Aminolysis of cyclic thioxocarbonate of (R,R)-di-tert-butyl tartrate: Efficient access to thio- and thiolcarbamates

Article abstract of DOI:10.1039/b201691e

Aminolysis of cyclic thioxocarbonates derived from (R,R)-dialkyl tartrates with secondary amines is described to afford efficiently thio- and thiolcarbamates in a fast and high yielding reaction. Their stereochemistry and mechanism of formation are discus

Full text of DOI:10.1039/b201691e

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Aminolysis of cyclic thioxocarbonate of (R,R)-di-tert-butyl
tartrate: efficient access to thio- and thiolcarbamates†
Ludovic Faissat, Claude Chavis, Jean-Louis Montéro and Marc Lucas*
1
ENSCM, Laboratoire de Chimie Biomoléculaire, UMR 5032, 8 Rue de l’Ecole Normale,
34296 Montpellier Cédex 05, France. E-mail: lucas@univ-montp2.fr
Received (in Cambridge, UK) 18th February 2002, Accepted 5th April 2002
First published as an Advance Article on the web 24th April 2002
Aminolysis of cyclic thioxocarbonates derived from (R,R)-dialkyl tartrates with secondary amines is described to
afford efficiently thio- and thiolcarbamates in a fast and high yielding reaction. Their stereochemistry and mechanism
of formation are discussed.
expected α-amino β-hydroxy succinates anti-3 we obtained the
optically active thiocarbamate syn-4 and/or a mixture of syn-
and anti-thiolcarbamates 5, altogether corresponding to an
Introduction
Cyclic carbonates are known to react slowly at room temper-
ature at their carbonyl centre with amines to yield carbamates,
exclusive primary nucleophilic attack at the thiocarbonyl centre
but their reactivity can be enhanced in nucleophilic additions
and in a ratio dependent on the amine (Scheme 2, Table 1).
by using the more reactive thiocarbonyl group. For example,
the cyclic thioxocarbonate of 3-O-phenylglycerol reacts
with n-hexylamine or benzylamine at ambient temperature in
dimethyl sulfoxide to afford two hydroxythiourethane isomers
(88 : 12) where the secondary alcohol predominates;1 similarly,
the regioselective ring-opening of the 4,6-O-benzylidene-α--
glucopyranoside 2,3-thiocarbonate by liquid ammonia or
piperidine produces a mixture of 2- and 3-thiocarbamates in a
3.6 : 1 ratio.2 Considering cyclic thioxocarbonates derived from
C2-symmetric chiral dialkyl tartrates, the electron-withdrawing
carboxylic esters will increase the electrophilic character of the
carbinol carbons and consequently nucleophilic substitutions at
these positions will be favoured . This possibility has been
developed until recently with cyclic thioxocarbonates3–7 which
mimic the corresponding cyclic sulfites and sulfates8–10 used as
epoxide surrogates, in regio- and stereoselective functionalis-
ations or deoxygenation reactions. Thus numerous nucleo-
philes, except amines, have been reported to open the cyclic
thioxocarbonates of dialkyl tartrates with inversion of
configuration and with the production of anti-α-substituted
β-hydroxy diesters (Scheme 1) by an exclusive attack at the two
chemically equivalent carbinol carbons.
Scheme 1
In this report we focus on the peculiar reactivity of the cyclic
thioxocarbonates of dialkyl tartrates as ambident substrates
towards secondary amines.
Scheme 2 Reagents and conditions: i, thioxocarbonate 1 (1 equiv.),
amines 2a–i (2 equiv.) or 2j (0.5 equiv.), dichloromethane, room temp.,
30 min. or 12 h.
It is noteworthy that the reactions reached completion very
quickly (30 min) with amines 2a–e or 2j and much more slowly
Results and discussion
Surprisingly, we found that when secondary amines 2 reacted
with the cyclic thioxocarbonate of (R,R)-di-tert-butyl tartrate 1
in dichloromethane at room temperature, instead of the
with others (2f–i, 12 h). Moreover, when the reaction proceeded
rapidly, the thiocarbamates syn-4a–e or the bis(thiocarbamate)
syn–syn-4j were exclusively formed with retention of configur-
ation, whereas in the case of the reported slow reactions
(amines 2f–h) a diastereomeric mixture of syn–anti-thiol-
carbamates 5 was produced concomitantly with 4. Finally it
† In this paper thioxocarbonate refers to thiocarbonate-O,O-diesters
and the IUPAC name for thiolcarbamate is thiocarbamate.
DOI: 10.1039/b201691e
J. Chem. Soc., Perkin Trans. 1, 2002, 1253–1259
This journal is © The Royal Society of Chemistry 2002
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Table 1 Reactions of thioxocarbonate 1 with amines 2a–j in dichloromethane at room temp.
d, e
Yield (%)
4 ϩ 5
syn-4a–j
δH2, J2–3, δC2
syn- ϩ anti-5a–j
δH2, J2–3, δC2
Run
Amine
Time/h
0.5
4 : 5
1
2
3
4
5
6
7
8
9
2a
100 : 0
50 : 50a
100 : 0
100 : 0
100 : 0
100 : 0b
50 : 50
88 : 12
0 : 100a
39 : 61
0 : 100
100 : 0f
95
63a
6.1, 2.3, 78.3
6.1, 2.3, 79.2
6.1, 2.3, 77.6
6.1, 2.4, 79.2
5.9, 2.5, 79.4
6.0, 2.1, 79.2
4.75, 2.9, 53.0
2b
2c
2d
2e
2f
0.5
0.5
0.5
0.5
12
Quant.
Quant.
Quant.
Quant.
90
4.8, 2.9, 52.9
2gc
12
87
98a
6.1, 2.3, 79.1
6.1, 2.3, 79.5
4.7, 3.1, 52.4
4.7, 2.8, 53.1
4.7, 3.0, 52.0
10
11
12
2h
2i
2j
12
12
0.5
64
70
84
6.0, 2.1, 79.5
e
a DMF was used as the solvent. b NR2 = NH2. c See ref 23. d Ratio not determined. J2–3anti ≈ J2–3syn (see chemical correlation of anti-5i).
f The bis(thiocarbamate) syn–syn was exclusively formed.
appeared that thiolcarbamates 5 were the only products
obtained with diisopropylamine 2i. As can be seen, the results
so far obtained obviously rule out either the influence of the
amine basicity or the presence of a silicon moiety on the reac-
tion outcome, favouring thiolcarbamate versus thiocarbamate
formation. In fact the silylated bis(2-hydroxyethyl)amines 2g
(O-TBDMS) and 2h (O-TBDPS) yielded 12 and 61% of the
thiolcarbamoyl derivatives 5g and 5h, respectively while di-
isopropylamine 2i gave the thiolcarbamate 5i exclusively. On
the other hand, piperidine, diethylamine and diisopropylamine
which exhibit essentially very similar basicities produced the
thiocarbamate 4 for the first two reactions and inversely the syn-
and anti-thiolcarbamates 5 for the last one, and conversely,
piperidine and morpholine which are compounds characterised
by a similar bulkiness but a substantial difference in their basic
character, solely produced thiocarbamates 4c and 4d. At this
stage, it is obvious that the bulkiness of the amine, associated
with its nucleophilic properties take a prominent role in the
mechanism of the reaction; the following order (2c, 2d < 2a <
2b) < (2g < 2h < 2f < 2i) < 2e depicts schematically the increas-
ing steric hindrance around the nitrogen atom, and it appears
that the more hindered the amine is, the more favoured is the
thiolcarbamate formation: the first pool of amines 2a–d afford
exclusively the corresponding thiocarbamates 4a–d (100%) and
the following group 2f–i, yields together with 4f–i, the thiol-
carbamates 5f–i (12 to 100%). The case of HMDS 2e is more
peculiar since it is a known silylating agent and is theoretically
more crowded than diisopropylamine 2i. The results may be
explained by an initial in situ desilylation of this reagent to
afford ammonia which reacts with the cyclic thioxocarbonate 1;
the O-TMS thiocarbamoyl derivative (NR2=NH2) was isolated
as a stable intermediate which afforded compound 4e after
acidic hydrolysis.
Table 2) and observed the exclusive formation of the thio-
carbamate syn-7a with the reactive amine 2a, and that of the
syn-and anti-thiolcarbamates 8i with the hindered amine 2i,
suggesting that secondary amines behave similarly when faced
with any cyclic thioxocarbonate derived from dialkyl tartrates.
Structural assignment of the reaction products, thio-
carbamates (4a–j, 7a) and thiolcarbamates (5a–j, 8i), was easily
1
achieved using H and 13C NMR spectroscopies (Tables 1 and
2): thiocarbamates (UV absorbing) being characterised by
upfield signals for 2-H (6.1 ppm, J2–3 2.1–2.5 Hz) and 2-C (78–
79 ppm), whereas the thiolcarbamates exhibited downfield
signals for 2-H (4.7–4.8 ppm) and 2-C (52–53 ppm) and a
slightly larger coupling constant (J2–3 2.8–3.1 Hz) (we presume
that the Jsyn and Janti values are very similar as we found 3.0 Hz
in the case of the pure thiolcarbamate anti-5i compared
with 3.1 Hz for the mixture of syn-and anti-5i). It is worth
noting that any diastereomeric mixtures of syn-and anti-
thiolcarbamates were inseparable and appeared as single
products by 1H NMR spectroscopy, whereas 13C NMR showed
a splitting of several signals (weak differences of ca. 40 Hz) and
thus allowed us to distinguish what was assumed to be the two
epimers at 2-C.
In order to ascertain both the structure and the relative con-
figuration of all the products, we prepared unequivocally the
thiocarbamate syn-4a and the thiolcarbamate anti-5i. Thio-
carbamate syn-4a was easily obtained, although in very low
yield, by direct reaction of (R,R)-di-tert-butyl tartrate11 with
sodium hydride in DMF and diethylthiocarbamoyl chloride
(Scheme 4); it exhibited analytical data and optical rotation in
good agreement with those obtained for 4a generated from the
cyclic thioxocarbonate 1.
The cyclic sulfate 9 of (R,R)-di-tert-butyl tartrate was used as
a starting material for the preparation of the thiolcarbamate
Since the cyclic thioxocarbonate 6 of (R,R)-diisopropyl tar-
trate was reported4 to react normally with nucleophiles at its
carbinol centres, could the steric hindrance of the ester moiety
possibly be responsible for the preferred nucleophilic attack of
the incoming amine at the thiocarbonyl carbon instead of the
electrophilic carbinol carbons? To investigate this, we subjected
6 to a reaction with diethylamine 2a and diisopropylamine 2i
using the same experimental conditions as above (Scheme 3 and
Scheme 4 Reagents and conditions: i, SOCl2, Et3N, CH2Cl2, 0 ЊC, then
RuCl3ؒH2O, NaIO4, CCl4, CH3CN, H2O, 0 ЊC, 82%; ii, a) MeC(᎐O)SK,
᎐
acetone, room temp., b) conc. H2SO4 (cat.), H2O (0.5–1.0 equiv.), THF,
quant.; iii, a) NH2NH2ؒAcOH, DMF, room temp., b) (Pri)2NC(᎐O)Cl,
᎐
Scheme 3 Reagents and conditions: thioxocarbonate 6 (1 equiv.),
amine 2a or 2i (2 equiv.), dichloromethane, room temp., 30 min or 12 h.
Et3N, CH2Cl2, room temp., 27%; iv, NaH, Et2NC(᎐S)Cl, DMF, 90 ЊC,
᎐
7%.
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J. Chem. Soc., Perkin Trans. 1, 2002, 1253–1259

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Table 2 Reactions of thioxocarbonate 6 with amine 2a or 2i in dichloromethane at room temp.
Yield (%)
7 ϩ 8
syn-7a
δH2, J2–3, δC2
syn- ϩ anti-8i
δH2, J2–3, δC2
Amine
Time/h
7 : 8
2a
2i
0.5
12
100 : 0
0 : 100
93
58
6.1, 2.4, 78.6
4.8, 3.3, 51.8
anti-5i. Ring-opening8 of 9 with inversion of configuration by
potassium thioacetate in acetone gave the corresponding thio-
acetate S-ester anti-10 (quant.). Treatment of 10 with hydrazin-
ium acetate followed by the in situ regioselective reaction of the
resulting thiol with diisopropylcarbamyl chloride afforded the
expected thiolcarbamate anti-5i (27%, two steps from 10). All
attempts to synthesise the pure syn-5i epimer failed; further-
more the ring opening of 9 with tetrabutylammonium bromide
gave the corresponding bromohydrin with a net inversion of
configuration, but any nucleophilic substitution (i.e. potassium
thioacetate) on the O-protected bromohydrin in order to carry
out the second inversion proceeded non stereospecifically and
afforded a mixture of syn- and anti-isomers; an observation in
accordance with some non pure S2 processes reported on
related tartrate12,13 and malate14 structures. Nevertheless, com-
pounds syn-4a and anti-5i thus obtained by unequivocal syn-
theses enabled us to ascertain the chemical structures proposed
for the thio- and thiolcarbamates obtained by reaction of cyclic
thioxocarbonates 1 and 6 with secondary amines. From the
known 13C NMR spectrum of anti-5i and a careful examination
of the corresponding spectra of all mixtures of syn- and anti-
thiolcarbamates 5a–j, we were able to conclude that the syn-
isomer predominated in all cases (ca. 70–80% as tentatively
estimated by integration of signals on the 13C NMR spectra).
In order to find a reasonable mechanism of formation for
thio- and thiolcarbamates, we checked that when the pure thio-
carbamate syn-4f was reacted with diisobutylamine 2f using
the standard experimental conditions the corresponding thiol-
carbamates 5f were not produced (syn ϩ anti), and conversely
the thiocarbamate syn-4f was not formed from the thiolcarb-
amates 5f (syn ϩ anti) and diisobutylamine 2f. Furthermore,
we observed (13C NMR monitoring) that the thiolcarbamate
anti-5i isomerised into a mixture of syn- and anti-5i (anti-5i >
syn-5i) when one equivalent of diisopropylamine in dichloro-
methane was added during a 12 h reaction. This valuable
information allows us access to a better understanding of the
reaction mechanism. Castro et al.15–19 have investigated kinetic
studies on the aminolysis of alicyclic thioxocarbonates and pro-
posed the formation of a zwitterionic tetrahedral intermediate
which undergoes a deprotonation step with amine R2NH to
afford the anionic tetrahedral intermediate A (Scheme 5).
At this stage, three conceivable competitive pathways can
occur according to the nature of the amine reagent. In the
case of reactive amines, the thiolate anion normally expels the
alcoholate (better leaving group than amide) from the unstable
anionic intermediate A (path a) in a fast reaction to provide the
thiocarbamate syn-4. In contrast to this path a remains dis-
favoured with hindered amines for reasons unclear to us; so we
firstly envisioned the nucleophilic attack of the thiolate ion on
one carbinol carbon bearing the carboxylate ester to afford
thiolcarbamates, but this disfavoured 4-endo-tet process20 was
dismissed.21 Since a breaking of the acetalic C–O bond is neces-
sary to explain the thiolcarbamate formation, we hypothesise
the formation of the unstrained opened intermediate B from
the reaction of a second molecule of amine on A with inversion
of configuration (path b), followed by the ring closure (second
inversion) with the more nucleophilic thiolate ion to give the
intermediate C (path c); the latter is able to afford the thiol-
carbamate 5-syn (major isomer formed) which isomerises into
the anti-isomer by an equilibrating process probably via a tran-
sient enolate intermediate at the 2-C centre. The double inver-
sion mechanism leading to C is closely related to the proposed
pathway invoked for the rearrangement of cyclic thioxo-
carbonates into corresponding cyclic thiolcarbonates with
bromine ions.4,22
Path c of this mechanism could be strengthened by the very
marked solvent effect we found in substituting dichloromethane
for the polar aprotic solvent, DMF: thus in the case of
the reactive diethylamine 2a, the ratio of 4a : 5a changed from
100 : 0 (run 1) to 1 : 1 (run 2, DMF), whereas the silylated amine
2g (O-TBDMS) gave the thiolcarbamate 5g [0 : 100 (run 9,
DMF) vs. 88 : 12 (run 8)] exclusively. These results firstly
exemplified the well known anion nucleophilicity enhancer
properties of DMF applied in our case to a thiolate ion, and
secondly they may be used to take advantage of this solvent
effect in order to partially direct the synthesis towards thiol-
carbamate formation in the case of very reactive amines.
In conclusion, we have shown that secondary amines react
initially exclusively at the thiocarbonyl centre of the cyclic
thioxocarbonates derived from (R,R)-dialkyl tartrates to afford
either the syn-thiocarbamates with retention of configuration
and/or the diastereomeric mixture of syn-and anti-thiol-
carbamates. The efficient and high yielding formation of
both thio- and thiolcarbamates by this method obviates their
cumbersome and non straightforward synthesis. Our findings
should be of value in further synthetic work in this area.
Experimental
Elemental analyses were performed by the ‘Service de Micro-
1
analyse de l’Ecole Supérieure de Chimie de Montpellier’. H
NMR spectra were determined on a Bruker 200 spectrometer
(200 MHz frequency) and 13C NMR spectra on a Bruker AC
400 spectrometer (100.6 MHz frequency). Mass spectra were
obtained with a JEOL JMS-DX-300 instrument by the FAB
ionisation method (positive mode) with p-nitrobenzyl alcohol
(NBA) as the matrix; specific optical rotations were measured
in a 0.1 dm cell on a Perkin-Elmer 241 polarimeter in units of
10Ϫ1 deg cm2 gϪ1. Petroleum ether refers to the fraction boiling
in the range 40–65 ЊC.
(4R,5R)-2-Thioxo-4,5-bis-(tert-butyloxycarbonyl)-1,3-dioxolane
1
To a stirred solution of (R,R)-di-tert-butyl tartrate11 (5 g, 19
mmol)inTHF(80cm3)wasaddeddropwiseat0ЊCthiocarbonyl-
diimidazole (9.4 g, 47.5 mmol) in THF (150 cm3). After 12 h at
Scheme 5
J. Chem. Soc., Perkin Trans. 1, 2002, 1253–1259
1255

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room temp. diethyl ether was added and the organic phase was
successively washed with an aqueous solution of citric acid
(5%), a saturated solution of NaHCO3, a saturated solution
of NaCl and dried over Na2SO4 and the solvents evaporated
under reduced pressure. Chromatography on silica gel and
elution with petroleum ether–ethyl acetate (6 : 1) afforded the
title compound as a solid (3.5 g, 60%); mp 124–127 ЊC; Rf
0.57 [petroleum ether–ethyl acetate (6 : 2)]; [α]2D0 Ϫ 57.4 0.1
(c 1.0, chloroform); δH (200 MHz; CDCl3) 1.54 (18 H, s, 2 × But)
and 5.14 (2 H, s, 2 × CH); δC (100 MHz; CDCl3) 28.2
(6 C, 2 × CMe3), 80.2 (2 C, 2 × CMe3), 85.9 (2 C, 2 × CH),
164.6 (2 C, 2 × CO), and 189.1 (1 C, CS); m/z (NBA) 305
[M ϩ H]ϩ (Found: C, 51.1; H, 6.4. C13H20O6S requires C, 51.3;
H, 6.6%).
(1 C, CMe3), 84.3 (1 C, CMe3), 166.4 (1 C, CO2), 170.9 (1 C,
CO ) and 186.0 (1 C, OC᎐S); m/z (NBA) 378 [M ϩ H]ϩ, 400 [M
᎐
2
ϩ Na]ϩ (Found: C, 54.4; H, 8.5. C17H31NO6S requires C, 54.1;
H, 8.3%).
(3S)-Di-tert-butyl
2-diethylcarbamoylsulfanyl-3-hydroxy-
succinates syn- and anti-5a. The title compounds were obtained
as an oil according to the aforementioned procedure in DMF
(63% overall yield) together with the thiocarbamate isomer 4a
in a 1 : 1 ratio; Rf 0.15 [petroleum ether–ethyl acetate (85 : 15)];
δH (200 MHz; CDCl3) 1.25 (6 H, m, 2 × CH3CH2), 1.45 (9 H, s,
But), 1.50 (9 H, s, But), 3.39 (4 H, m, 2 × CH2Me), 3.50 (1 H, d,
JOH-3 6.8 Hz, OH), 4.40 (1 H, dd, J3-OH 6.8, J3–2 2.9 Hz, 3-H)
and 4.75 (1 H, d, J2–3 2.9 Hz, 2-H); δC(100 MHz; CDCl3) 12.2
(1 C, CH2Me), 13.5 (1 C, CH2Me), 28.2 (3 C, CMe3), 28.5 (3 C,
CMe3), 44.3 (1 C, CH2Me), 48.6 (1 C, CH2Me), 52.9 (1 C,
2-Csyn), 53.1 (1 C, 2-Canti), 71.9 (1 C, 3-Canti), 72.8 (1 C, 3-Csyn),
83.3 (1 C, CMe3), 84.6 (1 C, CMe3), 166.1 (1 C, CO2anti), 166.2
N,N-Bis(tert-butyldiphenylsilyloxyethyl)amine 2h
To a stirred mixture of tert-butylchlorodiphenylsilane (17.8
cm3, 68.5 mmol) and imidazole (9.7 g, 142.6 mmol) dissolved in
anhydrous dimethylformamide (DMF) (55 cm3) was added
dropwise bis(hydroxyethyl)amine (diethanolamine) (2 g, 19
mmol). After 30 min at room temp. and addition of dichloro-
methane, the organic phase was washed with brine, dried over
Na2SO4 and evaporated under reduced pressure. Chromato-
graphy on silica gel with methanol (0 to 2%) in dichloro-
methane afforded quantitatively the title compound as a white
solid (11 g); Rf 0.84 [dichloromethane–methanol (95 : 5)]; mp
64–66 ЊC; δH (200 MHz; CDCl3) 1.40 (18 H, s, 2 × But),
2.79 (4 H, t, JCH2CH2 5.4 Hz, 2 × CH2N), 3.60 (4 H, t, JCH2CH2
5.4 Hz, 2 × CH2O) and 7.35 (20 H, m, aromatics); δC (100 MHz;
CDCl3) 27.3 (3 C, CMe3), 52.1 (1 C, CH2N), 63.9 (1 C, CH2O),
78.1 (1 C, CMe3), 128.1 (4 C, Cm aromatics), 130.0 (2 C,
Cp aromatics); 134.1 (2 C, Cq aromatics) and 136.0 (4 C, Co
aromatics); m/z (NBA) 582 [M ϩ H]ϩ (Found: C, 74.5; H, 8.2.
C36H47NO2Si2 requires C, 74.3; H, 8.1%).
(1 C, CO2syn), 168.7 (1 C, SC᎐Osyn), 169.0 (1 C, SC᎐Oanti), 170.8
᎐
᎐
(1 C, CO2anti) and 171.1 (1 C, CO2syn); m/z (NBA) 378 [M ϩ H]ϩ,
400 [M ϩ Na]ϩ (Found: C, 54.0; H, 8.1. C17H31NO6S requires C,
54.1; H, 8.3%).
(2R,3R)-Di-tert-butyl 2-[bis(2-hydroxyethyl)]thiocarbamoyl-
oxy-3-hydroxysuccinate syn-4b. The title compound was
obtained quantitatively as an oil according to the afore-
mentioned procedure; Rf 0.62 [ethyl acetate–methanol (98 : 2)];
[α]2D0 Ϫ 65.6 0.4 (c 2.6, chloroform); δH (200 MHz; CDCl3,
D2O) 1.48 (9 H, s, But), 1.53 (9 H, s, But), 3.43–4.25 (8 H, m,
2 × CH2N and 2 × CH2OH), 4.65 (1 H, d, J3–2 2.3 Hz, 3-H) and
6.10 (1 H, d, J2–3 2.3 Hz, 2-H); δC (100 MHz; CDCl3) 28.2 (3 C,
CMe3), 28.4 (3 C, CMe3), 54.4 (1 C, CH2N), 58.5 (1 C, CH2N),
60.7 (1 C, CH2O), 61.0 (1 C, CH2O), 71.4 (1 C, 3-C), 79.2 (1 C,
2-C), 84.2 (1 C, CMe3), 84.6 (1 C, CMe3), 166.9 (1 C, CO2),
170.7 (1 C, CO ) and 188.1 (1 C, OC᎐S); m/z (NBA) 410 [M ϩ
᎐
2
H]ϩ (Found: C, 50.3; H, 7.8. C17H31NO8S requires C, 49.9; H,
7.6%).
General procedure for the ring opening of thioxocarbonates 1 or 6
by amines 2
To a solution of thioxocarbonate 1 or 6 (0.2 mmol) in
anhydrous dichloromethane (or DMF in two cases specified in
the text) (2 cm3) was added under nitrogen at room temp. amine
2a–i (0.4 mmol) and the solution stirred for 30 min for amines
2a–e,j and 12 h for amines 2f–i. After concentration under
vacuum the crude residue was chromatographed on silica gel
with ethyl acetate (0 to 4%) in petroleum ether to afford the
expected thiocarbamates 4a–j, 7a (UV absorbing at 254 nm)
and thiolcarbamates 5a–j, 8i.
(2R,3R)-Di-tert-butyl
2-(piperidinothiocarbonyloxy)-3-
hydroxysuccinate syn-4c. The title compound was obtained
quantitatively according to the aforementioned general pro-
cedure as a colourless oil; Rf 0.73 [petroleum ether–ethyl acetate
(97 : 3)]; [α]2D0 Ϫ42.3 0.5 (c 1.8, chloroform); δH (200 MHz;
CDCl3, D2O) 1.47 (9 H, s, But), 1.52 (9 H, s, But), 1.70 (6 H, m,
3 × CH2), 3.48–4.18 (4 H, m, 2 × CH2N), 4.65 (1 H, d, J3–2
2.3 Hz, 3-H) and 6.10 (1 H, d, J2–3 2.3 Hz, 2-H); δC (100 MHz;
CDCl3) 23.2–24.8 (3 C, 3 × CH2), 27.0 (6 C, 2 × CMe3), 45.7–
50.6 (2 C, 2 × CH2N), 70.1 (1 C, 3-C), 77.6 (1 C, 2-C), 81.8 (1 C,
CMe3), 82.9 (1 C, CMe3), 164.9 (1 C, CO2), 169.4 (1 C, CO2)
(2R,3R)-Di-tert-butyl 2-diethylthiocarbamoyloxy-3-hydroxy-
succinate syn-4a. Method A via the thioxocarbonate 1. The title
compound was obtained as a colourless oil according to the
aforementioned procedure (95% yield).
and 184.2 (1 C, OC᎐S); m/z (NBA) 390 [M ϩ H]ϩ, 412 [M ϩ
᎐
Na]ϩ (Found: C, 55.8; H, 8.3. C18H31NO6S requires C, 55.5; H,
8.0%).
Method B via direct thiocarbamoylation of (R,R)-di-tert-
butyl tartrate. To the di-tert-butyl tartrate (100 mg, 0.38 mmol)
dissolved in DMF (2 cm3) was added at 0 ЊC sodium hydride
(19 mg, 0.76 mmol) and the solution stirred for 1.5 h at room
temp.. Diethylthiocarbamoyl chloride (91 mg, 0.57 mmol) was
then added and the reaction maintained at room temp. for 5 h
and warmed to 90 ЊC for 1 h. After concentration under
reduced pressure and chromatography on silica gel (see general
procedure) the title compound was obtained as a colourless oil
(10 mg, 7%); Rf 0.44 [petroleum ether–ethyl acetate (8 : 2)]; [α]2D0
Ϫ 73.5 0.9 (c 1.2, chloroform); δH (200 MHz; CDCl3) 1.21
(6 H, t, J 7.3 Hz, 2 × CH2CH3), 1.45 (9 H, s, But), 1.49 (9 H, s,
But), 3.16 (1 H, d, JOH-3 6.9 Hz, OH), 3.49 (2 H, q, J 7.3 Hz,
CH2Me), 3.68 (1 H, m, CHaMe), 3.90 (1 H, m, CHbMe), 4.65
(1 H, dd, J3-OH 6.9, J3–2 2.3 Hz, 3-H) and 6.10 (1 H, d, J2–3
2.3 Hz, 2-H); δC (100 MHz; CDCl3) 12.1 (1 C, CH2Me), 13.5
(1 C, CH2Me), 28.2 (3 C, CMe3), 28.4 (3 C, CMe3), 44.2 (1 C,
CH2N), 48.5 (1 C, CH2N), 71.6 (1 C, 3-C), 78.3 (1 C, 2-C), 83.2
(2R,3R)-Di-tert-butyl
2-(morpholinothiocarbonyloxy)-3-
hydroxysuccinate syn-4d. The title compound was obtained
quantitatively according to the aforementioned general pro-
cedure as a colourless oil; Rf 0.48 [petroleum ether–ethyl acetate
(7 : 3)]; [α]2D0 Ϫ36.5 0.9 (c 1.0, chloroform); δH (200 MHz;
CDCl3) 1.47 (9 H, s, But), 1.51 (9 H, s, But), 3.53–4.10 (8 H, m,
4 × CH2), 3.22 (1 H, d, JOH-3 6.5 Hz, OH), 4.66 (1 H, dd,
J3-OH 6.5, J3–2 2.4 Hz, 3-H) and 6.06 (1 H, d, J2–3 2.4 Hz, 2-H);
δC (100 MHz; CDCl3) 28.4 (6 C, 2 × CMe3), 46.6 (1 C, CH2N),
50.5 (1 C, CH2N), 66.5 (1 C, CH2O), 66.7 (1 C, CH2O), 71.4
(1 C, 3-C), 79.2 (1 C, 2-C), 83.5 (1 C, CMe3), 84.4 (1 C, CMe3),
166.0 (1 C, CO ), 170.7 (1 C, CO ) and 186.7 (1 C, OC᎐S); m/z
᎐
2
2
(NBA) 392 [M ϩ H]ϩ (Found: C, 51.9; H, 7.3. C17H29NO7S
requires C, 52.2; H, 7.5%).
(2R,3R)-Di-tert-butyl
succinate syn-4e. The O-TMS-derivative was obtained
2-thiocarbamoyloxy-3-hydroxy-
1256
J. Chem. Soc., Perkin Trans. 1, 2002, 1253–1259

View Article Online
according to the aforementioned general procedure, followed
by an acidic treatment THF–HCl 0.5 M (1.2 cm3) for 30 min to
afford after neutralisation, extraction with THF, drying of
organic phases and concentration under vacuum then chrom-
atography on silica gel as described in the general procedure,
the title compound as a colourless oil (quant.); Rf 0.51 [petrol-
eum ether–ethyl acetate (7 : 3)]; [α]2D0 Ϫ37.9 0.7 (c 1.4, chloro-
form); δH (200 MHz; CDCl3) 1.47 (9 H, s, But), 1.50 (9 H,
s, But), 3.79 (1 H, br s, OH), 4.67 (1 H, d, J3–2 2.5 Hz, 3-H),
5.92 (1 H, d, J2–3 2.5 Hz, 2-H), 6.60 (1 H, br s, NH) and
6.73 (1 H, br s, NH); δC (100 MHz; CDCl3) 28.2 (3 C,
CMe3), 28.4 (3 C, CMe3), 71.5 (1 C, 3-C), 79.4 (1 C, 2-C),
83.9 (1 C, CMe3), 84.8 (1 C, CMe3), 166.6 (1 C, CO2), 170.7
(2R,3R)-Di-tert-butyl 2-[bis(tert-butyldimethylsilyloxyethyl)-
thiocarbamoyloxy]-3-hydroxysuccinate syn-4g and (3S)-di-tert-
butyl 2-[bis(tert-butyldimethylsilyloxyethyl)carbamoylsulfanyl]-
3-hydroxysuccinates syn- and anti-5g. The title compounds were
obtained (87% overall yield) according to the aforementioned
procedure in a 88 : 12 ratio.
Thiocarbamate syn-4g. Rf 0.87 [petroleum ether–ethyl acetate
(8 : 2)]; mp 89–90 ЊC; [α]2D0 Ϫ34.3 0.7 (c 1.3, chloroform); δH
(200 MHz; CDCl3) 0.06 (3 H, s, SiMe), 0.07 (3 H, s, SiMe), 0.08
(6 H, s, 2 × SiMe), 0.89 (9 H, s, SiBut), 0.90 (9 H, s, SiBut), 1.47
(9 H, s, But), 1.51 (9 H, s, But), 3.14 (1 H, d, JOH-3 6.8 Hz, OH),
3.95 (8 H, m, 2 × CH2N and 2 × CH2O), 4.65 (1 H, dd, J3-OH 6.8,
J3–2 2.3 Hz, 3-H) and 6.12 (1 H, d, J2–3 2.3 Hz, 2-H); δC (100
MHz; CDCl3) Ϫ5.0 (2 C, 2 × SiMe), Ϫ4.9 (2 C, 2 × SiMe), 26.3
(6 C, 2 × CMe3), 28.3 (3 C, OCMe3), 28.4 (3 C, OCMe3), 53.9
(1 C, CH2N), 57.6 (1 C, CH2N), 60.8 (1 C, CH2O), 61.6 (1 C,
CH2O), 71.5 (1 C, 3-C), 79.1 (1 C, 2-C), 83.2 (2 C, 2 × CMe3),
84.3 (2 C, 2 × CMe3), 166.2 (1 C, CO2), 170.9 (1 C, CO2) and
(1 C, CO ) and 191.5 (1 C, SC᎐O); m/z (NBA) 322 [M ϩ
᎐
2
H]ϩ (Found: C, 48.9; H, 7.4. C13H23NO6S requires C, 48.6; H,
7.2%).
Di-tert-butyl
(2R)-[4-(1R,2R)-bis-(tert-butoxycarbonyl-2-
hydroxyethoxythiocarbonyl)piperazinothiocarbonyloxy]-(3R)-
hydroxysuccinate syn–syn-4j. The title compound was obtained
according to the aforementioned general procedure [piperazine
2j (1 equiv.), thioxocarbonate 1 (2 equiv.)] as a colourless oil
(84%); Rf 0.29 [petroleum ether–ethyl acetate (8 : 2)]; [α]2D0 Ϫ36.4
0.5 (c 0.2, chloroform); δH (200 MHz; CDCl3) 1.42 (18 H, s,
2 × But), 1.48 (18 H, s, 2 × But), 3.20 (2 H, d, JCHOH 6 Hz,
2 × OH), 3.47–4.26 (8 H, m, 4 × CH2N), 4.63 (2 H, dd, J3–2
2.1, JCHOH 6 Hz, 2 × CHOH) and 6.01 (2 H, d, J2–3 2.1 Hz,
2 × CHOCS); δC (100 MHz; CDCl3) 28.2–28.8 (12 C,
4 × CMe3), 45.0 (1 C, CH2N), 45.1 (1 C, CH2N), 49.1 (1 C,
CH2N), 49.2 (1 C, CH2N), 71.2 (1 C, CHOH), 71.3 (1 C,
CHOH), 79.5 (2 C, CHOCS), 83.6 (1 C, CMe3), 83.7
(1 C, CMe3), 84.3 (1 C, CMe3), 84.5 (1 C, CMe3), 166.0
(2 C, 2 × CO2), 170.5 (1 C, CO2), 170.6 (1 C, CO2) and 187.0
187.4 (1 C, OC᎐S); m/z (NBA) 638 [M ϩ H]ϩ, 660 [M ϩ Na]ϩ
᎐
(Found: C, 54.4; H, 9.1. C29H59NO8SSi2 requires C, 54.6; H,
9.3%).
Thiolcarbamates syn- and anti-5g. colourless oil; Rf 0.59
[petroleum ether–ethyl acetate (85 : 15)]; δH (200 MHz; CDCl3)
0.06 (3 H, s, SiMe), 0.07 (3 H, s, SiMe), 0.08 (6 H, s, 2 × SiMe),
0.86 (18 H, s, 2 × SiBut), 1.49 (9 H, s, But), 1.50 (9 H, s, But),
3.45 (1 H, d, JOH-3 7.0 Hz, OH), 3.48–3.82 (8 H, m, 2 × NCH2-
CH2O), 4.36 (1 H, dd, J3–2 3.1, J3-OH 7.0 Hz, 3-H) and 4.72
(1 H, d, J2–3 3.1 Hz, 2-H); δC (100 MHz; CDCl3) Ϫ5.02 (1 C,
SiMe), Ϫ4.99 (1 C, SiMe), Ϫ4.96 (2 C, 2 × SiMe), 26.1 (6 C,
2 × SiCMe3), 28.3 (6 C, 2 × OCMe3), 52.2 (2 C, 2 × CH2N), 52.4
(1 C, 2-Csyn), 53.1 (1 C, 2-Canti), 61.7 (2 C, 2 × CH2O), 72.0 (1 C,
3-Canti), 72.7 (1 C, 3-Csyn), 83.2 (4 C, 4 × CMe3), 166.1 (1 C,
CO2anti), 166.4 (1 C, CO2syn), 168.4 (1 C, SC᎐Osyn), 168.8 (1 C,
᎐
(2 C, 2 × OC᎐S); m/z (NBA) 695 [M ϩ H]ϩ, 717 [M ϩ Na]ϩ
SC᎐Oanti), 171.2 (1 C, CO2syn) and 171.3 (1 C, CO2anti); m/z
᎐
᎐
(Found: C, 51.6; H, 7.0. C30H50N2O12S2 requires C, 51.9; H,
7.2%).
(NBA) 638 [M ϩ H]ϩ; 660 [M ϩ Na]ϩ (Found: C, 54.3; H, 9.0.
C29H59NO8SSi2 requires C, 54.6; H, 9.3%).
(2R,3R)-Di-tert-butyl
2-diisobutylthiocarbamoyloxy-3-
(2R,3R)-Di-tert-butyl 2-[bis(tert-butyldiphenylsilyloxyethyl)-
thiocarbamoyloxy]-3-hydroxysuccinate syn-4h and (3S)-di-tert-
butyl 2-[bis-(tert-butyldiphenylsilyloxyethyl)carbamoylsulfanyl]-
3-hydroxysuccinates syn- and anti-5h. The title compounds were
obtained as colourless oils according to the aforementioned
procedure (64% overall yield) in a 39 : 61 ratio.
hydroxysuccinate syn-4f and (3S)-di-tert-butyl 2-diisobutyl-
carbamoylsulfanyl-3-hydroxysuccinates syn- and anti-5f. The
title compounds were obtained as colourless oils according to
the aforementioned procedure in 90% overall yield in a 1 : 1
ratio.
Thiocarbamate syn-4f. Rf 0.74 [petroleum ether–ethyl acetate
(85 : 15)]; [α]2D0 Ϫ38.6 0.9 (c 1.1, chloroform); δH (200 MHz;
CDCl3) 0.92 (12 H, m, 4 × Me), 1.48 (9 H, s, But), 1.51 (9 H, s,
But), 2.21 (2 H, m, 2 × CHMe2), 3.09 (1 H, d, JOH-3 6.7 Hz, OH),
3.50 (4 H, m, 2 × CH2N), 4.65 (1 H, dd, J3-OH 6.7, J3–2 2.1 Hz,
3-H) and 6.04 (1 H, d, J2–3 2.1 Hz, 2-H); δC (100 MHz; CDCl3)
20.56 (1 C, Me), 20.58 (1 C, Me), 20.84 (1 C, Me), 20.88
(1 C, Me), 26.8 (1 C, CHMe2), 27.8 (1 C, CHMe2), 28.3 (6 C,
2 × CMe3), 58.7 (1 C, CH2N), 62.2 (1 C, CH2N), 71.6 (1 C, 3-C),
79.2 (1 C, 2-C), 83.1 (1 C, CMe3), 84.2 (1 C, CMe3), 166.4 (1 C,
Thiocarbamate syn-4h. Rf 0.65 [petroleum ether–ethyl acetate
(9 : 1)]; [α]2D0 Ϫ33.6 1.0 (c 1.1, chloroform); δH (200 MHz;
CDCl3) 1.08 (18 H, s, 2 × SiBut), 1.39 (9 H, s, But), 1.48 (9 H, s,
But), 3.05 (1 H, d, JOH-3 7.0 Hz, OH), 4.05 (8 H, m, 2 × CH2N
and 2 × CH2OSi), 4.61 (1 H, dd, J3-OH 7.0, J3–2 2.3 Hz, 3-H),
6.08 (1 H, d, J2–3 2.3 Hz, 2-H) and 7.55 (20 H, m, aromatics);
δC (100 MHz; CDCl3) 27.2 (6 C, 2 × CMe3), 28.3 (6 C,
2 × CMe3), 53.5 (1 C, CH2N), 57.3 (1 C, CH2N), 61.9 (1 C,
CH2O), 62.6 (1 C, CH2O), 71.5 (1 C, 3-C), 79.2 (1 C, 2-C), 83.1
(1 C, CMe3), 84.2 (2 C, 2 × CMe3), 85.6 (1 C, CMe3), 128.2 (8 C,
Cm aromatics), 130.1 (4 C, Cp aromatics), 133.7 (4 C, Cq aro-
matics), 136 (8 C, Co aromatics), 166.1 (1 C, CO2), 170.9 (1 C,
CO ) and 187.4 (1 C, OC᎐S); m/z (NBA) 886 [M ϩ H]ϩ, 908
CO ), 171.1 (1 C, CO ) and 187.4 (1 C, OC᎐S); m/z (NBA) 434
᎐
2
2
[M ϩ H]ϩ, 456 [M ϩ Na]ϩ (Found: C, 58.0; H, 9.3. C21H39NO6S
requires C, 58.2; H, 9.1%).
᎐
2
Thiolcarbamates syn- and anti-5f. Rf 0.57 [petroleum ether–
ethyl acetate (85 : 15)]; δH (200 MHz; CDCl3) 0.9 (12 H, m,
4 × Me), 1.46 (9 H, s, But), 1.52 (9 H, s, But), 2.0 (2 H, m,
2 × CHMe2), 3.33 (4 H, m, 2 × CH2N), 3.50 (1 H, d, JOH-3 7.0
Hz, OH), 4.39 (1 H, dd, J3-OH 7.0, J3–2 2.9 Hz, 3-H) and 4.79
(1 H, d, J2–3 2.9, 2-H); δC (100 MHz; CDCl3) 20.5 (4 C, 4 × Me),
27.1 (1 C, CHMe2), 27.9 (1 C, CHMe2), 28.3 (6 C, 2 × CMe3),
52.5 (1 C, 2-Csyn), 52.9 (1 C, 2-Canti), 55.7 (1 C, CH2N), 56.0
(1 C, CH2N), 71.9 (1 C, 3-Canti), 72.8 (1 C, 3-Csyn), 83.1 (2 C,
2 × CMe3), 166.4 (1 C, 1-CO2anti), 166.7 (1 C, 1-CO2syn), 168.8
[M ϩ Na]ϩ (Found: C, 66.1; H, 7.4. C49H67NO8SSi2 requires
C, 66.4; H, 7.6%).
Thiolcarbamates syn- and anti-5h. Rf 0.51 [petroleum
ether–ethyl acetate (9 : 1)]; δH (200 MHz; CDCl3) 1.08 (18 H, s,
2 × SiBut), 1.39 (9 H, s, But), 1.48 (9 H, s, But), 3.50 (1 H, d,
JOH-3 7.0 Hz, OH), 3.74 (8 H, m, 2 × CH2N and 2 × CH2OSi), 4.33
(1 H, dd, J3-OH 7.0, J3–2 2.8 Hz, 3-H), 4.73 (1 H, d, J2–3 2.8, 2-H)
and 7.55 (20 H, m, aromatics); δC (100 MHz; CDCl3) 28.3 (6 C,
2 × CMe3), 30.1 (6 C, 2 × CMe3), 51.5 (2 C, 2 × CH2N), 52.8
(1 C, 2-Csyn), 53.1 (1 C, 2-Canti), 62.6 (2 C, 2 × CH2O), 72.7 (1 C,
3-Canti), 72.8 (1 C, 3-Csyn), 83.3 (2 C, 2 × CMe3), 83.6 (1 C,
CMe3), 83.7 (1 C, CMe3), 128.2 (8 C, Cm aromatics), 130.2 (4 C,
Cp aromatics), 133.5 (4 C, Cq aromatics), 135.9 (8 C, Co aro-
matics), 166.50 (1 C, CO2anti), 166.55 (1 C, CO2syn), 168.34 (1 C,
(1 C, SC᎐O ), 169.2 (1 C, SC᎐Oanti), 171.3 (1 C, CO2anti) and
᎐
᎐
syn
171.4 (1 C, CO2syn); m/z (NBA) 434 [M ϩ H]ϩ, 456 [M ϩ Na]ϩ
(Found: C, 58.3; H, 9.4. C21H39NO6S requires C, 58.2; H,
9.1%).
J. Chem. Soc., Perkin Trans. 1, 2002, 1253–1259
1257

View Article Online
SC᎐O ), 168.39 (1 C, SC᎐Oanti), 171.2 (1 C, CO2anti) and 171.3
with a saturated solution of NaCl and the organic phases
᎐
᎐
syn
(1 C, CO2syn); m/z (NBA) 886 [M ϩ H]ϩ, 908 [M ϩ Na]ϩ
(Found: C, 66.2; H, 7.3. C49H67NO8SSi2 requires C, 66.4; H,
7.6%).
dried over Na2SO4. The solvent was evaporated under reduced
pressure. Chromatography on silica gel and elution with
dichloromethane afforded the title compound as a white solid
(5 g, 82%); mp 52–54 ЊC; Rf 0.74 (dichloromethane); [α]2D0 Ϫ67.1
0.6 (c 1.7, chloroform); δH (200 MHz; CDCl3) 1.56 (18 H, s, 2
× But) and 5.29 (2 H, s, 2 × CH); δC (100 MHz; CDCl3) 28.2
(6 C, 2 × CMe3), 78.1 (2 C, 2 × CMe3), 86.4 (2 C, 2 × CH) and
163.7 (2 C, 2 × CO); m/z (NBA) 325 [M ϩ H]ϩ, 347 [M ϩ Na]ϩ,
269 [M ϩ H Ϫ But]ϩ, 210 [M ϩ H Ϫ 2 But]ϩ (Found: C, 44.7; H,
6.3. C12H20O8S requires C, 44.4; H, 6.2%).
(3S)-Di-tert-butyl
2-diisopropylcarbamoylsulfanyl-3-
hydroxysuccinates syn- and anti-5i. The title compounds were
obtained in 70% overall yield according to the aforementioned
general procedure as a colourless oil; Rf 0.56 [petroleum ether–
ethyl acetate (8 : 2)]; δH (200 MHz; CDCl3) 1.47 (9 H, s, But),
1.52 (9 H, s, But), 1.53 (12 H, m, 4 × Me), 3.54 (1 H, m,
CHMe2), 3.57 (1 H, d, JOH-3 7.1 Hz, OH), 4.17 (1 H, m,
CHMe2), 4.41 (1 H, d, J3–2 3.0, J3-OH 7.1 Hz, 3-H) and 4.71 (1 H,
d, J2–3 3.0 Hz, 2-H); δC (100 MHz; CDCl3) 20.9 (2 C, CHMe2),
21.0 (2 C, CHMe2), 28.3–28.5 (6 C, 2 × CMe3), 46.7 (1 C,
CHMe3), 49.7 (1 C, CHMe3), 52.0 (1 C, 2-Csyn), 52.5 (1 C,
2-Canti), 72.0 (1 C, 3-Canti), 72.6 (1 C, 3-Csyn), 83.0 (1 C, CMe3),
83.6 (1 C, CMe3), 163.3 (1 C, CO2anti), 163.6 (1 C, CO2syn), 168.9
(S,S)-Di-tert-butyl 2-acetylsulfanyl-3-hydroxysuccinate anti-10
To the cyclic sulfate 9 (300 mg, 0.9 mmol) dissolved in acetone
(5 cm3) was added at room temp. potassium thioacetate
(127 mg, 1.1 mmol) and the solution stirred at room temp. for
30 min followed by the addition at 0 ЊC of conc.H2SO4 (cat.)
and water (17 µl, 0.9 mmol). The reaction was stirred for 3 h at
room temp. and concentrated under vacuum, dissolved in
dichloromethane (10 cm3), neutralised with a 5% solution of
NaHCO3 and the organic phase was dried, concentrated to give
quantitatively the pure title compound (295 mg) as a white
solid; mp 52–54 ЊC; Rf 0.40 [petroleum ether–ethyl acetate
(85 : 15)]; [α]2D0 Ϫ66.1 0.6 (c 1.6, chloroform); δH (200 MHz;
CDCl3, D2O) 1.43 (9 H, s, But), 1.49 (9 H, s, But), 2.46 (3 H, s,
Ac), 4.29 (1 H, d, J3–2 3.1 Hz, 3-H) and 4.69 (1 H, d, J2–3 3.1 Hz,
2-H); δC (100 MHz; CDCl3) 28.3 (3 C, CMe3), 28.4 (3 C, CMe3),
30.6 (1 C, MeCO), 51.3 (1 C, 2-C), 72.2 (1 C, 3-C), 83.7 (1 C,
CMe3), 84.1 (1 C, CMe3), 167.7 (1 C, CO2), 171.1 (1 C, CO2)
(1 C, SC᎐O ), 169.3 (1 C, SC᎐Oanti), 171.47 (1 C, CO2anti) and
᎐
᎐
syn
171.50 (1 C, CO2syn); m/z (NBA) 406 [M ϩ H]ϩ, 428 [M ϩ Na]ϩ
(Found: C, 56.5; H, 8.9. C19H35NO6S requires C, 56.3; H, 8.7%).
(2R,3R)-Diisopropyl 2-diethylthiocarbamoyloxy-3-hydroxy-
succinate syn-7a. The title compound was obtained in 93% yield
according to the aforementioned general procedure as a colour-
less oil; Rf 0.26 [petroleum ether–ethyl acetate (85 : 15)]; [α]2D0
Ϫ69.1 0.4 (c 2.7, chloroform); δH (200 MHz; CDCl3) 1.16–
1.30 (18 H, m, 6 × Me), 3.12 (1 H, d, JOH-3 7.3 Hz, OH), 3.49
(2 H, q, JCH -Me 7.0 Hz, CH2Me), 3.77 (2 H, m, CH2Me), 4.70
2
and 193.9 (1 C, SC᎐O); m/z (NBA) 321 [M ϩ H]ϩ, 343 [M ϩ
(1 H, dd, J3-OH 7.3, J3–2 2.4 Hz, 3-H), 5.11 (2 H, m, 2 × CO2CH )
and 6.14 (1 H, d, J2–3 2.4 Hz, 2-H); δC (100 MHz; CDCl3) 12.1
(1 C, CH2Me), 13.4 (1 C, CH2Me), 21.9 (1 C, Me), 22.1 (1 C,
Me), 22.2 (1 C, Me), 44.3 (1 C, CH2Me), 48.6 (1 C, CH2Me),
70.0 (1 C, CO2CH), 70.2 (1 C, CO2CH), 71.5 (1 C, 3-C), 78.6
(1 C, 2-C), 166.9 (1 C, CO2), 171.2 (1 C, CO2) and 186.0 (1 C,
᎐
Na]ϩ (Found: C, 52.3; H, 7.7. C14H24O6S requires C, 52.5; H,
7.5%).
(S,S)-Di-tert-butyl 2-diisopropylcarbamoylsulfanyl-3-hydroxy-
succinate anti-5i from 10
OC᎐S); m/z (NBA) 350 [M ϩ H]ϩ (Found: C, 51.7; H, 7.6.
᎐
To the thioacetate 10 (250 mg, 0.8 mmol) in DMF (1 cm3) was
added hydrazine acetate (93 mg, 1 mmol) and the solution
stirred at room temp. for 15 min. Then triethylamine (652 µl, 4.7
mmol) and diisopropylcarbamyl chloride (638 mg, 3.9 mmol) in
dichloromethane (2 cm3) were added and the reaction main-
tained at room temp. for 12 h. The solution was extracted with
dichloromethane and the organic phase was washed with brine,
dried and evaporated under reduced pressure. After a chrom-
atography on silica gel with ethyl acetate (0 to 6%) in petroleum
ether, the title compound (86 mg, 27%) was obtained as a
colourless oil; Rf 0.56 [petroleum ether–ethyl acetate (8 : 2)];
C15H27NO6S requires C, 51.6; H, 7.8%).
(3S)-Diisopropyl 2-diisopropylcarbamoylsulfanyl-3-hydroxy-
succinates syn- and anti-8i. The title compounds were obtained
in 58% overall yield according to the aforementioned general
procedure as a colourless oil; Rf 0.28 [petroleum ether–ethyl
acetate (85 : 15)]; δH (200 MHz; CDCl3, D2O) 1.16–1.31 (24 H,
m, 8 × Me), 4.48 (1 H, d, J3–2 3.3 Hz, 3-H), 4.76 (1 H, d, J2–3
3.3 Hz, 2-H), 4.82 (2 H, m, 2 × NCHPri) and 5.16 (2 H, m,
2 × CO2CHPri); δC (100 MHz; CDCl3) 20.9–22.3 (4 C, 4 × Me),
46.3 (1 C, NCH), 50.3 (1 C, NCH), 51.4 (1 C, 2-Csyn), 51.8 (1 C,
2-Canti), 69.8 (1 C, CO2CH), 70.2 (1 C, CO2CH), 71.7 (1 C,
3-Canti), 72.4 (1 C, 3-Csyn), 163.1 (1 C, CO2anti), 163.4 (1 C,
[α]2D0 Ϫ34.5
0.9 (c 1.1, chloroform); δH (200 MHz; CDCl3,
D2O) 1.45 (9 H, s, But), 1.52 (9 H, s, But), 1.53 (12 H, m,
4 × Me), 3.57 (1 H, m, CHMe2), 4.16 (1 H, m, CHMe2), 4.38
(1 H, d, J3–2 3.1 Hz, 3-H) and 4.71 (1 H, d, J2–3 3.1 Hz, 2-H);
δC (100 MHz; CDCl3) 20.5 (2 C, CHMe2), 20.7 (2 C, CHMe2),
27.8 (3 C, CMe3), 28.0 (3 C, CMe3), 46.7 (1 C, NCH), 49.7 (1 C,
NCH), 52.0 (1 C, 2-C), 72.1 (1 C, 3-C), 83.1 (1 C, CMe3), 83.2
CO2syn), 169.1 (1 C, SC᎐O ), 169.5 (1 C, SC᎐Oanti), 171.7 (1 C,
᎐
᎐
syn
CO2syn) and 171.9 (1 C, CO2anti); m/z (NBA) 378 [M ϩ H]ϩ
(Found: C, 54.3; H, 8.4. C17H31NO6S requires C, 54.1; H, 8.3%).
(4R,5R)-Di-tert-butyl 2,2-dioxo-1,3,2-dioxathiolane-4,5-
dicarboxylate 2,2-dioxide 9
(1 C, CMe ), 163.0 (1 C, CO ), 168.9 (1 C, SC᎐O) and 171.0
᎐
3
2
(1 C, CO2); m/z (NBA) 406 [M ϩ H]ϩ, 428 [M ϩ Na]ϩ (Found:
To a stirred solution of (R,R)-di-tert-butyl tartrate (5 g, 19.1
mmol) and triethylamine (10.6 cm3, 76.2 mmol) dissolved in
dichloromethane (60 cm3) was added dropwise under nitrogen
at 0 ЊC thionyl chloride (2.1 cm3, 28.5 mmol) in dichlorometh-
ane (5 cm3). After 1.5 h at room temp. cold diethyl ether (200
cm3) was added and the organic phase was washed with cold
water and a cold saturated solution of NaCl and the solvent
evaporated under reduced pressure to afford the intermediate
cyclic sulfite as a brown oil. To the crude sulfite dissolved in a
cold mixture of carbon tetrachloride–acetonitrile–water [200
cm3, (1.2 : 1.2 : 1.7)] were added at 0 ЊC RuCl3ؒH2O (20 mg, 0.1
mmol, 0.5%) and NaIO4 (8.15 g, 38 mmol). The mixture was
vigorously stirred for 30 min at room temp. and filtered on a
celite pad; the filtrates were extracted with diethyl ether, washed
C, 56.2; H, 8.5. C19H35NO6S requires C, 56.3; H, 8.7%).
Acknowledgements
We are grateful to the Ministère de la Recherche et de la Tech-
nologie and C.N.R.S for their financial support of this research.
L. F. is pleased to acknowledge the Mayoly Spindler Company
and ‘la Région Languedoc Roussillon’ for providing a grant.
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