 9 Reagents and conditions: i, oxalyl chloride, DMSO, Et3N,
CH2Cl2, Ϫ78 ЊC, 98%.
Baylis–Hillman style reaction of vinylphosphine oxide 6a and
the aldehyde 16 resulted in a mixture of the two hydroxy-
phosphine oxides 18 and 19 (Scheme 10). Hydrolysis of the ester
was achieved with lithium hydroxide. The diol 17 was success-
fully derivatised with (1S)-(ϩ)-camphor-10-sulfonyl chloride,
but we were unable to separate the resulting diastereoisomers.
The absolute stereochemistry of the hydroxyphosphine
oxides was determined from the corresponding allenes 20,
synthesised via the Horner–Wittig elimination reaction of
the hydroxyphosphine oxides (Scheme 11, Table 2). The
Horner–Wittig elimination proceeds in good yield except in
the case where R1 = iPr (entry 2), due to the allene’s high vol-
atility. Comparing the specific rotation of the resulting allenes
with literature values22 and assuming the stereospecific syn
Scheme 12
2242
J. Chem. Soc., Perkin Trans. 1, 2001, 2240–2249

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Table 2 Synthesis of allenes 20 from compounds 7 and 8
Entry
R1
R2
Yield (%)
[α]D/10Ϫ1 deg dm2 gϪ1
ϩ46
ϩ5
ϩ28
Lit.22 [α]D/10Ϫ1 deg dm2 gϪ1
ϩ370
ϩ110
ϩ124
1
2
3
Ph
iPr
tBu
tBu
tBu
tBu
89
5
74
forward. We believe that the lithiated phosphine oxide 22 is the
product of the conjugate addition as lithiated phosphine oxides
have been shown to have an sp3 configuration.27,28 The aldehyde
then approaches the carbon–lithium bond of the lithiated
species 22. The oxygen atom of the aldehyde is chelated to the
lithium atom and the R group of the aldehyde can adopt one of
two possible positions 23 or 24. The R group has a steric inter-
action with one of the two phenyl rings, attached either to the
phosphine oxide or to the end of the alkyl chain. These two
groups are very similar; hence, the observed enantioselectivity is
low. The interaction between the R group and the phenyl ring
on the phosphine oxide is less than the corresponding inter-
action with the other phenyl ring because the P–C bond
between the phenyl ring and phosphorus is longer, as is the P–C
bond between the reacting centre and phosphorus. This sug-
gests that conformation 23 is preferred, leading to the (R)-
enantiomer. This explanation is consistent with the observ-
ation that when the phenyl group on the alkyl chain is replaced
with a tert-butyl group, the selectivity increases (Table 1, entries
1 and 7).
Fig. 1 Graph showing integration of the α-proton of 6e against time.
Baylis–Hillman reactions
A similar route to racemic hydroxyphosphine oxides such as 7
and 8 would be to perform a Baylis–Hillman reaction, using a
tertiary amine, on vinylic phosphine oxides. Baylis–Hillman
reactions of vinyl diethylphosphonate have been reported by
Villiéras and co-workers, although reaction times are 7–29
days.29 We started our investigation with vinyldiphenylphos-
phine oxide 6e, butanal and a range of nucleophilic catalysts:
DABCO 25, 3-hydroxyquinuclidine 26, DBU, DMAP, tri-
Scheme 13 Reagents and conditions: i, 26, CD3OD, 50 ЊC.
hydroxyphosphine oxides, which can undergo Horner–Wittig
elimination to produce enantiomerically enriched allenes.
Baylis–Hillman reactions of vinylphosphine oxides are not
observed due to the slow reaction of the intermediate 27 with
aldehydes.
phenylphosphine and tricyclohexylphosphine. It was not
possible to repeat the solvent-free reaction conditions of
Villiéras as the phosphine oxide is a crystalline solid and so the
reaction was attempted in dichloromethane. In all cases the
starting material was recovered after 2–4 days. Use of high
pressure (80 bar) and lanthanide Lewis acids, which have
previously been used to accelerate the Baylis–Hillman reac-
tion,3,4,30 also resulted in no reaction. A change of solvent to the
more polar deuterated DMSO and deuterated methanol also
gave recovered starting material after three days, although in
the case of deuterated methanol, partial deuteration of the
α-position was observed. This observation suggests that nucleo-
philic addition of 3-hydroxyquinuclidine 26 to the vinylphos-
phine oxide 6e was occurring. The reaction was repeated at
50 ЊC, recording an NMR spectrum every 30 minutes. Fig. 1
shows a graph of the integration value of the signal correspond-
ing to the α-proton against time, showing pseudo first-order
kinetics with a half-life of approximately 10 hours (at 50 ЊC).
This confirms that conjugate addition of the nucleophile is
occurring, forming 27, but nothing can be said about the
position of any of the equilibria in Scheme 13. We expect
that reaction of the zwitterion 27 with an aldehyde to be even
slower than deuteration. Thus, this could be the reason that no
reaction is observed.
Experimental
All solvents were distilled before use. THF was freshly distilled
from lithium aluminium hydride with triphenylmethane as the
indicator. Dichloromethane, diethyl ether and methanol were
distilled from calcium hydride. Pyridine was dried by stirring
over and distilling from calcium and was stored over 4 Å
molecular sieves. Triethylamine was dried in the same way but
stored over calcium hydride. Anhydrous dimethyl sulfoxide was
bought from Aldrich and stored over 4 Å molecular sieves. n-
Butyllithium was titrated against diphenylacetic acid before use.
All non-aqueous reactions were carried out under argon using
oven- and vacuum-dried glassware. Column chromatography
was performed with Merck Kieselgel 60 (230–400 mesh). Thin
layer chromatography was carried out on pre-coated plates
(Merck Kieselgel 60F254).
Analytical chiral HPLC was carried out using a Daicel
Chiralpak AD column and guard column with a Spectra-
Physics SP8800 pump, a Spectra-Physics SP8450 UV detection
system and a ChromJet single channel integrator. Proton and
carbon NMR spectra were recorded on Bruker DPX250,
DPX400, DRX400, DRX500 Fourier transform spectrometers
using an internal deuterium lock. Chemical shifts are quoted in
parts per million (ppm) downfield from tetramethylsilane. The
In conclusion, we have demonstrated that vinylic phosphine
oxides undergo a Baylis–Hillman style reaction producing
J. Chem. Soc., Perkin Trans. 1, 2001, 2240–2249
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symbol “*” after a proton NMR signal indicates that the signal
General method for asymmetric Baylis–Hillman style reactions
disappears after a D2O shake. Carbon NMR were recorded with
A
solution of freshly prepared (R)-N-benzyl-N-lithio-1-
“ϩ”
broadband proton decoupling, the symbol
after a carbon
phenylethylamine at Ϫ78 ЊC [prepared by the addition of
n-butyllithium (1.1 mmol) to a solution of (R)-N-benzyl-1-
phenylethylamine32 (1.2 mmol), in dry THF (15 cm3)] was
added by cannula to a solution of the phosphine oxide
(1 mmol) and the electrophile (2 mmol) in dry THF (25 cm3)
at Ϫ78 ЊC. The reaction mixture was stirred at Ϫ78 ЊC for
30 minutes and allowed to warm to room temperature over
30 minutes. The reaction was quenched by addition of satur-
ated aqueous ammonium chloride solution (15 cm3) and water
(30 cm3). The layers were separated and the aqueous layer was
extracted with dichloromethane (3 × 100 cm3). The combined
organic extracts were evaporated under reduced pressure and
dissolved in dichloromethane (100 cm3). This solution was
washed with 10% citric acid solution (100 cm3), water (100 cm3),
brine (100 cm3), dried (MgSO4) and evaporated under reduced
pressure to yield a crude product.
NMR chemical shift indicates an odd number of attached pro-
“Ϫ”
tons, whereas the symbol
indicates an even number, as
determined by APT or DEPT analysis. Coupling constants for
proton and carbon NMR signals are quoted in Hz, rounded
to the nearest 0.5 Hz and are reported as observed. Electron
impact (EI) mass spectra were recorded on a Kratos double
focusing magnetic sector instrument using a DS503 data system
for high-resolution analysis or a MSI double focusing magnetic
sector Concept IH instrument. Fast atom bombardment (FAB)
mass spectra were obtained from a Kratos MS 890 instrument.
Electrospray (ESI) mass spectra were recorded using a Brucker
Bio-Apex II FT-ICR instrument or a Micromass Q-Tof
machine. Liquid secondary ion mass spectra (LSIMS) were
recorded on an MSI double focusing Concept IH instrument.
Microanalyses were carried out by the staff of the University
Chemical Laboratory using a Leeman Labs CE440 Elemental
Analyzer (C, H and N) and LBK Biochrom Ultrospec 4050 (P).
Melting points were measured on a Stuart Scientific SMP1
melting point apparatus and are uncorrected. Infra-red spectra
were recorded using a Perkin Elmer 1600 (FT-IR) spectrometer
and optical rotations were recorded on a Perkin Elmer 241
polarimeter using to the sodium D line (589 nm) at room
(E )-4,4-Dimethyl-2-diphenylphosphinoyl-3-hydroxy-1-
phenylpent-1-ene 7a
By the general method, (E)-1-diphenylphosphinoyl-2-phenyl-
ethene14 6a (1.20 g, 4 mmol), (R)-N-benzyl-1-phenylethylamine
2 (1.00 g, 4.7 mmol), n-butyllithium (1.4 M in hexane, 3.1 cm3,
4.3 mmol) and pivalaldehyde (0.680 g, 860 µl, 8 mmol) gave
a crude product that was chromatographed (SiO2, EtOAc–
hexane, 1 : 1 to 1 : 0) to give the hydroxyphosphine oxide 7a
(1.34 g, 87%) as needles, mp 174–175 ЊC (from EtOAc); [α]D
Ϫ75 (c. 1.0 in CHCl3); Rf(EtOAc) 0.60; νmax(Nujol)/cmϪ1 3500–
temperature and are given in units of 10Ϫ1 deg dm2 gϪ1
.
(E )-2-Diphenylphosphinoyl-1-phenylprop-1-ene 4
A solution of freshly prepared (R)-N-benzyl-N-lithio-1-phenyl-
ethylamine at Ϫ78 ЊC [prepared by the addition of n-butyl-
lithium (1.4 M in hexane, 250 µl, 0.39 mmol) to a solution of
(R)-N-benzyl-1-phenylethylamine (83 mg, 0.39 mmol), in dry
THF (10 cm3)] was added by cannula to a solution of (E)-1-
diphenylphosphinoyl-2-phenylethene14 6a (100 mg, 0.33 mmol)
and methyl iodide (47 mg, 21 µl, 0.66 mmol) in dry THF (7 cm3)
at Ϫ78 ЊC. The reaction mixture was stirred at Ϫ78 ЊC for
30 minutes and allowed to warm to room temperature over
30 minutes. The reaction was quenched by addition of satur-
ated aqueous ammonium chloride solution (15 cm3) and water
(30 cm3). The layers were separated and the aqueous layer was
extracted with dichloromethane (3 × 100 cm3). The combined
organic extracts were evaporated under reduced pressure and
dissolved in dichloromethane (100 cm3). This solution was
washed with 10% citric acid solution (100 cm3), water (100 cm3),
brine (100 cm3), dried (MgSO4) and evaporated under reduced
pressure to yield a crude product. The residue was chromato-
graphed (SiO2, EtOAc) to give a 8 : 92 mixture of starting
material–vinylphosphine oxide31 4 (87 mg) as a colourless gum
which we were unable to separate. Yield of product 80 mg
(76%).
3000 (br, OH), 1440 (P–Ph) and 1153 (P᎐O); δ (400 MHz;
᎐
H
CDCl3) 7.95–7.85 (2H, m, Ph2PO), 7.70–7.20 (13H, m, Ph and
Ph2PO), 6.88 (1H, d, J 23.5, CHPh), 5.53* (1H, d, J 11, OH),
4.92 (1H, dd, J 23.5 and 11, CHOH) and 0.77 (9H, s, CMe3);
δC(100 MHz; CDCl3) 145.6ϩ (d, J 12.5, CHPh), 136–127 (m,
Ph, Ph2PO and Ph2PO-C), 79.2ϩ (d, J 4.5, CHOH), 36.9Ϫ
(CMe3) and 26.1ϩ (CMe3); m/z (FAB) 391 (100%, MHϩ), 373
(87, M Ϫ OH), 333 (44, M Ϫ tBu) and 201 (58, Ph2PO) (Found:
MHϩ, 391.1806. C25H28O2P requires M, 391.1827) (Found:
C, 76.6; H, 7.1; P, 7.9. C25H27O2P requires C, 76.9; H, 7.0; P,
7.9%). Chiral HPLC analysis (70 : 30 isohexane–propan-2-ol
(IPA), τmajor 7.4 min, τminor 15.0 min) of this material showed an
enantiomeric excess of 28%.
(E )-2-Diphenylphosphinoyl-3-phenyl-1-(1Ј-phenylsulfanylcyclo-
hexyl)prop-2-en-1-ol 7b
By the general method, (E)-1-diphenylphosphinoyl-2-phenyl-
ethene14 6a (200 mg, 0.65 mmol), (R)-N-benzyl-1-phenyl-
ethylamine 2 (164 mg, 0.73 mmol), n-butyllithium (1.4 M in
hexane, 517 µl, 0.79 mmol) and 1-(phenylsulfanyl)-
cyclohexanecarbaldehyde33 (290 mg, 1.32 mmol) gave a crude
product that was chromatographed (SiO2, EtOAc–hexane, 1 : 1
to 2 : 1) to give the hydroxyphosphine oxide 7b (188 mg, 55%) as
prisms, mp 174–175 ЊC (from EtOAc–hexane); [α]D Ϫ23 (c. 0.72
in CHCl3); Rf(EtOAc) 0.57; νmax(CHCl3)/cmϪ1 3500–3100 (br,
(E )-1-Diphenylphosphinoyl-1-(1Ј-hydroxycyclobutyl)-
2-phenylethene 5
In a similar way, (E)-1-diphenylphosphinoyl-2-phenylethene14
6a (100 mg, 0.33 mmol), (R)-N-benzyl-1-phenylethylamine 2
(82 mg, 0.39 mmol), n-butyllithium (1.4 M in hexane, 260 µl,
0.36 mmol) and cyclobutanone (28 mg, 30 µl, 0.66 mmol) gave a
crude product that was chromatographed (SiO2, EtOAc) to give
the hydroxyphosphine oxide 5 (60 mg, 50%) as a colourless gum;
Rf(EtOAc) 0.29; νmax(CHCl3)/cmϪ1 3500–3200 (br, OH), 1438
OH), 1438 (P–Ph) and 1158 (P᎐O); δ (400 MHz; CDCl ) 7.93–
᎐
H
3
7.83 (2H, m, Ph2PO), 7.70–6.80 (19H, m, Ph, SPh, Ph2PO and
CHPh), 5.71* (1H, d, J 8, OH), 5.11 (1H, dd, J 23 and 8,
CHOH) and 1.90–0.90 (10H, m, 5 × CH2); δC(100 MHz;
CDCl3) 148.5ϩ (d, J 12.5, CHPh), 140–128 (m, Ph, SPh, Ph2PO
and Ph2PO-C), 76.4ϩ (d, J 4, CHOH), 62.6Ϫ (CSPh), 31.3Ϫ,
31.1Ϫ, 26.0Ϫ, 22.2Ϫ and 21.8Ϫ (5 × CH2); m/z (FAB) 525
(71%, MHϩ), 415 (31, M Ϫ SPh), 397 (54, M Ϫ SPh Ϫ OH),
201 (100, Ph2PO) and 191 (54, C6H10SPh) (Found: MHϩ,
525.2009. C33H34O2PS requires M, 525.2017) (Found: C, 75.2;
H, 6.5; P, 5.7. C33H33O2PS requires C, 75.5; H, 6.3; P, 5.9%).
Chiral HPLC analysis (70 : 30 isohexane–IPA, τmajor 10.7 min,
τminor 20.6 min) of this material showed an enantiomeric excess
of 13%.
(P–Ph) and 1158 (P᎐O); δ (400 MHz; CDCl ) 7.80–7.70 (4H,
᎐
H
3
m, Ph2PO), 7.60–7.25 (11H, m, Ph and Ph2PO), 6.67 (1H, d,
J 23, CHPh), 4.43* (1H, br s, OH), 2.05–1.80 (5H, m, CH2) and
1.43–1.32 (1H, m, CH2); δC(100 MHz; CDCl3) 143.3ϩ (d, J, 13,
CHPh), 136–127 (m, Ph, Ph2PO and Ph2PO-C), 77.6ϩ
(CHOH), 36.7Ϫ (CH2), 36.6Ϫ (CH2) and 16.2Ϫ (CH2); m/z (FAB)
375 (53%, MHϩ), 357 (88, M Ϫ OH), 201 (80, Ph2PO) and 154
(100, M Ϫ OH Ϫ Ph2PO) (Found: MHϩ, 375.1515. C24H24O2P
requires M, 375.1514).
2244
J. Chem. Soc., Perkin Trans. 1, 2001, 2240–2249

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(E )-4,4-Dimethyl-2-diphenylphosphinoyl-3-hydroxy-1-
phenylhepta-1,6-diene 7c
432.2225. C28H33O2P requires M, 432.2218). Chiral HPLC
analysis (85 : 15 isohexane–EtOH, τ1 24.2 min, τ2 32.4 min) of
this material showed an enantiomeric excess of 0%.
By the general method, (E)-1-diphenylphosphinoyl-2-phenyl-
ethene14 6a (200 mg, 0.66 mmol), (R)-N-benzyl-1-phenyl-
ethylamine 2 (164 mg, 0.73 mmol), n-butyllithium (1.4 M in
hexane, 517 µl, 0.79 mmol) and 2,2-dimethylpent-4-enal (164
mg, 200 µl, 1.32 mmol) gave a crude product that was chrom-
atographed (SiO2, EtOAc–hexane, 1 : 1 to 2 : 1) to give the
hydroxyphosphine oxide 7c (184 mg, 67%) as a colourless gum;
[α]D Ϫ48 (c. 1.9 in CHCl3); Rf(EtOAc) 0.64; νmax(CHCl3)/cmϪ1
3,3-Dimethyl-1-diphenylphosphinoylbutan-2-ol
n-Butyllithium (1.4 M in hexane, 50.9 cm3) was added to a
stirred solution of the methyldiphenylphosphine oxide (14.0 g,
65 mmol) in dry THF (400 cm3) at Ϫ78 ЊC. The orange solution
was stirred for 30 minutes and pivalaldehyde (6.69 g, 8.5 cm3, 77
mmol) was added. The reaction mixture was stirred at Ϫ78 ЊC
for 30 minutes and allowed to warm to room temperature over
1 hour. The reaction was quenched by the addition of saturated
aqueous ammonium chloride solution (20 cm3). The layers were
separated and the aqueous layer was extracted with dichloro-
methane (3 × 30 cm3). The combined organic extracts were
washed with brine (50 cm3), dried (MgSO4) and evaporated
under reduced pressure to yield the crude β-hydroxyphosphine
oxide. The crude product was recrystallised from EtOAc–
hexane to give the hydroxyphosphine oxide (17.25 g, 88%) as
needles, mp 142–143 ЊC (from EtOAc–hexane) (lit.,34 137–
138 ЊC from toluene–petroleum ether), which has previously
been reported34 with incomplete data; Rf(EtOAc) 0.37;
νmax(CHCl3)/cmϪ1 3500–3200 (br, OH), 1438 (P–Ph) and 1151
3400–3200 (br, OH), 1436 (P–Ph) and 1160 (P᎐O); δ (400
᎐
H
MHz; CDCl3) 7.95–7.85 (2H, m, Ph2PO), 7.70–7.20 (13H, m,
Ph and Ph2PO), 6.88 (1H, d, J 23.5, CHPh), 5.80–5.30 (2H, m,
CHCH2 and OH), 5.03 (1H, d, J 23.5, CHOH), 4.86 (1H, dd,
J 10 and 2.5 CHcisHtrans), 4.77 (1H, dd, J 17 and 2.5, CHcisHtrans),
2.10 (1H, dd, J 13.5 and 7.5, CHAHB), 1.81 (1H, dd, J 13.5 and
7, CHAHB), 0.79 (3H, s, Me) and 0.59 (3H, s, Me); δC(100 MHz;
CDCl3) 146.1ϩ (d, J 12.5, CHPh), 135–127 (m,CH᎐CH ,
᎐
2
Ph2PO-C, Ph and Ph2PO), 116.6Ϫ (CH᎐CH ), 78.0ϩ (d, J 4.5,
᎐
2
CHOH), 43.2Ϫ (CH2), 22.8ϩ (Me) and 22.7ϩ(Me); m/z (FAB)
417 (100%, MHϩ), 399 (83, M Ϫ OH), 333 (67, M Ϫ C6H11)
and 201 (72, Ph2PO) (Found: MHϩ, 417.1986. C27H30O2P
requires M, 417.1983). Chiral HPLC analysis (70 : 30
isohexane–IPA, τmajor 6.9 min, τminor 16.0 min) of this material
showed an enantiomeric excess of 23%.
(P᎐O); δ (400 MHz; CDCl ) 7.80–7.66 (4H, m, Ph PO), 7.57–
᎐
H
3
2
7.42 (6H, m, Ph2PO), 4.36* (1H, s, OH), 3.67 (1H, br t, J 10.5,
CHOH), 2.44–2.23 (2H, m, CH2) and 0.88 (9H, s, CMe3);
δC(100 MHz; CDCl3) 134.1Ϫ (d, J 100, ipso-Ph2PO), 132.4ϩ
(para-Ph2PO), 132.4ϩ (para-Ph2PO), 132.0Ϫ (d, J 97, ipso-
Ph2PO), 131.4ϩ (d, J 9, ortho-Ph2PO), 130.8ϩ (d, J 9.5,
ortho-Ph2PO), 129.2ϩ (d, J 11.5, meta-Ph2PO), 129.1ϩ (d, J 12,
meta-Ph2PO), 74.6ϩ (d, J 5, CHOH), 35.5Ϫ (d, J 12, CMe3),
31.5Ϫ (d, J 72, CH2) and 28.8ϩ (CMe3); m/z (LSIMS) 303 (92%,
MHϩ), 285 (45, M Ϫ OH) and 201 (100, Ph2PO) (Found: MHϩ,
303.1488. C18H24O2P requires M, 303.1498).
(E )-2-Diphenylphosphinoyl-3-hydroxy-4-methyl-1-phenylpent-
1-ene 7d
By the general method, (E)-1-diphenylphosphinoyl-2-phenyl-
ethene14 6a (100 mg, 0.33 mmol), (R)-N-benzyl-1-phenyl-
ethylamine 2 (83 mg, 0.39 mmol), n-butyllithium (1.4 M in
hexane, 250 µl, 0.39 mmol) and isobutyraldehyde (48 mg, 60 µl,
0.66 mmol) gave a crude product that was chromatographed
(SiO2, EtOAc–hexane, 2 : 3 to 3 : 2) to give the hydroxyphos-
phine oxide 7d (77 mg, 62%) as a colourless gum; Rf(EtOAc)
0.55; νmax(CHCl3)/cmϪ1 3500–3200 (br, OH), 1437 (P–Ph) and
(E )-3,3-Dimethyl-1-diphenylphosphinoylbut-1-ene 6b
By method of Santelli-Rouvier,14 3,3-dimethyl-1-diphenylphos-
phinoylbutan-2-ol (15.0 g, 50 mmol), pyridine (5.10 g, 5.4 cm3,
65 mmol), trimethylsilyl chloride (5.94 g, 6.9 cm3, 55 mmol) and
sodium hydride (60% dispersion in mineral oil, 2.19 g, 55 mmol)
gave a crude product that was recrystallised (EtOAc–hexane) to
give the unsaturated phosphine oxide 6b (9.25 g, 65%) as prisms,
mp 161–162 ЊC (from EtOAc–hexane); Rf(EtOAc) 0.33;
νmax(CHCl3)/cmϪ1 1438 (P–Ph) and 1176 (P᎐O); δ (400 MHz;
CDCl3) 7.72–7.63 (4H, m, Ph2PO), 7.53–7.40 (6H, m, Ph2PO),
6.74 (1H, dd, J 20.5 and 17.5, CHCMe3), 6.09 (1H, dd, J 24.5
and 17.5, PCH) and 1.01 (9H, s, CMe3); δC(100 MHz; CDCl3)
160.4ϩ CHCMe3), 131.6Ϫ (d, J 104, ipso-Ph), 129.7ϩ (d, J 1.5,
para-Ph), 129.4ϩ (d, J 10, ortho-Ph), 126.6ϩ (d, J 12, meta-Ph),
114.6ϩ (d, J 103.5, Ph2PO-C), 33.4Ϫ (d, J 15, CMe3) and 26.8ϩ
(CMe3); m/z (FAB) 285 (100%, MHϩ), 201 (6, Ph2PO) (Found:
MHϩ, 285.1390. C18H22OP requires M, 285.1403) (Found:
C, 75.8; H, 7.5; P, 11.0. C18H21OP requires C, 76.0; H, 7.4;
P, 10.9%).
1159 (P᎐O); δ (400 MHz; CDCl ) 7.95–7.85 (2H, m, Ph PO),
᎐
H
3
2
7.75–7.65 (2H, m, Ph2PO), 7.65–7.40 (6H, m, Ph2PO and Ph),
7.37–7.23 (5H, m, Ph2PO and Ph), 6.83 (1H, d, J 23, CHPh),
4.65* (1H, d, J 10.5, OH), 4.46 (1H, dt, J 23 and 10.5, CHOH),
2.10–2.00 (1H, m, CHMe2), 0.98 (3H, d, J 6.5, Me) and 0.46
(3H, d, J 6.5, Me); δC(100 MHz; CDCl3) 144.5ϩ (d, J 12.5,
CHPh), 139–128 (Ph2PO, Ph and Ph2PO-C), 78.0ϩ (d, J 5.5,
CHOH), 34.0ϩ (CHMe2), 19.9ϩ (Me) and 19.8ϩ (Me); m/z (EI)
376 (1%, Mϩ), 333 (100, M Ϫ iPr) and 201 (43, Ph2PO) (Found:
Mϩ, 376.1579. C24H24O2P requires M, 376.1592). Chiral HPLC
analysis (70 : 30 isohexane–IPA, τ1 7.5 min, τ2 10.0 min) of this
material showed an enantiomeric excess of 0%.
᎐
H
(E )-2-Diphenylphosphinoyl-3-hydroxy-1-phenyldec-1-ene 7e
By the general method, (E)-1-diphenylphosphinoyl-2-phenyl-
ethylene14 6a (100 mg, 0.33 mmol), (R)-N-benzyl-1-phenyl-
ethylamine 2 (83 mg, 0.39 mmol), n-butyllithium (1.4 M in
hexane, 250 µl, 0.39 mmol) and octanal (84 mg, 103 µl, 0.66
mmol) gave a crude product that was chromatographed (SiO2,
EtOAc–hexane, 2 : 3 to 2 : 1) to give the hydroxyphosphine oxide
7e (47 mg, 33%) as a colourless gum; Rf(EtOAc) 0.60;
νmax(CHCl3)/cmϪ1 3500–3200 (br, OH), 1437 (P–Ph) and 1158
(E )-4-Diphenylphosphinoyl-3-hydroxy-2,2,6,6-tetramethylhept-
4-ene 8a
By the general method, (E)-3,3-dimethyl-1-diphenylphosphino-
ylbut-1-ene 6b (1.42 g, 5.0 mmol), (R)-N-benzyl-1-phenylethyl-
amine 2 (1.27 g, 6.0 mmol), n-butyllithium (1.4 M in hexane, 3.9
cm3, 5.5 mmol) and pivalaldehyde (0.86 g, 1.1 cm3, 10 mmol)
gave a crude product that was chromatographed (SiO2, EtOAc–
hexane, 2 : 3 to 3 : 2) to give the vinyl phosphine oxide 8a (1.08 g,
58%) as needles, mp 142–144 ЊC (from dichloromethane–
hexane); [α]D Ϫ79 (c. 0.86 in CHCl3); Rf(EtOAc) 0.63;
νmax(CHCl3)/cmϪ1 3550–3200 (br, OH), 1437 (P–Ph) and 1156
(P᎐O); δ (400 MHz; CDCl ) 7.90–7.80 (2H, m, Ph PO),
᎐
H
3
2
7.73–7.65 (2H, m, Ph2PO), 7.63–7.43 (6H, m, Ph2PO and Ph),
7.37–7.18 (5H, m, Ph2PO and Ph), 6.69 (1H, d, J 22.5, CHPh),
4.95–4.80 (1H, m, CHOH), 4.60* (1H, d, J 10.5, OH), 1.95–
1.80 (1H, m, CH2), 1.61–1.50 (1H, m, CH2), 1.44–1.32 (1H, m,
CH2), 1.25–0.95 (9H, m, CH2) and 0.83 (3H, t, J 7, Me); δC(100
MHz; CDCl3) 140.8ϩ (d, J 12.5, CHPh), 136–126 (Ph2PO, Ph
and Ph2PO-C), 69.9 (d, J 5, CHOH), 51.4Ϫ, 35.7Ϫ, 29.8Ϫ, 27.1Ϫ,
24.1Ϫ, 20.6Ϫ (6 × CH2) and 12.1ϩ (Me); m/z (EI) 432 (1%, Mϩ),
333 (100, M Ϫ C7H15) and 201 (31, Ph2PO) (Found: Mϩ,
(P᎐O); δ (400 MHz; CDCl ) 7.87–7.80 (2H, m, Ph PO), 7.64–
᎐
H
3
2
7.32 (8H, m, Ph2PO), 5.74* (1H, d, J 1.5, OH), 5.72 (1H, d,
J. Chem. Soc., Perkin Trans. 1, 2001, 2240–2249 2245

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J 37, C᎐CH), 4.96 (1H, dd, J 27.5 and 10.5, CHOH), 1.12 (9H,
pivalaldehyde (172 mg, 220 µl, 2 mmol) gave a crude product
᎐
s, CMe3) and 0.90 (9H, s, CMe3); δC(125 MHz; CDCl3) 157.9ϩ
(d, J 10.5, Ph2PO-CCH), 136.7Ϫ (d, J 104, ipso-Ph2PO), 131.9ϩ
(para-Ph2PO), 131.8ϩ (d, J 9, ortho-Ph2PO), 131.6ϩ (d, J 9.5,
ortho-Ph2PO), 131.5ϩ ( para-Ph2PO), 131.1Ϫ (d, J 99, Ph2PO-C),
130.4Ϫ (d, J 103, ipso-Ph2PO), 128.5ϩ (d, J 11.5, meta-Ph2PO),
128.2ϩ (d, J 12, meta-Ph2PO), 77.9ϩ (d, J 5.5, CHOH), 36.5ϩ
(d, J 17, C᎐CHCMe ), 36.3Ϫ (CMe3), 30.7ϩ and 27.6ϩ (CMe3);
that was chromatographed (SiO2, EtOAc–hexane, 2 : 3 to 3 : 2)
to give the hydroxyphosphine oxide 8d (122 mg, 39%) as prisms,
mp 179–180 ЊC (from EtOAc–hexane); Rf(EtOAc) 0.35;
τmax(CHCl3)/cmϪ1 3600–3100 (br, OH), 1438 (P–Ph) and 1166
(P᎐O); δ (400 MHz; CDCl ) 7.77–7.70 (2H, m, Ph PO), 7.68–
᎐
H
3
2
7.60 (2H, m, Ph2PO), 7.60–7.40 (6H, m, Ph2PO), 6.08 (1H, d,
J 43.5, CHcisHtrans), 5.51 (1H, d, J 21, CHcisHtrans), 4.34* (1H, d,
J 8, OH), 4.20 (1H, dd, J 15 and 8, CHOH) and 0.91 (9H, s,
CMe3); δC(100 MHz; CDCl3) 151.4Ϫ (d, J 89.5, Ph2PO-C), 141–
136 (m, Ph2PO and CH2), 91.0ϩ (CHOH), 44.0Ϫ (CMe3) and
34.1ϩ (CMe3); m/z (FAB) 315 (15%, MHϩ) (Found: MHϩ,
315.1518. C19H24O2P requires M, 315.1514) (Found: C, 72.5;
H, 7.3; P, 10.1. C19H23O2P requires C, 72.6; H, 7.4; P, 9.9%).
Chiral HPLC analysis (90 : 10 isohexane–IPA, τmajor 16.5 min,
τminor 14.2 min) of this material showed an enantiomeric excess
of 5%.
᎐
3
m/z (LSIMS) 271 (42%, MHϩ), 353 (100, M Ϫ OH), 313 (15,
M Ϫ CMe3) and 201 (79, Ph2PO) (Found: MHϩ, 371.2149.
C23H32O2P requires M, 371.2124) (Found: C, 74.5; H, 8.5; P,
8.5. C23H31O2P requires C, 74.6; H, 8.4; P, 8.4%). Chiral HPLC
analysis (90 : 10 isohexane–IPA, τmajor 9.1 min, τminor 19.6 min)
of this material showed an enantiomeric excess of 51%.
(E )-4-Diphenylphosphinoyl-3-hydroxy-2,2,6-trimethylhept-4-ene
8b
By the general method, (E)-1-diphenylphosphinoyl-3-methyl-
butene10 (100 mg, 0.37 mmol), (R)-N-benzyl-1-phenylethyl-
amine 2 (94 mg, 0.44 mmol), n-butyllithium (1.4 M in hexane,
290 µl, 0.41 mmol) and pivalaldehyde (63 mg, 81 µl, 0.74 mmol)
gave a crude product that was chromatographed (SiO2, EtOAc–
hexane, 1 : 1 to 2 : 1) to give the hydroxyphosphine oxide 8b (70
mg, 53%) as a colourless gum; [α]D Ϫ15 (c. 0.84 in CHCl3);
Rf(EtOAc) 0.50; νmax(CHCl3)/cmϪ1 3500–3100 (br, OH), 1614
(1ЈR)-N-Benzyl-N-(1Ј-methylbenzyl)-4,4-dimethyl-2-diphenyl-
phosphinoyl-3-hydroxypentylamine 9. Compound 9 was also
isolated (as a 1.9 : 1 mixture of diastereoisomers). Colour-
less gum (64 mg, 12%), 1.9 : 1 mixture of diastereoisomers,
Rf(EtOAc) 0.57; νmax(CHCl3)/cmϪ1 3500–3300 (br, OH), 1438
(P–Ph), 1158 (P᎐O); δ (400 MHz; CDCl ) 7.83–7.07 (18H
᎐
H
3
major
and 18Hminor, m, Ph), 7.05 (2Hminor, br d, J 7.5, Ph), 7.00 (2Hmajor
,
br d, J 7, Ph), 3.76–3.60 (2Hmajor and 2Hminor, m, CHMe and
CHOH), 3.49 (1Hminor, d, J 15, NCH2), 3.39 (1Hmajor, d, J 15,
NCH2), 3.31–3.15 (3Hmajor and 2Hminor, m, NCH2), 3.00–2.90
(1Hminor, m, NCH2), 2.77–2.57 (1Hmajor and 1Hminor, m, PCH),
1.12 (3Hminor, d, J 7, CHMe), 0.98 (3Hmajor, d, J 7, CHMe),
0.80 (9Hminor, s, CMe3) and 0.71 (9Hmajor, s, CMe3), no OH
peaks observed; δC(100 MHz; CDCl3) 138.8Ϫ (Phmajor), 138.7Ϫ
(Phminor), 138.2Ϫ (Phmajor), 137.4Ϫ (Phminor) and 132–122 (m,
Phmajor and Phminor), 75.3ϩ (CminorHOH), 74.8ϩ (CmajorHOH),
(C᎐C), 1437 (P–Ph) and 1155 (P᎐O); δ (400 MHz; CDCl )
᎐
᎐
H
3
7.82–7.74 (2H, m, Ph2PO), 7.62–7.43 (6H, m, Ph2PO), 7.40–
7.34 (2H, m, Ph2PO), 5.73* (1H, br d, J 10, OH), 5.61 (1H, ddd,
J 24, 10.5 and 0.5, C᎐CH), 4.53 (1H, dd, J 23 and 10, CHOH),
᎐
2.89–2.75 (1H, m, CHMe2), 0.97 (3H, d, J 6.5, Me), 0.90 (3H, d,
J 6.5, Me) and 0.88 (9H, s, CMe3); δC(100 MHz; CDCl3) 154.9ϩ
(d, J, C᎐CH), 134.4Ϫ (d, J 103.5, ipso-Ph), 131–130 (m, ortho-
᎐
and para-Ph), 130.1Ϫ (d, J 98.5, ipso-Ph), 127.9Ϫ (d, J 91,
Ph2PO-C), 127.1ϩ (d, J 12, meta-Ph), 126.8ϩ (d, J 12, meta-Ph),
79.6ϩ (d, J 5.5, CHOH), 35.2Ϫ (CMe3), 27.2ϩ (CHMe2), 25.4ϩ
(CMe3), 20.3ϩ (Me) and 20.0ϩ (Me); m/z (LSIMS) 357 (100%,
MHϩ), 339 (8, M Ϫ OH) (Found: MHϩ, 357.1983. C22H30O2P
requires M, 357.1978). Chiral HPLC analysis (90 : 10 iso-
hexane : IPA, τmajor 8.1 min, τminor 6.7 min) of this material
showed an enantiomeric excess of 12%.
58.4ϩ (NCminorHMe), 57.2ϩ (NCmajorHMe), 52.4Ϫ (NCmajor
-
H2Ph), 51.8 (NCminorH2Ph), 44.6Ϫ (CHCminorH2N), 42.7Ϫ
(CHCmajorH2N), 35.8ϩ (d, J 68.5, PCminorH), 35.5ϩ (d, J 68.5,
PCmajorH), 34.3ϩ and 34.3ϩ (CmajorMe3 and CminorMe3), 24.9ϩ
and 24.9ϩ (CMe3
and CMe3 minor), 17.2ϩ (Meminor) and
major
11.5ϩ (Memajor); m/z (LSIMS) 526 (73%, MHϩ), 422 (44,
M Ϫ CHMePh), 340 (100, M Ϫ CH2Ph Ϫ Ph Ϫ OH), 303 (41,
M Ϫ CH2NBn(CHMePh)) and 201 (46, Ph2PO) (Found: MHϩ,
526.2858. C34H41NO2P requires M, 526.2859).
(E )-5,5-Dimethyl-3-diphenylphosphinoyl-4-hydroxyhex-2-ene 8c
By the general method, (E)-1-diphenylphosphinoylprop-1-ene
6d (300 mg, 1.23 mmol), (R)-N-benzyl-1-phenylethylamine 2
(253 mg, 1.2 mmol), n-butyllithium (1.4 M in hexane, 785 µl, 1.1
mmol) and pivalaldehyde (172 mg, 220 µl, 2 mmol) gave a crude
product that was chromatographed (SiO2, EtOAc–hexane, 1 : 1)
to give the hydroxyphosphine oxide 8c (1.99 mg, 47.5%) as white
plates, mp 174–176 ЊC (from EtOAc–hexane); Rf(EtOAc) 0.56;
[2H3]Methyldiphenylphosphine oxide
Chlorodiphenylphosphine (11.03g, 50 mmol) in dry ether (25
cm3) was added slowly to a solution of [2H3]methylmagnesium
iodide (1.0 M in ether, 50 cm3, 50 mmol), at 0 ЊC. The reaction
mixture was stirred for 2h, warming to room temperature.
Water (40 cm3) was slowly added and the layers were separated.
The aqueous layer was washed with dichloromethane (3 × 30
cm3), the combined organic extracts were washed with brine
(100 cm3), dried (MgSO4) and evaporated under reduced pres-
sure. The residue was dissolved in dichloromethane (40 cm3)
and aqueous hydrogen peroxide was added dropwise until no
further temperature rise was observed. Water (20 cm3) was
added, the layers were separated and the aqueous layer was
washed with dichloromethane (3 × 30 cm3). The combined
organic extracts were washed with brine (50 cm3), dried
(MgSO4) and evaporated under reduced pressure to give the
deuterated phosphine oxide (9.90 g, 90%) as needles, mp 111–
112 ЊC (from EtOAc–hexane) whose data matched those
previously reported.36
νmax(CHCl3)/cmϪ1 3600–3200 (br, OH), 1437 (Ph-P), 1218 (P᎐
᎐
O); δH(500 MHz; CDCl3) 7.77 (2H, ddt, J 11.5, 7 and 1.5, Ph),
7.58 (1H, tq, J 7.5 and 1.5, Ph), 7.54–7.45 (5H, m, Ph), 7.39
(2H, dtd, J 7.5, 3 and 1.5, Ph), 6.03 (1H, dqd, J 23.5, 7 and 1,
CHCH3), 5.69* (1H, d, J 10, OH), 4.55 (1H, ddd, J 22.5, 10 and
1, CHOH), 1.85 (3H, dd, J 7 and 3.3, Me), 0.90 (9H, s, Me3);
δC(125 MHz; CDCl3) 144.2ϩ (d, J 12, CHMe), 135.5Ϫ (d, J 103,
ipso-Ph), 134.2Ϫ (d, J 93, ipso-Ph), 131.9–131.6ϩ (m, ortho-
and para-Ph), 131.7Ϫ (d, J 99, Ph2PO-C), 128.4ϩ (d, J 25.5,
meta-Ph), 128.4ϩ (d, J 25.8, meta-Ph), 80.4ϩ (d, J 5.4, COH),
37.7Ϫ (CMe3), 26.8ϩ (CMe3), 16.0ϩ (d, J 16.5, Me). Chiral
HPLC analysis (80 : 20 isohexane–IPA, τmajor 21.7 min, τminor
14.3 min) of this material showed an enantiomeric excess of
11%.
2,2-Dideuterio-2-diphenylphosphinoyl-1-phenylethanol
4,4-Dimethyl-2-diphenylphosphinoyl-3-hydroxypent-1-ene 8d
In a similar way to the synthesis of 3,3-dimethyl-1-diphenyl-
phosphinoylbutan-2-ol, [2H3]methyldiphenylphosphine oxide
(6.60 g, 30 mmol), benzaldehyde (3.82g, 3.6 cm3, 36 mmol)
and n-butyllithium (1.4 M in hexane, 23.6 cm3, 33 mmol) gave
By the general method, vinyldiphenylphosphine oxide35 6e (228
mg, 1 mmol), (R)-N-benzyl-1-phenylethylamine 2 (253 mg, 1.2
mmol), n-butyllithium (1.4 M in hexane, 785 µl, 1.1 mmol) and
2246
J. Chem. Soc., Perkin Trans. 1, 2001, 2240–2249

View Article Online
a crude product that was recrystallised from dichlorometh-
ane–hexane to give the hydroxyphosphine oxide (6.16 g, 63%)
as prisms, mp 142–143 ЊC (from dichloromethane–hexane);
Rf(EtOAc) 0.35; νmax(CHCl3)/cmϪ1 3600–3200 (br, OH), 1437
(100 cm3), brine (100 cm3), dried (MgSO4) and evaporated
under reduced pressure. The residue was purified by Kugelrohr
distillation (oven temperature 145 ЊC, 0.1 mmHg) to give the
aldehyde 16 (1.17 g, 98%) as a pale yellow oil; νmax(liquid
(P–Ph) and 1168 (P᎐O); δ (400 MHz; CDCl ) 7.80–7.75 (2H,
film)/cmϪ1 2971, 2839, 2713 (CH), 1713 (br, 2 × C᎐O), 1607 and
᎐
᎐
H
3
m, Ph2PO), 7.70–7.65 (2H, m, Ph2PO), 7.54–7.42 (6H, Ph2PO
and Ph), 7.34–7.20 (5H, m, Ph2PO and Ph), 5.16 (1H, d, J 9,
CHOH) and 5.02* (1H, d, J 1.5, OH); δC(100 MHz; CDCl3)
143.8Ϫ (d, J 13.5, ipso-Ph), 134–125 (Ph2PO and Ph), 69.1ϩ (d,
J 4, CHOH) and 38.7Ϫ (m, CD2); m/z (LSIMS) 325 (42%,
MHϩ), 307 (35, M Ϫ OH), 201 (100, Ph2PO) (Found: MHϩ,
325.1313. C20H18D2O2P requires M, 325.1310).
1512 (C6H4OMe); δH(400 MHz; CDCl3) 9.59 (1H, s, CHO),
7.89 (2H, br d, J 9, meta-C6H4OMe), 6.86 (2H, br d, J 9, ortho-
C6H4OMe), 4.29 (2H, s, CH2), 3.75 (3H, s, OMe) and 1.16 (6H,
s, 2 × Me); δC(100 MHz; CDCl3) 201ϩ (CHO), 163.8Ϫ and
161.5Ϫ (para-C H OMe and C᎐O), 129.5ϩ (ortho-C6H4OMe),
᎐
6
4
119.9Ϫ (ipso-C6H4OMe), 111.6ϩ (meta-C6H4OMe), 66.0Ϫ (CH2),
53.3ϩ (OMe), 44.5Ϫ (CMe2) and 16.8ϩ (CMe2); m/z (ESI) 259
(95%, MNaϩ) (Found: MNaϩ, 259.0936. C13H16O4Na requires
M, 259.0946).
(E )-1-Deuterio-1-diphenylphosphinoyl-2-phenylethene 10
By the method of Santelli-Rouvier,14 2,2-dideuterio-2-diphenyl-
phosphinoyl-1-phenylethanol (4.1 g, 12.7 mmol), pyridine (1.30
g, 1.4 cm3, 16.5 mmol), trimethylsilyl chloride (1.51 g, 1.7 cm3,
14.0 mmol) and sodium hydride (60% dispersion in mineral oil,
335 mg, 13.9 mmol) gave a crude product that was chromato-
graphed (SiO2, EtOAc) to give the unsaturated phosphine oxide
10 (10.10 g, 71%) as needles. The deuterium content on the
α-position was approximately 80% by NMR; Rf(EtOAc) 0.36;
νmax(CHCl3)/cmϪ1 1439 (P–Ph) and 1175, (P᎐O); δ (400 MHz;
CDCl3) 7.80–7.70 (4H, m, Ph2PO), 7.60–7.30 (12H, m, Ph,
Ph2PO and CHPh) and 6.83 (0.2H, dd, J 22.5 and 17.5, PCH);
δC(100 MHz; CDCl3) 147.5ϩ (d, J 3.5, CHPh), 135.1Ϫ (d, J 17.5,
ipso-Ph), 133.0Ϫ (d, J 105, ipso-Ph2PO), 131.9ϩ (d, J 2.5, para-
Ph2PO), 131.4ϩ (d, J 10, ortho-Ph2PO), 130.1ϩ (Ph), 128.9ϩ
(Ph), 128.6ϩ (d, J 12, meta-Ph2PO), 127.8ϩ (Ph), 119.3ϩ (d,
J 104, PCD); m/z (EI) 305 (100%, Mϩ), 228 (19, M Ϫ Ph), 202
(58, Ph2PO), 153 (74, M Ϫ 2 × Ph), 136 (47, PCDCHPh)
(Found: MHϩ, 305.1072. C20H18D2O2P requires M, 305.1079).
(E )-4,4-Dimethyl-2-diphenylphosphinoyl-3-hydroxy-1-
phenylpent-1-en-5-yl 4-methoxybenzoate 18
By the general method, (E)-1-diphenylphosphinoyl-2-phenyl-
ethene 6a (575 mg, 1.9 mmol), (R)-N-benzyl-1-phenylethyl-
amine 2 (480 mg, 2.3 mmol), n-butyllithium (1.4 M in hexane,
1.5 cm3, 2.1 mmol) and 2,2-dimethyl-3-(4-methoxybenzoyl-
oxy)propanal 16 (670 mg, 2.83 mmol) gave a crude product that
was chromatographed (SiO2, EtOAc–hexane, 1 : 1 to 1 : 0) to
give the hydroxyphosphine oxide 18 (470 mg, 46%) as needles,
mp 153–154 ЊC (from dichloromethane–hexane); [α]D Ϫ22
(c. 0.73 in CHCl3); Rf(EtOAc) 0.54; νmax(CHCl3)/cmϪ1 3200–
3500 (br, OH), 1707 (C᎐O), 1437 (P–Ph), 1168 (P᎐O); δ (400
᎐
H
᎐
᎐
H
MHz; CDCl3) 7.97–7.88 (2H, m, Ph2PO), 7.70–7.61 (7H, m,
Ph2PO, Ph and meta-C6H4OMe), 7.53–7.40 (3H, m, Ph2PO and
Ph), 7.30–7.19 (5H, m, Ph2PO and Ph), 6.95 (1H, d, J 23.5,
CHPh), 6.82 (2H, br d, J 9, ortho-C6H4OMe), 5.74* (1H, d,
J 10.5, OH), 5.39 (1H, ddd, J 23.5, 10.5 and 1, CHOH), 4.19
(1H, d, J 11, CHAHB), 3.85 (3H, s, OMe), 3.83 (1H, d, J 11,
CHAHB), 0.94 (3H, s, Me) and 0.70 (3H, s, Me); δC(100 MHz;
(E )-1,3-Diphenyl-2-diphenylphosphinoyl-1-phenylsulfonyl-
aminoprop-1-ene 13
CDCl3) 165.6Ϫ and 162.7Ϫ (para-C H OMe and C᎐O), 147.0 ϩ
᎐
6
4
(d, J 12.5, CHPh), 136–127 (m, Ph2PO, Ph, ortho-C6H4OMe
and Ph2PO-C), 122.5Ϫ (ipso-C6H4OMe), 113.0ϩ (meta-
C6H4OMe), 74.7ϩ (d, J 4.5, CHOH), 70.1Ϫ (CH2), 55.0ϩ (OMe),
40.5Ϫ (CMe2), 22.3ϩ (Me) and 20.9ϩ (Me); m/z (LSIMS) 541
(57%, MHϩ), 523 (100, M Ϫ OH), 333 (57, M Ϫ CMe2CH2O-
COAr), 201 (95, Ph2PO) (Found: MHϩ, 541.2137. C33H34O5P
requires M, 541.2128) (Found: C, 73.1; H, 6.2; P, 5.9.
C33H33O5P requires C, 73.3; H, 6.15; P, 5.9%). Chiral HPLC
analysis (70 : 30 isohexane–IPA, τmajor 14.4 min, τminor 44.9 min)
of this material showed an enantiomeric excess of 18%.
By the general method, (E)-1-diphenylphosphinoyl-2-phenyl-
ethene14 6a (200 mg, 0.66 mmol), (R)-N-benzyl-1-phenyl-
ethylamine 2 (164 mg, 0.79 mmol), n-butyllithium (1.4 M
in hexane, 520 µl, 0.72 mmol) and N-benzylidenebenzene-
sulfonamide37 12 (322 mg, 1.32 mmol) gave a crude product
that was chromatographed (SiO2, EtOAc–hexane, 1 : 1 to 1 : 0)
to give the aminophosphine oxide 13 (160 mg, 44%) as needles,
mp 162–164 ЊC (from EtOAc–hexane); Rf(EtOAc) 0.65;
νmax(CHCl3)/cmϪ1 3233 (NH), 1437 (P–Ph), 1331 (SO2) and
1162 (P᎐O and SO ); δ (400 MHz; CDCl ) 8.20* (1H, d, J, 9.5,
᎐
2
H
3
NH), 7.65–6.80 (25H, m, PhSO2, 2 × Ph and Ph2PO), 6.74 (1H,
(E )-4,4-Dimethyl-5-hydroxy-2-diphenylphosphinoyl-1-
d, 20.5, C᎐CH) and 6.33 (1H, dd, J 22.6 and 9.5, CHN); δ (100
᎐
C
phenylpent-1-en-3-yl 4-methoxybenzoate 19. Compound 19 was
also isolated. Amorphous white solid (300 mg, 30%), [α]D Ϫ36
(c. 1.0 in CHCl3); Rf(EtOAc) 0.42; νmax(CHCl3)/cmϪ1 3100–3500
MHz; CDCl3) 143–125 (m, PhSO2, 2 × Ph, Ph2PO, CHPh and
Ph2PO-C) and 55.9ϩ (d, J 6, CHN); m/z (FAB) 550 (29%, MHϩ)
408 (15, M Ϫ PhSO2), 393 (35, M ϪPhSO2NH), 201 (55,
Ph2PO), 154 (100, PhCHNHSO) and 136 (81, PhCHNHS)
(Found: MHϩ, 550.1610. C33H29O3NPS requires M, 550.1606).
Chiral HPLC analysis (50 : 50 isohexane–IPA, τmajor 9.5 min,
τminor 11.7 min) of this material showed an enantiomeric excess
of 5%.
(br, OH), 1712 (C᎐O), 1438 (P–Ph) and 1166 (P᎐O); δ (400
᎐
᎐
H
MHz; CDCl3) 7.70–7.07 (17H, m, Ph2PO, Ph and meta-
C6H4OMe), 6.85 (1H, d, J 23.5, CHPh), 6.73 (2H, br d, J 9,
ortho-C6H4OMe), 6.72 (1H, d, J 17.1, CHOCOAr), 6.51* (t,
J 7.5, CH2OH), 3.82 (3H, s, OMe), 3.67 (2H, d, J 7.5, CH2OH),
0.84 (3H, s, Me) and 0.55 (3H, s, Me); δC(100 MHz; CDCl3)
166.0Ϫ and 163.6Ϫ (para-C H OMe and C᎐O), 147.8ϩ (d,
᎐
6
4
2,2-Dimethyl-3-(4-methoxybenzoyloxy)propanal 16
J 12.5, CHPh), 137–128 (m, Ph2PO, Ph, ortho-C6H4OMe and
Ph2PO-C), 121.8Ϫ (ipso-C6H4OMe), 113.4ϩ (meta-C6H4OMe),
Oxalyl chloride (0.83 g, 570 µl, 6.5 mmol) in dry dichlorometh-
ane (5 cm3) was added to a solution of dry dimethyl sulfoxide
(1.2 g, 5 mmol) in dry dichloromethane (30 cm3) at Ϫ78 ЊC.
After 30 minutes 2,2-dimethyl-3-hydroxypropyl 4-methoxy-
benzoate21 15 (1.2 g, 5 mmol) in dry dichloromethane (15 cm3)
was added and the reaction was stirred for a further 30 minutes.
Triethylamine (3.06 g, 4.2 cm3, 30 mmol) was added and the
reaction was allowed to warm to room temperature over 22
hours. Water (100 cm3) was added and the layers were separ-
ated. The aqueous layer was extracted with diethyl ether (3 × 50
cm3), the combined organic extracts were washed with water
77.7ϩ
(CHOC᎐O), 68.0Ϫ (CH2), 55.8ϩ (OMe), 44.1Ϫ (CMe2),
᎐
24.0
ϩ (Me) and 23.0ϩ (Me); m/z (LSIMS) 541 (68%, MHϩ), 389
(55, M Ϫ OCOAr), 201 (100, Ph2PO) (Found: MHϩ, 541.2127.
H34O5P requires M, 541.2128). Chiral HPLC analysis
C33
(50 : 50 isohexane–IPA, τmajor 6.8 min, τminor 18.2 min) of this
material showed an enantiomeric excess of 13%.
(E )-4,4-Dimethyl-3,5-dihydroxy-2-diphenylphosphinoyl-1-
phenylpent-1-ene 17
Lithium hydroxide (135 mg, 3.1 mmol) was added to a solution
J. Chem. Soc., Perkin Trans. 1, 2001, 2240–2249
2247

View Article Online
of (E)-4,4-dimethyl-2-diphenylphosphinoyl-3-hydroxy-1-phen-
ylpent-1-en-5-yl 4-methoxybenzoate 18 (830 mg, 1.5 mmol,
18% ee) in methanol (20 cm3). The reaction was stirred for 23
hours and the solvent was evaporated under reduced pressure.
The residue was dissolved in dichloromethane–water (1 : 1, 40
cm3) and the layers were separated. The aqueous layer was
extracted with dichloromethane (3 × 20 cm3), the combined
organic extracts were washed with brine (50 cm3), dried
(MgSO4) and evaporated under reduced pressure to give diol
17 (582 mg, 92%) as prisms, mp 157–158 ЊC (from EtOAc–
hexane); [α]D Ϫ35 (c. 0.96 in CHCl3); Rf(EtOAc) 0.41;
νmax(CHCl3)/cmϪ1 3600–3000 (br, OH), 1437 (P–Ph) and 1153
CH2 minor), 24.7Ϫ
(CMe2), 24.6Ϫ
(CMe2), 21.5ϩ, 21.4ϩ,
major
minor
19.6ϩ, 19.6ϩ, 19.5ϩ and 19.4ϩ (4 × Memajor and 4 × Meminor);
m/z (ESI) 643 (100%, MNaϩ) (Found: MNaϩ, 643.2268.
C35H41NaO6PS requires M, 643.2259).
General procedure for the synthesis of allenes
The hydroxyphosphine oxide (1 mmol) in dry DMF (12 cm3)
was added to a stirred suspension of sodium hydride (2 mmol)
in dry DMF (5 cm3) at 20 ЊC. The reaction mixture was stirred
at 60 ЊC for 30 minutes, allowed to cool to room temper-
ature and poured into saturated ammonium chloride solution
(25 cm3). The aqueous layer was extracted with ether (3 × 25
cm3) and the combined organic extracts were washed with water
(30 cm3), brine (30 cm3), dried (MgSO4) and evaporated under
reduced pressure at 0 ЊC to give the crude allene.
(P᎐O); δ (400 MHz; CDCl ) 7.87–7.80 (2H, m, Ph PO), 7.73–
᎐
H
3
2
7.67 (2H, m, Ph2PO), 7.60–7.48 (6H, m, Ph2PO and Ph), 7.36–
7.20 (5H, m, Ph2PO and Ph), 6.85 (1H, d, J 24.5, CHPh), 5.72*
(1H, t, J 6.5, CH2OH), 5.22 (1H, dd, J 20.5 and 9.5, CHOH),
4.61* (1H, br d, J 9.5, CHOH), 3.82 (1H, dd, J 12 and 7,
CHAHB), 3.32 (1H, dd, J 12 and 6, CHAHB), 0.97 (3H, s, Me)
and 0.48 (3H, s, Me); δC(100 MHz; CDCl3) 145.8ϩ (d, J 12.5,
CHPh), 138–127 (m, Ph2PO, Ph and Ph2PO-C), 78.2ϩ
(CHOH), 69.3Ϫ (CH2OH), 41.4Ϫ (CMe2), 23.1ϩ (Me) and 22.0ϩ
(Me); m/z (ESI) 429 (100%, MNaϩ), 407 (92, MHϩ) (Found:
MHϩ, 407.1777. C25H28O3P requires M, 407.1776) (Found: C,
73.9; H, 6.7; P, 7.7. C25H28O3P requires C, 73.9; H, 6.7; P, 7.6%).
4,4-Dimethyl-1-phenylpenta-1,2-diene 20a
By the general method, (E)-4,4-dimethyl-2-diphenylphos-
phinoyl-3-hydroxy-1-phenylpent-1-ene 7a (150 mg, 0.38 mmol)
and sodium hydride (60% dispersion in mineral oil, 31 mg, 0.77
mmol) gave a crude product that was purified by Kugelrohr
distillation (9 mmHg, oven temperature 110 ЊC) to give the
allene 20a (59 mg, 89%) as a colourless oil; [α]D ϩ46.0 (c. 1.65
in EtOH) (lit.,22 ϩ370 (in EtOH)) whose data matched those
previously reported.22
Derivatisation of diol 17; (E )-5-[(S)-(camphor-10-sulfonyl)oxy]-
4,4-dimethyl-2-diphenylphosphinoyl-3-hydroxy-1-phenylpent-
1-ene
2,2,6,6-Tetramethylhepta-3,4-diene 20b
By the general method, (E)-4-diphenylphosphinoyl-3-hydroxy-
2,2,6,6-tetramethylhept-4-ene 8a (150 mg, 0.40 mmol) and
sodium hydride (60% dispersion in mineral oil, 32 mg, 0.81
mmol) gave a crude product that was purified by Kugelrohr
distillation (8 mmHg, oven temperature 60 ЊC) to give the allene
20b (47 mg, 74%) as a colourless oil; [α]D ϩ28 (c. 1.4 in EtOH)
(lit.,22 ϩ124 (in EtOH)) whose data matched those previously
reported.22
Triethylamine (5 drops) and catalytic DMAP were added to
a solution of (E)-4,4-dimethyl-3,5-dihydroxy-2-diphenylphos-
phinoyl-1-phenylpent-1-ene 17 (100 mg, 0.25 mmol, 10% ee) in
dichloromethane (10 cm3). (1S)-(ϩ)-Camphor-10-sulfonyl
chloride (74 mg, 0.30 mmol) was added and the reaction mix-
ture was stirred for 20 hours. Water (20 cm3) was added and the
layers were separated. The aqueous layer was extracted with
dichloromethane (3 × 20 cm3), the combined organic extracts
were washed with brine (50 cm3), dried (MgSO4) and evapor-
ated under reduced pressure to give the crude product. The
residue was chromatographed (SiO2, EtOAc–dichloromethane,
1 : 1) to give a mixture of diastereoisomers of the camphor
derived phosphine oxide (128 mg, 84%) as a colourless gum.
Rf(EtOAc) 0.63; νmax(CDCl3)/cmϪ1 3500–3100 (br, OH and
2,2,6-Trimethylhepta-3,4-diene 20c
By the general method, (E)-4-diphenylphosphinoyl-3-hydroxy-
2,2,6-trimethylhept-4-ene 8b (250 mg, 0.70 mmol) and sodium
hydride (60% dispersion in mineral oil, 37 mg, 0.91 mmol) gave
a crude product that was purified by Kugelrohr distillation (105
mmHg, oven temperature 80 ЊC) to give the allene 20c (5 mg,
5%) as a colourless oil; [α]D ϩ4.5 (c. 0.25 in CDCl3) (lit.,22 ϩ110
(in EtOH)) whose data matched those previously reported.22
NH), 1745 (C᎐O), 1438 (P–Ph), 1356 (SO ) and 1163 (P᎐O and
᎐
᎐
2
SO2); δH(500 MHz; CDCl3) 7.97–7.90 (2Hmajor and 2Hminor, m,
Ph2PO), 7.66–7.23 (13Hmajor and 13Hminor, m, Ph2PO and Ph),
6.92 (1Hmajor, d, J 23.5, CHPh), 6.91 (1Hminor, d, J 23.5, CHPh),
5.76 (1Hmajor and 1Hminor, br d, J 10.5, OH), 5.30–5.20 (1Hmajor
and 1Hminor, m, CHOH), 4.22 (1Hmajor and 1Hminor, d, J 9.5,
CHAHBO), 3.81 (1Hminor, d, J 9.5, CHAHBO), 3.78 (1Hmajor, d,
J 9.5, CHAHBO), 3.47 (1Hminor, d, J 15, CHAHBSO2), 3.43
(1Hmajor, d, J 15, CHAHBSO2), 2.92 (1Hmajor, d, J 15, CHAHB-
SO2), 2.84 (1Hminor, d, J 15, CHAHBSO2), 2.44–2.31 (2Hmajor and
2Hminor, m, camphor), 2.09–1.86 (5Hmajor and 5Hminor, m, cam-
Acknowledgements
We thank Fraser Kerr and Fiona Bell of AstraZeneca
for assistance with chiral HPLC and the EPSRC for a grant to
JAM.
phor), 1.57 (1Hmajor, dd, J 9.5 and 4.5, camphor), 1.55 (1Hminor
,
References
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᎐
᎐
major
minor
147.6ϩ
(d, J 12.5, CHPh), 147.5ϩ
(d, J 12.5, CHPh),
major
minor
136–128 (m, Ph2PO, Ph and Ph2PO-C), 76.0Ϫ
(CH2O),
(CHOH),
major
76.0Ϫ
(CH2O), 74.6ϩ
(CHOH), 74.6ϩ
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57.7Ϫmajor (CH2SO2), 57.6Ϫminor (CH2SO2), 47.8Ϫ (CCH2SO2 major
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(CH C᎐O), 46.4Ϫ
(CH2-
(CH on cam-
᎐
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2
minor
C᎐O), 42.8ϩ
(CH on camphor), 42.7ϩ
᎐
major
minor
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and CMe2 minor), 41.2Ϫ
(CH2 on
major
major
camphor), 41.2Ϫ
(CH2 on camphor), 26.8Ϫ (CH2
and
minor
major
2248
J. Chem. Soc., Perkin Trans. 1, 2001, 2240–2249

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