Epoxide rearrangements using dilithiated aminoalcohols as chiral bases

Article abstract of DOI:10.1016/S0040-4020(02)00374-5

Dilithiated norephedrine and ephedrine have been utilised in the enantioselective rearrangement of cyclic epoxides to allylic alcohols, with dilithiated norephedrine generally giving the best enantioselectivity. Dilithiated ephedrine offered better levels

Full text of DOI:10.1016/S0040-4020(02)00374-5

TETRAHEDRON
Pergamon
Tetrahedron 58 =2002) 4675±4680
Epoxide rearrangements using dilithiated aminoalcohols
as chiral bases
Paul C. Brookes, David J. Milne, Patrick J. Murphyp and Barbara Spolaore
Department of Chemistry, University of Wales, Bangor, Gwynedd LL57 2UW, UK
Received 4 January 2002;accepted 22 February 2002
AbstractÐDilithiated norephedrine and ephedrine have been utilised in the enantioselective rearrangement of cyclic epoxides to allylic
alcohols, with dilithiated norephedrine generally giving the best enantioselectivity. Dilithiated ephedrine offered better levels of substrate
conversion, but with lower enantioselectivity. q 2002 Published by Elsevier Science Ltd.
1. Introduction
that since 1998 these two reviews have been cited nearly
200 times and based on this evidence, there appears to be a
continued growth in the interest in this area of chemistry.
Some of the most exciting recent developments are the use
of catalytic systems that employ chiral lithium amide bases4
and also the use of magnesium amides5 in enantioselective
deprotonation, both of which will no doubt generate more
interest in this fascinating area of chemistry.
The discovery of new processes for effecting asymmetric
transformations still represents one of the major goals of
organic chemistry. Of the stoichiometric methods available1
for asymmetric synthesis, those employing chiral reagents
are potentially superior to auxiliary based methods, as trans-
formations can be effected in a single step without the need
for the attachment and removal of auxiliary groups. One of
the most powerful of these methods, the use of chiral lithium
amide bases offers a further advantage in that it is possible to
conveniently recycle the base and thus increase its effective-
ness and cost ef®ciency.
In 1993 we reported6 our ®ndings which related to the
enantioselective rearrangement of epoxides utilising
dilithiated aminoalcohols. We had proposed that these
chiral bases would be suitable based on work performed
by Mulzer7 and on a rationale which arose from considera-
tion of the LIDAKOR bases =lithium amide bases used in
conjunction with potassium tert-butoxide) developed by
Schlosser.8 We have continued to investigate this area and
wish to report our ®ndings in more detail.
Inspection of the available literature on chiral lithium amide
bases illustrates that over the last 20 years they have
developed into a frequently used methodology, particularly
for enolisations of prochiral ketones and rearrangement
reactions. The ®rst review of this area by Simpkins2 covered
the literature from 1980 to 1991 and cited 44 references on
the use of chiral lithium amide bases. A second compre-
hensive review by O'Brien3 covered the period from 1991
to 1997 and cited a further 120 references. It is worth noting
2. Results and discussion
During our original experiments6 we found that the best
Table 1. Rearrangement of epoxides 1a/b using norephedrine and ephedrine
Entry
Substrate
R
Basea
Equivalents
Yield =%)
Ratiob 2/3
eeb =%)
1
2
3
4
5
6
1a
1a
1b
1b
1b
1b
Bn
Bn
TBS
TBS
TBS
TBS
4 =2NED)
5 =1NED)
4 =2NED)
5 =1NED)
6 =2EPH)
7 =1EPH)
3
3
3.5
3.5
4
91
92
70
77
90
90
93:07
10:90
79:21
15:85
70:30
39:61
86
80 =78)
58
70 =65)
40
22
4
a
Conditions: base in THF/hexane at 2788C warmed to rt over 16 h.
Determined from the H NMR of the =R)-O-acetyl mandelate esters. Figures in brackets refer to values determined by optical rotation measurements.
b
1
Keywords: enantiospeci®city;rearrangements;epoxides;basicity.
Corresponding author. Tel.: 144-1248-382392;e-mail: paddy@bangor.ac.uk;chs027@bangor.ac.uk
p
0040±4020/02/$ - see front matter q 2002 Published by Elsevier Science Ltd.
PII: S0040-4020=02)00374-5

4676
P. C. Brookes et al. / Tetrahedron 58 '2002) 4675±4680
Scheme 1.
Scheme 2. =a) =R)-O-acetyl mandelic acid, DMAP, DCCI, DCM, rt, 18 h;quantitative conversion = 1H NMR). =b) 2 equiv. PCC, DCM, rt, 1±2 h.
chiral bases for effecting the rearrangement of the cis-
epoxide 1a =RˆBn) into the allylic alcohols 2a or 3a
=RˆBn) were the dilithiated =1R,2S)-norephedrine 4
=2NED) =Table 1, entry 1) or =1S,2R)-norephedrine 5
=1NED) =Table 1, entry 2). We found that the optimum
conditions for this transformation were when 3 equiv. of
base were employed and the reaction was conducted at
2788C and allowed to warm to rt over 16 h =Scheme 1).
measurement for this alcohol was determined as 223.2
=aˆ20.174, cˆ0.75, CHCl3) which corresponds to an
optical purity of 78% based on a reported [a]25 of 229.9
D
at 100% ee10 for the =1S,4R)-alcohol 3a. Final con®rmation
that the compound has this absolute con®guration was
shown when 3a was oxidised to the =S)-enone 9a which
has an [a]D20 =245.5, cˆ0.9, CHCl3) which is of the oppo-
16
site sign to that reported for the =R)-enone =[a]D ˆ142,
cˆ0.9, CHCl3).11 We can thus con®rm that the stereoselec-
tivity of the reaction for 1NED is selective for the forma-
tion of the =1S,4R)-alcohol 3a as detailed in Table 1 =entries
1 and 2) and thus the predominant sense of asymmetric
induction indicated in our original communication6 should
be reversed.
After the publication of our original communication some
concern was raised over the assignment of the absolute
²
stereochemistry of the products isolated from the rearrange-
ment of these epoxides. The method we had adopted was
based upon work published by Leonard and involved the
preparation of =R)-O-acetyl mandelate derivatives of the
alcohols 3.9 In order to con®rm the assignment of these
products we treated a sample of the allylic alcohol 3a
obtained from the rearrangement of 1a using dilithiated
=1S,2R)-norephedrine 5 with =R)-O-acetyl mandelic acid to
prepare the mandelate derivative 8a which gave as the major
signal a resonance at dˆ2.79 ppm for the H-5a proton;by
comparison of the relative intensity of this signal with that
of the minor diastereoisomer =dˆ2.68 ppm) we were able to
With the work on the epoxide substrate 1a in hand, we
proceeded to investigate the rearrangement of the
corresponding cis-tert-butyldimethylsilyloxycyclopentene
epoxide 1b and found that the reaction was less facile
than for the benzyl substituted analogue. However when
the substrate 1b was treated with 3.5 equiv. of the dilithiated
aminoalcohols 4 or 5 =Table 1, entries 3 and 4), the reaction
proceeded to the corresponding allylic alcohols 2a and 2b in
reasonable yield over the same time-scale and with the same
sense of asymmetric induction as in the previous case. In
addition, we found that allowing the reaction to proceed for
a longer period of time or using more equivalents of base did
20
determine the enantiomeric excess =Scheme 2). The [a]D
²
Inconsistencies in the sense of asymmetric induction were brought to our
attention by Dr D. M. Hodgson.14,16

P. C. Brookes et al. / Tetrahedron 58 '2002) 4675±4680
4677
1
Scheme 3. =a) =R)-O-acetyl mandelic acid, DMAP, DCCI, DCM, 08C±rt, 18 h;quantitative conversion = H NMR). =b) 2 equiv. PCC, DCM, rt, 1±2 h.
Scheme 4. =a) 5 =3 equiv.) THF:PhH =1:1) 08C±rt 24 h;57%, 95% ee. =b) 4 =3 equiv.) THF:PhH =1:1) 08C±rt 24 h;66%, 95% ee.
not have a signi®cant effect upon the yield of the reaction or
indeed the levels of enantioselectivity. We also investigated
the use of the stronger bases and found that if the dilithiated
salts of =1R,2S)-ephedrine 6 =2EPH) or =1S,2R)-ephedrine
7 =1EPH) were utilised =Table 1, entries 5 and 6) the
reactions proceeded in better yield, however the ees were
diminished.
4, or 1NED 5 led to formation of alcohols 11 or 12, respec-
tively in exceptionally high ees =.95% ee) =Scheme 4).
However it was also observed that trityl- and benzyl-
protected derivatives of 10 failed to undergo this rearrange-
ment under similar conditions. This observation indicates
that the presence of an internal co-ordination site in close
proximity to the point of deprotonation is required to give
effective transformation and that introduction of a protect-
ing group precludes both the formation of an anion for direct
base co-ordination and may hinder any potential chelation
with the oxygen function. When applying these criteria to
our systems it is apparent that the benzyl protected epoxide
1a may offer less steric resistance to the formation of a
highly ordered transition state than does the tert-butyl-
With the problems encountered in the determination of
absolute con®guration of the benzyl substituted series we
decided to re-investigate the assignment procedure for the
TBS-substituted alcohols. Thus treatment of 1b =RˆTBS)
with the dilithiated salt of 1NED led to an alcohol which
20
had an [a]D ˆ214.2 =aˆ20.074, cˆ0.52, CHCl3) which
³
corresponds to an optical purity of 65% based on a literature
dimethylsilyl group in compound 1b.
reported12 value of [a]D ˆ222 =cˆ0.52, 100% ee, CHCl3)
20
for the =1S,4R)-alcohol 3b. Derivatisation of this alcohol
with the previously employed =R)-O-acetyl mandelic acid
gave 8b which had as the major signal a resonance at
dˆ2.77 for the H-5a proton, gave an ee of 70%. Interest-
ingly this observation, that the =1S,4R)-=R)-O-acetyl
mandelate derivative 8b has a resonance at dˆ2.77, contra-
dicts the data reported by Leonard and Hendrie.9 Final proof
of the absolute con®guration was obtained when this alcohol
In order to investigate this reaction further we prepared the
trans-epoxides 13a, b and extended our studies to this
system. Somewhat disappointingly neither of these epoxides
were cleanly converted into the allylic alcohols 14 and 15
under the previously employed conditions =Scheme 5). It
was felt that this was possibly due to low basicity on the
part of the dilithiated norephedrines and also that the lack of
a secondary co-ordination site adjacent to the epoxide might
have a signi®cant role to play in this failure to react. We then
turned our attention to the use of dilithiated =1R,2S)-
ephedrine 6 =2EPH) and found that treatment of the
epoxide 13a =RˆBn) with four equivalents of this base
led to the formation of the allylic alcohols 14a and 15a in
20
was oxidised to the enone 9b, which gave an [a]D ˆ238.9
20
=aˆ20.389, cˆ1.0, MeOH) which is of the opposite sign to
that reported for the =R)-enone =[a]D ˆ166.6, cˆ1.0,
MeOH)13 =Scheme 3).
It is possible that steric factors are producing the differences
in reactivity and enantioselectivity between the benzyl and
tert-butyldimethylsilyl protected epoxides, indeed work
performed by Hodgson et al.14 offers some additional
support to this premise. They observed that treatment of
meso-epoxide 10 with the dilithiated salts of either 2NED
³
Asami has reported that the rearrangement of the TBDMS derivative of
10 proceeds in poor yield =28%, 72% ee), when compared to the
corresponding TBDMS protected trans-isomer =74% yield, 83% ee);it
was proposed that steric factors were the cause of this difference in
reactivity.15

4678
P. C. Brookes et al. / Tetrahedron 58 '2002) 4675±4680
4. Experimental
4.1. General
Column chromatography was carried out on Kieselgel
=230±400 mesh) with the eluant speci®ed. TLC was
conducted on precoated Kieselgel 60 F254 =Art. 5554;
Merck) glass plates. All reactions were conducted in
oven-dried apparatus under an atmosphere of argon. Light
petroleum refers to the fraction boiling in the range 35±
608C. Dichloromethane, diethyl ether, benzene and THF
were dried and distilled before use. Chemical shifts are
reported as d values relative to TMS as an internal standard.
1H NMR spectra were recorded in deuterochloroform on a
Bruker AC250 spectrometer. IR were recorded as thin ®lms
or as chloroform solutions on a Perkin±Elmer 1600 series
instrument. Mass spectra were recorded on a VG Masslab
Model 12/253 spectrometer using CI =ammonia) or EI. All
compounds were oils unless otherwise stated. Optical rota-
tions were determined on a POLAAR 2001 instrument.
Scheme 5.
53% yield =81% based on recovered starting material). The
optical yield of this reaction was calculated by oxidation of
a sample of the alcohol =[a]D20 of 225.4, cˆ0.55, CHCl3) to
16
the corresponding =S)-enone 9a ==R)-enone [a]D ˆ142,
cˆ0.9, CHCl3)11 which with an [a]D of 213.9 =cˆ0.55,
16
CHCl3) gave an optical purity for the =2)-alcohol 15a of
34%.
Similarly treatment of the epoxide 13b =RˆTBS) with four
equivalents of =1R,2S)-ephedrine 6 =2EPH) led to the
formation of the allylic alcohols 14b and 15b in a lower
yield of 38% =62% based on recovered starting material),
Compounds 1b and 13b were prepared by literature
methods;9 allylic alcohols 2/3b, and 14b/15b displayed
spectral data consistent with that reported previously.10b
with an optical purity of 36% ==[a]25 ˆ242, cˆ1.0, CHCl3,
D
lit. [a]25 ˆ265, cˆ0.9, CHCl3 at 55% ee).10 =Table 2).
D
Again it was observed that extending the reaction time or
the number of equivalents of base had no signi®cant
enhancing effect on either the ee or the yield of the product.
Overall the ees for these transformations were low and again
probably re¯ect the differences in structure of the two
substrates, in that the trans-epoxides lack a secondary
co-ordination site for the bases.
4.1.1. 4-Benzyloxycyclopentene. Sodium hydride =0.79 g,
19.0 mmol) was added to a cooled =08C), stirred solution of
cyclopenten-4-ol18 =1.23 g, 14.6 mmol) in THF =50 mL).
After effervescence had ceased, benzyl bromide =3.25 g,
19.0 mmol) was added dropwise over 5 min and the result-
ing mixture was allowed to warm to rt over 4 h. Excess
sodium hydride was quenched with methanol =6 mL) and
the mixture diluted with water =100 mL), the two layers
separated and the aqueous layer extracted with ether
=3£25 mL). The combined organic extracts were washed
with water =50 mL), dried over magnesium sulfate, ®ltered
and the ®ltrate evaporated under reduced pressure. Flash
chromatography =80:20 petrol/EtOAc; Rfˆ0.65) gave
4-benzyloxycyclopentene =2.37 g, 95%) as a colourless oil.
3. Conclusions
The overall conclusions from both this work and the
available literature are that steric factors acting on both
the base and substrate play a considerable role in the
ef®ciency and enantioselectivity of these epoxide rearrange-
ments. In addition a duality of mechanism is also possible in
these reactions and care must be taken to investigate
the detailed mechanism of any of these processes before
arriving at any ®rm mechanistic conclusions.16 We are at
present involved in the development of these and struc-
turally related bases and their application to further
synthetic methodology and it is hoped that with further
experimentation, more speci®c guidelines as to the choice
of base or substrate protection criteria will become clear. In
addition, the commercially availability of these and other17
readily available dilithiated bases and their ease of use
and re-isolation will add to the signi®cance of these
applications.
dH 7.35 =5H, m, Ph), 5.72 =2H, s, H-3, H-4), 4.52 =2H, s,
Ph-CH2), 4.31 =1H, m, H-1), 2.6 =2H, dd, Jˆ15.3, 7.3 Hz,
H-2a or H-2b, H-5a or H-5b), 2.45 =2H, dd, Jˆ15.3,
7.3 Hz, H-2a or H-2b, H-5a or H-5b). dC 138.5 =C),
128.82 =CH), 128.58 =CH), 127.2 =CH), 78.5 =CH2), 71.9
=CH), 70.6 =CH2), 39.1 =CH2). nmax =liquid ®lm) 3062, 2903
=C±H), 1454 =CvC), 1072 =C±O). m/z =EI);174 =10%,
[M]1). HRMS =CI NH3) found 174.1045. C12H14O =[M]1)
requires: 174.1045.
4.1.2. cis-+1a) and trans-4-Benzyloxycyclopentan-1,2-
epoxide +13a). m-Chloroperoxybenzoic acid =9.40 g,
2 equiv., 50±60% purity) was added in one portion to a
Table 2. Rearrangement of epoxides 13a/b using ephedrine
Entry
Substrate
R
Basea
Equivalents
Yieldb
Ratioc 14/15
OPc
1
2
13a
13b
Bn
TBS
6 =2EPH)
7 =2EPH)
4
4
53 =81)
38 =62)
33:67
32:68
34
36
a
Conditions: base, THF, hexane, 2788C warmed to rt over 16 h.
Yields in brackets represent yields based on recovered starting material.
OPˆoptical purity, see text.
b
c

P. C. Brookes et al. / Tetrahedron 58 '2002) 4675±4680
4679
stirred, cooled =08C) solution of 4-benzoxycyclopentene
=2.37 g, 13.63 mmol) in dichloromethane =10 mL). The
mixture was stirred to rt. overnight. Excess m-Chloro-
peroxybenzoic acid was reduced by addition of saturated
sodium metabisulphite solution until a negative starch-
iodide test was observed;the mixture was then neutralised
with calcium hydroxide =2 g) and ®ltered through celite.
After drying over magnesium sulfate and ®ltration, the
®ltrate was evaporated under reduced pressure and the
crude product was re-dissolved in diethyl ether to precipitate
any remaining impurities;®ltration, evaporation under
reduced pressure and chromatography =75:25 petrol/diethyl
ether) gave the cis-epoxide 1a =1.067 g, 45%, Rfˆ0.13) and
the trans-product 13a =1.047 g, 44%, Rfˆ0.60).
[M1NH4]1). HRMS =CI, NH3): found 208.1338.
C12H18O2N, =[M1NH4]1) requires 208.1338.
4.2.2. Data for +1S,4S)/+1R,4R)-trans-1-Benzyloxycyclo-
pent-2-en-4-ol 14a/15a +RˆBn). Colourless oils.
[a]D20=15a)ˆ225.4 =cˆ0.55, CHCl3, 34% optical purity)
dHˆ7.38±7.20 =5H, m, Ph), 6.12 =1H, dd, Jˆ6.5, 1.0 Hz,
CH) 6.08 =1H, dd, Jˆ6.5, 1.0 Hz, CH), 5.05 =1H, m, CH),
4.82 =1H, m, CH), 4.56 =1H, d, Jˆ11.5 Hz, PhCH), 4.40
=1H, d, Jˆ11.5 Hz, PhCH), 2.23 =1H, ddd, Jˆ14.5, 7.0,
4.0 Hz, CH), 2.00 =1H, ddd, Jˆ14.5, 6.5, 3.0 Hz, CH)
1.65 =1H, br s, OH). dC 138.33 =C), 137.87 =CH) 134.89
=CH), 128.41, =2£ArH), 127.79 =2£ArH), 127.66 =ArH),
83.05 =CH2), 76.10 =CH), 71.15 =CH), 40.97 =CH2). nmax
=liquid ®lm)?3394 =O±H), 3030 =3060) 2932, 2862
=C±H), 1453 =CvC). m/z =CI, NH3) 208 =100%, [M1
NH4]1). HRMS =CI, NH3): found 208.1338. C12H18O2N,
=[M1NH4]1) requires 208.1338.
Data for 1a: colourless oil dH 7.35 =5H, m, Ph), 4.57 =1H, s,
Ph-CH2), 4.07 =1H, t, Jˆ7.3 Hz, CH), 3.54 =2H, s, 2£CH),
2.23 =2H, d, Jˆ15.3 Hz, 2£CH), 1.97 =2H, dd, Jˆ7.3,
15.3 Hz, 2£CH). dC 138.3 =C), 128.1 =CH), 127.5 =CH),
127.2 =CH), 77.2 =CH), 70.6 =CH), 57.4 =CH2), 34.8
=CH2). nmax =liquid ®lm) 3028, 2924 =C±H), 1496, 1095.
m/z =CI, NH3) 191 =90% [M1H]1). HRMS =CI, NH3):
found 191.1072. C12H14O2 =[M1H]1) requires 191.1072.
4.3. General method for determining enantiomeric
excesses
A solution of dicyclohexylcarbodiimide =1.5 equiv.) in
dichloromethane =ca. 1 mL) was added dropwise to a stirred
solution of =R)-O-acetyl mandelic acid =1.5 equiv.), the
protected cis-2-cyclopenten-4-ol =1 equiv.) and DMAP
=cat) dissolved in dichloromethane =ca. 1 mL per 0.5
mmol substrate) at 08C and the reaction stirred at rt for
18 h. The white precipitate of dicyclohexyl urea was
removed by ®ltration and the ®ltrate washed successively
with water =5 mL) and copper=II) sulphate solution =5 mL,
saturated), dried =magnesium sulfate) and evaporated under
reduced pressure. The crude compound was used directly
for determination of enantiomeric excess after ensuring that
a complete reaction had occurred
Data for 17a: colourless oil. dH 7.35 =5H, m, Ph), 4.56 =2H,
s, Ph-CH2), 3.89 =1H, app quintet Jˆ7.0, CH), 3.52 =2H, s,
2£CH), 2.53 =2H, dd, Jˆ7.0, 14.0 Hz, 2£CH), 1.73 =2H, dd,
Jˆ7.0, 14.0 Hz, 2£CH). dCˆ138.3 =C), 128.5 =CH), 127.8
=CH), 75.8 =CH), 72.0 =CH), 55.9 =CH2), 34.4 =CH2). nmax
=liquid ®lm)?3030, 2922 =C±H), 1494, 1112 =C±O). m/z
=CI, NH3) 208 =40%, [M1NH4]1). HRMS =CI, NH3):
found 208.1338. C12H18O2N, =[M1NH4]1) requires
208.1338.
4.2. General method for epoxide rearrangements using
dilithiated bases
1H signals for the H-5a proton at dˆ2.79 ppm correspond to
the mandelate derivative =8a) of the benzylated alcohol 3a
and dˆ2.68 ppm for the alcohol 2a.
1H signals for the H-5a proton at dˆ2.77 ppm correspond to
the mandelate derivative =8b)of the tert-butyldimethysilyl-
ated alcohol 3b and dˆ2.65 ppm for the alcohol 2b.
n-Butyl lithium =6±8 equiv. of 1.5±2.1 M hexane solution)
was added to a solution of the requisite base =3±4 equiv.) in
THF =1 mL per 0.5 mmol of base) at =08C) under nitrogen;
the solution was then stirred for 10 min and cooled to 278±
1008C. The epoxide =1 equiv.) dissolved in THF =1 mL per
0.5 mmol) was then added via syringe and the reaction
allowed to warm to rt over 16 h. The reaction was quenched
by the addition of HCl =2 M, excess) and the reaction diluted
with water =ca. 50 mL), extracted with diethyl ether =ca.
2£50 mL), dried over magnesium sulfate, ®ltered and
evaporated under reduced pressure. The products were
puri®ed by ¯ash column chromatography =ether/petrol).
4.4. General method for pyridinium chlorochromate
oxidations
Pyridinium chlorochromate =2 equiv.) was added in one
portion to a stirred solution of the required alcohol
=0.1±0.3 mmol) dissolved in dry dichloromethane =ca.
2 mL). After stirring to completion, ca. 1±2 h =TLC) the reac-
tion was diluted with ether =5 mL), ®ltered through a pad of
silica gel, which was washed with excess ether =ca. 50 mL).
After evaporation of the ®ltrate the products were puri®ed by
¯ash column chromatography =diethyl ether/petrol).
4.2.1. Data for +1R,4S)/+1S,4R)-cis-1-Benzyloxycyclo-
pent-2-en-4-ol
2a/3a
+RˆBn).
Colourless
oils
[a]D20=3a)ˆ223.2 =cˆ0.75, CHCl3, 78% optical purity).10
dHˆ7.30 =5H, m, Ph), 6.06 =2H, m, 2£CH), 4.57 =1H, dd,
Jˆ4.0, 7.0, CH), 4.63 =1H, d, Jˆ15.3 Hz, PhCH), 4.49 =1H,
d, Jˆ15.3 Hz, PhCH), 4.45 =1H, dd, Jˆ4.0, 7.0 Hz, CH),
2.67 =1H, app dt, Jˆ14.0, 7.0 Hz, CH), 1.72 =1H, br s, OH),
1.43 =1H, app dt, Jˆ14.0, 4.0 CH). dC 138.30 =C), 137.22
=CH) 134.13 =CH), 128.43, =2£ArH), 127.84 =2£ArH),
127.69 =ArH), 81.49 =CH2), 75.01 =CH), 71.07 =CH),
40.94 =CH2). nmax =liquid ®lm) 3350 =O±H), 2953, 2856
=C±H), 1448 =CvC). m/z =CI, NH3) 208 =100%,
4.4.1. +4S)-4-Benzyloxycyclopent-2-en-1-one +9a). 71%.
20
Rfˆ0.30 =50% diethyl ether in petrol). [a]D ˆ245.5,
16
cˆ0.9, CHCl3 ='R)-enone is reported as [a]D ˆ142, cˆ
0.9, CHCl311).
4.4.2. +4S)-4-tert-Butyldimethylsilyloxycyclopent-2-en-1-
one +9b). 55% Rfˆ0.20 =25% diethyl ether in petrol).

4680
P. C. Brookes et al. / Tetrahedron 58 '2002) 4675±4680
20
[a]D ˆ238.9, cˆ1.0, MeOH ==R)-enone is reported as
Moir, J. H. Chem. Commun. 2001, 1722±1723. =c) Henderson,
K. W.;Kerr, W. J.;Moir, J. H. Synlett 2001, 1253±1256.
[a]D20166.6, cˆ1.0, MeOH13).
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Acknowledgements
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Thanks are given to the European Social Fund for funding
=D. J. M. and P. C. B.), to the EPSRC for an earmarked
studentship =P. C. B.) and to the ERASMUS scheme
=B. S.). The support of the EPSRC Mass spectrometry centre
at Swansea is also acknowledged. Our gratitude is also
extended to Dr John Leonard =Salford) and Dr David M.
Hodgson =Oxford) for their comments on this work and
other useful information.
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