Synthesis and reactions of some optically active epoxides formally derived from tertiary allylic alcohols

Article abstract of DOI:10.1039/b008275i

The epoxyketones 2, 3 and 7-9 reacted with Grignard reagents in a highly stereocontrolled manner to give the epoxyalcohols 20, 4-6 and 11-13 in high yields. The epoxyalcohol 12 underwent a Payne rearrangement on base treatment to give the isomer 15 while

Full text of DOI:10.1039/b008275i

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Synthesis and reactions of some optically active epoxides formally
derived from tertiary allylic alcohols
Jamie F. Bickley, Adam T. Gillmore, Stanley M. Roberts, John Skidmore and
Alexander Steiner
1
Department of Chemistry, University of Liverpool, Liverpool, UK L69 7ZD.
E-mail: sj11@liv.ac.uk
Received (in Cambridge, UK) 13th October 2000, Accepted 26th February 2001
First published as an Advance Article on the web 21st March 2001
The epoxyketones 2, 3 and 7–9 reacted with Grignard reagents in a highly stereocontrolled manner to give the
epoxyalcohols 20, 4–6 and 11-13 in high yields. The epoxyalcohol 12 underwent a Payne rearrangement on base
treatment to give the isomer 15 while epoxyalcohols 4, 5, 12 and 20 suffered ring-opening (with retention of
configuration) using tin() chloride to afford chlorodiols 18, 17, 19 and 21 respectively. On the other hand, the
alcohols 4, 5 and 12 reacted with trialkylsilyl chlorides to furnish the chlorodiols 22, 24 and 23 respectively with
inversion of configuration.
Recent advances in the poly(α-amino acid)-catalysed epoxid-
ation of conjugated enones has resulted in ready access to a
range of α,β-epoxyketones in single enantiomer form.1 For
example, the enone 1 is converted into the epoxide 2 (a com-
pound required for the present study—see later) using the
recently reported reaction conditions that utilise sodium
percarbonate as the cheap, easy-to-use oxidant and base
(Scheme 1).2
Scheme
1
Reagents and conditions: i) Na2CO3ؒ1.5H2O2, poly-
(-leucine), H2O, DME, 18 h, rt, 78%, 97% ee.
Fig. 1 X-Ray crystal structure of 13.
As well as expanding the range of readily available, optically
active epoxyketones we have been anxious to develop further
the chemistry of these compounds through reaction at the
carbonyl group and/or the epoxide moiety. In this paper we
report in full some of our initial investigations in this area.3
the case of the methyl ketone 10 was a mixture of diastereomers
obtained on reaction with phenylmagnesium bromide, the
major product 14 being contaminated with a small amount of
the diastereoisomer 4 (ratio 4 : 14, 1 : 6).4
Results and discussion
The epoxyketone 3 suffers attack by a range of Grignard
reagents in a highly stereoselective fashion to afford the corre-
sponding tertiary alcohols 4–6, as essentially single diastereo-
isomers (dr as determined by 1H NMR of the crude product was
>99 : 1 in each case). The yields range from excellent (87%) for
the alcohol 4 to a modest 41% for the tert-butyl compound 6.
The stereochemistry of the compounds 53 and 13 (Fig. 1)
was ascertained by X-ray crystallography. The formation of
the tertiary alcohols 4–6 and 11–13 in a stereochemically-
controlled manner is explained by chelation of the organo-
magnesium reagent to the epoxide and carbonyl moieties prior
to attack by the nucleophile from the less-hindered Re-face
(Fig. 2).4,5 It is interesting to note that the well-known Sharpless
asymmetric epoxidation methodology does not work with any
degree of success for allylic tertiary alcohols.6
Similarly, the epoxyketones 7–9 were treated with phenyl-
magnesium bromide to give single compounds (11–13 respec-
tively) in each case, with yields ranging from 67 to 97%. Only in
DOI: 10.1039/b008275i
J. Chem. Soc., Perkin Trans. 1, 2001, 1109–1115
This journal is © The Royal Society of Chemistry 2001
1109

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Fig. 2 Chelation controlled attack by Grignard reagents on epoxy-
ketones 3 and 7–9.
In a complementary fashion, treatment of the epoxyalcohols
4 and 12 with tert-butyldimethylsilyl chloride (5 mol equiva-
lents), in the absence of imidazole, produced the chlorodiols
22 and 23 (60–61% yield) through inversion of configuration
at the carbon atom undergoing substitution. Trimethylsilyl
chloride (2 mol equivalents) promoted the same reaction, con-
verting the epoxyalcohol 5 into chlorodiol 24 in 57% yield.
Payne rearrangement7 of the tertiary alcohol 12 furnished
the secondary alcohol 15 as the major product (ratio 12 : 15,
3 : 97) and subsequent Dess–Martin oxidation of the latter
alcohol afforded the epoxyketone 16 (Scheme 2). This illustrates
Epoxide opening with trialkylsilyl halides has been docu-
mented previously with most cases displaying inversion of
configuration at the participating carbon centre.12 Activation
of the epoxide unit by the oxaphilic silicon species followed
by rear-side attack on the benzylic centre by chloride ion is
a generally accepted mechanism leading to the observed
products.
Scheme 2 Reagents and conditions: (i) NaOH, ButOH, 2 h, rt, 97%; (ii)
Dess–Martin periodinane, CH2Cl2, 16 h, rt, 67%.
In order to clearly establish the stereochemical relationship
of the two chlorodiols 19 and 23, both compounds were
hydrodehalogenated, independently, with tri-n-butyltin hydride
and AIBN in hot toluene to give the diol 25 in each case.
In summary, we have shown that diastereoselective
addition of Grignard reagents to non-racemic α,β-epoxy-
ketones generates the corresponding alcohols with excellent
diastereoselectivity. A range of transformations of these
alcohols has also been presented; further work, aimed at
the production of longer carbon chains carrying a variety of
substituents at adjacent positions with strictly controlled
stereochemistry, is ongoing.
new methodology for the production of epoxides formally
derived from β,β-disubstituted enones, compounds which do
not undergo asymmetric epoxidation directly using poly-
(α-amino acids) as catalysts.
Attempts to induce a tin() chloride-catalysed semi-pinacol
rearrangement8 on the epoxyalcohol 5 were thwarted by the
onset of an epoxide ring-opening reaction, giving the chloro-
diol 17, resulting from opening of the three-membered ring
with retention of configuration at the reacting carbon atom.
The relative stereochemistry of the substituents in compound
17 was confirmed by X-ray crystallography.9
Experimental
General procedures
NMR spectra were recorded on Bruker AC200, Bruker
AMX400, Bruker Avance 400 or Varian Gemini300 instru-
ments. The following abbreviations are used to describe the
multiplicities: s, singlet; d, doublet; t, triplet; q, quartet; sept,
septet; m, multiplet; br, broad. J values are given in Hz. NMR
spectral data are referenced to the residual protonated solvent
peak (DMSO, δH 2.52) or TMS. Shifts in 13C NMR spectra
have been assigned using DEPT. IR spectra were recorded
on a Perkin Elmer Paragon 1000 spectrophotometer. The
designations s (sharp) and br (broad) are used to describe the
peaks observed in the IR spectrum. Diagnostic signals from
the IR spectrum are listed with assignments accompanied by a
selection of strong peaks in the fingerprint region to aid further
comparisons. Melting points were measured on a Gallenkamp
melting point apparatus and are uncorrected. Optical rotations
were measured on an Optical Activity AA-1000 polarimeter
The same protocol performed on the epoxides 4 and 12 gave
rise to the corresponding halodiols 18 and 19 respectively. The
yields for all three reactions were within the range 80–86%. The
mechanism for this reaction is believed to proceed as illustrated
in Scheme 3. The Lewis acid coordinates to the oxygen atoms of
the epoxide unit and the alcohol moiety. Donation of electrons
into the empty d-orbital of the metal can take place from either
of the oxygen atoms and normally it would be anticipated
that the alcohol group would be the major contributor.10 How-
ever, strong co-ordination to the epoxide oxygen atom leads
to favourable neighbouring group participation by the phenyl
group and consequent opening of the three-membered ring.
Fast, intramolecular migration of chloride ion from the metal
(possibly by a caged ion-pair mechanism) would then deliver
the nucleophile to the benzylic carbon atom with retention of
configuration.11
with a 0.1 dm cell and are quoted in units of 10Ϫ1 deg cm2 gϪ1
.
As expected, on the basis of this proposed mechanism, a
compound having an electron-poor aromatic ring reacts more
slowly: thus the epoxyalcohol 20, prepared from the ketone 2 in
93% yield using methylmagnesium bromide, reacted sluggishly
with tin() chloride (4 h versus 1.5 h for complete reaction) yet
still gave the chloro-compound 21 in almost quantitative yield.
Low resolution EI mass spectra were measured on a Fisons
Trio1000 spectrometer; CI and accurate mass spectra were
measured on a VG Analytical 7070E double focusing magnetic
mass spectrometer. Elemental analysis was performed on a
Carlo Erba Elemental Analyser model 1106. Chiral HPLC was
performed on a Gilson chromatograph with isocratic pump at a
1110
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flow rate of 1 ml minϪ1 using a Chiralpak® AD column (4.6
cm × 25 cm) with UV detection at 254 nm.
dimethoxyethane and water [20 cm3 (1 : 1)] until the reaction
was judged to be complete by TLC. The catalyst was separated
by filtration and washed with EtOAc (150 cm3). The filtrate was
washed with saturated aqueous sodium sulfite (2 × 50 cm3),
water (2 × 50 cm3) and brine (50 cm3) before drying (MgSO4).
Removal of the solvent under reduced pressure afforded the
crude product.
All reactions were monitored by thin layer chromatography,
which was performed on 200–250 µm thickness Merck silica gel
plates (60F254). Compounds were detected by ultraviolet light
or by staining with ceric ammonium molybdate or potassium
permanganate solutions followed by heat as a developing
agent. Retention factors (Rf) are quoted to the nearest 0.05.
Column chromatography was performed on Merck-60 silica gel
(230–400 mesh).
Recycling of the catalysts
Polystyrene-supported poly(-leucine) was recycled by washing
with water, water–acetone (1 : 1), acetone and EtOAc sequen-
tially before drying on a glass sinter. SiO2–poly(-leucine) is
incompatible with aqueous solutions, so the residual urea was
removed by washing with EtOH and THF sequentially before
drying on a glass sinter.
Petroleum ether refers to the light petroleum fraction bp
40–60 ЊC and was distilled prior to use. Tetrahydrofuran and
diethyl ether were heated under reflux over (and distilled from)
sodium–benzophenone ketyl; CH2Cl2 was heated under reflux
over (and distilled from) calcium hydride prior to use; tert-
butyl alcohol was dried using 3 Å molecular sieves; anhydrous
toluene was purchased from Aldrich. All materials were
purchased and used directly from commercial suppliers unless
otherwise stated.
(Ϫ)-(1S,2R)-1,2-Epoxy-3-phenyl-1-(4-trifluoromethylphenyl)-
propan-3-one (2)
trans-(1S,2R)-Epoxychalcone13 (3) and (Ϫ)-(1S,2R)-1,2-
epoxy-4,4-dimethyl-1-phenylpentan-3-one13 (9) were prepared
as described previously.
Epoxidation of enone 1 (1.00 g, 3.62 mmol) according to
general procedure B was complete after 18 hours. Standard
workup followed by recrystallisation from n-hexane gave the
title compound 2 (829 mg, 2.84 mmol, 78%) as white needles,
mp 93–96 ЊC (n-hexane); Rf [petroleum ether–Et2O (3 : 1)] 0.3;
General procedure A for epoxidation of enones: biphasic
conditions
[α]2D2 = Ϫ205 (c 1.0, CHCl3); νmax(KBr)/cmϪ1 1684 (C᎐O), 1659,
᎐
1330, 1113, 1069, 854 and 691; δH (300 MHz; CDCl3; Me4Si)
4.16 (1 H, d, J 1.8, CH), 4.26 (1 H, d, J 1.8, CH), 7.49–7.54
(4 H, m, ArH), 7.62–7.69 (3 H, m, ArH), 8.00–8.03 (2 H, m,
ArH); δC (100 MHz; CDCl3; Me4Si) 58.4 and 61.0 (CH), 123.9
(q, 1JC–F 272, CF3), 125.8 (q, 3JC–F 4, ArC-C-CF3), 126.2, 128.4
and 129.0 (ArCH), 131.3 (q, 2JC–F 33, ArC-CF3), 134.2 (ArCH),
The enone (2.90 mmol), urea–H2O2 (324 mg, 3.44 mmol, 1.2 eq),
DBU (0.64 cm3, 4.3 mmol, 1.5 eq) and polystyrene-supported
poly(-leucine)14 (2.00 g) or SiO2-poly(-leucine)15 (5.20 g) were
stirred in dry THF (30 cm3) until the reaction was judged to be
complete by TLC. The catalyst was separated by filtration and
washed with EtOAc (150 cm3). The filtrate was washed with
saturated aqueous sodium sulfite (2 × 50 cm3), water (2 × 50
cm3) and brine (50 cm3) before drying (MgSO4). Removal of the
solvent under reduced pressure afforded the crude product.
135.4 and 139.7 (ArCipso), 192.5 (C᎐O); HRMS (CI) C -
᎐
16
H12O2F3 [M + H]+ requires 293.0789, found 293.0792; m/z (EI)
105 (5%), 87 (10), 71 (100), 57 (25); ee 97% (Chiralpak® AD;
5% EtOH in n-hexane; major enantiomer 23.0 min, minor
enantiomer 19.8 min).
General procedure B for epoxidation of enones: sodium
percarbonate conditions
General procedure for the addition of Grignard reagents to
epoxyketones
The enone (2.90 mmol), sodium percarbonate (Na2CO3ؒ
1.5H2O2, 1.35 g, 8.60 mmol, 3.0 eq) and polystyrene-supported
poly(-leucine)14 (2.00 g) were stirred in a mixture of 1,2-
To a stirred solution of the Grignard reagent (2.8 mmol) in THF
(20 cm3) at Ϫ78 ЊC was added the epoxyketone (1.4 mmol) as a
Scheme 3
J. Chem. Soc., Perkin Trans. 1, 2001, 1109–1115
1111

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solution in THF (10 cm3) under a nitrogen atmosphere. The
reaction was stirred at Ϫ78 ЊC for 1.5 h, quenched by addition
of saturated aqueous ammonium chloride (10 cm3), allowed to
warm to room temperature and extracted with EtOAc (3 × 25
cm3). The combined organic extracts were washed with water
(2 × 50 cm3) and brine (50 cm3) before drying (MgSO4).
Removal of the solvent under reduced pressure gave the crude
product which was analysed by NMR to measure the diastereo-
isomeric ratio of Re : Si products16 before purification.
1450, 1360, 1170 and 880; δH (400 MHz; CDCl3; Me4Si) 1.02
(9 H, s, C(CH3)3), 2.83 (1 H, s, OH), 3.59 (1 H, d, J 2.4, CH), 3.8
(1 H, d, J 2.4, CH), 7.17–7.33 (10 H, m, ArH); δC (100 MHz;
CDCl3; Me4Si) 25.4 (C(CH3)3), 39.2 (C(CH3)2), 54.9 and 64.3
(CH), 76.1 (C(3)ipso), 125.6, 126.9, 127.2, 128.2 and 128.6
(ArCH), 136.8 and 142.4 (ArCipso); m/z (EI) 225 (M+ Ϫ C4H9,
7%), 207 (18), 105 (100).
(Ϫ)-(1S,2R)-1,2-Epoxy-1-phenylpentan-3-one (7)
Epoxidation of 1-phenylpent-1-en-3-one (500 mg, 3.12 mmol)
according to general procedure A using SiO2–poly(-leucine) as
the catalyst was complete after 18 h. Purification by column
chromatography [petroleum ether–Et2O (9 : 1)] followed by
recrystallisation from MeOH furnished the title compound 7
(138 mg, 0.78 mmol, 25%) as white needles; mp 45–48 ЊC
(MeOH); Rf [petroleum ether–Et2O (6 : 1)] 0.35 (Found: C,
75.3; H, 6.9; C11H12O2 requires: C, 75.0; H, 6.9%); [α]2D2 = Ϫ111
(c 1.0, CHCl3); νmax(KBr)/cmϪ1 2973 (C–H), 1710 (saturated
(Ϫ)-(1S,2R,3S)-1,3-Diphenyl-1,2-epoxybutan-3-ol (4)
Reaction of methylmagnesium bromide (3.0 M in Et2O, 1.5
cm3, 4.5 mmol) with trans-(1S,2R)-epoxychalcone (3) (500 mg,
2.23 mmol) following the general procedure gave the desired
tertiary alcohol with a Re : Si ratio16 of >99 : 1. The crude
product was purified by column chromatography [petroleum
ether–Et2O (6 : 1)] followed by recrystallisation from n-hexane
to give the title compound 4 (468 mg, 1.95 mmol, 87%) as
white crystals; mp 100–102 ЊC (n-hexane); Rf [petroleum ether–
Et2O (3 : 1)] 0.3 (Found: C, 79.7; H, 6.8; C16H16O2 requires: C,
80.0; H, 6.7%); [α]2D2 Ϫ45.8 (c 0.5, CHCl3); νmax(KBr)/cmϪ1 3485
(O–H), 1632, 1497 and 1446; δH (400 MHz; CDCl3; Me4Si) 1.70
(3 H, s, C(4)H3), 2.85 (1 H, s, C(3)OH), 3.23 (1 H, d, J 2.2, CH),
4.03 (1 H, d, J 2.2, CH), 7.3 (10 H, m, ArH); δC (100 MHz;
CDCl3; Me4Si) 27.7 (C(4)H3), 55.9 and 68.6 (CH), 71.4
(C(3)ipso), 125.21, 125.9, 127.64, 128.4 and 128.6 (ArCH),
136.8 and 143.6 (ArCipso); m/z (EI) 121 (34%), 120 (86), 105
(91), 91 (100), 77 (62).
C᎐O), 1457, 1408, 1173 and 884; δH (400 MHz; CDCl3; Me4Si)
᎐
1.12 (3 H, t, J 7.2, CH3), 2.49 (1 H, dq, J 18.4, 7.2) and 2.59 (1
H, dq, J 18.4, 7.2, CH2), 3.52 (1 H, d, J 1.9, CH), 3.98 (1 H, d, J
1.9, CH), 7.26–7.38 (5 H, m, ArH); δC (100 MHz; CDCl3;
Me4Si) 7.0 (CH3), 31.1 (CH2), 58.1 and 63.1 (CH), 125.8, 128.8
and 129.0 (ArCH), 135.4 (ArCipso), 206.5 (C᎐O); m/z (EI) 176
᎐
(M+, 21%), 131 (12), 120 (41), 91 (100).
(Ϫ)-(1S,2R)-1,2-Epoxy-4-methyl-1-phenylpentan-3-one (8)
Epoxidation of 4-methyl-1-phenylpent-1-en-3-one (1.0 g, 5.74
mmol) according to general procedure A using SiO2–poly-
(-leucine) as the catalyst was complete after 18 h. Purification
by column chromatography [petroleum ether–Et2O (6 : 1)]
followed by recrystallisation from n-hexane furnished the title
compound 8 (621 mg, 3.26 mmol, 57%) as white needles; mp
56–57 ЊC (n-hexane); Rf [petroleum ether–Et2O (6 : 1)] 0.4
(Found: C, 75.8; H, 7.4; C12H14O2 requires: C, 75.8; H, 7.4%);
(Ϫ)-(1S,2R,3S)-1,2-Epoxy-1,3-diphenylheptan-3-ol (5)
To a stirred suspension of magnesium turnings (108 mg, 4.46
mmol) in Et2O (10 cm3) was added n-bromobutane (0.48 cm3,
4.5 mmol) under a nitrogen atmosphere at such a rate as to
maintain reflux. After complete reaction of the magnesium,
THF (10 cm3) was added and the contents of the flask were
cooled to Ϫ78 ЊC. trans-(1S,2R)-Epoxychalcone (3) (500 mg,
2.23 mmol) was added either via a solid addition tube or as a
solution in THF (5.0 cm3). After 4 h, the reaction was quenched
and worked up according to the general procedure, except that
Et2O (3 × 50 cm3) was employed instead of EtOAc. The desired
tertiary alcohol had a Re : Si ratio16 of >99 : 1. The crude
product was purified by column chromatography [petroleum
ether–Et2O (6 : 1)] and recrystallised from n-hexane to afford
5 (378 mg, 1.34 mmol, 60%) as white crystals, mp 82–84 ЊC
(n-hexane); Rf [petroleum ether–Et2O (3 : 1)] 0.4 (Found: C,
80.9; H, 7.8; C19H22O2 requires: C, 80.8; H, 7.9%); [α]2D2 = Ϫ50.0
(c 1.0, CHCl3); νmax(KBr)/cmϪ1 3494 (O–H), 1212, 961 and 881;
δH (400 MHz; CDCl3; Me4Si) 0.88 (3 H, m, C(7)H3), 1.17–1.47
(4 H, m, C(5,6)H2), 1.93–2.09 (2 H, m, C(4)H2), 2.35 (1 H, s,
C(3)OH), 3.35 (1 H, d, J 2.2, CH), 3.92 (1 H, d, J 2.2, CH),
7.17–7.47 (10 H, m, ArH); δC (100 MHz; CDCl3; Me4Si) 14.6
(C(7)H3), 23.7 and 25.9 (CH2), 41.7 (C(4)H2), 55.7 and 68.6
(CH), 73.9 (C(3)ipso), 125.7, 126.4, 127.7, 128.8, 129.0 and
129.0 (ArCH), 136.8 and 142.6 (ArCipso); m/z (EI) 163 (20%),
120 (83), 105 (100), 91 (81), 77 (59).
[α]2D2 = Ϫ208 (c 1.0, CHCl3); νmax(KBr)/cmϪ1 1711 (C᎐O), 1458,
᎐
1417 and 1052; δH (400 MHz; CDCl3; Me4Si) 1.16 (3 H, d, J 7.0)
and 1.17 (3 H, d, J 7.0, CH(CH3)2), 2.83 (1 H, sept, J 7.0,
C(4)H), 3.61 (1 H, d, J 2.0, CH), 3.93 (1 H, d, J 2.0, CH), 7.29–
7.38 (5 H, m, ArH); δC (100 MHz; CDCl3; Me4Si) 17.3 and 18.1
(CH(CH3)2), 37.0 (C(4)H), 58.4 and 61.9 (CH), 125.7, 128.7
and 129.0 (ArCH), 135.4 (ArCipso), 208.7 (C᎐O); m/z (EI) 190
᎐
(M+, 4%), 174 (57), 148 (88), 147 (77); ee >99% (Chiralpak®
AD, 5% EtOH in n-hexane; major enantiomer 8.9 min, minor
enantiomer 23.4 min).
(؉)-(1S,2R,3R)-1,2-Epoxy-1,3-diphenylpentan-3-ol (11)
Reaction of phenylmagnesium bromide (1 M in THF, 1.1 cm3,
1.1 mmol) with epoxyketone 7 (100 mg, 0.57 mmol) following
the general procedure gave a product with a Re : Si ratio16 of
>99 : 1. The product was purified by column chromatography
[petroleum ether–Et2O (12 : 1)] to give the title compound 11
(141 mg, 0.55 mmol, 97%) as a colourless oil; Rf [petroleum
ether–Et2O (6 : 1)] 0.3; [α]2D2 = +44 (c 1.0, CHCl3); νmax(thin
film)/cmϪ1 3454 (O–H), 2972 and 2937 (alkyl C–H), 1495, 1448,
1311, 1060 and 886; δH (200 MHz; CDCl3; Me4Si) 0.86 (3 H, t, J
6.6, CH3), 1.93 (2 H, q, J 6.6, CH2), 2.59 (1 H, br s, OH), 3.41 (1
H, d, J 2.2, CH), 4.08 (1 H, d, J 2.2, CH), 7.30–7.51 (10 H, m,
ArH); δC (100 MHz; CDCl3; Me4Si) 7.8 (CH3), 32.2 (CH2), 56.0
and 68.0 (CH), 74.2 (COH), 125.5, 125.8, 127.4, 128.4, 128.5
and 128.7 (ArCH), 137.0 and 144.4 (ArCipso); m/z (EI) 148
(M+ Ϫ C6H5 Ϫ C2H5, 56%), 120 (50), 105 (100), 77 (67).
(Ϫ)-(1S,2R,3S)-4,4-Dimethyl-1,3-diphenyl-1,2-epoxypentan-
3-ol (6)
Reaction of tert-butylmagnesium chloride (2 M in Et2O,
1.0 cm3, 1.9 mmol) with trans-(1S,2R)-epoxychalcone (3) (217
mg, 0.97 mmol) following the general procedure gave a product
with a Re : Si ratio16 of >99 : 1. The crude product was purified
by column chromatography [petroleum ether–Et2O (9 : 1)]
followed by recrystallisation from n-hexane to furnish the title
compound 6 (113 mg, 0.40 mmol, 41%) as white crystals,
mp 99–101 ЊC (n-hexane); Rf [petroleum ether–Et2O (6 : 1)] 0.5
(Found: C, 80.7; H, 7.9; C19H22O2 requires: C, 80.8; H, 7.85%);
[α]2D2 = Ϫ95 (c 1.0, CHCl3); νmax(KBr)/cmϪ1 3526 (O–H), 1495,
(؉)-(1S,2R,3R)-1,2-Epoxy-1,3-diphenyl-4-methylpentan-3-ol
(12)
Reaction of phenylmagnesium bromide (1 M in THF, 2.6 cm3,
2.6 mmol) with epoxyketone 8 (247 mg, 1.30 mmol) following
the general procedure gave a product with a Re : Si ratio16 of
1112
J. Chem. Soc., Perkin Trans. 1, 2001, 1109–1115

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>99 : 1. The product was purified by recrystallisation from
n-hexane to give the title compound 12 (191 mg, 0.94 mmol,
71%) as white needles, mp (n-hexane) 106–107 ЊC; Rf [petrol-
eum ether–Et2O (6 : 1)] 0.3 (Found: C, 80.4; H, 7.55; C18H20O2
requires: C, 80.6; H, 7.5%); [α]2D2 = +64 (c 1.0, CHCl3);
νmax(KBr)/cmϪ1 3491 (O–H), 1470, 1448, 1287 and 1059; δH (400
MHz; CDCl3; Me4Si) 0.85 (3 H, d, J 6.9) and 0.99 (3 H, d,
J 6.9, CH(CH3)2), 1.54 (1 H, s, OH), 2.22 (1 H, sept, C(4)H),
3.45 (1 H, d, J 2.1, CH), 4.13 (1 H, d, J 2.1, CH), 7.25–7.52 (10
H, m, ArH); δC (100 MHz; CDCl3; Me4Si) 16.9 and 17.5
(CH(CH3)2), 36.2 (C(4)H), 56.6 and 67.2 (CH), 76.0 (COH),
125.6, 127.2, 128.3 and 128.6 (ArCH), 136.9 and 144.6
(ArCipso); m/z (EI) 225 (M+ Ϫ C3H7, 5%), 147 (45), 120 (36),
105 (100), 91 (87).
50 cm3) and brine (50 cm3) before drying (MgSO4). Removal
of the solvent under reduced pressure, followed by column
chromatography [petroleum ether–Et2O (6 : 1)] gave the epoxy-
ketone 16, which was further purified by recrystallisation from
n-hexane to afford title compound 16 (34 mg, 0.13 mmol,
67% from epoxyalcohol 12) as fine white needles, mp 91–92 ЊC
(n-hexane); Rf [petroleum ether–Et2O (3 : 1)] 0.4 (Found: C,
80.7; H, 6.8; C18H18O2 requires: C, 81.2; H, 6.8%); [α]2D2 = +125
(c 1.0, CHCl3); νmax(KBr)/cmϪ1 2963 (C–H), 1684 (aryl C᎐O),
᎐
1465, 1448 1230, 766; δH (300 MHz; CDCl3; Me4Si) 1.05 (3 H,
d, J 6.6) and 1.08 (3 H, d, J 6.6, CH(CH3)2), 2.23 (1 H, sept,
J 6.6, C(4)H), 4.40 (1 H, s, CH), 7.16–7.57 (8 H, m, ArH),
7.83–7.87 (2 H, m, ArH); δC (75 MHz; CDCl3; Me4Si) 17.8
and 18.6 (CH(CH3)2), 35.0 (C(4)H), 63.7 (C(2)H), 71.0 (C(3)),
127.7, 127.8, 128.2, 128.6 and 133.4 (ArCH), 134.7 and 136.0
(ArCipso), 193.5 (C᎐O); m/z (EI) 223 (M+ Ϫ C H , 3%), 71
(؉)-(1S,2R,3R)-1,2-Epoxy-4,4-dimethyl-1,3-diphenylpentan-3-
ol (13)
᎐
3
7
(100).
Reaction of phenylmagnesium bromide (1 M in THF, 2.7 cm3,
2.7 mmol) with epoxyketone 9 (279 mg, 1.37 mmol) following
the general procedure gave a product with a Re : Si ratio16 of
>99 : 1. The product was purified by recrystallisation from
n-hexane to furnish the title compound 13 (261 mg, 0.92 mmol,
67%) as white crystals, mp 91–92 ЊC (n-hexane); Rf [petroleum
ether–Et2O (6 : 1)] 0.6 (Found: C, 81.2; H, 8.0; C19H22O2
requires: C, 80.8; H, 7.9%); [α]2D2 = +60 (c 1.0, CHCl3);
νmax(KBr)/cmϪ1 3470 (O–H), 1498, 1461, 1326 and 979; δH (400
MHz; CDCl3; Me4Si) 0.98 (9 H, s, CH3), 2.18 (1 H, s, OH), 3.76
(1 H, d, J 2.0, CH), 4.21 (1 H, d, J 2.0, CH), 7.35–7.37 (8 H,
m, ArH), 7.57–7.59 (2 H, m, ArH); δC (100 MHz; CDCl3;
Me4Si) 26.6 (C(CH3)3), 38.2 (C(CH3)3), 57.9 and 66.4 (CH),
78.3 (COH), 126.3, 127.9, 128.1, 128.2, 129.0 and 129.3
(ArCH), 137.5 and 143.8 (ArCipso); m/z (EI) 225 (M+ Ϫ C4H9,
3%), 207 (4), 105 (100).
General procedure for epoxide opening with retention of
configuration
To a stirred solution of the epoxyalcohol (0.21 mmol) in
anhydrous CH2Cl2 (5.0 cm3) was added tin() chloride (1 M
in CH2Cl2, 0.25 cm3, 0.25 mmol) at Ϫ78 ЊC under a nitrogen
atmosphere. Stirring was continued at Ϫ78 ЊC for 1.5 h before
quenching by the addition of saturated aqueous ammonium
chloride (5.0 cm3). The product was extracted with CH2Cl2
(3 × 25 cm3) and the combined organic extracts were washed
with water (2 × 25 cm3) and brine (25 cm3) before drying
(MgSO4). Removal of the solvent under reduced pressure gave
the crude chlorodiol, which was purified by column chroma-
tography or recrystallisation.
(؉)-(1S,2S,3S)-1-Chloro-1,3-diphenylheptane-2,3-diol (17)
Epoxyalcohol 5 (60 mg, 0.21 mmol) was treated with tin()
chloride (1 M in CH2Cl2, 0.25 cm3, 0.25 mmol) following the
general procedure. Purification of the crude product by column
chromatography [petroleum ether–Et2O (4 : 1)] followed by
recrystallisation from n-hexane furnished the title compound
17 (53 mg, 0.17 mmol, 80%) as white crystals, mp 80–83 ЊC
(n-hexane); Rf [petroleum ether–Et2O (3 : 1)] 0.2; [α]2D2 = +26 (c
1.0, CHCl3); νmax(KBr)/cmϪ1 3408 (br, O–H), 2948, 1491, 1447,
1226, 1071, 762 and 699; δH (400 MHz; CDCl3; Me4Si) 0.78
(3 H, t, J 7.2, C(7)H3), 1.12–1.34 (4 H, m, C(5,6)H2), 1.73–1.74
(1 H, m) and 2.18–2.21 (1 H, m, C(4)H2), 2.89 (1 H, s, C(3)OH),
3.12 (1 H, d, J 9.2, C(2)OH), 4.11 (1 H, dd, J 9.2, 2.0, C(2)H),
4.73 (1 H, d, J 2.0, C(1)H), 7.24–7.39 (10 H, m, ArH); δC (100
MHz; CDCl3; Me4Si) 14.6 (C(7)H3), 23.6, 25.7 and 40.6 (CH2),
65.2 and 79.4 (CH), 80.9 (C(3)), 125.2, 127.3, 127.6, 128.3,
128.5 and 128.7 (ArCH), 140.7 and 143.3 (ArCipso); HRMS
(CI) C19H27NO235Cl [M + NH4]+ requires 336.1730, found
336.1734; m/z (EI) 163 (43%), 120 (100), 105 (75), 91 (53), 77
(28).
(Ϫ)-(1S,2S,3R)-2,3-Epoxy-4-methyl-1,3-diphenylpentan-1-ol
(15)
Epoxyalcohol 12 (150 mg, 0.56 mmol) and sodium hydroxide
(25.0 mg, 0.61 mmol) were stirred in anhydrous tert-butyl
alcohol (10 cm3) at 30 ЊC for 2 hours under a nitrogen
atmosphere. The reaction mixture was quenched by addition of
saturated aqueous ammonium chloride (10 cm3) and extracted
with EtOAc (3 × 25 cm3). The combined organic extracts were
washed with water (2 × 50 cm3) and brine (50 cm3) before
drying (MgSO4). Removal of the solvent under reduced
pressure gave the crude product which was purified by column
chromatography [petroleum ether–Et2O (6 : 1)] to afford the
title compound 15 (146 mg, 0.54 mmol, 97%) as a colourless
oil, Rf [petroleum ether–Et2O (3 : 1)] 0.35; [α]2D2 = Ϫ171 (c 1.0,
CHCl3); νmax(thin film)/cmϪ1 3426 (br, O–H), 2964 (C–H), 1603
(phenyl C᎐C), 1494, 1445, 1365, 1025, 937, 765 and 701; δ (300
᎐
H
MHz; CDCl3; Me4Si) 0.88 (3 H, d, J 6.6) and 0.96 (3 H, d, J 6.6,
CH(CH3)2), 1.93 (1 H, sept, J 6.6, C(4)H), 2.08 (1 H, br s,
OH), 3.18 (1 H, d, J 8.8, C(2)H), 3.76 (1 H, d, J 8.8, C(1)H),
7.27–7.45 (10 H, m, ArH); δC (75 MHz; CDCl3; Me4Si) 17.4 and
18.8 (CH(CH3)2), 34.9 (C(4)H), 65.6 (CH), 70.7 (C(3)), 71.8
(CH), 126.1, 127.7, 128.0, 128.1 and 128 (ArCH), 136.9 and
141.8 (ArCipso); HRMS (CI): C18H24NO2 [M + NH4]+ requires
286.1807, found 286.1814; m/z (EI) 250 (3%), 207 (24), 162 (23),
161 (29), 149 (64), 120 (70), 117 (100), 105 (70), 91 (93), 77 (95).
(؉)-(1S,2S,3S)-1-Chloro-1,3-diphenylbutane-2,3-diol (18)
Epoxyalcohol 4 (50 mg, 0.21 mmol) was treated with tin()
chloride (1 M in CH2Cl2, 0.25 cm3, 0.25 mmol) following
the general procedure. The product was purified by column
chromatography [petroleum ether–Et2O (4 : 1)] followed by
recrystallisation from n-hexane to yield the title compound 18
(43 mg, 0.16 mmol, 76%) as white crystals, mp 70–71 ЊC (n-
hexane); Rf [petroleum ether–Et2O (3 : 2)] 0.4 (Found: C, 69.4;
H, 6.2; Cl, 12.6; C16H17O2Cl requires: C, 69.4; H, 6.2; Cl,
12.8%); [α]2D2 = +46 (c 0.54, CHCl3); νmax(KBr)/cmϪ1 3520 (br,
O–H), 3085, 3060, 2978, 2930 (C–H stretch), 1446, 1494 and
1599; δH (400 MHz; DMSO-D6) 1.53 (3 H, s, C(4)H3), 3.80
(1 H, dd, J 8.3, 2.8, C(2)H), 5.14 (1 H, d, J 2.8, C(1)H), 5.18
(1 H, s, C(3)OH), 5.26 (1 H, d, J 8.3, C(2)OH); HRMS (CI)
C16H21NO235Cl [M + NH4]+ requires 294.1261, found 294.1259.
(؉)-(2S,3R)-2,3-Epoxy-4-methyl-1,3-diphenylpentan-1-one (16)
Crude epoxyalcohol 15 (50 mg, 0.19 mmol) and Dess–Martin
periodinane (89 mg, 0.21 mmol) were stirred in anhydrous
CH2Cl2 (10 cm3) under a nitrogen atmosphere for 16 hours. The
reaction was quenched by addition of a mixture of saturated
aqueous sodium bicarbonate and saturated aqueous sodium
sulfite [10 cm3, (1 : 1)] and extracted with CH2Cl2 (3 × 25 cm3).
The combined organic extracts were washed with water (2 ×
J. Chem. Soc., Perkin Trans. 1, 2001, 1109–1115
1113

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(؉)-(1S,2S,3R)-1-Chloro-4-methyl-1,3-diphenylpentane-2,3-diol
(19)
reduced pressure gave the crude product, which was purified by
column chromatography.
Epoxyalcohol 12 (64 mg, 0.24 mmol) was treated with tin()
chloride (1 M in CH2Cl2, 0.3 cm3, 0.3 mmol) following the
general procedure. The crude product was purified by column
chromatography [petroleum ether–Et2O (6 : 1)] to give the title
compound 19 (63 mg, 0.21 mmol, 86%) as a colourless oil, Rf
[petroleum ether–Et2O (3 : 1)] 0.45; [α]2D2 = +42 (c 1.0, CHCl3);
δH (300 MHz; CDCl3; Me4Si) 0.55 (3 H, d, J 6.9) and 1.07 (3 H,
d, J 6.9, CH(CH3)2), 1.38 (1 H, br s, C(3)OH), 2.55 (1 H, sept,
J 6.9, C(4)H), 2.89 (1 H, d, J 4.2, C(2)OH), 4.34 (1 H, dd, J 4.2,
6.2, C(2)H), 4.84 (1 H, d, J 6.2, C(1)H), 7.19–7.24 (2 H, m,
ArH), 7.29–7.37 (6 H, m, ArH), 7.41–7.46 (2 H, m, ArH);
δC (300 MHz; CDCl3; Me4Si) 16.5 and 16.6 (CH(CH3)2), 34.8
(C(4)H), 67.2 and 77.7 (CH), 80.0 (C(3)OH), 126.4, 127.2,
127.9, 128.3, 128.8 and 129.0 (ArCH), 139.4 and 142.2
(ArCipso); HRMS (CI) C18H25NO235Cl [M + NH4]+ requires
322.1574, found 322.1576; m/z (EI) 149 (60%), 120 (100), 105
(64), 91 (52), 77 (27).
(1R,2S,3S)-1-Chloro-1,3-diphenylbutane-2,3-diol (22)
Epoxyalcohol 4 (100 mg, 0.42 mmol) was treated with TBSCl
(124 mg, 0.82 mmol) following the general procedure. Purifica-
tion of the crude product by column chromatography [petrol-
eum ether–Et2O (6 : 1)] gave the title compound 22 (69 mg, 0.25
mmol, 60%) as a colourless oil; Rf [petroleum ether–Et2O
(3 : 1)] 0.15; δH (300 MHz; CDCl3; Me4Si) 1.60 (3 H, s, C(4)H3),
1.77 (1 H, s, C(3)OH), 2.71 (1 H, d, J 6.6, C(2)OH), 4.44 (1 H,
dd, J 6.6, 3.3, C(2)H), 4.77 (1 H, d, J 3.3, C(1)H), 7.22–7.40 (10
H, m, ArH); δC (75 MHz; CDCl3; Me4Si) 29.7 (C(4)H3), 63.6
and 81.7 (CH), 125.1, 127.5, 128.5, 128.6, 128.9 and 129.0
(ArCH), 138.9 and 145.2 (ArCipso); m/z (EI) 120 (100%), 105
(20), 91 (35), 77 (14).
(Ϫ)-(1R,2S,3R)-1-Chloro-1,3-diphenyl-4-methylpentane-2,3-diol
(23)
Epoxyalcohol 12 (200 mg, 0.75 mmol) was treated with TBSCl
(560 mg, 3.73 mmol) following the general procedure. The
crude product was purified by column chromatography [petrol-
eum ether–Et2O (6 : 1)] to afford the title compound 23 (140
mg, 0.46 mmol, 61%) as a colourless oil, Rf [petroleum ether–
Et2O (3 : 1)] 0.3; [α]2D2 = Ϫ14 (c 1.0, CHCl3); δH (300 MHz;
CDCl3; Me4Si) 0.70 (3 H, d, J 6.6) and 1.03 (3 H, d, J 6.6,
CH(CH3)2), 1.86 (1 H, d, J 3.3, exchangeable with D2O,
C(2)OH), 2.47 (1 H, sept, J 6.6, C(4)H), 2.82 (1 H, s, exchange-
able with D2O, C(3)OH), 4.47 (1 H, dd, J 7.7, 3.3, C(2)H), 4.60
(1 H, d, J 7.7, C(1)H), 7.23–7.38 (8H, m, ArH), 7.50–7.55 (2 H,
m, ArH); δC (75 MHz; CDCl3; Me4Si) 16.6 and 16.9
(CH(CH3)2), 34.7 (C(4)H), 62.4 and 78.2 (CH), 80.7 (COH),
126.2, 126.9, 127.7, 128.3 and 128.6 (ArCH), 138.3 and 142.3
(ArCipso); HRMS (CI) C18H25NO235Cl [M + NH4]+ requires
322.15254, found 322.15758; m/z (EI) 149 (53%), 120 (54), 105
(100), 91 (67), 77 (53).
(Ϫ)-(1S,2R,3S)-1,2-Epoxy-3-phenyl-1-(4-trifluoromethylphenyl)-
butan-3-ol (20)
Reaction of methylmagnesium bromide (3 M in Et2O, 1.1 cm3,
3.3 mmol) with epoxyketone 2 (500 mg, 1.7 mmol) following
the general procedure gave a Re : Si ratio16 of >99 : 1. The
crude product was purified by recrystallisation from n-hexane
to afford the title compound 20 (486 mg, 1.58 mmol, 93%) as
white plates, mp 71–73 ЊC (n-hexane); Rf [petroleum ether–Et2O
(3 : 1)] 0.3; [α]2D2 = Ϫ51 (c 1.0, CHCl3); νmax(KBr)/cmϪ1 3534
(br, O–H), 1325 (C–OH), 1169, 1124, 1068, 759, 700 and 645;
δH (300 MHz; CDCl3; Me4Si) 1.73 (3 H, s, CH3), 2.73 (1 H, br s,
COH), 3.21 (1 H, d, J 2.2, CH), 4.09 (1 H, d, J 2.2, CH), 7.26–
7.52 (9 H, m, Ar); δC (100 MHz; CDCl3; Me4Si) 27.7 (CH3),
1
55.5 and 69.4 (CH), 71.8 (COH), 124.5 (q, JC–F 272, CF3),
125.5 (ArCH), 125.8 (q, 3JC–F 4, ArC-C-CF3), 126.4, 128.1 and
2
128.9 (ArCH), 130.7 (q, JC–F 32, ArC-CF3), 141.3 and 143.8
(ArCipso); HRMS (CI) C17H19NO2F3 [M + NH4]+ requires
326.1368, found 326.1370; m/z (EI) 87 (9%), 71 (100), 57 (23).
(1R,2S,3S)-1-Chloro-1,3-diphenylheptane-2,3-diol (24)
Epoxyalcohol 5 (100 mg, 0.35 mmol) was treated with TMSCl
(0.05 cm3, 0.42 mmol) following the general procedure. Another
equivalent of TMSCl was added after 5 hours followed by a
further 2.5 equivalents after 27 hours. The crude product was
purified by column chromatography [petroleum ether–Et2O
(6 : 1)] to give the title compound 24 (64 mg, 0.20 mmol,
57%) as a colourless oil, Rf [petroleum ether–Et2O (3 : 1)] 0.15;
νmax(thin film)/cmϪ1 3540 (br, O–H), 1600, 1495, 1453, 1265,
1115 and 967; δH (200 MHz; CDCl3; Me4Si) 0.75 (3 H, t, J 7.1,
C(7)H3), 1.07–1.27 (4 H, m, C(5,6)H2), 1.53 (1 H, s, C(3)OH),
1.69–1.80 (1 H, m) and 2.06–2.16 (1 H, m, C(4)H2), 2.93 (1 H,
d, J 7.1, C(2)OH), 4.44 (1 H, dd, J 7.1, 2.8, C(2)H), 4.73 (1 H, d,
J 2.8, C(1)H), 7.17–7.43 (10 H, m, ArH); δC (100 MHz; CDCl3;
Me4Si) 13.9 (C(7)H3), 22.8 and 24.9 (CH2), 40.6 (C(4)H2),
63.2 (CH), 79.1 (C(3)), 81.1 (CH), 125.6, 127.3, 128.4, 128.6,
128.8 and 129.1 (ArCH), 137.7 and 142.3 (ArCipso); HRMS
(FAB) C19H22O35Cl [M Ϫ H2O + H]+ requires 301.13592, found
301.13553; m/z (EI) 163 (56%), 120 (100), 105 (56), 91 (62), 77
(36).
(؉)-(1S,2S,3S)-1-Chloro-3-phenyl-1-(4-trifluoromethylphenyl)-
butane-2,3-diol (21)
Reaction of epoxyalcohol 20 (150 mg, 0.49 mmol) with tin()
chloride (1 M in CH2Cl2, 0.6 cm3, 0.6 mmol) according to
the general procedure was complete after 4 hours. The crude
product was purified by recrystallisation from n-hexane to
give the title compound 21 (162 mg, 0.47 mmol, 96%) as white
needles, mp 97–99 ЊC (n-hexane); Rf [petroleum ether–Et2O
(3 : 1)] 0.2; [α]2D2 = +36 (c 1.0, CHCl3); νmax(KBr)/cmϪ1 3396 (br,
O–H), 1330 (C–OH), 1172, 1120, 1070, 763 and 699; δH (400
MHz; CDCl3; Me4Si) 1.63 (3 H, s, CH3), 2.77 (1 H, s, exchange-
able with D2O, C(3)OH), 3.11 (1 H, d, J 8.8, exchangeable with
D2O, C(2)OH), 4.10 (1 H, dd, J 8.8 and 3.2, C(2)H), 4.83 (1 H,
d, J 3.2, C(1)H), 7.26–7.46 (9 H, ArH); δC (100 MHz; CDCl3;
Me4Si) 29.0 (CH3), 63.94 (CH), 77.8 (COH), 79.11 (CH), 124.2
1
3
(q, JC–F 272, CF3), 125.0 (ArCH), 125.7 (q, JC–F 4, ArC-C-
2
CF3), 127.8, 128.4 and 129.0 (ArCH), 130.7 (q, JC–F 33, ArC-
CF3), 144.1 and 144.6 (ArCipso); HRMS (FAB) C17H15OF335Cl
[M Ϫ H2O + H]+ requires 327.07635, found 327.07527; m/z (EI)
188 (27%), 159 (12), 121 (100), 105 (20), 91 (11), 77 (16).
(؉)-(2S,3R)-4-Methyl-1,3-diphenylpentane-2,3-diol (25)
A stirred solution of chlorodiol 19 (75 mg, 0.25 mmol) and
AIBN (3.0 mg, 0.02 mmol) in anhydrous toluene (10 cm3)
was degassed by purging with a stream of nitrogen for 15 min.
Tri-n-butyltin hydride (0.07 cm3, 0.28 mmol) was added and the
reaction mixture was heated to 90 ЊC in a nitrogen atmosphere.
After 12 hours the reaction was cooled to room temperature
and partitioned between CH3CN (20 cm3) and n-hexane (20
cm3). The n-hexane layer was extracted with further portions of
CH3CN (3 × 20 cm3) and the combined CH3CN extracts were
General procedure for epoxide opening with inversion of
configuration
The epoxyalcohol (0.40 mmol) and TBSCl (300 mg, 2.0 mmol)
were stirred in dry DMF (10 cm3) under a nitrogen atmosphere
for 24 h. The reaction was quenched by addition of water (20
cm3) and extracted with EtOAc (3 × 25 cm3). The combined
organic extracts were washed with water (2 × 50 cm3) and brine
(50 cm3) before drying (MgSO4). Removal of the solvent under
1114
J. Chem. Soc., Perkin Trans. 1, 2001, 1109–1115

View Article Online
washed with n-hexane (4 × 50 cm3). Removal of the solvent
under reduced pressure gave the crude product which was puri-
fied by recrystallisation from n-hexane to give title compound
25 (26 mg, 0.1 mmol, 40%). The reaction was also carried out
with chlorodiol 24 (87 mg, 0.29 mmol) to give the title com-
pound 25 (19 mg, 0.07 mmol, 24%) as white needles, mp 118–
119 ЊC (n-hexane); Rf [petroleum ether–Et2O (6 : 1)] 0.1 (Found:
C, 80.2; H, 8.3; C18H22O2 requires: C, 80.0; H, 8.2%); [α]2D2 = +7
(c 0.3, CHCl3); νmax(KBr)/cmϪ1 3665 (s, O–H), 3455 (br, O–H),
1495, 1258, 1073, 1006 and 956; δH (400 MHz; CDCl3; Me4Si)
0.83 (3 H, d, J 6.8) and 0.89 (3 H, d, J 6.8, CH(CH3)2), 1.47 (1
H, d, J 3.2, exchangeable with D2O, C(2)OH), 2.42 (1 H, s,
exchangeable with D2O, C(3)OH), 2.44 (1 H, dd, JAX 10.8,
JAB 14.0, C(1)HAHB), 2.45 (1 H, sept, J 6.8, C(4)H), 3.06 (1 H,
dd, JBX 2.0, JAB 14.0, C(1)HAHB), 4.30 (1 H, app dt, J 2.0,
10.8, C(2)H), 7.23–7.37 (8 H, m, ArH), 7.51–7.53 (2 H, m,
ArH); δC (100 MHz; CDCl3; Me4Si) 17.6 and 17.7 (CH(CH3)2),
34.0 (C(4)H), 38.0 (C(1)H2), 76.6 (C(2)H), 81.1 (C(3)), 127.2,
127.3, 127.6, 128.5, 129.3 and 130.1 (ArCH), 139.9 and 143.0
(ArCipso); m/z (EI) 181 (5%), 150 (33), 149 (100), 131 (8), 105
(27), 91 (42), 77 (22).
References
1 For a recent review see M. J. Porter, S. M. Roberts and J. Skidmore,
Bioorg. Med. Chem., 1999, 7, 2145 for comparison with
other methods for the epoxidation of electron-deficient enones
see M. J. Porter and J. Skidmore, Chem. Commun., 2000, 1215.
2 J. V. Allen, K.-H. Drauz, R. W. Flood, S. M. Roberts and
J. Skidmore, Tetrahedron Lett., 1999, 40, 5417.
3 Preliminary communication: A. T. Gillmore, S. M. Roberts,
M. B. Hursthouse and K. M. Malik, Tetrahedron Lett., 1998, 39,
3315.
4 L. Carde, D. H. Davies and S. M. Roberts, J. Chem. Soc., Perkin
Trans. 1, 2000, 2455.
5 P. A. Bentley, S. Bergeron, M. W. Cappi, D. E. Hibbs,
M. B. Hursthouse, T. C. Nugent, R. Pulido, S. M. Roberts and
L. E. Wu, Chem. Commun., 1997, 739.
6 For pertinent reviews see (a) A. Pfenniger, Synthesis, 1986, 89;
(b) R. A. Johnson and K. B. Sharpless, in Comprehensive Organic
Synthesis, eds. B. M. Trost and I. Fleming, Pergamon, New York,
1991, p. 389–486.
a
7 G. B. Payne, J. Org. Chem., 1962, 27, 3819.
8 See, for example (a) K. Maruoka, M. Hasegawa and H. Yamamoto,
J. Am. Chem. Soc., 1986, 108, 3827; (b) K. Suzuki, M. Miyazawa
and G. Tsuchihashi, Tetrahedron Lett., 1987, 28, 3515; (c) C. M.
Marston, A. J. Walker, J. Pickering and A. D. Hobson, J. Org.
Chem., 1993, 58, 5944.
Crystal structure determination (؉)-(1S,2R,3R)-1,2-epoxy-4,4-
dimethyl-1,3-diphenylpentan-3-ol (13) †
9 A. T. Gillmore, PhD Thesis, University of Liverpool, 1999.
10 S. Searles, M. Tamres and E. R. Lippencott, J. Am. Chem. Soc.,
1953, 75, 2775.
Crystal data for 13: C19H22O2, M = 282.4. Mo-Kα radiation
(λ = 0.71073 Å), trigonal, space group R3, a = 18.759(2),
c = 12.2520(16) Å, U = 3733.7(8) Å3, Z = 9, µ(Mo-Kα) = 0.072
mmϪ1. Total number of reflections measured = 6683 of which
2168 were unique (Rint = 0.0523). Refinement by full-matrix
least squares method on F2 with 278 parameters gave
R1 = 0.0336 (I > 2.0σ(I)), wR2 = 0.0806 (all data). Data were
collected on a Stoe IPDS diffractometer. The structure was
solved and refined using SHELX97.17
11 Opening of epoxides with tin() chloride to give chlorohydrins with
retention of configuration has been observed previously: L. Thijs,
P. J. M. Cillisen and B. Zwanenburg, Tetrahedron, 1992, 48, 9985
opening of epoxide rings with retention of configuration using other
nucleophiles is known; for example, starting from an epoxyester, see
ref. 13.
12 H. R. Kricheldorf, G. Morber and W. Regel, Synth. Commun.,
1981, 383 our report (ref. 3 above) that these conditions produced
a Payne rearrangement was in error.
13 B. M. Adger, J. V. Barkley, S. Bergeron, M. W. Cappi, B. E.
Flowerdew, M. P. Jackson, R. McCague, T. C. Nugent and
S. M. Roberts, J. Chem. Soc., Perkin Trans. 1, 1997, 3501.
14 S. Itsuno, M. Sakakura and K. Ito, J. Org. Chem., 1990, 55,
6047.
15 Obtained on adsorbing the polyamino acid on to “flash” silica:
T. Geller and S. M. Roberts, J. Chem. Soc., Perkin Trans. 1, 1999,
1397.
† CCDC reference number 151889. See http://www.rsc.org/suppdata/
p1/b0/b008275i/ for crystallographic data in CIF or other electronic
format.
Acknowledgements
16 Re : Si ratio refers to the ratio of products derived by attack of the
nucleophile from the Re- and Si-faces of the carbonyl group
respectively.
17 G. M. Sheldrick, SHELX97, Crystal structure determination
program, Göttingen, 1997.
We thank the EPSRC, DTI, GlaxoWellcome and ChiroTech for
a studentship (to A. T. G.) under the Asymmetric Synthesis
LINK Scheme.
J. Chem. Soc., Perkin Trans. 1, 2001, 1109–1115
1115