The reactivity, as electrogenerated bases, of chiral and achiral phenazine radical-anions, including application in asymmetric deprotonation

Article abstract of DOI:10.1039/b506309d

Radical-anions, electrochemically generated in aprotic solvent from C ₂ symmetric homochiral phenazine derivatives, act as chiral electrogenerated bases (EGBs) in the desymmetrisation by selective deprotonation of a prochiral epoxide (3,4-epoxy

Full text of DOI:10.1039/b506309d

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A R T I C L E
The reactivity, as electrogenerated bases, of chiral and achiral
phenazine radical-anions, including application in asymmetric
deprotonation†
A. Mateo Alonso, Roberto Horcajada, Majid Motevalli, James H. P. Utley* and
Peter B. Wyatt*
Department of Chemistry, Queen Mary, University of London, Mile End Road,
London, UK E1 4NS. E-mail: p.b.wyatt@qmul.ac.uk, j.utley@qmul.ac.uk
Received 5th May 2005, Accepted 1st June 2005
First published as an Advance Article on the web 1st July 2005
Radical-anions, electrochemically generated in aprotic solvent from C2 symmetric homochiral phenazine derivatives,
act as chiral electrogenerated bases (EGBs) in the desymmetrisation by selective deprotonation of a prochiral epoxide
(3,4-epoxy-2,3,4,5-tetrahydrothiophene-1,1-dioxide); the anion produced is trapped by mesitoic anhydride. The
phenazines may be recovered in high yield by air oxidation. Enantiomeric excesses are modest (8–34%) but this is to
our knowledge the first demonstration of such stereoselective electrochemically-initiated deprotonation. The reactivity
of phenazine radical-anions as EGBs has also been explored by measurements of the rates of proton transfer;
the prochiral epoxide was found to have a kinetic acidity similar to that of the methyltriphenylphosphonium cation.
Introduction
Electrochemical reduction of neutral substrates (‘probases’)
generates radical-anions and dianions that may be used as
electrogenerated bases (EGBs) in synthetic transformations.1
Previous studies have shown that the radical-anion of phenazine
+
Scheme 1 Desymmetrisation of epoxide 10.
is able to deprotonate phosphonium ions such as Ph3PCH3
at conveniently measurable rates.2 There have not hitherto
been any descriptions of the use of electrogenerated bases in
asymmetric deprotonation from prochiral acids, although N-
acylation of chiral oxazolidin-2-ones has been achieved3 through
formation of the required nitrogen anion using achiral EGBs.
We have reported4,5 the synthesis of a good number of phenazine
derivatives (1–9) including several C2 symmetric homochiral
phenazine derivatives and their resolution.
Most of these may be cathodically converted into radical-
anions, and those pertinent to this study are displayed as (4,
8 and 9). A preliminary account of their enantioselectivity
in the rearrangement of a prochiral epoxide (10) (Scheme 1)
has been given.4 Conveniently, the spent electrogenerated base
(the corresponding 5,10-dihydrophenazine) may be efficiently
regenerated through simple air oxidation.
Herein, we fully report on the use of cathodically generated
chiral phenazine radical-anions for asymmetric deprotonation
and describe what we believe to be the first demonstration of
enantioselective deprotonation using an electrogenerated base.
Quantitative aspects of the kinetic basicity of chiral and achiral
phenazine radical-anions have been determined with a view to
identifying features that relate to the observed stereoselectivity.
Results and discussion
Enantioselective proton transfer
Chiral bases are conventionally used to select between
enantiotopic acidic hydrogens in compounds such as 4-t-
butylcyclohexanone or cis-2,6-dimethylcyclohexanone; these
† Electro-organic reactions Part 59. Part 58 is ref. 11.
2 8 4 2
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 2 8 4 2 – 2 8 4 7
T h i s j o u r n a l i s
T h e R o y a l S o c i e t y o f C h e m i s t r y 2 0 0 5
©

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and similar experiments have been well reviewed.6,7 The cyclo-
hexanones are insufficiently acidic to allow deprotonation by
phenazine radical-anions; no reaction could be detected on the
slowest cyclic voltammetric time scale. Therefore desymmetrisa-
tion of the epoxysulfone 10 (Scheme 1), that cyclic voltammetry
shows to react with phenazine radical-anions (see below), was
chosen as the test reaction and mesitoic anhydride was chosen
as the trapping electrophile.
Having ascertained by cyclic voltammetry that chiral and
achiral phenazine radical-anions reacted with 10, preparative ex-
periments were performed by controlled potential co-electrolysis
of the phenazine (at close to its E0 value) in the presence of 10
and an electrophilic trapping agent. We found that less-hindered
candidates (acetic anhydride, benzoic anhydride) reacted with
the phenazine radical anions to acylate at the nitrogen. Further-
more, trapping with mesitoic anhydride provided a chromophore
in the product 11 for analysis of products by chiral HPLC. The
structure of rac-11 was confirmed by X-ray crystallography
(Fig. 1).‡ The sulfone 10 is readily available through epoxidation
of butadiene sulfone.8,9
Table 1 Conversion of epoxide 10 into ester 11 using chiral electrogen-
erated basesa
Probase
Additive b Yield of 11 eec of 11 Recovery of probase
6
—
—
—
—
—
53
50d
50d
63
33
53
38
43
77
39
48d
0
—
+8
100
72
—
74
71
78
57
100
100
100
67
(R,R)-4a
(S,S)-4a
(R,R)-4b
(+)-(pR)-8
−8
+18
<10
+20
<10
+34
+28
+32
+28
—
(+)-(pR)-8 LiClO4
(−)-(pS)-8
—
—
LiClO4
—
—
Yb(OTf)3
—
LiClO4
9a
9a
9a
9a
9a
9b
9b
9b
—
100
80
63
72
+16
+24
<10
Mg(OTf)2 19
100
a Experiments were conducted in DMSO with Bu4NPF6 as supporting
electrolyte unless indicated otherwise. b 3 equiv relative to probase.
c Determined by chiral HPLC on Daicel Chiralpak OT-(+) eluted with
9 : 1 hexane : propan-2-ol; a positive ee value indicates an excess of the
(R)-enantiomer, which we have synthesised independently (Scheme 2)
and found to have a longer retention time than the (S)-form. d DMF
was used as solvent.
Fig. 1 X-Ray crystallographic structure of 11.
The chiral probases used were (R,R)- and (S,S)-4a, (R,R)-4b,
(−)-(pS)-8, (+)-(pR)-8, (pS,R,R)-9a and (pR,R,R)-9b with the
product being isolated by short column chromatography and
analysed by chiral HPLC. The probase was recovered by air
oxidation and chromatography.
Results are summarised in Table 1, which includes an example
of ring-opening using an achiral EGB. The unambiguous
synthesis of the (R)-enantiomer of 11, was carried out according
to Scheme 2. The configuration was established by X-ray
crystallography on the intermediate a-methoxyphenylacetate 13
(Fig. 2).
Scheme 2 Unambiguous synthesis of R-11.
The first experiments with 4a gave low stereoselectivity but
the enantiomers of the probase reacted to give the product
11 in moderate yield and with the enantiomeric excess in
equal amount and, according to chiral HPLC, in the opposite
direction. The diastereoisomers of 9 give higher and significant
ee values; changes in reaction conditions so far bring no
significant improvement in results.
For the phenazines, an important feature is the easy regen-
eration of the starting phenazine by air oxidation of the 5,10-
dihydrophenazine product (PBH2 formed in step 4, Scheme 3).
Fig. 2 X-Ray crystallographic structure of 13.
‡ CCDC reference numbers CCDC 266539 and 269382. See http://dx.
doi.org/10.1039/b506309d for crystallographic data in CIF or other
electronic format.
Scheme 3 DISP mechanism.
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 2 8 4 2 – 2 8 4 7
2 8 4 3

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Table 2 Reduction potentialsa of phenazine derivatives
Compound
Phenazine
1a
1b
1c
2a
3b
4a
5
6
7
8
9
−E0
−E0
1.10
1.13b
1.77
1.98b
1.34
1.83
1.31
1.72
0.97
1.33
0.89
2.09
0.97
—
0.91
—
1.21
1.94
1.25
1.16b
1.76
2.04b
1
1.14b
2.08b
1.36b
2.22b
1.10b
2.05b
2
a Hg/Pt, DMF–Bu4NPF6 (0.1 M), scan rates 1–100 V s−1, V vs. SCE. b DMSO–Bu4NPF6 (0.1 M).
This means that investment in the synthesis of relatively complex
phenazine derivatives is not wasted and they can be recovered
from product mixtures. Most of the examples given in Table 1
indicate efficient recovery of the phenazine probase.
Phenazine 8 has been resolved on a small scale but it is not
particularly effective as a probase. Its efficiency is improved in
the presence of lithium cation, probably through chelation to the
crown ether function. However, it seems that planar chirality on
its own does not produce enantioselective behaviour and the
proximity of the bulky trans-1,2-substituted cyclohexane unit,
as in 9a and 9b and evident from X-ray crystallography (see
previous preparative paper5), is needed to reinforce the effect of
planar chirality.
Kinetics of proton transfer
Cyclic voltammetry (CV) and digital simulation (BAS DigiSim
3.03), assuming the mechanism in Scheme 3 and several
experimentally determined parameters (diffusion coefficients,
E0 values), allows the measurement of rate constants (k2) for
the rate-limiting proton transfer (step 2). This provides an
estimation of relative kinetic acidities of the carbon acids and
of the kinetic basicities of the phenazine radical-anions. The
same approach has been successful in a study of the kinetics of
cleavage of oxalate radical-anions.11
For CV runs giving ipc/ipa between 0.2–0.4, allowing k2 to
float gave excellent fits between experimental and simulated
CVs (see Fig. 3) except for the very slowest reactions. For
each rate coefficient determination, the values were averaged
from experiments conducted over a range of probase and
acid concentrations and at several scan rates and excellent
internal consistency was found. The successful application of
digital simulation over such a variety of conditions is powerful
support for the mechanism assumed and for the validity of
the rate constants. Because digital simulation can mislead,
especially by assumption of a false mechanism, justification of
the approach is required. The DISP mechanism10 (Scheme 3) is
universally accepted for the cathodic hydrogenation of aromatic
hydrocarbons, the first proton transfer is undoubtedly the slow
step, and the results are consistent over a considerable range
of scan rates and concentrations. An alternative mechanism,
the ECE route, can be ruled out because on the voltammetric
time scale used (see Fig. 3) some radical-anion survives, i.e.,
the chemical step is relatively slow. The ECE route demands
very rapid chemical reaction (the C step) so that the product of
the chemical step is close to the cathode for subsequent direct
reduction. This is only the case for very fast reactions, e.g., the
cathodic cleavage of alkyl or benzyl halides.
Reactivity and mechanism
With a view to understanding better factors that may con-
trol the enantioselectivity described above the electrochemical
behaviour of the phenazines was studied. In particular, the
mechanism of proton transfer was determined and for several
cases the rates of proton transfer in the slow step measured.
Cyclic voltammetry
Cyclic voltammetry in aprotic solvents (DMF or DMSO) shows
the phenazine derivatives to give two reduction peaks each for
1e transfer, the first being chemically reversible at modest scan
rates (< 1 V s−1) and the second being reversible at relatively
high scan rates (up to 100 V s−1); E0 values are given in Table 2.
Reaction between an added carbon acid and the radical-
anion formed at the first reduction potential results in loss of
reversibility of the first peak and a consequent doubling of peak
height. This is characteristic of the well-established mechanism
set out in Scheme 3, in which the second electron transfer (step
3) involves a second equivalent of the radical-anion (DISP).10
Confirmation of this mechanism comes from the kinetic
results.
Further confirmation of the acceptability of the application
of DigiSim comes from a comparison of the proton transfer rate
coefficients obtained for reaction in DMSO between phenazine
radical-anion and benzyltriphenylphosphonium ion obtained in
+
Fig. 3 Experimental (solid line) and simulated (solid circles) cyclic voltammograms for reaction between phenazine radical-anion and Ph3PCH3
;
DMF–Bu4NPF6 (0.1 M), EGB 1 mM, carbon acid 10 mM, 10 V s−1
.
2 8 4 4
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 2 8 4 2 – 2 8 4 7

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our laboratory and in an earlier study using derivative cyclic
voltammetry. Our experiments gave a value (per acidic H) of
(6.94 0.07) × 102 M−1 s−1 whereas the earlier study2 gave 8 ×
102. These results, from different laboratories using different
methods, agree with a concordance of 14% and are well within
acceptable limits. We therefore have high confidence in the
kinetic results presented herein.
We have chosen to use true carbon acids, i.e., those involving
unambiguous proton transfer from carbon, where complications
from tautomerism are avoided. For instance, it has been
established that proton transfer from carbonyl-activated CH
functions, using EGBs, often involves prior enolisation12,13 with
subsequent proton transfer from oxygen. Phosphonium salts
and the epoxysulfone (10) are in this sense true carbon acids.
A selection of the rate constants is given in Table 3. Because
the carbon acids used have differing numbers of acidic hydrogen
atoms the rate constants are adjusted accordingly and expressed
as rate per hydrogen atom. For the four potentially acidic
hydrogens of the epoxysulfone (10) only two are in the favourable
stereoelectronic arrangement with the epoxy group and hence
the overall rate constant is divided by 2.
From the kinetic data we conclude: (i) that proton transfer
is faster in DMF than in DMSO; (ii) that the kinetic acidity of
the benzyltriphenylphosphonium ion is much greater than that
of the methyltriphenylphosphonium ion, which is comparable
to that of the epoxysulfone 10; (iii) that comparison of the
data involving the methyltriphenylphosphonium ion, which is
presumably the least affected by steric hindrance, indicates
that 1,6-diamino substitution is slightly rate-enhancing (1b
vs. phenazine in DMSO) but that the radical anions of the
macrocycle 3b and probase 4a are significantly less reactive. In
the 1,6-dioxy series the radical-anion of 6 is more reactive than
that of phenazine, suggesting that the electronic effect of dioxy
substitution is rate enhancing. However, the relative reactivity
in DMSO of the radical-anions of the macrocycles (7–9) is in
the order 8 > phenazine ≈ 7 > 9. We propose that this reflects
relative steric hindrance to proton transfer.
0.005%), supplied over molecular sieves. Bu4NPF6 was Fluka
electrochemical grade. Cyclic voltammetry (cv) experiments
were run using a Princeton Applied Research EG & G VersaStat
II 263A potentiostat. The potentiostat was controlled and the
voltammograms were saved using Model 270/250 Research
Electrochemistry Software v4.00 or Condecom 2000CV v.2.00.
A Hg-coated Pt electrode (diameter 1 mm) was used as the
working electrode, platinum wire as the counter electrode and
the reference electrode was a simple Ag wire in a glass tube.
Because the potential of the Ag wire reference electrode can vary
over a relatively short timescale, the E0 value for anthracene
was measured at the beginning and at the end of a series of
measurements, against the Ag wire electrode, so that reduction
potentials could be consistently referred to the SCE electrode
(E0 for anthracene = −1.92 V vs. SCE in DMF14). The cv
measurements were obtained in an undivided cell using a 10 ml
solution of 0.1 M Bu4NPF6 in DMSO. The concentration of
the probase was 1 mM. Preparative electrolyses were performed
using a Potentiostat Type DT 2101 (Hi-Tek Intruments) with an
electronic integrator built in our department. Flash chromatog-
raphy was performed on BDH silica gel (33–70 lm). All new
compounds were homogeneous as assessed by TLC and high
field NMR. Melting points were determined using a Reichert
hot stage microscope. Specific rotations were determined on
an Optical Activity Ltd AA-1000 polarimeter with a path
length of 0.5 dm. IR spectra were recorded using a Shimadzu
FTIR 8300; samples were prepared as films by evaporation of
CH2Cl2 solutions on NaCl plates. NMR spectra were recorded
on Jeol EX270 or Bruker AMX400 spectrometers. FAB mass
spectra were recorded on a ZAB-SE4F machine at the School
of Pharmacy, University of London; other mass spectra were
obtained by the EPSRC National Service in Swansea using a
Finnigan MAT 900. All HPLC experiments were performed
using a Hewlett-Packard 1100 series liquid chromatography
system equipped with Daicel Chiralpak OT(+) chiral columns
(0.46 cm × 5 cm guard column and 0.46 cm × 25 cm main
column) and a UV absorbance detector.
The electrochemical results have an important bearing on
the preparative results. The slow step of the overall process is
undoubtedly proton transfer of prochiral protons to the chiral
radical-anions. Furthermore the low reactivity of the radical-
anion of 9 is significant as this was the most effective chiral base
in the enantioselective proton transfer experiments (Table 1); this
an example of the common situation whereby slow reactions
(high free energies of activation) discriminate well between
diastereoselective transition states.
rac-3-(2,4,6-Trimethylbenzoyl)oxy-2,3-dihydrothiophene-1,1-
dioxide (rac-11): example procedure using an electrochemically
generated base
The electrochemical cell was equipped with a mercury pool cath-
ode, a carbon rod as the anode and a silver wire reference elec-
trode; the electrode compartments were separated by sintered
glass partitions. 1,6-Dimethoxyphenazine (9 mg, 0.037 mmol),
3,4-epoxy-2,3,4,5-tetrahydrothiophene-1,1-dioxide8,9 10 (10 mg,
0.0745 mmol) and mesitoic anhydride (35 mg, 0.112 mmol)
were dissolved in a 0.1 M solution of tetrabutylammonium
hexafluorophosphate in DMSO (7 ml) and placed in the cathode
Experimental
‘Petrol’ or ‘petroleum spirit’ refers to the fraction of bp 40–
60 ◦C. DMF and DMSO were Fluka puriss. grade (H2O ≤
Table 3 Rate constants for proton transfera
+
+
Carbon acid
Probase
PhCH2PPh3
CH3PPh3
Epoxysulfone (10)
kHA per H
Solvent
kHA per H/M−1 s−1
kHA per H
Phenazine
DMF
DMSO
DMF
DMSO
DMF
DMF
4800 100
840 60
2.8
—
5.6 0.14
560 10
770 10
—
1370 46
—
—
—
33
2.6 0.7
—
—
—
—
694
7
1b
—
141
1
3b
—
5
2500 150
250 15
979 15
—
1830 49
—
240
28
3
1
4a
DMF
6
DMSO
DMSO
DMSO
DMSO
DMSO
3.9 0.3
2.1 0.5
16.4 0.7
0.35
7
8
(pS,R,R)-9a
(pR,R,R)-9b
—
0.40
a By digital simulation of cyclic voltammetry using BAS DigiSim v 3.1.
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 2 8 4 2 – 2 8 4 7
2 8 4 5

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compartment under nitrogen. The anode compartment was then
filled with a 0.1 M solution of tetrabutylammonium hexafluo-
rophosphate in DMSO (9 ml). A potential of −1.5 V was applied
until the current fell to its background value and 2.2 F passed
through the solution. The solutions in the cathode and the anode
compartments were diluted with water and extracted twice with
ether. The ether extracts were dried (MgSO4) and concentrated
under vacuum. The residue was subjected to flash chromatog-
raphy (CH2Cl2) to yield rac-3-(2,4,6-trimethylbenzoyl)oxy-2,3-
dihydrothiophene-1,1-dioxide (rac-11) (11 mg, 53%) as a white
solid and 1,6-dimethoxyphenazine (9 mg, 100% recovery).
A crystal of rac-11 suitable for single crystal X-ray diffrac-
tion was obtained by slow evaporation of a propan-2-ol
solution.
82.2 (CH), 74.8 (CH), 57.6 (CH3), 57.5 (CH), 54.3 (CH2), 53.9
(CH3); mmax/cm−1 (film) 3422, 1760, 1749, 1313, 1184, 1137,
+
1100; m/z (ESI) 336.0664 (M+NH4 , C13H19ClNO5S requires
336.0667).
Non-racemic 3-(2,4,6-trimethylbenzoyl)oxy-2,3-dihydrothiophene-
1,1-dioxide (11) from (aR,3S,4R)-3-(a-methoxyphenylacetoxy)-
4-chlorotetrahydrothiophene-1,1-dioxide (13)
(aR,3S,4R)-3-(a-Methoxyphenylacetoxy)-4-chlorotetrahydro-
thiophene-1,1-dioxide (13) (138 mg, 0.439 mmol) was heated
in toluene (9.2 ml) at 100 ◦C in the presence of triethylamine
(0.168 ml, 1.21 mmol) for 1 h. The solvent was then evaporated
and the residue was dissolved in CH2Cl2; the solution was
washed with 2 M HCl and then with water. The organic phase
was dried (MgSO4) and the solvent evaporated to leave a residue
(45 mg), which was then stirred for 1 h at room temperature with
a mixture of NaOH (8 mg, 0.19 mmol), water (1 ml), EtOH (2 ml)
and MeOH (1 ml). The pH of the mixture was then adjusted to
7 using dilute hydrochloric acid and the solvent was evaporated.
The residue was dissolved in CH2Cl2 (2 ml) and treated
with pyridine (0.015 ml, 0.189 mmol) and mesitoyl chloride
(0.035 ml, 0.189 mmol), then stirred at room temperature for
24 h. The solution was diluted with CH2Cl2 and washed with
2 M hydrochloric acid followed by water. The organic phase was
dried (MgSO4) and subjected to flash chromatography (CH2Cl2)
to give 3-(2,4,6-trimethylbenzoyl)oxy-2,3-dihydrothiophene-
1,1-dioxide (11) (5 mg), [a]2D8 −17 (c 0.2, CH2Cl2), identical
by 1H NMR (270 MHz, CDCl3) with material prepared
by the action of electrochemically generated bases on 3,4-
epoxy-2,3,4,5-tetrahydrothiophene-1,1-dioxide in the presence
of mesitoic anhydride; tR/min [Daicel Chiralpak OT (+),
hexane–propan-2-ol (9 : 1), 0.5 ml min−1, 5 ◦C, 261 nm detector]
26.1 (S)-enantiomer (8%), 29.1 (R)-enantiomer (92%).
rac-3-(2,4,6-Trimethylbenzoyl)oxy-2,3-dihydrothiophene-1,1-
dioxide (rac-11) had mp 111–113 ◦C, dH (270 MHz, CDCl3)
=
6.87–6.83 (4H, m, Ar + CH CH), 6.17–6.12 (1H, m, OCH),
3.83 (1H, dd, J 14.1, 7.7 Hz, CH2), 3.31 (1H, dd, J 14.1,
3.3 Hz, CH2), 2.30 (9H, s, CH3); dC (68 MHz, CDCl3) 169.7,
141.0, 136.4, 136.1 135.9, 129.0, 128.7, 69.6, 54.3, 21.4, 20.0;
m
max/cm−1 (film) 3090, 3080, 2922, 1728, 1311, 1072; m/z (FAB)
303.0650 (M+Na+, C14H16SNa requires 303.0677); HPLC,
tR/min [Daicel Chiralpak OT (+), hexane-propan-2-ol (9:1),
0.5 ml min−1, 5 ◦C, 261 nm detector] 26.1 (S)-enantiomer (50%),
29.1 (R)-enantiomer (50%).
Non-racemic 3-(2,4,6-trimethylbenzoyl)oxy-2,3-
dihydrothiophene-1,1-dioxide (11) using an
electrochemically generated chiral base
This was performed similarly to the preceding experiment, using
(R,R,pS)-(+)-7(1,2)-cyclohexana-1(1,6)phenazina-2,6,8,12-tetra-
oxacyclododecaphane (9a) (15 mg, 0.029 mmol), 3,4-epoxy-
2,3,4,5-tetrahydrothiophene-1,1-dioxide (10) (10 mg, 0.0745
mmol), mesitoic anhydride (35 mg, 0.112 mmol) and lithium
perchlorate (12 mg, 0.112 mmol) in a 0.1 M solution of
tetrabutylammonium hexafluorophosphate in DMSO (14 ml).
A potential of −1.5 V was applied until the current fell to
its background value and 2 F passed through the solution.
The solutions in the cathode and the anode compartments
were diluted with water and extracted twice with ether. The
ether extracts were dried (MgSO4) and concentrated under
vacuum. The residue was subjected to flash chromatography
(CH2Cl2, then CHCl3) to yield 3-(2,4,6-trimethylbenzoyl)oxy-
2,3-dihydrothiophene-1,1-dioxide 11 (16 mg, 77%) and then
(R,R,pS)-(+)-7(1,2)-cyclohexana-1(1,6)phenazina-2,6,8,12-tetra-
oxacyclododecaphane (9a) (15 mg, 100% recovery). HPLC on
11 showed 28% ee in favour of the (R)-enantiomer.
Crystal data for rac-11‡. C14H16O4S, M = 280.33, mono-
˚
clinic, a = 21.102(8), b = 10.963(6), c = 5.929(2) A, a = 90.00,
◦
3
˚
b = 92.57(5), c = 90.00 , V = 1370.2(10) A , space group P21/c,
Z = 4, Dc = 1.359 Mg m−3, l = 0.243 mm−1, reflections measured
2730, reflections unique 2394 with Rint = 0.0192, T = 160 (2) K,
final R indices [I > 2 r(I)] R1 = 0.0521, wR2 = 0.1250 and for
all data R1 = 0.1293, wR2 = 0.1498. CCDC reference number
269382.
Crystal data for 13‡. C13H15ClO5S, M = 318.76, orthorhom-
˚
bic, a = 6.8530(2), b = 9.6726(3), c = 21.2802(7) A, a = 90.00,
◦
3
˚
b = 90.00, c = 90.00 , V = 1410.59(8) A , space group P212121,
Z = 4, Dc = 1.501 Mg m−3, l = 0.434 mm−1, reflections measured
10821, reflections unique 3199 with Rint = 0.0472, T = 120 (2) K,
final R indices [I > 2 r(I)] R1 = 0.0276, wR2 = 0.0666 and for
all data R1 = 0.0309, wR2 = 0.0683, Flack parameter −0.05(5).
CCDC reference number 266539.
(aR,3S,4R)-3-(a-Methoxyphenylacetoxy)-4-
chlorotetrahydrothiophene-1,1-dioxide (13)
rac-3-Hydroxy-4-chlorotetrahydrothiophene-1,1-dioxide (12)
(660 mg, 3.86 mmol) was dissolved in pyridine (30 ml)
and treated with (R)-a-methoxyphenylacetyl chloride (1.5 g,
8.13 mmol) in CH2Cl2, which was added dropwise at room
temperature over 10 min. The mixture was stirred at room
temperature for 24 h, then diluted with Et2O, and washed
with 2 M hydrochloric acid, followed by water. The organic
phase was dried (MgSO4) and concentrated to leave a
yellow solid residue which was recrystallised six times from
methanol to give (aR,3S,4R)-3-(a-methoxyphenylacetoxy)-4-
chlorotetrahydrothiophene-1,1-dioxide (13) (138 mg, 11%) as
Acknowledgements
We thank Queen Mary, University of London (studentship for
RH), the EPSRC (AMA project studentship and MS mea-
surements at the National Mass Spectrometry Service Centre,
Swansea) and the EPSRC National Crystallography Service for
data collection.
References
◦
white crystals, mp 120–122 C, [a]2D8 +43 (c 1, CH2Cl2). dH
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