Enantioselective synthesis of phospholanes using chiral lithium amide desymmetrisation

Article abstract of DOI:10.1016/S0040-4020(02)00366-6

The enantioselective deprotonation of 1,2,5-triphenylphospholane oxide with a chiral base, followed by electrophilic quenching, gives a range of chiral products in good yield and in ca. 85% ee. The absolute and relative configuration of two of the products was determined by X-ray crystallography. A number of the chiral phospholane oxides were subjected to further transformations, in particular reduction to give enantiomerically pure phospholanes.

Full text of DOI:10.1016/S0040-4020(02)00366-6

TETRAHEDRON
Pergamon
Tetrahedron 5872002) 4589±4602
Enantioselective synthesis of phospholanes using chiral
lithium amide desymmetrisation
Alexander J. Blake, Stephen C. Hume, Wan-Sheung Li and Nigel S. Simpkinsp
School of Chemistry, University of Nottingham, University Park, Nottingham NG7 2RD, UK
Received 8October 2001; accepted 9 January 2002
AbstractÐThe enantioselective deprotonation of 1,2,5-triphenylphospholane oxide with a chiral base, followed by electrophilic quenching,
gives a range of chiral products in good yield and in ca. 85% ee. The absolute and relative con®guration of two of the products was
determined by X-ray crystallography. A number of the chiral phospholane oxides were subjected to further transformations, in particular
reduction to give enantiomerically pure phospholanes. q 2002 Published by Elsevier Science Ltd.
1. Introduction
system with chiral lithium amide 4, followed by quenching
with a range of electrophiles, gave the desired products 5±
15 in good yield and enantiomeric excess, Table 1.
As part of our efforts to delineate the applications of chiral
lithium amide base reagents, we have described desym-
metrisation reactions of diverse types of substrate, including
ketones, sulfoxides, chromium arene complexes and various
dicarbonyl compounds.1,2 Extension of this type of process
to phosphorus containing compounds was deemed attrac-
tive, especially since chiral phosphines are such valuable
ligands in asymmetric catalysis. We therefore became inter-
ested in an asymmetric approach to such compounds involv-
ing reaction of a prochiral cyclic phosphine oxide with a
chiral base, exempli®ed in its simplest form by the conver-
sion of 1 into 2, Scheme 1.3
Preliminary reactions showed that the inclusion of LiCl at
very low temperature gave better results than reactions at
2788C without this additive.7 Chiral base 4 also gave better
selectivities than a number of alternative bases that were
tried.
In each case only one diastereomer was found in respect of
the ring stereochemistry, in which electrophilic quenching
had occurred to maintain the all-syn arrangement of ring
phenyl substituents. Evidence for this was obtained from
NMR spectroscopy experiments in which nOe enhance-
ments 72±4%) were found between the C-5H proton and
protons on the newly introduced substituent, as illustrated
for 16, thereby indicating a syn relationship.
As in similar established chiral lithium amide reactions, it
was anticipated that chiral base discrimination between
enantiotopic protons located at the two acidic sites 7a and
a0) would lead to a chiral, non-racemic organolithium inter-
mediate, which upon electrophilic quenching would give
potentially useful chiral products. This plan presented a
number of challenges, especially since the levels of
diastereocontrol required in both the deprotonation and
electrophilic quenching steps could not be guaranteed.4,5
2. Chiral base reactions of a substituted phospholane
After some preliminary work we decided to investigate in
detail the chemistry of the triphenyl substituted phospholane
oxide 3, which is readily available in three steps, via the
corresponding phosphole and phosphole oxide, starting
from 1,3-diphenylbutadiene.6 Pleasingly, reaction of this
Keywords: asymmetric synthesis; chiral lithium amide; phospholane.
Corresponding author. Fax: 144-115-9513564;
e-mail: nigel.simpkins@nottingham.ac.uk
p
The adducts with benzaldehyde and cyclohexylcarboxalde-
hyde, 11 and 12, respectively, were formed as mixtures of
0040±4020/02/$ - see front matter q 2002 Published by Elsevier Science Ltd.
PII: S0040-4020702)00366-6

4590
A. J. Blake et al. / Tetrahedron 58 (2002) 4589±4602
Scheme 1.
diastereoisomers at the newly formed carbinol centre. In
the case of 12, no selectivity was observed, but in the case
of 11 a 7:1 mixture was obtained, the major product
having the stereochemistry illustrated 7as shown by X-
ray crystallography). The quenches involving picolyl
chloride, leading to 14, and 2-chloromethyl-4,4-dimethy-
loxazoline, leading to 15, were carried out with the idea of
introducing additional functionality with potential for
metal chelation.
Figure 1. Structure of compound 11.
by X-ray crystallography using enantiomerically enriched
samples. The structures of compounds 11 7major diastereo-
mer) and 13 were determined in this way 7Figs. 1 and 2), the
collection of low temperature data, including Friedel
equivalents, allowing us to determine the Flack parameter
and so assign the absolute con®gurations.
Lithiated phosphine oxides have been demonstrated to be
con®gurationally unstable under the types of reaction condi-
tions that we are employing.8 Therefore, the high level of
diastereocontrol seen in the above reactions is likely to be
the result of very effective steric shielding of one face of the
reactive intermediate by the two ®xed phenyl substituents,
rather than due to con®gurational stability of the chiral
organolithium.
The structure of 11 also shows clearly the full relative
stereochemistry, as indicated earlier. Both structures show
evidence for intramolecular O±H´´´OvP hydrogen bonding
Ê
Ê
Ã
for 11 [O´´´O, 2.71 A; H´´´O, 1.8 5 A; O±H´´´O, 1578].
The levels of enantioselectivity are synthetically useful,
especially since several of the products are readily enriched
to .98% ee by recrystallisation 7see Section 6). The small
variations in the ee of the products, around an average of
about 85%, are probably not signi®cant and do not seem to
correlate in any way with the nature of the electrophile
employed.
In previous reports we have rationalised the outcome of the
chiral base reactions by a simple model, shown in revised
form for the phosphine oxide deprotonation in Fig. 3.9
The model invokes the free monomer of the lithium amide
as the active base in the conformation shown for the solid
state 7where the base is actually in the form of a homochiral
dimer).10 Approach of the phosphine oxide to the base is via
an unhindered quadrant, leading to proton abstraction
following co-ordination of the base to the PvO group.
Although this primitive representation of the process
ignores complications caused by aggregates and mixed
aggregates, and possible conformational changes in the
base, it seems to have some general predictive power in
most cases encountered to date.11
Since all of the products come from a common intermediate
organolithium they must all have the same absolute con-
®guration. We sought to assign the absolute con®guration
Table 1. Enantioselective substitution of phospholane oxide 3
During the course of our studies a related paper appeared by
Entry
Electrophile
MeI
EtI
Compound 7%)
ee 7%)a
84
1
2
3
4
5
6
7
5 787)
6 789)
7 762)
8 772)
9 793)
10 760)
11 782)c
12 774)c
13 785)
14 761)
15 774)
90
b
BnBr
Allyl bromide
Prenyl bromide
PhSSO2Ph
PhCHO
87
88
82
92
80
86
84
82
8Cyclohexyl-CHO
9
10
11
Acetone
Picolyl chloride
Oxazolined
a
Measured by HPLC.
Not determined.
Mixture of diastereomers.
2-Chloromethyl-4,4-dimethyloxazoline.
b
c
d
Figure 2. Structure of compound 13.

A. J. Blake et al. / Tetrahedron 58 (2002) 4589±4602
4591
Figure 3.
Fiaud and co-workers.12 In this work they attempted the
enantioselective conversion of 3 into a chiral trans-isomer
17 by deprotonation with sec-butyllithium-sparteine and
reprotonation with various proton sources. This procedure
gave either low chemical yields of the desired chiral
compound or low enantioselectivities and the results are
not easily compared with our own.
Even when compounds such as 23 or 24 were re-exposed to
an excess of the organolithium derived from 3 none of the
desired bis-phospholane oxide was observed. This line of
investigation was not pursued further.
Although we were unable to obtain trans compound 17 in
non-racemic form from our chiral base reactions, we did
observe isomerisation of 3 to give this isomer on prolonged
treatment with bases under protic conditions. This result
prompted us to isomerise some of the enantiomerically
pure phosphine oxides that had been obtained earlier, as
shown in Scheme 2.
Although we were pleased with the levels of asymmetric
induction obtained in the chiral base reactions, phosphine
oxide 3 is clearly a rather special case that bene®ts from
additional benzylic stabilisation of the derived organo-
lithium. We brie¯y screened a range of chiral bases in simi-
lar reactions with the simpler system, 1-phenylphospholane
oxide, lacking the additional ¯anking phenyl substituents.
However, this gave unsatisfactory results, both in the low
yields obtained and in the negligible levels of enantiomeric
excess.
In each case most of the starting material was converted into
the corresponding C-5 diastereoisomer, the transformation
being accompanied in each case by a distinctive up®eld shift
1
in the C-5H signal in the H NMR spectrum.
3. Further synthetic transformations of chiral
phospholane oxides
Along similar lines, we were also able to effect an additional
substitution reaction using enantiomerically pure phospho-
lane 5, Scheme 3.
In view of the great interest in phosphines having additional
heteroatom functionality, it was of interest to examine the
range of transformations possible with some of the phos-
phine oxides that we had generated in very high enantio-
meric purity. Oxidative transformations successfully carried
out on enantiomerically pure allyl derivative 8 included
hydroboration and oxidative cleavage, leading to new pro-
ducts 26 and 27, Scheme 4.
Deprotonation with n-BuLi followed by quenching with
either acetic anhydride or benzaldehyde gave 21 and 22,
respectively, again as single C-5 isomers, presumably with
the stereochemistry shown.
A further aspect that we were intrigued to explore was the
possibility of using the chiral base reaction to link two
phospholane rings together. Such an approach might
ultimately lead to chiral bis-phosphines, which are a
very important family of ligands for transition metal cata-
lysis, and the use of linked phospholanes has precedent in
the DuPhos ligands.13 To test this idea we carried out the
metallation of 3 with n-BuLi and then added various diha-
lides, including 7Z)-1,4-dichlorobutene, 7E)-1,4-dibromo-
butene and a,a0-dibromo-m-xylene. However, in each
case we obtained only the mono-alkylated products 23±
25.
Although we could have further manipulated the acid 27
or ester 28 in order to obtain the corresponding aldehyde,
we found that it was more straightforward to obtain this
compound by ozonolysis of the prenyl derivative 9. As
shown in Scheme 5, this also allowed easy access to poten-
tially useful alcohol and mesylate derivatives.
Some further transformations were not successful. For
example, attempted McMurry reactions of aldehyde 29
gave only pinacol type diols as mixtures of inseparable
Scheme 3.
Scheme 2.

4592
A. J. Blake et al. / Tetrahedron 58 (2002) 4589±4602
Scheme 4.
Scheme 5.
Scheme 6.
diastereomers and further elimination did not prove pos-
sible. Similarly, attempted substitution reactions of mesyl-
ate 31 with secondary amines, or with Ph2PLi, did not give
the desired products. However, aldehyde 29 did prove
amenable to reductive amination, albeit in modest yield,
e.g. to give 32 and 33, Scheme 6.
amounts of any isomers observed, indicating that both the
reduction and oxidation are at least highly stereoselective
7possibly even stereospeci®c).
A number of other phosphine oxides were reduced in this
way to give the corresponding enantiomerically pure phos-
phines, Table 2.
These preparations were not fully optimised, and indeed we
found that higher yields 7.50%) could be obtained by an
alternative two step procedure involving a separate imine
formation step, followed by reduction with NaBH4.
In most cases the reductions were straightforward, the
product phosphines being isolated as single isomers in
good yield. However, several aspects deserve further
comment. It was not possible to reduce the hydroxymethyl
types of phospholane oxide 11±13 without retro-addition
taking place. Therefore, the reduction of compound 11
was carried out on the acetate derivative. The reduction of
amine containing systems 32 and 33 was found to be some-
what unreliable, these compounds having a tendency to
undergo epimerisation at the C-5 position, as illustrated
earlier in Scheme 2. These compounds were best reduced
immediately after puri®cation.
4. Reduction of phosphine oxides to give
enantiomerically pure phosphines
With a number of highly enantiomerically enriched samples
of phospholane oxides available it was important to estab-
lish if they could be reduced to the corresponding phos-
phines. A wide range of reagents is available for such a
transformation, but we chose to focus on the use of the
trichlorosilane±pyridine combination in benzene.14 This
reagent has been shown to reduce phosphine oxides with
retention of con®guration at phosphorus, although we could
not be certain that this stereochemical outcome would
prevail in our systems. To check this, we ®rst reduced
oxide 5 to give a phosphine assigned the structure 34,
Scheme 7.
5. Summary and conclusion
The chiral lithium amide base reactions of phospholane
oxide 3 enable the synthesis of novel chiral phosphine
oxides in good yield and enantiomeric excess. This in turn
allowed the synthesis of a range of chiral phosphines
following reduction. To date we have been unable to carry
out substantial screening of these ligands in appropriate
metal catalysed processes, but the ease of synthesis and
As shown, the phosphine was then re-oxidised using hydro-
gen peroxide, giving back only compound 5, with data
identical to the initial sample. At no stage were signi®cant

A. J. Blake et al. / Tetrahedron 58 (2002) 4589±4602
Table 2. Reduction of phospholane oxides to phospholanes
4593
Entry
R
Phosphine oxide
Phosphine
Yield 7%)
Scheme 7.
1
2
3
4
5
6
7
Me
Et
2-picolyl
Oxazoline
CH7OAc)Ph
7CH2)3OH
CH2CO2Me
2)2NEt2
5
6
34
35
36
37
38
39
40
41
42
80
96
84
76
76
81
75
44
79
14
15
11a
26
28
32
33
range of functional substituents available makes these
compounds interesting for further study.
87CH
9
6. Experimental
7CH2)2NHBn
6.1. General details
a
Reduced in the form of the acetate derivative.
Melting points were determined using a Ko¯er hot-stage
melting point apparatus and are uncorrected. Melting points
for all phosphines were determined in sealed tubes after
purging with N2. Infrared 7IR) spectra were recorded
using a Perkin±Elmer 1600 Series FTIR spectrometer.
Mass spectra were recorded on a VG Micromass 70E or
VG Autospec spectrometer, using electron impact 7EI) or
fast atom bombardment 7FAB). Micro analyses were
performed at the microanalytical laboratory of the Univer-
sity of Nottingham using a Perkin±Elmer 240B elemental
analyser. Optical rotations were recorded using a JASCO
DIP-370 digital polarimeter, and are recorded in units of
1021 deg cm2 g21. All NMR spectra were recorded on either
a Bruker AM250, JEOL EX270, Bruker AM400 or Bruker
DRX500, with tetramethylsilane as internal standard.
Trimethylphosphite was used as an external reference for
31P NMR spectra. J values are recorded in Hertz and abbre-
viations used are sÐsinglet, dÐdoublet, tÐtriplet, qÐ
quartet, mÐmultiplet, ddÐdouble doublet etc. Multi-
plicities indicated for 13C NMR were obtained using a
DEPT sequence.
chloride salt 7259 mg, 0.99 mmol) in THF 75 mL), under
N2 at ca. 21008C, with n-BuLi 71.4 M in hexanes)
71.39 mL, 1.94 mmol). The suspension was allowed to
warm to room temperature over a period of 20 min,
during which time all the solid dissolved and the solution
turned pale yellow in colour. The reaction mixture was
recooled to 21008C 7ethanol/N2) and a solution of 1,2,5-
triphenylphospholane oxide 3 7300 mg, 0.90 mmol) in
THF 79 mL) was added dropwise over a period of
30 min, maintaining the temperature at 21008C. After
stirring the deep orange/red solution at 21008C for a
further 30 min, methyl iodide 70.56 mL, 9.04 mmol) was
added and stirring of the resultant yellow/orange solution
was continued for 2 min before the reaction was quenched
with saturated aqueous NH4Cl 710 mL). In some cases the
reaction mixture was stirred for a longer period of time
before aqueous quenching, or was allowed to warm up,
until TLC indicated complete consumption of starting
material.
Flash column chromatography was performed using Fluka
silica gel 60 7220±440 mesh). Analytical thin layer chroma-
tography 7tlc) was performed using CAMLAB silica gel F254
precoated plastic plates which were visualised under ultra-
violet light and developed with basic potassium permangan-
ate solution. HPLC was performed on Chiralcel OD or OJ
columns using a Waters 600E System Controller and a
Waters 484 Tuneable Absorbance Detector.
The organic layer was removed and the aqueous layer
extracted with CH2Cl2 73£10 mL), the combined organic
extracts dried 7MgSO4) and the solvent evaporated under
reduced pressure to give an off-white solid. Puri®cation by
column chromatography 72% EtOH/Et2O) yielded the title
compound 5 as a white solid 7272 mg, 87%), mp 197±
23
2018C; [a]D ˆ136 7c 1.09 in CHCl3); 7Found: C, 79.39;
H, 6.75. C23H23OP requires C, 79.05; H, 6.69%); nmax
7CHCl3) 7cm21) 2968, 1600, 1495, 1454, 1376, 1158,
1108and 1072; dH 7400 MHz, CDCl3) 1.87 73H, d,
Jˆ13.1 Hz, CH3), 2.32±2.54 72H, m, C-3H or C-4H), 2.69
71H, m, C-3H or C-4H), 2.92 71H, m, C-3H or C-4H), 4.02
71H, app. dt, Jˆ23.6 and 9.1 Hz, C-5H), 6.87±7.27 715H, m,
ArH); dC 768MHz, CDCl 3) 24.0 7d, Jˆ12 Hz, CH2, C-3),
27.2 7CH3), 34.2 7d, Jˆ15 Hz, CH2, C-4), 45.6 7d, Jˆ59 Hz,
C and CH, C-2 and C-5), 125.8±131.3 7aromatic CH),
129.1, 136.0 and 142.7 7aromatic C); m/z 7EI) 346 7M1,
97%), 220 748), 205 724), 143 731), 118 784) and 91 7100)
7HRMS: Found M1, 346.1502. C23H23OP requires M,
346.1487).
Organic solvents and reagents were dried from the follow-
ing as required: THF 7Na-benzophenone ketyl), acetone
7CaSO4), pyridine, triethylamine, dimethyl sulfoxide,
dimethylformamide and dichloromethane 7calcium hy-
dride). Petrol refers to the fraction boiling between 40 and
608C and was distilled before use. Unless otherwise stated
all other solvents and reagents were used as received from
commercial suppliers.
6.2. Typical procedure for chiral base reactions *Table 1)
6.2.1. *1S,2R,5S)-2-Methyl-1,2,5-triphenylphospholane-
1-oxide 5. A solution of chiral base 4 containing an equi-
molar amount of LiCl was prepared by treatment of a
suspension of the corresponding secondary amine hydro-
HPLC analysis using a Chiralcel OD column 730% propan-
2-ol in hexane as eluent) indicated that the product
contained a 92.1:7.9 mixture of enantiomers 784% ee).

4594
A. J. Blake et al. / Tetrahedron 58 (2002) 4589±4602
Flow rate 1 mL min21. Detection at 256 nm. Retention
times 5.2 min 7major) and 11.0 min 7minor).
6.2.4. *1S,2R,5S)-2-*Prop-20-enyl)-1,2,5-triphenylphos-
pholane-1-oxide 8. The typical conditions described
above were employed, starting with
1.0 mmol). Puri®cation of the crude product by column
3
7332 mg,
Recrystallisation from EtOH/H2O afforded material with an
enantiomeric excess of 96 and 69% recovery. Alternatively
recrystallisation from MeOH/H2O 7£3) afforded material
chromatography 7Et2O) yielded the title compound 8 as a
23
white solid 7269 mg, 72%), mp 183±1898C; [a]D ˆ192 7c
25
with an enantiomeric excess of $99%Ð[a]D ˆ143 7c
1.01 in CHCl3); 7Found: C, 80.46; H, 6.58. C25H25OP
requires C, 80.61; H, 6.77%); nmax 7CHCl3) 7cm21) 2975,
1638, 1600, 1495, 1450, 1158 and 1106; dH 7250 MHz,
CDCl3) 2.31±2.74 74H, m, C-3H and C-4H), 2.86 71H,
ddd, Jˆ5.5, 8.8 and 14.2 Hz, C-10H), 3.10 71H, m, C-
10H), 3.93 71H, app. dt, Jˆ23.5 and 9.1 Hz, C-5H), 4.97
71H, d, Jˆ10.1 Hz, 7E)-C-30H), 5.02, 71H, d, Jˆ17.1 Hz,
7Z)-C-30H), 5.32 71H, m, C-20H) and 6.77±7.19 715H, m,
ArH); dC 768MHz, CDCl 3) 24.3 7d, Jˆ12 Hz, CH2, C-3),
30.7 7d, Jˆ15 Hz, CH2, C-4), 42.1 7CH2, C-10), 46.5 7d,
Jˆ59 Hz, CH, C-5), 49.1 7d, Jˆ61 Hz, C, C-2), 118.4
7CH2, C-30), 125.2±132.7 7aromatic CH), 132.9 7CH, C-
20) and 129.3, 136.2, 140.1 7aromatic C); m/z 7EI) 372
7M1, 100%), 331 727), 268713), 205 79), 129 719) and 91
738) 7HRMS: Found M1, 372.1639. C25H25OP requires M,
372.1643).
1.04 in CHCl3), and 30% recovery.
6.2.2. *1S,2R,5S)-2-Ethyl-1,2,5-triphenylphospholane-1-
oxide 6. The typical conditions described above were
employed, starting with 3 7332 mg, 1.0 mmol). Puri®cation
of the crude product by column chromatography 72%
EtOH/Et2O) yielded the title compound 6 as a white
21
solid 7322 mg, 89%), mp 196±1978C; [a]D ˆ155 7c
1.08in CHCl ); 7Found: C, 80.10; H, 6.95. C24H25OP
3
requires C, 79.98; H, 6.99); nmax 7CHCl3) 7cm21) 2969,
1600, 1495, 1450, 1157 and 1107; dH 7400 MHz, CDCl3)
0.74 73H, t, Jˆ7.3 Hz, CH3), 2.27 71H, m, C-10H), 2.36±
2.53 73H, m, C-10H, C-3H and C-4H), 2.61 71H, m, C-4H),
2.8 0 71H, m, C-3H), 3.98 71H, app. dt,Jˆ23.7 and 8.8 Hz,
C-5H) and 6.85±7.19 715H, m, ArH); dC 7100 MHz,
CDCl3) 7.8 7CH3), 24.6 7d, Jˆ12 Hz, CH2, C-3), 30.4
7CH2, C-10), 30.5 7d, Jˆ15 Hz, CH2, C-4), 46.6 7d,
Jˆ59 Hz, CH, C-5), 49.9 7d, Jˆ62 Hz, C, C-2), 125.8±
131.5 7aromatic CH), 129.87d, Jˆ58 Hz, C, P±CAr), 136.3
and 140.1 7aromatic C); dP7202 MHz, CDCl3) 63.4; m/z
7EI) 360 7M1, 81%), 345 778), 332 7100), 256 731), 216
723), 117 745) and 91 758) 7HRMS: Found M1, 360.1653.
C24H25OP requires M, 360.1643).
HPLC analysis using a Chiralcel OD column 730% propan-
2-ol in hexane as eluent) indicated that the product
contained a 93.6:6.4 mixture of enantiomers 787% ee).
Flow rate 1 mL min21. Detection at 256 nm. Retention
times 4.8min 7major) and 7.0 min 7minor).
Material of $99% ee was obtained with 59% recovery by a
single recrystallisation from EtOAc.
HPLC analysis using a Chiralcel OD column 730% propan-
2-ol in hexane as eluent) indicated that the product
contained a 95:5 mixture of enantiomers 790% ee). Flow
rate 1 mL min21. Detection at 256 nm. Retention times
4.6 min 7major) and 7.3 min 7minor).
6.2.5. *1S,2R,5S)-2-*30-Methylbut-20-enyl)-1,2,5-triphenyl-
phospholane-1-oxide 9. The typical conditions described
above were employed, starting with 3 74.0 g, 12.0 mmol).
Puri®cation of the crude product by column chromato-
graphy 7Et2O) yielded the title compound 9 as a white
27
Recrystallisation from EtOH/H2O 7£2) afforded material of
$99% ee with 57% recovery.
solid 74.74 g, 93%), mp 172±1758C; [a]D ˆ169 7c 1.09
in CHCl3); 7Found: C, 81.11; H, 7.45. C27H29OP requires C,
80.96; H, 7.3%); nmax 7CHCl3) 7cm21) 2969, 1600, 1495,
1451, 1377, 1155 and 1106; dH 7400 MHz, CDCl3) 1.58
73H, s, CH3), 1.61 73H, s, CH3), 2.41±2.51 72H, m, C-4H,
2.55±2.74 72H, m, C-3H), 4.03 71H, app. dt, Jˆ23.3
and 9.1 Hz, C-5H), 4.81 71H, t, Jˆ6.5 Hz, C-20H) and
6.86±7.21 715H, m, ArH); dC 7100 MHz, CDCl3) 18.0
7CH3), 24.5 7d, Jˆ11 Hz, CH2, C-4), 25.87CH 3), 30.8
7d, Jˆ14 Hz, CH2, C-3), 36.1 7CH2, C-10), 46.4 7d,
Jˆ58Hz, CH, C-5), 49.7 7d, Jˆ61 Hz, C, C-2), 118.1
7CH, C-20), 125.9±131.6 7aromatic CH), 129.4, 135.1,
135.1 and 140.6 7aromatic C and C-30); m/z 7EI) 400 7M1,
17%), 332 7100), 216 715), 103 711), 91 713) and 47 76)
7HRMS: Found M1, 400.1954. C27H29OP requires M,
400.1956).
6.2.3. *1S,2R,5S)-2-Benzyl-1,2,5-triphenylphospholane-
1-oxide 7. The typical conditions described above were
employed, starting with 3 7332 mg, 1.0 mmol). Puri®cation
of the crude product by column chromatography 720%
petrol/Et2O) yielded the title compound 7 as a white solid
22
7261 mg, 62%), mp 193±1958C; [a]D ˆ1117 7c 0.83 in
CHCl3); 7Found: C, 82.35; H, 6.55. C29H27OP requires C,
82.33; H, 6.17%); nmax 7CHCl3) 7cm21) 2953, 1602, 1496,
1454, 1310, 1154 and 1107; dH 7400 MHz, CDCl3) 2.34±
2.53 73H, m, C-3H and C-4H), 2.75 71H, m, C-3H or C-4H),
3.56 71H, dd, Jˆ6.3 and 13.9 Hz, C-10H), 3.66 71H, dd,
Jˆ6.3 and 13.9 Hz, C-10H), 4.13 71H, app.dt, Jˆ23.7 and
9.6 Hz, C-5H), 6.66±7.26 720H, m, ArH); dC 768MHz,
CDCl3) 24.6 7d, Jˆ11 Hz, CH2, C-4), 30.6 7d, Jˆ15 Hz,
CH2, C-3), 43.0 7CH2, C-10), 46.7 7d, Jˆ59 Hz, CH, C-5),
50.9 7d, Jˆ61 Hz, C, C-2), 125.8±131.8 7aromatic CH),
129.5, 136.3, 136.6 and 140.3 7aromatic C); m/z 7EI) 422
7M1, 50%), 331 734), 210 725), 149 780) and 84 7100)
7HRMS: Found M1, 422.1786. C29H27OP requires M,
422.1780).
HPLC analysis using a Chiralcel OD column 730% propan-
2-ol in hexane as eluent) indicated that the product
contained a 93.9:6.1 mixture of enantiomers 788% ee).
Flow rate 1 mL min21. Detection at 256 nm. Retention
times 7.18min 7major) and 9.90 min 7minor).
Recrystallisation from EtOH/H2O 7£3) afforded material
24
of $99% ee 7[a]D ˆ174 7c 0.49 in CHCl3)) with 45%
HPLC analysis using a Chiralcel OD, OJ or Chiralpak AD
column failed to separate the enantiomers.
recovery.

A. J. Blake et al. / Tetrahedron 58 (2002) 4589±4602
4595
6.2.6. *1S,2R,5S)-2-Phenylsulfanyl-1,2,5-triphenylphos-
pholane-1-oxide 10. The typical conditions described
above were employed, starting with 3 7332 mg, 1.0 mmol).
Puri®cation of the crude product by column chromato-
graphy 735% light petrol/Et2O!Et2O) yielded the title
compound 10 as a white solid 7264 mg, 60%), mp 219±
137.9 7aromatic C); m/z 7FAB) 439 7[M1H]1, 34%), 421
732), 332 732), 154 797), 136 769), 69 787) and 57 7100)
7HRMS: Found [M1H]1, 439.1827. C29H27OP requires
[M1H], 439.1827).
HPLC analysis using a Chiralcel OD column 730% propan-
2-ol in hexane as eluent) indicated that the major diaster-
eomer contained a 96:4 mixture of enantiomers 792% ee).
Flow rate 1 mL min21. Detection at 256 nm. Retention
times 7.0 min 7minor) and 8.7 min 7major).
21
2228C; [a]D ˆ1100 7c 1.01 in CHCl3); 7Found: C,
76.26; H, 5.65; S, 7.30. C28H25OPS requires C, 76.34; H,
5.72; S, 7.28); nmax 7CHCl3) 7cm21) 2982, 1600, 1495, 1457,
1374 and 1046; dH 7400 MHz, CDCl3) 2.35±2.56 72H, m,
C-3H and C-4H), 2.73 71H, m, C-3H), 2.99 71H, m, C-4H),
4.51 71H, ddd, Jˆ6.3, 10.6 and 24.7 Hz, C-5H) and 6.91±
7.33 720H, m, ArH); dC 768MHz, CDCl 3) 23.2 7d, Jˆ9 Hz,
CH2, C-4), 31.6 7d, Jˆ16 Hz, CH2, C-3), 44.4 7d, Jˆ64 Hz,
CH, C-5), 59.7 7d, Jˆ61 Hz, C, C-2), 125.3±136.6
7aromatic CH), 129.0, 136.1 and 139.87aromatic C);
dP7202 MHz, CDCl3) 61.4; m/z 7EI) 440 7M1, 62%), 332
756), 206 719), 129 740), 103 761) and 91 7100) 7HRMS:
Found M1, 440.1363. C28H25OPS requires M, 440.1364).
Recrystallisation of a sample of 11 from EtOH/H2O
provided material of 100% ee with 70% recovery.
6.2.8. *1S,10R/S,2R,5S)-2-*Cyclohexyl-10-hydroxymethyl)-
1,2,5-triphenyl phospholane-1-oxide 12. The typical
conditions described above were employed, starting with
3 7332 mg, 1.0 mmol). Puri®cation of the crude product
by column chromatography 760% petrol/Et2O) yielded the
title compound 12 as a white solid and inseparable mixture
of two diastereomers 7329 mg, 74%); dH 7400 MHz, CDCl3)
0.78±1.79 722H, m, C-2 0H-C-70H), 2.28±2.68 75H, m, C-
3H or C-4H), 2.85±3.13 73H, m, C-3H or C-4H), 3.86 71H,
ddd, Jˆ7.6, 12.9 and 24.5 Hz, C-5H), 4.05 71H, app. dt,
Jˆ23.6 and 9.5 Hz, C-5H), 4.36 71H, s, C-10H), 4.50 71H,
d, Jˆ10.9 Hz, C-10H), 5.11 71H, s, OH) 7D2O exchange),
5.73 71H, s, OH) 7D2O exchange) and 6.76±7.44 730H, m,
ArH); m/z 7FAB) 445 7[M1H]1, 38%), 427 718), 345 721),
332 728), 83 741) and 69 7100) 7HRMS: Found [M1H]1,
445.2312. C29H33O2P requires [M1H], 445.2296).
HPLC analysis using a Chiralcel OD column 730% propan-
2-ol in hexane) indicated that the product contained a
90.6:8.3 mixture of enantiomers 782% ee). Flow rate
1 mL min21. Detection at 256 nm. Retention times 6.0 min
7minor) and 10.2 min 7major).
24
Material of $ 99% eeÐ [a]D ˆ1124 7c 1.03 in CHCl3),
was obtained with 40% recovery by a single recrystallisa-
tion from EtOH/H2O.
6.2.7. *1S,10R,2R,5S)-2-*Phenyl-10-hydroxymethyl)-1,2,5-
triphenyl phospholane-1-oxide 11 *accompanied by
minor *10S)-isomer). The typical conditions described
above were employed, starting with 3 7332 mg, 1.0 mmol).
Puri®cation of the crude product by column chromato-
graphy 730% petrol/Et2O!Et2O) yielded ®rstly the major
diastereomer 11 as a white solid 7314 mg, 72%), mp 157±
HPLC analysis of the mixture of diastereomers using a
Chiralcel OD column 730% propan-2-ol in hexane as eluent)
indicated that the major diastereomer contained a 57:7
mixture of enantiomers 780% ee). Flow rate 1 mL min21
.
Detection at 256 nm. Retention times 18.3 min 7major) and
22.2 min 7minor).
23
1618C, [a]D ˆ197 7c 1.04 in CHCl3); 7Found: C, 79.60; H,
6.25. C29H27O2P requires C, 79.43; H, 6.21%); nmax 7CHCl3)
7cm21) 3355, 2939, 1808, 1601, 1454, 1326 and 1081; dH
7400 MHz, CDCl3) 2.25±2.45 72H, m, C-3H or C-4H), 2.61
71H, m, C-3H or C-4H), 3.0871H, m, C-3H or C-4H), 4.01
71H, ddd, Jˆ7.0, 13.4 and 25.4 Hz, C-5H), 5.72 71H, dd,
Jˆ2.5 and 5.1 Hz, C-10H), 6.12 71H, d, Jˆ2.5 Hz, OH)
and 6.80±7.11 720H, m, ArH); dC 768MHz, CDCl 3) 25.3
7d, Jˆ10 Hz, CH2, C-3 or C-4), 25.5 7d, Jˆ11 Hz, CH2, C-3
or C-4), 50.9 7d, Jˆ57 Hz, CH, C-5), 58.1 7d, Jˆ59 Hz, C,
C-2), 78.9 7d, Jˆ2 Hz, CH, C-10), 126.3±131.5 7aro-
matic CH), 129.3, 135.3, 137.6 and139.0 7aromatic C);
dP7202 MHz, CDCl3) 67.5; m/z 7FAB) 439 7[M1H]1,
87%), 421 7100), 332 775), 154 736), 69 756) and 57 759)
7HRMS: Found [M1H]1, 439.1865. C29H27OP requires
[M1H], 439.1827). Followed by the 710S)-epimer of 11 as
6.2.9. *1S,2R,5S)-2-*10-Hydroxy-10-methylethyl)-1,2,5-
triphenylphospholane-1-oxide 13. The typical conditions
described above were employed, starting with 3 7332 mg,
1.0 mmol). Puri®cation of the crude product by column
chromatography 715% petrol/Et2O) yielded the title
compound 13 as a white solid 7332 mg, 85%), mp 175±
23
1778C; [a]D ˆ1100 7c 1.03 in CHCl3); 7Found: C,
77.31; H, 6.97. C25H27O2P requires C, 76.90; H, 6.97%);
nmax 7CHCl3) 7cm21) 3392, 2981, 1601, 1496, 1451, 1378,
1129 and 1102; dH 7400 MHz, CDCl3) 1.20 73H, s, CH3),
1.49 73H, s, CH3), 2.21 71H, m, C-4H), 2.55 71H, m, C-4H),
2.98±3.21 72H, m, C-3H), 3.98 71H, ddd Jˆ7.2, 13.4 and
25.6 Hz, C-5H), 5.25 71H, s, OH) 7D2O exchange) and
6.88±7.25 715H, m, ArH); dC 768MHz, CDCl 3) 25.2 7d,
Jˆ11 Hz, CH2, C-4), 27.0 7CH3), 29.0 7CH3), 29.5 7d,
Jˆ10 Hz, CH2, C-3), 51.1 7d, Jˆ59 Hz, CH, C-5), 60.4 7d,
Jˆ59 Hz, C, C-2), 77.3 7C, C-10), 125.1±132.1 7aromatic C-
H), 129.9 7d, Jˆ86 Hz, C, P±CAr), 135.8and 137.1
7aromatic C); m/z 7FAB) 391 7[M1H]1, 38%), 373 756),
332 735), 154 745), 69 781) and 55 7100) 7HRMS: Found
[M1H]1, 391.1852. C25H28O2P requires [M1H],
390.1827).
21
a white solid 745 mg, 10%) mp 140±1438C [a]D ˆ165 7c
1.23 in CHCl3); nmax 7CHCl3) 7cm21) 3356, 2927, 1602,
1496, 1454 and 1106; dH 7400 MHz, CDCl3) 2.41±2.57
73H, m, C-3H and C-4H), 2.54 71H, m, C-3H or C-4H),
4.27 71H, app. dt, Jˆ22.9 and 9.1 Hz, C-5H), 5.76 71H, d,
Jˆ5 Hz, C-10H), 5.94 71H, s, OH) and 6.81±7.23 720H, m,
ArH); dC 768MHz, CDCl 3) 24.7 7d, Jˆ11 Hz, CH2, C-4),
31.6 7d, Jˆ12 Hz, CH2, C-3), 47.0 7d, Jˆ60 Hz, CH, C-5),
54.9 7d, Jˆ60 Hz, C, C-2), 78.5 7d, Jˆ3 Hz, CH, C-10),
125.5±131.7 7aromatic CH), 135.5, 135.7, 137.8and
HPLC analysis using a Chiralcel OD column 730% propan-
2-ol in hexane as eluent) indicated that the product

4596
A. J. Blake et al. / Tetrahedron 58 (2002) 4589±4602
contained a 93.1:6.9 mixture of enantiomers 786% ee). Flow
rate 1 mL min21. Detection at 256 nm. Retention times
5.6 min 7major) and 7.5 min 7minor).
contained a 91:9 mixture of enantiomers 782% ee). Flow
rate 1 mL min21. Detection at 256 nm. Retention times
15.3 min 7major) and 20.9 min 7minor).
Recrystallisation from EtOH/H2O afforded material of 97%
ee with 69% recovery. X-Ray crystals were grown by slow
recrystallisation from EtOAc in a coldroom overnight.
Recrystallisation from MeOH/H2O 7£3) afforded material
22
of $99% ee 7[a]D ˆ191 7c 0.9 in CHCl3)) with 55%
recovery.
6.2.10. *1S,2R,5S)-2-*20-Pyridylmethyl)-1,2,5-triphenyl-
phospholane-1-oxide 14. The typical conditions described
above were employed, starting with 3 71.0 g, 3.01 mmol).
Puri®cation of the crude product by column chromato-
graphy 75% EtOH/Et2O) yielded the title compound 14 as
a pale yellow solid 7778mg, 61%), mp 193±194 8C;
6.3. Typical procedure for isomerisation of phospholane
oxides
6.3.1. *1S,2R,5R)-2-Ethyl-1,2,5-triphenylphospholane-1-
oxide 18. To a mixture of potassium tert-butoxide 733 mg,
0.29 mmol) and oxide 6 7100 mg, 0.28mmol, of $99% ee
material), under N2 at room temperature, was added tert-
butanol 74 mL). The solution was allowed to stir at room
temperature for 18h before quenching with NH 4Cl 75 mL).
The organic layer was removed and the aqueous layer
extracted with CH2Cl2 73£5 mL), the combined organic
extracts were washed with saturated NaHCO3 75 mL),
H2O 75 mL), dried 7MgSO4) and the solvent evaporated
under reduced pressure to give a white solid. Puri®cation
by column chromatography 72.5% EtOH/Et2O) yielded the
title compound 18 as a white solid 789 mg, 89%), mp 181±
24
[a]D ˆ1146 7c 1.04 in CHCl3); 7Found: C, 79.47; H,
6.14; N, 3.30. C28H26NOP requires C, 79.41; H, 6.19; N,
3.31%); nmax 7CHCl3) 7cm21) 2965, 1590, 1569, 1495, 1449
and 1106; dH 7400 MHz, CDCl3) 2.41±2.56 72H, m, C-3H
or C-4H), 2.79±3.02 72H, m, C-3H or C-4H), 3.75 72H,
collapsed AB system, C-10H), 4.15 71H, ddd, Jˆ7.4, 10.3
0
and 23.1 Hz, C-5H), 6.21 71H, d, Jˆ7.8Hz, C-3 H), 6.90±
0
7.25 717H, m, ArH) and 8.51 71H, d, Jˆ5.8Hz, C-6 H); dC
7100 MHz, CDCl3) 23.9 7d, Jˆ12 Hz, CH2, C-4), 29.6 7d,
Jˆ14 Hz, CH2, C-3), 44.6 7CH2, C-10), 45.6 7d, Jˆ59 Hz,
CH, C-5), 50.3 7d, Jˆ61 Hz, C, C-2), 121.1 7CH, C-30),
124.6 7CH, C-50), 125.9±131.6 7aromatic CH), 128.6 7d,
Jˆ87 Hz, C, P±CAr), 135.0 7CH, C-40), 136.5 7aromatic
C), 140.1 7aromatic C), 148.4 7CH, C-60) and 157.3 7C-
20); m/z 7EI) 423 7M1, 100%) 331 787), 304 781), 195 784)
and 93 743) 7HRMS: Found M1, 423.1755. C28H26NOP
requires M, 423.1752).
23
1828C; [a]D ˆ1140 7c 1.00 in CHCl3); nmax 7CHCl3)
7cm21) 3020, 2399, 1601, 1520, 1477, 1424, 1234 and
1190; dH 7400 MHz, CDCl3) 0.69 73H, t, Jˆ7.4 Hz, CH3),
2.28±2.70 76H, m, C-3H, C-4H and C-1 0H), 3.4871H, app.
dt, Jˆ11.0 and 8.7 Hz, C-5H) and 6.96±7.40 715H, m,
ArH); dC 768MHz, CDCl 3) 9.1 7CH3), 28.8 7CH2, C-3),
31.4 7CH2, C-4 or C-10), 31.5 7CH2, C-4 or C-10), 48.6 7d,
Jˆ61 Hz, CH, C-5), 53.2 7d, Jˆ62 Hz, C, C-2), 127.4±
132.7 7aromatic CH), 134.1 7d, Jˆ87 Hz, C, P±CAr),
137.6 and 142.2 7aromatic C); m/z 7EI) 360 7M1, 43%),
345 757), 332 7100), 256 728), 216 728) and 91 784)
7HRMS: Found M1, 360.1643. C24H25OP requires M,
360.1643).
HPLC analysis using a Chiralcel OD column 730% propan-
2-ol in hexane as eluent) indicated that the product
contained a 92:8mixture of enantiomers 784% ee). Flow
rate 1 mL min21. Detection at 256 nm. Retention times
6.68min 7minor) and 11.02 min 7major).
6.2.11. *1S,2R,5S)-2-*40,40-Dimethyloxazolinyl-20-methyl)-
1,2,5-triphenyl phospholane-1-oxide 15. The typical
conditions described above were employed, starting with
3 71.50 g, 4.52 mmol) Puri®cation of the crude product by
column chromatography 78% EtOH/Et2O) yielded the title
6.3.2. *1S,2R,5R)-2-*Prop-20-enyl)-1,2,5-triphenylphos-
pholane-1-oxide 19. The above procedure was employed,
starting with 8 7166 mg, 0.45 mmol). Puri®cation of the
crude product by column chromatography 73% EtOH/
Et2O) yielded the title compound 19 as a white solid
21
compound 15 as a pale yellow crystalline solid 71.49 g,
7121 mg, 73%), mp 191±1938C; [a]D ˆ1139 7c 1.34 in
24
CHCl3); nmax 7CHCl3) 7cm21) 2977, 1637, 1600, 1494,
1451, 1170 and 1109; dH 7400 MHz, CDCl3) 2.31±2.68
74H, m, C-3H and C-4H), 2.9871H, ddd, Jˆ4.9, 9.0 and
14.3 Hz, C-10H), 3.07 71H, m, C-10H), 3.4871H, app. dt,
Jˆ12.2 and 9.6 Hz, C-5H), 5.01 71H, d, Jˆ10 Hz, 7Z)-C-
30H), 5.10 71H, d, Jˆ17 Hz, 7E)-C-30H), 5.29 71H, m, C-
20H) and 6.88±7.41 715H, m, ArH); dC 768MHz, CDCl 3)
29.5 7d, Jˆ7 Hz, CH2, C-3 or C-4), 30.5 7d, Jˆ11 Hz, CH2,
C-3 or C-4), 39.6 7CH2, C-10), 47.4 7d, Jˆ61 Hz, CH, C-5),
50.6 7d, Jˆ62 Hz, C, C-2), 118.6 7CH2, C-30), 126.0±133.0
7aromatic CH and C-20) and 131.6, 135.9 and 140.6
7aromatic C); m/z 7EI) 372 7M1, 100%), 331 767), 268
743), 205 726), 143 721) and 91 775) 7HRMS: Found M1,
372.1649. C25H25OP requires M, 372.1643).
74%), mp 188±1908C; [a]D ˆ173 7c 1.28in CHCl );
3
nmax CHCl3) 7cm21) 2959, 1660, 1601, 1495, 1451, 1358,
1107, 988 and 907; dH 7400 MHz, CDCl3) 0.93 73H, s, CH3),
1.10 73H, s, CH3), 2.49 71H, m, C-4H), 2.74 71H, m, C-4H),
2.83±2.99 72H, m, C-3H), 3.07 71H, dd, Jˆ3.7 and 14.4 Hz,
C-10H), 3.41 71H, dd, Jˆ8.0 and 14.4 Hz, C-10H), 3.52 71H,
d, Jˆ8.0 Hz, C-40H), 3.61 71H, d, Jˆ8.0 Hz, C-40H), 4.0
71H, app. dt, Jˆ24.0 and 9.2 Hz, C-5H), 6.87±7.19 715H, m,
ArH); dC 7100 MHz, CDCl3) 24.1 7d, Jˆ11 Hz, CH2, C-4),
27.4 7CH3), 27.7 7CH3), 31.4 7d, Jˆ13 Hz, CH2, C-3), 35.4
7CH2, C-10), 46.2 7d, Jˆ59 Hz, CH, C-5), 48.0 7d, Jˆ60 Hz,
C, C-2), 66.0 7C, C-40), 77.9 7CH2, C-50), 125.6±131.1
7aromatic CH), 128.2, 135.5 and 138.4 7aromatic C) and
161.9 7CvN); m/z 7EI) 443 7M1, 69%), 324 758), 215
7100), 91 727) and 77 719) 7HRMS: Found M1, 443.2002.
C28H30NO2P requires M, 443.2014).
6.3.3. *1S,2R,5R)-2-*30-Methylbut-20-enyl)-1,2,5-triphenyl-
phospholane-1-oxide 20. The above procedure was
employed, starting with 9 7100 mg, 0.25 mmol). Puri®cation
of the crude product by column chromatography 72% EtOH/
HPLC analysis using a Chiralcel OD column 730% propan-
2-ol in hexane as eluent) indicated that the product

A. J. Blake et al. / Tetrahedron 58 (2002) 4589±4602
4597
Et2O) yielded the title compound 20 as a white solid 782 mg,
7400 MHz, CDCl3) 1.97 73H, d, Jˆ13.3 Hz, CH3), 2.20±
2.5873H, m, C-3H and C-4H), 3.1871H, ddd, Jˆ5.0, 14.3
and 14.3 Hz, C-3H or C-4H), 5.72 71H, d, Jˆ4 Hz, C-10),
6.3871H, s, OH) and 6.76±7.11 720H, m, ArH); dC
768MHz, CDCl 3) 23.6 7d, Jˆ12 Hz, CH2, C-3), 25.8
7CH3), 33.5 7d, Jˆ14 Hz, CH2, C-4), 48.6 7d, Jˆ59 Hz, C,
C-2), 59.2 7d, Jˆ55 Hz, C, C-5), 78.3 7C, C-10), 125.2±
131.9 7aromatic C-H), 131.9, 137.6, 139.3 and 143.7
7aromatic C); dP7202 MHz, CDCl3) 73.8; m/z 7FAB) 453
7[M1H]1, 46%), 435 733), 346 740), 307 726), 154 7100)
and 136 769) 7HRMS: Found [M1H]1, 453.1988.
C30H29O2P requires [M1H], 453.1983. Followed by the
minor diastereomer of 22 as a white solid 715 mg, 12%),
22
82%), mp 178±1798C; [a]D ˆ1110 7c 0.78in CHCl );
3
nmax 7CHCl3) 7cm21) 2970, 2361, 1602, 1496, 1451, 1377
and 1109; dH 7400 MHz, CDCl3) 1.60 76H, s, 2£CH3),
2.27±2.67 74H, m, C-3H and C-4H), 2.85 710H, m, C-10H),
3.13 71H, ddd, Jˆ5.4, 9.2 and 14.8Hz, C-1 H), 3.47 71H,
app. dt, Jˆ11.8and 9.0 Hz, C-5H), 4.70 71H, dd, Jˆ5.4 and
6.6 Hz, C-20H) and 6.93±7.42 715H, m, ArH); dC 768MHz,
CDCl3) 18.3 7CH3), 25.9 7CH3), 30.0 7d, Jˆ9 Hz, CH2, C-3
or C-4), 30.7 7d, Jˆ11 Hz, CH2, C-3 or C-4), 33.6 7CH2, C-
10), 47.87d, Jˆ61 Hz, CH, C-5), 51.4 7d, Jˆ62 Hz, C, C-2),
118.3 7C-20), 125.9±131.2 7aromatic CH) and 132.87d,
Jˆ87 Hz, C, P±CAr), 135.1 7aromatic C), 136.1 7C-30) and
141.1 7aromatic C); m/z 7EI) 400 7M1, 48%), 332 7100), 216
753), 171 715) and 91 731) 7HRMS: Found M1, 400.1951.
C27H29OP requires M, 400.1956).
23
mp 135±1368C; [a]D ˆ172 7c 0.22 in CHCl3); nmax
7CHCl3) 7cm21) 3358, 2929, 1600, 1496, 1454, 1146 and
1104; dH 7400 MHz, CDCl3) 2.02 73H, d, Jˆ13.5 Hz, CH3),
2.43±2.59 73H, m, C-3H and C-4H), 2.88 71H, m, C-3H or
C-4H), 5.77 71H, dd, Jˆ2.7 and 5.6 Hz, C-10H), 5.92 71H, d,
Jˆ2.7 Hz, OH) and 6.69±7.17 720H, m, ArH); dC
7100 MHz, CDCl3) 29.7 7CH3), 31.2 7d, Jˆ12 Hz, CH2, C-
3), 34.7 7d, Jˆ14 Hz, CH2, C-4), 48.0 7d, Jˆ58Hz, C, C-2),
6.3.4.
*1S,2R,5R)-2-Methyl-5-*10-oxoethyl)-1,2,5-tri-
phenylphospholane-1-oxide 21. To a stirred solution of 5
7100 mg, 0.29 mmol) in THF 75 mL), under N2 at 2788C,
was added n-BuLi 71.6 M in hexanes) 70.20 mL,
0.32 mmol). The orange solution was allowed to stir at
2788C for 30 min before the addition of Ac2O 70.27 mL,
2.9 mmol), and the resultant colourless solution stirred for
2 min before quenching with saturated aqueous NH4Cl
710 mL). The organic layer was removed and the aqueous
layer extracted with CH2Cl2 73£7 mL), the combined
organic extracts dried 7MgSO4) and concentrated under
reduced pressure to give a colourless oil. Puri®cation by
column chromatography 710% petrol/Et2O) yielded the
title compound 21 as a white solid 760 mg, 53%), mp
0
56.87d, Jˆ58Hz, C, C-5), 79.2 7CH, C-1 ), 126.0±131.4
7aromatic CH), 135.8, 138.4, 138.5 and 142.9 7aromatic C);
m/z 7FAB) 453 7[M1H]1, 35%), 435 737), 346 739), 154
7100), 136 773) and 69 758) 7HRMS: Found [M1H]1,
453.1987. C30H2O2P requires [M1H], 453.1983).
6.3.6. *1Sp,2Rp,20Z,5Sp)-2-*40-Chlorobut-*20)-enyl)-1,2,5-
triphenyl phospholane-1-oxide 23. To a stirred solution
of 1,2,5-triphenylphospholane oxide 3 7400 mg, 1.20 mmol)
in THF 78mL), at 2788C under N2, was added n-BuLi
71.6 M in hexanes) 70.83 mL, 1.33 mmol). Stirring of the
deep orange/red solution was continued for 30 min before
the addition of 7Z)-1,4-dichlorobut-2-ene 71.27 mL,
12.0 mmol). After stirring the brown solution at 2788C
for a further 5 min, the reaction was quenched with satur-
ated aqueous NH4Cl 710 mL). The organic layer was
removed and the aqueous layer extracted with CH2Cl2
73£15 mL), the combined organic extracts dried 7MgSO4)
and concentrated under reduced pressure to give a yellow
oil. Puri®cation by column chromatography 7Et2O) yielded
the title compound 23 as a white solid 7312 mg, 62%), mp
157±1588C; nmax 7CHCl3) 7cm21) 2963, 1601, 1495, 1452,
1154 and 1107; dH 7400 MHz, CDCl3) 2.41±2.54 72H, m,
C-3H and C-4H), 2.61±2.84 72H, m, C-3H and C-4H), 3.07
71H, m, C-10H), 3.20 71H, m, C-10H), 3.90 71H, dd, Jˆ6.9
and 11.6 Hz, C-40H), 4.04 71H, app. dt, Jˆ23.6 and 8.8 Hz,
C-5H), 4.12 71H, dd, Jˆ9.3 and 11.6 Hz, C-40H), 5.30 71H,
ddd, Jˆ2.0, 9.2 and 17.4 Hz, C-20H), 5.69 71H, app. q,
Jˆ9.3 and 17.4 Hz, C-30H) and 6.86±7.27 715H, m, ArH);
dC 7100 MHz, CDCl3) 24.6 7d, Jˆ12 Hz, CH2, C-3 or C-4),
31.3 7d, Jˆ14 Hz, CH2, C-3 or C-4), 35.4 7CH2, C-10), 39.2
7CH2, C-40), 46.87d, Jˆ58Hz, CH, C-5), 49.5 7d, Jˆ61 Hz,
C, C-2), 126.2±131.6 7aromatic CH, ole®n CH and 1
aromatic C), 136.1 and 139.87aromatic C); m/z 7FAB)
421 7[M1H]1, 81%), 385 741), 332 723), 136 737), 91
753), 69 792) and 55 7100) 7HRMS: Found [M1H]1,
421.1486. C26H26ClOP requires [M1H], 421.1488).
23
155±1578C; [a]D ˆ2204 7c 0.65 in CHCl3); nmax 7CHCl3)
7cm21) 2969, 1698, 1598, 1494, 1456, 1356, 1103 and 888;
dH 7400 MHz, CDCl3) 1.6873H, d, Jˆ14.0 Hz, CH3), 2.28±
2.46 72H, m, C-3H or C-4H), 2.46 73H, s, COCH3), 2.80
71H, m, C-3H or C-4H), 3.65 71H, m, C-3H or C-4H) and
7.00±7.28715H, m, ArH); dC 768MHz, CDCl 3) 26.87CH 3),
28.3 7d, Jˆ15 Hz, CH2, C-3), 29.1 7COCH3), 31.87d,
Jˆ13 Hz, CH2, C-4), 45.7 7d, Jˆ65 Hz, C, C-2), 65.1 7d,
Jˆ53 Hz, C, C-5), 126.0±132.0 7aromatic CH), 130.3,
137.5 and 143.0 7aromatic C) and 203.6 7CvO);
dP7202 MHz, CDCl3) 62.6; m/z 7EI) 388 7M1, 4%), 346
762), 125 720), 115 755), 105 730) and 103 7100) 7HRMS:
Found M1, 388.1587. C25H25O2P requires M, 388.1592).
6.3.5.
*1S,10S,2R,5R)-2-Methyl-5-*phenyl-10-hydroxy-
methyl)-1,2,5-triphenyl phospholane-1-oxide 22 *accom-
panied by minor *10R)-isomer). To a stirred solution of 5
7100 mg, 0.29 mmol) in THF 75 mL), under N2 at 2788C,
was added n-BuLi 71.6 M in hexanes) 70.20 mL,
0.32 mmol). The orange solution was allowed to stir at
2788C for 30 min before the addition of freshly distilled
benzaldehyde 70.27 mL, 2.9 mmol). The colourless solution
was stirred for a further 2 min before the reaction was
quenched with saturated aqueous NH4Cl 710 mL). The
organic layer was removed and the aqueous layer extracted
with CH2Cl2 73£7 mL), the combined organics dried
7MgSO4) and concentrated under reduced pressure give a
colourless oil. Puri®cation by column chromatography
765% petrol/Et2O) yielded ®rstly the major diastereomer
6.3.7. *1Sp,2Rp,20E,5Sp)-2-*40-Bromobut-*20)-enyl)-1,2,5-
triphenyl phospholane-1-oxide 24. To a stirred solution
of 1,2,5-triphenylphospholane oxide 3 7150 mg, 0.45 mmol)
in THF 77 mL), at 2788C under N2, was added n-BuLi
of 22 as a white solid 798mg, 75%), mp 150±152 8C;
)
3346, 2930, 1600, 1494, 1456, 1327 and 987; dH
[a]D ˆ1112 7c 0.86 in CHCl3); nmax 7CHCl3) 7cm21
24

4598
A. J. Blake et al. / Tetrahedron 58 (2002) 4589±4602
71.55 M in hexanes) 70.32 mL, 0.50 mmol). Stirring of the
deep orange solution was continued for 30 min before the
addition of 7E)-1,4-dibromobut-2-ene 7483 mg, 2.26 mmol)
in THF 72 mL). After stirring for a further 5 min at 2788C,
the reaction was quenched with saturated aqueous NH4Cl
77 mL). The organic layer was removed and the aqueous
layer extracted with CH2Cl2 73£10 mL), the combined
organic extracts dried 7MgSO4) and the solvent evaporated
under reduced pressure to give a white solid. Puri®cation by
column chromatography 72% EtOH/Et2O) yielded the title
compound 24 as a white solid 7169 mg, 81%), mp 164±
1658C; 7Found: C, 67.39; H, 5.67. C26H26OPBr requires C,
67.10; H, 5.63%); nmax 7CHCl3) 7cm21) 2975, 1601, 1496,
1449, 1157, 1107 and 971; dH 7400 MHz, CDCl3) 2.42±2.52
72H, m, C-3H and C-4H), 2.55±2.79 72H, m, C-3H and C-
4H), 2.95 71H, ddd, Jˆ5.8, 9.0 and 14.7 Hz, C-10H), 3.15
71H, ddd, Jˆ5.8, 6.0 and 13.9 Hz, C-10H), 3.83 72H, d,
Jˆ7.7 Hz, C-40H), 3.99 71H, app. dt, Jˆ23.6 and 9.1 Hz,
C-5H), 5.39 71H, ddd, Jˆ5.1, 9.2 and 15.0 Hz, C-20H), 5.79
71H, ddd, Jˆ7.5, 7.7 and 15.0 Hz, C-30H) and 6.86±7.19
715H, m, ArH); dC 768MHz, CDCl 3) 24.6 7d, Jˆ11 Hz,
CH2, C-3 or C-4), 31.1 7d, Jˆ15 Hz, CH2, C-3 or C-4),
32.5 7CH2, C-10), 40.6 7CH2, C-40), 46.87d, Jˆ59 Hz, CH,
C-5), 49.5 7d, Jˆ61 Hz, C, C-2), 126.1±131.6 7aromatic
CH), 130.2 7CH, C-20), 130.5 7CH, C-30), 129.2, 136.2
and 139.9 7aromatic C); m/z 7FAB) 465 7[M1H]1, 36%),
385 732), 332 717), 154 752), 136 739), 69 794) and 57 7100)
7HRMS: Found [M1H]1, 465.0963. C26H27OPBr requires
[M1H], 465.0983).
720 mL), cooled to 08C under N2, was added a solution of
BH3´THF 71.0 M in THF) 74.84 mL, 4.84 mmol). Stirring
was continued for 60 min before the addition of MeOH
76 mL). After 5 min 2 M aqueous NaOH 712 mL) and
30% aqueous H2O2 72.7 mL) were added to the reaction
mixture and stirring continued for a further 60 min. The
reaction mixture was then diluted with H2O 710 mL),
extracted with CH2Cl2 73£10 mL), the combined organic
extracts dried 7MgSO4) and concentrated under reduced
pressure to give a pale yellow oil. Puri®cation by column
chromatography 76% EtOH/Et2O) yielded the title com-
24
pound 26 as a white foam 7459 mg, 73%), [a]D ˆ116
7c 1.24 in CHCl3); nmax 7CHCl3) 7cm21) 3340, 2955, 1601,
1496, 1454, 1155, 1106 and 1048; dH 7400 MHz, CDCl3)
1.20 71H, m, C-10H), 1.51 71H, m, C-10H), 2.30±2.52 74H,
m, 2£C-20H, C-3H and C-4H), 2.64 71H, m, C-3H or C-4H),
2.85 71H, m, C-3H or C-4H), 2.93 71H, bs, OH), 3.61 72H, t,
Jˆ6.4 Hz, C-30H), 4.00 71H, app. dt, Jˆ23.7 and 9.5 Hz, C-
5H) and 6.86±7.26 715H, m, ArH); dC 768MHz, CDCl 3)
26.0 7d, Jˆ12 Hz, CH2, C-3 or C-4), 28.3 7d, Jˆ10 Hz, CH2,
C-10), 32.6 7d, Jˆ13 Hz, CH2, C-3 or C-4), 35.4 7CH2, C-20),
47.9 7d, Jˆ59 Hz, CH, C-5), 50.7 7d, Jˆ61 Hz, C, C-2), 63.6
7CH2, C-30), 127.3±132.87aromatic CH), 130.5, 137.3 and
141.4 7aromatic C); m/z 7EI) 390 7M1, 45%), 332 7100), 205
1
73), 151 73), 118716) and 91 749) 7HRMS: Found M
390.1763. C25H27O2P requires 390.1749).
,
6.3.10. *1S,2R,5S)-2-Carboxymethyl-1,2,5-triphenylphos-
pholane-1-oxide 27. To a stirred suspension of enantio-
merically pure 7$99% ee) 8 7141 mg, 0.38mmol) in H 2O
72.5 mL)/CH3CN 71.7 mL)/CCl4 71.7 mL), at room tem-
perature, was added NaIO4 7340 mg, 1.59 mmol), followed
by RuCl3´3H2O 74 mg, 0.015 mmol). After stirring for
15 min the reaction mixture was extracted with CH2Cl2
73£10 mL), the combined organic extracts were dried
7MgSO4) and the solvent removed under reduced pressure
to give a black solid. Puri®cation by column chromato-
graphy 75% EtOH/Et2O) yielded the title compound 27
6.3.8. *1Sp,2Rp,5Sp)-2-*30-Bromomethylbenzyl)-1,2,5-tri-
phenylphospholane-1-oxide 25. To a stirred solution of
1,2,5-triphenylphospholane oxide 3 7150 mg, 0.45 mmol)
in THF 77 mL), at 2788C under N2, was added n-BuLi
71.55 M in hexanes) 70.32 mL, 0.50 mmol). Stirring of
the deep orange/red solution was continued for 30 min
before the addition of aa0-dibromo-m-xylene 7239 mg,
0.90 mmol) in THF 72 mL). After stirring at 2788C for a
further 5 min, the reaction was quenched with saturated
aqueous NH4Cl 77 mL). The organic layer was removed
and the aqueous layer extracted with CH2Cl2 73£10 mL),
the combined organic extracts dried 7MgSO4) and concen-
trated under reduced pressure to give a pale yellow oil.
Puri®cation by column chromatography 7Et2O) yielded the
title compound 25 as a white foam 7177 mg, 76%); nmax
7CHCl3) 7cm21) 2973, 1601, 1495, 1449 and 1106; dH
7400 MHz, CDCl3) 2.31±2.55 73H, m, C-3H and C-4H),
2.74 71H, m, C-3H or C-4H), 3.54 71H, dd, Jˆ6.1 and
as a colourless solid 7105 mg, 71%), mp 180±1828C;
)
[a]D ˆ1154 7c 2.1 in CHCl3); nmax 7CHCl3) 7cm21
24
2953, 2603, 1723, 1601, 1496, 1451, 1105 and 908; dH
7400 MHz, CDCl3) 2.50 71H, m, C-3H or C-4H), 2.69
71H, m, C-3H or C-4H), 2.84 71H, m, C-3H or C-4H),
3.19 71H, m, C-3H or C-4H), 3.32 71H, dd, Jˆ8.2 and
15.6 Hz, C-10H), 3.43 71H, dd, Jˆ11.4 and 15.6 Hz, C-
10H), 4.06 71H, ddd, Jˆ8.6, 10.5 and 24.6 Hz, C-5H) and
6.85±7.35 715H, m, ArH); dC 768MHz, CDCl 3) 25.7 7d,
Jˆ11 Hz, CH2, C-4), 32.87d, Jˆ12 Hz, CH2, C-3), 44.1
7CH2, C-10), 47.6 7d, Jˆ59 Hz, CH, C-5), 48.7 7d,
Jˆ60 Hz, C, C-2), 125.5±133.0 7aromatic CH1aromatic
C), 135.1, 138.9 7aromatic C) and 172.2 7CO2H); m/z 7EI)
390 7M1, 31%), 346 769), 250 7100), 220 732), 146 765) and
91 774) 7HRMS: Found M1, 390.1370. C24H23O3P requires
M, 390.1385).
0
13.8Hz, C-1 H), 3.63 71H, dd, Jˆ5.4 and 13.8Hz, C-
10H), 4.12 71H, app. dt, Jˆ23.4 and 8.8 Hz, C-5H), 4.27
72H, s, C-40H) and 6.60±7.26 719H, m, ArH); dC
768MHz, CDCl 3) 25.0 7d, Jˆ11 Hz, CH2, C-4), 31.1 7d,
Jˆ15 Hz, CH2, C-3), 33.9 7CH2, C-10), 43.4 7CH2, C-20),
47.2 7d, Jˆ59 Hz, CH, C-5), 51.2 7d, Jˆ61 Hz, C, C-2),
125.9±132.3 7aromatic CH), 136.9, 137.0, 137.3, 137.5
and 140.6 7aromatic C); m/z 7FAB) 515 7[M1H]1, 5%),
176 77), 154 737), 136 730), 83 747), 69 7100) and 55 793)
7HRMS: Found [M1H]1, 515.1138. C30H28OPBr requires
[M1H], 515.1139).
6.3.11.
*1S,2R,5S)-2-Methylcarboxymethyl-1,2,5-tri-
phenylphospholane-1-oxide 28. To a stirred solution of
27 7106 mg, 0.27 mmol) in DMF 72 mL), under N2 at
room temperature, was added KHCO3 741 mg, 0.41 mmol).
After stirring for 30 min MeI 70.03 mL, 0.54 mmol) was
added and stirring continued for a further 30 min. The solu-
tion was then poured into H2O 75 mL), extracted with
EtOAc 73£10 mL), the combined organic extracts dried
6.3.9. *1S,2R,5S)-2-*30-Hydroxypropyl)-1,2,5-triphenyl-
phospholane-1-oxide 26. To a stirred solution of enantio-
merically pure 7$99% ee) 8 7600 mg, 1.61 mmol) in THF

A. J. Blake et al. / Tetrahedron 58 (2002) 4589±4602
4599
7MgSO4) and concentrated under reduced pressure to give a
pale yellow oil. Puri®cation by column chromatography
73% EtOH/Et2O) yielded the title compound 28 as a white
solid 7103 mg, 94%), mp 170±1718C; [a]D ˆ153 7c 1.14
CH2, C-4), 33.1 7d, Jˆ13 Hz, CH2, C-3), 42.87CH , C-10),
2
46.0 7d, Jˆ60 Hz, CH, C-5), 49.3 7d, Jˆ61 Hz, C, C-2), 58.7
7CH2, C-20), 126.3±131.8 7aromatic CH), 128.8, 135.7 and
140.1 7aromatic C); m/z 7EI) 376 7M1, 29%), 332 753), 232
710), 117 726), 88 7100) and 49 739) 7HRMS: Found M1,
376.1598. C24H25O2P requires M, 76.1592).
21
in CHCl3); 7Found: C, 74.10; H, 6.23. C25H25O3P requires C,
74.24; H, 6.23%); nmax 7CHCl3) 7cm21) 2953, 1730, 1601,
1495, 1451, 1348, 1155 and 1107; dH 7250 MHz, CDCl3)
2.46±2.88 74H, m, C-3H and C-4H), 3.05±3.17 72H, m, C-
10H), 3.42 73H, s, CH3), 3.9871H, app. dt, Jˆ24.4 and
9.3 Hz, C-5H) and 6.87±7.18 715H, m, ArH); dC
768MHz, CDCl 3) 25.3 7d, Jˆ11 Hz, CH2, C-4), 32.3 7d,
Jˆ12 Hz, CH2, C-3), 42.1 7CH2, C-10), 47.4 7d, Jˆ59 Hz,
CH, C-5), 48.2 7d, Jˆ60 Hz, C, C-2), 51.3 7CH3, CO2CH3),
126.2±131.6 7aromatic CH), 128.4, 135.8 and 139.0
7aromatic C) and 170.9 7C, CO2); m/z 7EI) 404 7M1,
32%), 345 723), 285 7100), 160 756), 104 726) and 91 763)
7HRMS: Found M1, 404.1560. C25H25O3P requires M,
404.1541).
6.3.14. *1S,2R,5S)-2-*1,2,5-Triphenylphospholane-1-
oxido)ethyl methane sulfonate 31. To a stirred solution
of 30 7600 mg, 1.60 mmol) in CH2Cl2 77 mL) at 08C was
added Et3N 70.27 mL, 1.91 mmol) and the solution stirred
for 30 min before the addition of CH3SO2Cl 70.15 mL,
1.91 mmol). The reaction mixture was allowed to warm to
room temperature and stirred overnight before the solvent
was removed under reduced pressure to give an off-white
solid. Puri®cation by column chromatography 76% EtOH/
Et2O) yielded the title compound 31 as a white solid
23
7540 mg, 74%), mp 167±1698C; [a]D ˆ120 7c 1.16 in
CHCl3); nmax 7CHCl3) 7cm21) 2954, 1601, 1495, 1453,
1360, 1107, 972 and 903; dC 768MHz, CDCl 3) 25.2 7d,
Jˆ11 Hz, CH2, C-3 or C-4), 32.4 7d, Jˆ12 Hz, CH2, C-3
6.3.12. *1S,2R,5S)-2-*20-Oxoethyl)-1,2,5-triphenylphos-
pholane-1-oxide 29. Ozone was bubbled through a solution
of enantiomerically pure 9 7850 mg, 2.13 mmol) in CH2Cl2
720 mL) at 2788C for 45 min, after which time the solution
developed a permanent blue colouration. Nitrogen was then
bubbled through the solution to remove excess ozone,
before the addition of dimethylsul®de 72 mL). The mixture
was allowed to warm to room temperature and stirred for a
further 2 h before washing with H2O 710 mL). The organic
layer was separated, dried 7MgSO4) and the solvent evapor-
ated under reduced pressure to give a white foam. Puri®ca-
tion by column chromatography 74% EtOH/Et2O) yielded
or C-4), 36.87CH , C-10), 37.1 7CH3), 47.1 7d, Jˆ60 Hz,
2
CH, C-5), 48.3 7d, Jˆ60 Hz, C, C-2), 66.87d, Jˆ12 Hz,
CH2, C-20), 126.3±131.5 7aromatic CH and aromatic C)
and 135.4, 138.4 7aromatic C); m/z 7FAB) 455 7[M1H]1,
40%), 377 748), 359 720), 154 734), 95 758), 81 760) and 55
7100) 7HRMS: Found [M1H]1, 455.1439. C25H27OPS
requires [M1H], 455.1446).
6.3.15. *1S,2R,5S)-2-*Diethylaminoethyl)-1,2,5-triphenyl-
phospholane-1-oxide 32. To a stirred solution of enantio-
pure aldehyde 29 7100 mg, 0.27 mmol) in MeOH 72 mL),
under N2, was added Et2NH 70.14 mL, 1.34 mmol) and the
solution stirred at room temperature for 17 h. NaBH7OAc)3
7170 mg, 0.80 mmol) was then added to the reaction mixture
and stirring continued for a further 2 h before quenching
with 2 M aqueous NaOH 75 mL). The organic layer was
removed and the aqueous layer extracted with CH2Cl2
73£10 mL), the combined organic extracts dried 7MgSO4)
and concentrated under reduced pressure to give a yellow
glass. Puri®cation by column chromatography 78% MeOH/
CH2Cl2) yielded the title compound 32 as a colourless glass
the title compound 29 as a white foam 7601 mg, 75%);
)
[a]D ˆ18 9 c7 0.36 in CHCl3); nmax 7CHCl3) 7cm21
23
2970, 1719, 1600, 1495, 1450 and 1107; dH 7400 MHz,
CDCl3) 2.48±2.62 72H, m, C-4H), 2.67 71H, m, C-3H),
3.09±3.19 71H, overlapping m, C-3H), 3.16 71H, ddd,
Jˆ3.0, 5.7 and 16.2 Hz, C-10H), 3.57 71H, ddd, Jˆ1.2 Hz,
7.5 and 16.2, C-10H), 3.97 71H, app. dt, Jˆ24.5 and 9.5 Hz,
C-5H), 6.86±7.30 715H, m, ArH) and 9.52 71H, dd, Jˆ1.4
and 3.0 Hz, CHO); dC 768MHz, CDCl 3) 25.3 7d, Jˆ11 Hz,
CH2, C-4), 32.5 7d, Jˆ12 Hz, CH2, C-3), 47.2 7d, Jˆ60 Hz,
CH, C-5), 47.7 7d, Jˆ60 Hz, C, C-2), 51.0 7CH2, C-10),
124.9±131.7 7aromatic C and CH), 135.6, 139.0 7aromatic
C) and 201.1 7CHO); m/z 7FAB) 375 7[M1H]1, 82%), 307
730), 289 714), 154 7100), 136 768) and 91 726) 7HRMS:
Found [M1H]1, 375.1529. C24H23PO2 requires [M1H],
375.1514).
24
747 mg, 40%); [a]D ˆ139 7c 2.15 in CHCl3); nmax
7CHCl3) 7cm21) 2963, 2350, 1601, 1495, 1454, 1107 and
908; dH 7400 MHz, CDCl3) 1.14 76H, t, Jˆ7.2 Hz, 2£CH3),
2.44±2.59 74H, m, C-3H, C-4H and 2£C-40H), 2.65±2.96
78H, m, C-3H, C-4H, 2£C-10H, 2£C-20H and 2£C-40H),
4.03 71H, app. dt, Jˆ24.2 and 8.8 Hz, C-5H) and 6.88±
7.36 715H, m, ArH); dC 7100 MHz, CDCl3) 9.6 72£CH3),
24.87d, Jˆ11 Hz, CH2, C-3 or C-4), 31.2 7CH2, C-10), 31.7
7d, Jˆ13 Hz, CH2, C-3 or C-4), 46.4 72£CH2, C-40), 46.57
7CH2, C-20), 46.587d, Jˆ59 Hz, CH, C-5), 48.2 7d,
Jˆ61 Hz, C, C-2), 126.3±131.6 7aromatic CH and aromatic
C), 135.6 and 138.7 7aromatic C); m/z 7FAB) 432 7[M1H]1,
30%), 307 729), 259 714), 154 7100), 136 773) and 57 728)
7HRMS: Found [M1H]1, 432.2448. C28H34NOP requires
[M1H], 432.2456).
6.3.13. *1S,2R,5S)-2-*20-Hydroxyethyl)-1,2,5-triphenyl-
phospholane-1-oxide 30. To a stirred solution of 29
7650 mg, 1.74 mmol) in MeOH 710 mL) at 08C was added
NaBH4 7131 mg, 3.48mmol), portionwise. The solution was
stirred at 08C for 20 min before concentrating under reduced
pressure to give a colourless oil. Puri®cation by column
chromatography 710% EtOH/Et2O) yielded the title com-
pound 30 as a white foam 7610 mg, 93%), mp 116±1178C
22
7recrystallisation from EtOAc/petrol); [a]D ˆ162 7c 0.71
in CHCl3); nmax 7CHCl3) 7cm21) 3315, 2953, 1600, 1582,
1495, 1452, 1106, 1062 and 908; dH 7400 MHz, CDCl3);
2.39±2.49 72H, m, C-10H), 2.58±2.93 74H, m, C-3H and
C-4H), 3.51±3.61 72H, m, C-20H), 4.05 71H, app. dt,
Jˆ23.8and 9.0 Hz, C-5H), 4.43 71H, bs, OH) and 6.88±
7.23 715H, m, ArH); dC 768MHz, CDCl 3) 24.4 7d, Jˆ11 Hz,
6.3.16. *1S,2R,5S)-2-*Benzylaminoethyl)-1,2,5-triphenyl-
phospholane-1-oxide 33. To a stirred solution of enantio-
pure aldehyde 29 7150 mg, 0.40 mmol) in MeOH 72 mL),
under N2, was added BnNH2 70.046 mL, 0.43 mmol) and the
solution stirred at room temperature for 13 h. NaBH7OAc)3

4600
A. J. Blake et al. / Tetrahedron 58 (2002) 4589±4602
7136 mg, 0.64 mmol) was then added to the reaction mixture
and stirring continued for a further 22 h before quenching
with 2 M aqueous NaOH 77 mL). The reaction mixture was
extracted with CH2Cl2 73£15 mL), the combined organic
extracts dried 7MgSO4) and concentrated under reduced
pressure to give a yellow gum. Puri®cation by column
chromatography 76% MeOH/CH2Cl2) yielded the title com-
C-10H), 2.13±2.53 74H, m, C-3H, C-4H and C-10H), 2.79
71H, m, C-4H), 4.05 71H, app. dt, Jˆ12.4 and 8.9 Hz, C-5H)
and 6.67±7.36 715H, m, ArH); dC 768MHz, CDCl 3) 9.0
7d, Jˆ17 Hz, CH3), 31.0 7d, Jˆ5 Hz, CH2, C-3 or C-4),
34.7 7d, Jˆ4 Hz, CH2, C-3 or C-4), 36.1 7d, Jˆ31 Hz,
CH2, C-10), 45.5 7d, Jˆ17 Hz, CH, C-5), 55.4 7d,
Jˆ15 Hz, C, C-2), 125.3±135.0 7aromatic CH), 133.7,
140.3 and 144.4 7aromatic C); m/z 7EI) 344 7M1, 50%),
316 736), 234 712), 205 714), 115 716), 91 740) and 53
7100) 7HRMS: Found M1, 344.1697. C24H25P requires M,
344.1694).
23
pound 33 as a colourless glass 742 mg, 23%), [a]D ˆ122
7c 2.0 in CHCl3); nmax 7CHCl3) 7cm21) 3366, 2956, 1600,
1495, 1454, 1106 and 908; dH 7400 MHz, CDCl3) 2.31±2.91
79H, m, C-3H, C-4H, C-10H, C-20H and NH), 3.6872H, d,
Jˆ6.1 Hz, C-40H), 3.9871H, app. dt, Jˆ23.4 and 8.9 Hz, C-
5H) and 6.86±7.31 720H, m, ArH); dC 768MHz, CDCl 3)
24.87d, Jˆ11 Hz, CH2, C-4), 31.9 7d, Jˆ13 Hz, CH2, C-3),
37.5 7CH2, C-10), 44.5 7d, Jˆ10 Hz, CH2, C-20), 46.5 7d,
Jˆ59 Hz, CH, C-5), 49.0 7d, Jˆ61 Hz, C, C-2), 53.3
7CH2, C-40), 125.5±131.7 7aromatic CH), 128.9, 135.7,
139.0 and 139.6 7aromatic C); m/z 7FAB) 466 7[M1H]1,
11%), 307 732), 289 714), 154 7100) and 136 765) 7HRMS:
Found [M1H]1, 466.2303. C31H32NOP requires [M1H],
466.2300).
6.4.3. *1S,2R,5S)-2-*20-Pyridylmethyl)-1,2,5-triphenyl-
phospholane 36. The typical procedure described above
was followed, starting with 14 7350 mg of 84% ee material),
and the crude material puri®ed by column chromatography
7Et2O) to give the title compound 36 as a pale yellow solid
23
7283 mg, 84%), mp 123±1258C; [a]D ˆ1124 7c 1.17 in
CHCl3); nmax 7CHCl3) 7cm21) 2953, 1592, 1569, 1494,
1449, 1081 and 996; dH 7400 MHz, CDCl3) 2.51±2.64
73H, m, C-3H and C-4H), 2.79 71H, m, C-3H or C-4H),
3.43 71H, dd, Jˆ7.9 and 12.6 Hz, C-10H), 3.57 71H, dd,
Jˆ9.2 and 12.6 Hz, C-10H), 4.0 71H, app. dt, Jˆ13.1 and
6.4. Typical procedure for reduction of phospholane
oxides to corresponding phosphines *Table 2)
0
9.0 Hz, C-5H), 6.23 71H, d, Jˆ7.8Hz, C-3 H), 6.71±7.29
717H, m, aromatic CH, C-40H and C-50H) and 8.50 71H, d,
Jˆ4.6 Hz, C-60H); dC 768MHz, CDCl 3) 31.2 7d, Jˆ5 Hz,
CH2, C-4), 33.6 7d, Jˆ5 Hz, CH2, C-3), 45.3 7d, Jˆ17 Hz,
CH, C-5), 50.7 7d, Jˆ33 Hz, CH2, C-10), 56.1 7d, Jˆ15 Hz,
C, C-2), 121.3 7CH, C-30), 124.8±135.2 7aromatic CH),
133.4 7d, Jˆ28Hz, C, P±C Ar), 140.2 7aromatic C), 144.1
7aromatic C), 148.4 7CH, C-60) and 157.9 7d, Jˆ20 Hz, C,
C-20); m/z 7FAB) 4087[M 1H]1, 36%), 307 733), 288 730),
154 7100) and 137 764) 7HRMS: Found [M1H]1, 408.1884.
C28H26NP requires [M1H], 408.1881).
6.4.1. *1S,2R,5S)-2-Methyl-1,2,5-triphenylphospholane
34. To a stirred solution of Cl3SiH 70.70 mL, 6.94 mmol)
in benzene 72 mL) was added pyridine 71.68mL,
20.8mmol), under N 2. A solution of enantiomerically pure
phospholane oxide 5 7480 mg, 1.39 mmol) in benzene
710 mL) was added to the resulting white suspension and
the mixture heated to re¯ux until starting material was
consumed 73±5 h). After cooling the reaction mixture to
08C, ice-cold 2 M aqueous NaOH 765 mL) was added, the
reaction mixture extracted with benzene 72£20 mL), the
combined organic extracts dried 7MgSO4) and the solvent
removed under reduced pressure to give a white solid. Puri-
®cation by column chromatography 7Et2O) yielded the title
compound 34 as a white solid 7335 mg, 73%), mp 146±
6.4.4. *1S,2R,5S)-2-*40, 40-Dimethyloxazolinyl-20-methyl)-
1,2,5-triphenyl phospholane 37. The typical procedure
described above was followed, starting with enantiomeri-
cally pure 15 7182 mg), and the crude material puri®ed by
column chromatography 740% EtOAc/petrol) to give the
title compound 37 as a white solid 7133 mg, 76%), mp
28
1478C; [a]D ˆ188 7c 0.74 in CHCl3); 7Found: C, 83.20;
H, 6.96. C23H23P requires C, 83.60; H, 7.02%); nmax
7CHCl3) 7cm21) 2954, 2867, 1598, 1494, 1452 and 1074;
dH 7400 MHz, CDCl3) 1.70 73H, d, Jˆ17.9 Hz, CH3), 2.23
71H, m, C-3H or C-4H), 2.50±2.59 72H, m, C-3H or C-4H),
2.92 71H, m, C-3H or C-4H), 4.12 71H, app. dt, Jˆ9.3 and
11.0 Hz, C-5H), 6.67±7.35 715H, m, ArH); dC 7100 MHz,
CDCl3) 30.87d, Jˆ4 Hz, CH2, C-3), 33.0 7d, Jˆ30 Hz,
CH3), 38.3 7d, Jˆ5 Hz, CH2, C-4), 45.4 7d, Jˆ17 Hz, CH,
C-5), 51.0 7d, Jˆ14 Hz, C, C-2), 125.4±134.6 7aromatic
CH), 134.1, 140.1 and 147.2 7aromatic C); m/z 7FAB) 330
7M1, 100%), 259 720), 154 794), 136 764), 91 754) and 57
764) 7HRMS: Found M1, 330.1538. C23H23P requires M,
330.1537).
23
121±1238C; [a]D ˆ170 7c 0.55 in CHCl3); nmax 7CHCl3)
7cm21) 2964, 1660, 1598, 1494, 1462, 1366 and 990; dH
7400 MHz, CDCl3) 1.00 73H, s, CH3), 1.16 73H, s, CH3),
2.57±2.85 74H, m, C-3H and C-4H), 2.89 71H, dd, Jˆ5.7
and 13.7 Hz, C-10H), 3.12 71H, dd, Jˆ11.0 and 13.7 Hz, C-
10H), 3.62 71H, d, Jˆ8.0 Hz, C-30H), 3.67 71H, d, Jˆ8.0 Hz,
C-30H), 4.11 71H, app. dt, Jˆ12.6 and 9.0 Hz, C-5H) and
6.69±7.31 715H, m, ArH); dC 7100 MHz, CDCl3) 28.1
7CH3), 28.4 7CH3), 31.0 7d, Jˆ4 Hz, CH2, C-4), 35.0 7d,
Jˆ4 Hz, CH2, C-3), 45.4 7d, Jˆ18Hz, CH, C-5), 54.1 7d,
Jˆ15 Hz, C, C-2), 66.5 7C, C-4), 78.9 7CH2, C-30), 125.4±
134.9 7aromatic CH), 133.2, 139.9 and 143.0 7aromatic C);
m/z 7FAB) 4287[M 1H]1, 75%), 372 711), 308744), 154
7100) and 136 772) 7HRMS: Found [M1H]1, 428.2107.
C28H30NOP requires [M1H], 428.2143).
6.4.2. *1S,2R,5S)-2-Ethyl-1,2,5-triphenylphospholane 35.
The typical procedure described above was followed, start-
ing with enantiomerically pure 6 7800 mg), and the crude
material puri®ed by column chromatography 750% EtOAc/
petrol) to give the title compound 35 as a white solid
6.4.5. *1S,10R,2R,5S)-2-*10-Acetoxyphenylmethyl)-1,2,5-
triphenylphospholane 38. The typical procedure described
above was followed, starting with the O-acetate derivative
of enantiomerically pure 11 7449 mg, prepared by reacting
11 with Ac2O and DMAP in pyridine), and the crude
material puri®ed by column chromatography 7Etc2O) to
21
7724 mg, 96%), mp 120±1238C; [a]D ˆ110 7c 1.9 in
CHCl3); nmax 7CHCl3) 7cm21) 2965, 2873, 1598, 1494,
1450 and 1077; dH 7400 MHz, CDCl3) 0.7873H, t,
Jˆ7.3 Hz, CH3), 1.96 71H, ddd, Jˆ6.1, 7.3 and 15.7 Hz,

A. J. Blake et al. / Tetrahedron 58 (2002) 4589±4602
4601
give the title compound 38 as a white solid 7330 mg, 76%),
7c 0.7 in CHCl3); nmax 7CHCl3) 7cm21) 2950, 2351, 1600,
1494, 1455, 1071 and 907; dH 7400 MHz, CDCl3) 1.17 76H,
t, Jˆ6.9 Hz, 2£CH3), 2.20±2.62 74H, m, C-3H, C-4H and
2£C-40H), 2.65±2.90 78H, m, C-3H, C-4H, 2£C-10H, 2£C-
20H and 2£C-40H), 3.84 71H, app. dt, Jˆ11.0 and 7.0 Hz, C-
5H) and 6.95±7.34 715H, m, ArH); dC 7100 MHz, CDCl3)
11.0 72£CH3), 29.7 7CH2, C-3 or C-4), 30.9 7CH2, C-10),
2£C-40), 53.87d, Jˆ15 Hz, C, C-2), 48.0 7d, Jˆ18Hz, CH,
C-5), 125.4±135.0 7aromatic CH and one aromatic C),
139.8and 143.7 7aromatic C); m/z 7FAB) 416 7[M1H]1,
8%), 343 74), 109 721), 95 737), 69 770) and 55 7100)
7HRMS: Found [M1H]1, 416.2511. C28H34NP requires
[M1H], 416.2507).
28
mp 96±978C; [a]D ˆ1131 7c 1.39 in CHCl3); nmax
7CHCl3) 7cm21) 2957, 1738, 1598, 1494, 1452, 1372 and
1026; dH 7400 MHz, CDCl3) 2.30 73H, s, CH3), 2.48±2.63
74H, m, C-3H and C-4H), 3.95 71H, app. dt, Jˆ13.4 and
8.9 Hz, C-5H), 6.46 71H, d, Jˆ5.4 Hz, C-10H), 6.68±7.25
720H, m, ArH); dC 768MHz, CDCl 3) 21.5 7CH3), 31.6 7CH2,
C-3 or C-4), 32.2 7CH2, C-3 or C-4), 47.87d, Jˆ16 Hz, CH,
C-5), 61.3 7d, Jˆ20 Hz, C, C-2), 82.8 7d, Jˆ26 Hz, CH, C-
10), 125.5±136.2 7aromatic CH), 133.87d, Jˆ28Hz, C, P±
CAr), 137.5, 139.5, 141.5 7aromatic C) and 169.7 7CvO);
m/z 7FAB) 465 7[M1H]1, 7%) 421 713), 391 710), 307 744),
289 720), 154 7100) and 136 765) 7HRMS: Found [M1H]1,
465.1964. C31H29O2P requires [M1H], 465.1983).
35.6 7CH2, C-3), 45.4 7d, Jˆ17 Hz, CH2, C-20), 46.87CH ,
2
6.4.6. *1S,2R,5S)-2-*30-Hydroxypropyl)-1,2,5-triphenyl-
phospholane 39. The typical procedure described above
was followed, starting with enantiomerically pure 26
7400 mg), and the crude product puri®ed by column
6.4.9. *1S,2R,5S)-2-*Benzylaminoethyl)-1,2,5-triphenyl-
phospholane 42. The typical procedure described above
was followed, starting with enantiomerically pure 33
750 mg), and the crude product puri®ed by column
chromatography 75% MeOH/CH2Cl2) to give the title
chromatography 740% EtOAc/petrol) to give the title
25
22
compound 42 as a white solid 738mg, 79%); [ a]D ˆ116
compound 39 as a white foam 7312 mg, 81%), [a]D
ˆ
7c 0.51 in CHCl3); nmax 7CHCl3) 7cm21) 2953, 2757, 1682,
1599, 1495, 1456 and 1106; dH 7400 MHz, CDCl3) 2.31±
2.97 78H, m, C-3H, C-4H, C-10H and C-20H), 3.4871H, d,
1387 c 1.9 in CHCl3); nmax 7CHCl3) 7cm21) 3625, 2946,
2873, 1673, 1494, 1451, 1266 and 1047; dH 7400 MHz,
CDCl3) 1.23 71H, m, C-10H), 1.52 71H, m, C-10H), 2.37±
2.50 74H, 2£C-20H, C-3H and C-4H), 2.70 71H, m, C-3H or
C-4H), 2.83, 71H, m, C-3H or C-4H), 2.94 71H, bs, OH),
3.62 72H, t, Jˆ6.5 Hz, C-30H), 4.09 71H, app. q, Jˆ9.3 and
11.1 Hz, C-5H) and 6.69±7.32 715H, m, ArH); dC 768MHz,
CDCl3) 28.0 7CH2, C-3 or C-4), 31.0 7CH2, C-10), 35.3
7CH2, C-20), 39.6 7CH2, C-3 or C-4), 45.2 7d, Jˆ17 Hz,
CH, C-5), 54.6 7d, Jˆ13 Hz, C, C-2), 62.9 7CH2, C-30)
and 125.3±144.3 7aromatic C and CH); m/z 7FAB) 375
7[M1H]1, 4%), 316 73), 154 720), 95 737), 81 746), 69
774) and 55 7100) 7HRMS: Found [M1H]1, 375.1844.
C25H27OP requires [M1H], 375.1878).
0
Jˆ6.8Hz, C-4 H), 4.20 71H, app. q, Jˆ9.6 and 13.3 Hz, C-
5) and 6.66±7.53 720H, m, ArH); dC 7100 MHz, CDCl3)
30.9 7CH2, C-3 or C-4), 36.2 7CH2, C-3 or C-4), 45.1
7CH2, C-10), 48.3 7CH2, C-20), 51.5 7CH, d, Jˆ18Hz, C-
5), 53.87CH , C-40), 53.7 7CH2, d, Jˆ16 Hz, C-2) and
2
125.4±139.7 7aromatic C and CH); m/z 7FAB) 450
7[M1H]1, 6%), 207 712), 147 730), 133 761), 91 756) and
73 7100) 7HRMS: Found [M1H]1, 450.2326. C31H32NP
requires [M1H], 450.2351).
6.5. X-Ray crystallography
6.4.7. *1S,2R,5S)-2-*Methylcarboxymethyl)-1,2,5-tri-
phenylphospholane 40. The typical procedure described
above was followed, starting with enantiomerically pure
28 7100 mg), and the crude product puri®ed by column
chromatography 7Et2O) to give the title compound 40 as a
white solid 770 mg, 75%), mp 135±1368C; [a]Dˆ149 7c
1.65 in CHCl3); nmax 7CHCl3) 7cm21) 2952, 2927, 1728,
1599, 1494, 1451 and 1317; dH 7400 MHz, CDCl3) 2.52±
2.6873H, m, C-3H and C-4H), 2.80 71H, m, C-3H or C-4H),
2.88 71H, dd, Jˆ6.2 and 14.3 Hz, C-10H), 3.15 71H, dd,
Jˆ10.2 and 14.3 Hz, C-10H), 3.37 73H, s, CH3), 4.04 71H,
app. dt, Jˆ12.9 and 7.1 Hz, C-5H) and 6.60±7.22 715H,
ArH); dC 768MHz, CDCl 3) 31.1 7CH2, C-4), 34.9 7CH2,
C-3), 45.3 7d, Jˆ17 Hz, CH, C-5), 46.6 7CH2, C-10), 51.3
7CH3), 53.5 7d, Jˆ15 Hz, C, C-2), 125.4±135.0 7aromatic
CH and 1 aromatic C), 139.7 and 142.87aromatic C)
and 170.1 7CvO); m/z 7FAB) 388 7[M1H]1, 1%), 373
74), 281 77), 147 730), 91 711) and 73 7100) 7HRMS:
Found [M1H]1, 389.1677. C25H25O2P requires [M1H],
389.1670).
6.5.1. Benzaldehyde adduct 11. Crystal data: C29H27O2P,
Mˆ438.48, monoclinic, aˆ12.21976), bˆ7.52476), c ˆ
Ê
Ê 3
13.25875) A, bˆ108.4473)8, Uˆ1156.3712) A , Tˆ22072) K,
space group P21 7No. 4), Zˆ2, Dcˆ1.259 cm23
,
m7Mo Ka)ˆ0.143 mm21, 4019 unique re¯ections meas-
ured, corrected for absorption 7Rint 0.037) and crystal
decay 729%), and used in all calculations. Final R1 [3241
F.4s7F)]ˆ0.0687 and wR7all F2) was 0.189. The Flack
absolute structure parameter re®ned to 0.072). CCDC
number 172595.
6.5.2. Acetone adduct 13. Crystal data: C25H27O2P,
Mˆ390.44, monoclinic, aˆ11.74073), bˆ6.547379), c ˆ
Ê
Ê 3
13.50673) A, bˆ100.6572)8, Uˆ1020.374) A , Tˆ15072) K,
space group P21 7No. 4), Zˆ2, Dcˆ1.271 cm23
,
m7Mo Ka)ˆ0.153 mm21, 3568unique re¯ections meas-
ured, corrected for absorption 7Rint 0.042), and used in all
calculations. Final R1 [3016 F.4s7F)]ˆ0.0777 and wR7all
F2) was 0.215. The Flack absolute structure parameter
re®ned to 20.372). CCDC number 172594.
6.4.8. *1S,2R,5S)-2-*Diethylaminoethyl)-1,2,5-triphenyl-
phospholane 41. The typical procedure described above
was followed, starting with enantiomerically pure 32
745 mg), and the crude product puri®ed by column
chromatography 76% MeOH/CH2Cl2) to give the title
Acknowledgements
We thank the Engineering and Physical Sciences Research
Council 7EPSRC) for support of S. C. H., and for the provi-
sion of a four-circle diffractometer.
21
compound 41 as a white solid 718mg, 44%), [ a]D ˆ113

4602
A. J. Blake et al. / Tetrahedron 58 (2002) 4589±4602
7. Bunn, B. J.; Simpkins, N. S.; Spavold, Z.; Crimmin, M. J. J.
Chem. Soc., Perkin Trans. 1 1993, 32, 3113.
References
8. 7a) O'Brien, P.; Warren, S. J. Chem. Soc., Perkin Trans. 1
1996, 2567. 7b) Vedejs, E.; Garcia-Rivas, J. A. J. Org.
Chem. 1994, 59, 6517.
1. 7a) O'Brien, P. J. Chem. Soc., Perkin Trans. 1 1998, 1439.
7b) Cox, P. J.; Simpkins, N. S. Tetrahedron: Asymmetry 1991,
2, 1. 7c) Simpkins, N. S. Chimia 2000, 54, 53.
9. 7a) Simpkins, N. S. Asymmetric Deprotonation Reactions
using Enantiopure Lithium Amide Bases. In Advanced Asym-
metric Synthesis, Stephenson, G. R., Ed.; J. Org. Chem.;
Chapman and Hall: London, 1996; 59, pp. 111±125. 7b) Arif®n,
A.; Blake, A. J.; Ewin, R. A.; Li, W.-S.; Simpkins, N. S.
Advanced Asymmetric Synthesis. J. Chem. Soc., Perkin
Trans. 1 1999, 3177±125.
2. For our most recent contribution, see: Blake, A. J.; Kendall,
J. D.; Simpkins, N. S.; Westaway, S. J. Chem. Soc., Perkin
Trans. 1 2000, 153.
3. 7a) Hume, S. C.; Simpkins, N. S. J. Org. Chem. 1998, 63, 912.
For recent work describing the related enantioselective depro-
tonation of phospholane±borane complexes, see 7b) Kobayashi,
S.; Shiraishi, N.; Lam, W. W.-L.; Manabe, K. Tetrahedron Lett.
2001, 42, 7303.
10. Edwards, A. J.; Hockey, S.; Mair, F. S.; Raithby, P. R.; Snaith,
R.; Simpkins, N. S. J. Org. Chem. 1993, 58, 6942.
11. The aggregation state of the base 4 in solution, including the
effect of LiCl, has been studied, see: Sugasawa, K.; Shindo,
M.; Noguchi, H.; Koga, K. Tetrahedron Lett. 1996, 37, 7377.
12. Guillen, F.; Moinet, C.; Fiaud, J.-C. Bull. Soc. Chim. Fr. 1997,
134, 371.
4. In similar work with sulfoxides we found the diastereochemi-
cal outcome depended on the nature of the electrophile, see
Armer, R.; Begley, M. J.; Cox, P. J.; Persad, A.; Simpkins, N.
S.; J. Chem. Soc., Perkin Trans. 1 1993, 3099.
5. For analogous issues of diastereocontrol in substitutions of
phospholanic esters and amides, see 7a) Polniaszek, R. P.;
Foster, A. L. J. Org. Chem. 1991, 56, 3137. 7b) Polniaszek,
R. P. J. Org. Chem. 1992, 57, 5189.
13. Burk, M. J. Acc. Chem. Res. 2000, 33, 363.
14. Horner, L.; Balzer, W. D. Tetrahedron Lett. 1965, 33, 1157.
6. Fiaud, J.-C.; Legros, J.-Y. Tetrahedron Lett. 1991, 32, 5089.