N-t-butanesulfinyl amide: An optimised and versatile access from readily available starting materials

Article abstract of DOI:10.1016/j.crci.2013.03.001

We report the synthesis of t-butanesulfinylphthalimide and its complete regioselective ring opening by a range of nucleophiles. Further treatment of the obtained N-t-butanesulfinyl amides under basic conditions has been shown to give t-butanesulfinamide. Although the involvement of chiral nucleophiles in this process did not allow the isolation of enantiomerically pure t-butanesulfinamide, we have accessed in a rapid and efficient fashion the original compounds bearing two H-bond sites and two chiral centers that shall potentially exhibit some organocatalytic activity by comparison with known structurally related compounds.

Full text of DOI:10.1016/j.crci.2013.03.001

C. R. Chimie 16 (2013) 350–357
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Preliminary communication/Communication
N-t-butanesulfinyl amide: An optimised and versatile access from readily
available starting materials
Aurelien Honraedt a,b, Gilles Caillot a,b, Emmanuel Gras a,b,
*
´
a CNRS, Laboratoire de chimie de coordination (LCC), 205, route de Narbonne, BP 44099, 31077 Toulouse cedex 4, France
b Universite´ de Toulouse, UPS, INPT, 31077 Toulouse cedex 4, France
A R T I C L E I N F O
A B S T R A C T
Article history:
We report the synthesis of t-butanesulfinylphthalimide and its complete regioselective
ring opening by a range of nucleophiles. Further treatment of the obtained N-t-
butanesulfinyl amides under basic conditions has been shown to give t-butanesulfina-
mide. Although the involvement of chiral nucleophiles in this process did not allow the
isolation of enantiomerically pure t-butanesulfinamide, we have accessed in a rapid and
efficient fashion the original compounds bearing two H-bond sites and two chiral centers
that shall potentially exhibit some organocatalytic activity by comparison with known
structurally related compounds.
Received 3 December 2012
Accepted after revision 1st March 2013
Keywords:
Sulfinamide
Nucleophilic addition
Chemoselectivity
Regioselectivity
Amines
´
ß 2013 Academie des sciences. Published by Elsevier Masson SAS. All rights reserved.
Amides
Synthetic methods
t-Butanesulfinamide 1 (Fig. 1) has found a huge field of
applications for the synthesis of optically pure amines via
the intermediary of t-butanesulfinyl imines 2, either by
nucleophilic addition or by electrophilic trapping of the
sulfinylenamine after deprotonation by a base [1,2].
The use of this chiral auxiliary is highly wide in scope
via the sulfinylimines and it has also been extended to
higher oxidation levels as an elegant method to access
chiral amide or esters by alkylation of N-sulfinyl imidates 3
(Scheme 1) [3].
Moreover, whereas removal and/or recovery of the
chiral auxiliary remains one general concern in these
diastereoselection-based asymmetric synthetic methods,
the t-butane sulfinamides obtained easily release their
sulfinyl moiety via a simple anhydrous acidic treatment,
which also allows the isolation of the ammonium salt (and
potentially the recovery of the sulfinyl chloride) [4]. t-
Butanesulfinamide has recently found new applications
since reports have mentioned its use in t-butanesulfinyl-
based ligands to be used in transition metal asymmetric
catalysis, especially rhodium-catalyzed 1,4-addition of
organoboronic acids to activated double bonds (Fig. 2)
[5–7]. Expectedly, it has been shown that coordination of
the sulphur atom to the transition metal, such as in 4
provides a good stereochemical induction. Moreover, the
sulfinyl moiety attached to nitrogen has also been recently
widely exploited in the development of organocatalytic
methods where it has been shown either to act as an
organocatalyst, [8] or to modulate the properties of urea
and thiourea either by acidifying the adjacent proton or via
the H-acceptor ability of the S5O group [9–14]. This
illustrates the fact that the use of sufinyl adducts is far from
being restricted to a role as chiral auxiliary and therefore,
the establishment of methods for opening routes to new
sulfinyl containing compounds is a field currently regain-
ing interest.
In the course of our studies aiming at developing a new
route to t-butanesulfinamide 1, we have been willing to
explore the reactivity of t-butane sulfinylphthalimide 6
toward oxygen- and nitrogen-centred nucleophiles, as this
* Corresponding author.
E-mail address: emmanuel.gras@lcc-toulouse.fr (E. Gras).
1631-0748/$ – see front matter ß 2013 Acade´mie des sciences. Published by Elsevier Masson SAS. All rights reserved.
http://dx.doi.org/10.1016/j.crci.2013.03.001

A. Honraedt et al. / C. R. Chimie 16 (2013) 350–357
351
Scheme 1. Asymmetric synthesis of carboxylic derivatives by alkylation of N-sulfinyl imidates.
Fig. 1. t-Butanesulfinamide and t-butanesulfinyl imines.
Scheme 2. Synthesis of t-butanesulfinyl phthalimide from t-
butanesulfinyl chloride.
This seems to be mainly due to the poor stability of t-
butanesulfinyl chloride 5, which was then isolated only in
low yields regardless of its synthetic path. We therefore
explored an alternate approach, which could reliably allow
us to access t-butane sulfinylphthalimide 6 on a multi-
gram scale, in a cost-effective fashion.
The t-butane sulfinylphthalimide 6 might also be
prepared in two stages from t-butane mercaptan 7 by
the action of chlorine according to a known procedure in
industry to yield the unstable sulfenyl chloride 8 (Scheme
Fig. 2. Structure of a rhodium sulfinamide/alkene dimer.
could not only represent a desirable new route to t-
butanesulfinamide 1, but also a potential access to chiral
sulphur bidentate ligands. Although not widely developed
and used, sulfinylphthalimides have been known for many
decades [15].
Our first attempt to access t-butane sulfinylphthalimide
6 has been the most straightforward that can be identified,
i.e. the condensation of potassium phthalimide on t-
butanesulfinyl chloride 5 (Scheme 2). Although the yield
was very good on our first attempt, we had serious
concerns regarding the reproducibility of this reaction.
3). [16] By quenching
8 in situ with a source of
phthalimide, one can expect to access the sulfenylphtha-
limide 9, which then only requires oxidation to yield 6.
For the sake of practicality at the laboratory scale, and
keeping in mind that the reaction would ideally be carried
Scheme 3. Alternate access to t-butanesulfinylphthalimide.

352
A. Honraedt et al. / C. R. Chimie 16 (2013) 350–357
Scheme 4. Selectivity issue in the oxidative cleavage of di-t-butyldisulfide.
out on multi-gram scale, we found it advantageous to
replace chlorine by a more convenient oxidant. Moreover,
starting from the disulfide of t-butylmercaptan was
favoured, not only for cost-effectiveness, but also because
t-butyl mercaptan exhibits a significant disadvantageous
smell. Yet, the selective cleavage of the S–S bond has been
reported as a highly unfavoured process (Scheme 4) [17].
We nevertheless decided to tackle this synthetic
challenge and first explored the possibility to use N-
bromophthalimide, which could be both the oxidant and
the source of phthalimide [18]. The reaction was ideally
easy to set up as it was carried out by mixing the di-t-butyl
disulfide 10 and N-bromophthalimide under refluxing
chloroform (Scheme 5); yet, only a poor mass recovery was
observed and the isolated solid happened to be a mixture
of phthalimide 11 with a minor amount of sulfenylphtha-
limide 9, and a more important quantity of thiosulfe-
nylphthalimide 12.
As illustrated in Scheme 4, 9 is thought to arise from the
desired and expected cleavage of the S–S bond, whereas 12
is formed by the cleavage of the C–S bond favoured in the
case of di-t-butyl mercaptan and occurring with a loss of
isobutene. Because of the lack of efficiency and since the
separation of these two compounds appeared tedious, we
changed the oxidant to sulfuryl chloride (a source of Cl+
previously reported to cleave the S–S bond of a primary
Scheme 5. Reaction of 10 with bromophthalimide.
Scheme 6. Formation of t-butanesulfenyl phthalimide form 10.

A. Honraedt et al. / C. R. Chimie 16 (2013) 350–357
353
Table 1
Identification of the optimal reaction conditions for the synthesis of 9.
Entry
Solvent
Temperature (8C)
Recovery of 11
Ratio 9:12
Yield of 9 (%)
1
2
3
4
5
6
7
None
–30
–30
0
100
100
100
17
_
0
0
Pentane
None
_
_
0
Pentane
Pentane
Heptane
Heptane
30
36
30
80
92/8
83/17
9/91
61/39
76
41
7
50
20
44
34
alkyl disulfide) [19] in order to increase both the efficiency
and the 9:12 ratio (Scheme 6). We also explored the effect
of the solvent and the temperature on the reaction
outcome (Table 1).
was detected at any time. This is obviously the conse-
quence of the efficient transformation of one disulfide into
two sulfenylchloride.
Having an efficient and scaled-up approach to 9, we
performed its oxidation to 6 under classical conditions. 6
has been quantitatively formed in the presence of a
stoichiometric amount of mCPBA, as previously reported
[20], or peracetic acid (Scheme 7). The latter oxidising
reagent proved superior for preparative purposes as it
allowed the isolation of the sulfinyl phthalimide 6 in a
highly pure form in 93% yield, the acetic acid being
removed upon aqueous work-up. Oppositely, the mCPBA
oxidation required further purification. We have routinely
carried out this oxidation on a multi-gram scale, securing
an easy and reproducible access to t-butanesulfinyl
phthalimide 6.
The reaction was followed by GC to monitor the
consumption of the disulfide before the addition to a
solution of phthalimide and triethylamine (2 and 2.6 equiv
of both with regard to the initial disulfide, respectively) in
DMF. Precipitation was then induced by dilution with
water, and the ratio 9:12 was determined from 1H-NMR. At
low temperature (–30 8C and 0 8C) in pentane or under
solvent-free conditions, the solid that was finally isolated
after precipitation from water was only phthalimide 11. As
we could not isolate any other product from this reaction,
we moved to other conditions. Oppositely, when the
reaction was carried out at 30 8C in pentane, a good mass
recovery of a mixture of products is obtained with an
interesting ratio of 92/8 in favour of the sulfenylphthali-
mide 9. Raising the temperature to the boiling point of
pentane slightly lowers both the recovery and the ratio
(entry 5). Surprisingly, running the reaction in heptane at
30 8C also allows the isolation of a significant amount of
material, but in this case, the ratio between 9 and 12 was
inversed in favour of the thiosulfenylphthalimide 12 (entry
6). In heptane, it is only at 80 8C that a ratio in favour of 9
was observed again (entry 7) yet with a lower efficiency
compared to the reaction in pentane. We have so far no
evidence allowing an explanation of these experimental
observations. Nevertheless, the reaction carried out in
pentane at 30 8C was found to be highly reproducible up to
a 0.1 mol scale. With the 92/8 ratio between 9 and 12 at the
end of the reaction, we found that the sulfenylphthalimide
9 could be isolated in 76% yield by a simple precipitation in
five volumes of absolute ethanol. One interesting feature of
this reaction is that no volatile derivative of t-butyl
mercaptan is released and therefore no unpleasant smell
With this high-scale and reproducible approach, we
then explored the reactivity of the t-butanesulfinyl
phthalimide 6 toward oxygen- and nitrogen-centered
nucleophiles.
Although a simple nucleophilic displacement of phtha-
limide has been reported earlier for sulfinylphthalimides
6a, upon increase of the steric hindrance of the substituent
on sulphur, a complete inversion of selectivity has been
achieved, driving the reaction exclusively to the ring
opening of the phthalimide ring. [15] Yet, only one ring
opening of 6 by a bulky secondary alkoxide leading to 13
had been described as a side reaction in this report. A
similar ring opening had been previously described on a
range of sulfenylphthalimides 9 with an array of nucleo-
philes yielding 14 [21]. Owing to this general difference of
behaviour between sulfenyl- and sulfinylphthalimides, it
remained unclear whether at a higher level of oxidation of
the sulphur atom, one would still observe with any other
nucleophiles a ring opening rather than a phthalimide
substitution (Scheme 8).
We were first wondering whether a similar reactivity
would be achieved via acid catalysis. Therefore, we
explored the reactivity of the t-butanesufinyl phthalimide
6 with a pro-nucleophile in the presence of a Lewis acid.
We observed that although 6 is stable as a suspension in
ethanol, addition of 0.5 mol% of the Lewis acidic samarium
(III) triflate promotes the total consumption of the starting
material in half an hour and allows the isolation, in
quantitative yield, of the phthalimide ring-opened product
15, whose structure has been unambiguously determined
by X-ray diffraction (Scheme 9) [22].
Interestingly, the addition of aqueous ammonia to a
solution of 15 in dichloromethane allowed the isolation of
t-butane sulfinamide in 64% yield. As this was establishing
Scheme 7. Mono-oxidation of t-butane thiophtamilide.

354
A. Honraedt et al. / C. R. Chimie 16 (2013) 350–357
Scheme 8. Electrophilic site and regioselectivity from the literature.
Scheme 9. Ring opening under Lewis acid catalysis.
that a diastereo-controlled access to a derivative of 15
would provide an enantioselective access to t-butanesul-
finamide 1, we tried to apply these very mild ring opening
reaction conditions in the presence of a chiral alcohol such
as 1-phenyl ethanol. Unfortunately, we could not expand
the scope of this reaction to this bulkier alcohol, no
reaction being observed even in the presence of a heavier
load of catalyst. We therefore investigated the addition of
amines and alkoxides to t-butanesufinyl phthalimide 6.
in THF has also been carried out. Yields were in these cases
significantly lower (52% and 43% for 18 and 19, respec-
tively), and again we could not perform the separation of
the two diastereoisomers.
This diastereoselective approach has not allowed the
desired straightforward access to optically pure t-butane-
sulfinamide. Nevertheless, original t-butanesulfamides
have been accessed in a highly efficient fashion. They
represent an original class of compounds and those (16 and
17) incorporating two H-bond donors might find applica-
tions in organocatalysis considering that the linker
between these H-donors can be somehow modulated.
We are currently trying to take advantage of this easy, cost
efficient and scaled-up method, we have described here to
generate a range of potential organocatalysts based on
these original structures.
In order to favour
p-interactions that could ease the
separation of the diastereoisomers, we engaged chiral
amines bearing a pendent aromatic ring in these reactions
and found that addition of one equivalent of (R)-1-
phenylethylamine or (S)-1-naphthylethylamine in dichlor-
omethane allows the isolation of the desired ring-opened
products 16 and 17 in 91% and 87% yields, respectively
(Scheme 10). Unfortunately, although these compounds
are easily and efficiently accessed, none of the techniques
investigated allowed the separation of the two diastereoi-
somers. The addition of the sodium salts of chiral alcohols,
1. Experimental details
All the reactions requiring anhydrous conditions were
conducted in oven-dried apparatus under an atmosphere
such as (S)-1-phenylethanol or the diacetonide-D-glucose

A. Honraedt et al. / C. R. Chimie 16 (2013) 350–357
355
Scheme 10. Ring opening of 6 by a range of chiral nucleophiles.
of argon. Syringes and needles for the transfer of reagents
were dried at 110 8C and allowed to cool in a desiccator
over P2O5 before use. CH2Cl2, pentane, heptane were
distilled from CaH2 under argon. External reaction
temperatures are reported unless stated otherwise. The
reactions were monitored by TLC using commercially
available glass-backed plates, pre-coated with a 0.25 mm
layer of silica containing a fluorescent indicator. Flash
chromatography was carried out on Interchim Puriflash
solution of 26.48 g (0.18 mol) of phthalimide and 33.5 mL
(0.24 mol) of triethylamine in 30 mL of DMF. After 1 h,
300 mL of water are added to the reaction mixture, yielding
a white precipitate. After filtration and recrystallization
from hot absolute ethanol, the title compound is obtained
as a white powder (32.07 g, 76%).
1H-NMR (CDCl3, 400 MHz): 7.97 (m, 2H), 7.81 (m, 2H),
1.39 (s, 9H). 13C-NMR (CDCl3, 100 MHz): 169.1, 134.6,
132.0, 124.0, 51.1, 29.4. MS (DCI, NH3): 253 (MNH4+). IR
(ATR, cmÀ1): 3092, 3065, 2975, 2963, 1743, 1347, 1275,
1154, 1039, 867, 796, 717, 687. HRMS (DCI, CH4):
calculated for C12H13NO2S: 236.0745, found: 236.0748.
MP: 131–132 8C (lit. 130–131 8C).
430 using Interchim prepacked column (30
m
). 1H- and
13C-NMR spectra were recorded with a Bruker AV 300 or a
Bruker AV 400 spectrometer. Chemical shifts are reported
relative to tetramethylsilane. Coupling constants (J) are
given in Hz.
1.2. t-Butane thiosulfenylphthalimide 12
1.1. t-Butane sulfenylphthalimide 9
To a solution of di-t-butyl disulfide (17.84 g, 0.1 mol) in
200 mL of heptane at –20 8C are added 9 ml (0.11 mol) of
sulfuryl chloride. After 3 h, the reaction mixture is added
to a strongly stirred solution of 26.48 g (0.18 mol) of
phthalimide and 33.5 mL (0.24 mol) of triethylamine in
30 mL of DMF at 20 8C. After 1 h, 600 mL of cold water are
added and the resulting solid is filtrated, washed with
To a solution of di-t-butyl disulfide (17.84 g, 0.1 mol) in
200 mL of pentane at 30 8C are added dropwise 9 ml
(0.11 mol) of sulfuryl chloride to maintain the internal
temperature of the reaction medium above 28 8C. Once the
addition is completed, the reaction mixture is stirred at
30 8C for 3 h, and then slowly added to a strongly stirred

356
A. Honraedt et al. / C. R. Chimie 16 (2013) 350–357
50 mL of water and 50 mL of pentane. Crystallisation from
cold absolute ethanol yields to 14.5 g (54%) of the title
compound.
1H-NMR (CDCl3, 400 MHz): 7.94 (m, 2H), 7.82 (m, 2H),
1.43 (s, 9H). 13C-NMR (CDCl3, 100 MHz): 167.6, 134.7,
132.2, 124.0, 49.3, 29.9. MS (DCI, NH3): 285 (MNH4+). IR
(ATR, cmÀ1): 2958, 1778, 1724, 1699, 1466, 1457, 1363,
1342, 1251, 1163, 1050, 864, 792, 710. MP: 103–104 8C.
(m, 2H), 5.28–5.23 (m, 2H), 1.61–1.58 (m, 6H), 1.30 (s, 9H),
1.24 (s, 9H). 13C-NMR (CD2Cl2, 100,6 MHz): 143.0, 142.8,
134.9, 134.8, 132.8, 131.5, 130.7, 130.5, 130.4, 128.7, 127,9,
127,8, 127,5, 127,4, 126,2, 126,1, 56,4, 56,3, 50,1, 49,8, 22,0,
21,9, 21,5. MS (DCI): 373,0 (MH+), 390,0 (MNH4+). HRMS
(DCI): calculated for C20H24N2O3S: 373,1586, found:
373,1598. IR (cmÀ1): 3253, 3063, 2974, 1632, 1536, 1447,
1415, 1064, 868, 763, 697.
1.3. t-Butane sulfinylphthalimide 6
1.5.2. 2-(2-(N-t-butane sulfinyl)-N-acetyl)-N-((S)-1-
naphtylethyl) benzamide 17
To a solution of 32.07 g (136.3 mmol) of t-butane
thiophthalimide in 320 mL of dichloromethane at 0 8C is
added dropwise a 35% solution of peracetic acid (29.62 g,
136.6 mmol) in acetic acid. After 18 h of strong stirring,
100 mL of a 5% solution of sodium thiosulfate are added to
the reaction mixture. The organic phase is then washed
two times with 100 mL of a 5% solution of sodium
thiosulfate, dried over sodium sulphate and evaporated
under reduced pressure to yield 33.86 g (93%) of the title
compound as a white solid.
1H-NMR (CDCl3, 400 MHz): 7.92 (m, 2H), 7.82 (m, 2H),
1.48 (s, 9H). 13C-NMR (CDCl3, 100 MHz): 166.6, 135.0,
132.1, 124.1, 61.3, 23.5. MS (DCI, NH3): 269 (MNH4+). IR
(ATR, cmÀ1): 3088, 3027, 2979, 1725, 1460, 1365, 1261,
1117, 1040, 864, 796, 718. HRMS (DCI, CH4): calculated for
C12H13NO3S: 252.0694, found: 252.0694. MP: 136–137 8C
(lit. 133–136 8C).
The title product is a white solid isolated as a mixture of
the two diastereoisomers (1.85 g, 87%).
1H-NMR (CDCl3, 400 MHz): 8.17 (dd, 2 Â 1H J = 8.4 Hz,
J = 3.6 Hz), 7.93–7.83 (m, 2 Â 3H), 7.71–7.42 (m, 2 Â 6H),
7.35 (d, 2 Â 1H, J = 7.2 Hz), 6.74 (d, J = 8.2 Hz), 6.62 (d,
2 Â 1H, J = 8.2 Hz), 6.14–6.06 (m, 2 Â 1H), 1.80 (d,
2 Â 3H, J = 6.8 Hz), 1.39 (s, 9H), 1.26 (s, 9H). 13C-NMR
(CDCl3, 100,6 MHz): 137.6, 137.0, 134.7, 134.6, 134.0,
133.9, 132.4, 132.0, 131.7, 131.6, 131.1, 130.9, 130.6, 129.0,
128.9, 128.8, 128.6, 127.8, 127.6, 127.3, 126.7, 126.2, 126.0,
125.4, 125.2, 123.2, 123.0, 122.9, 122.8, 56.8, 56.6, 46.0,
45.8, 22.3, 22.2, 20.8, 20.3. MS (DCI): 423.1 (MH+), 440.1
(MNH4+). HRMS (DCI): calculated for C24H26N2O3S:
423.1742, found: 423.1729. IR (cmÀ1 Hz): 3275, 2974,
1660, 1623, 1545, 1463, 1057, 800, 780.
1.6. Addition of chiral alcohols to t-butane
sulfinylphthalimide, general procedure
1.4. 2-(t-butane sulfinylcarbamoyl) ethylbenzoate 15
To a solution of chiral alcohol in 15 volumes of distilled
THF is slowly added sodium hydride (1.5 equiv of 60%
suspension in mineral oil). After 1.5 h, t-butane sulfi-
nylphthalimide (1 equiv) is added and stirring is then
prolonged for 1 h. Thirty volumes of a saturated ammo-
nium chloride solution are added dropwise. The aqueous is
extracted three times with dichloromethane; the organic
phases are washed with brine, dried over sodium sulphate,
filtrated, and concentrated under vacuum. The residue is
purified by flash chromatography (gradient elution of
cyclohexane/diethyl ether: 50/50 to 0/100 Hz).
To
a suspension of t-butane sulfinylphthalimide
(100 mg, 0.4 mmol) in absolute ethanol is added 23.8 mg
of samarium (III) triflate (0.04 mmol). Once the solution
becomes homogeneous (0.5 h), the solvent is removed
under vacuum, the solid is dissolved in 20 mL of dichlor-
omethane, washed with water and brine (2 Â 10 mL), dried
over sodium sulphate and concentrated under vacuum to
yield the title compound (118.1 mg, 100%) as a white solid.
1H-NMR (CDCl3, 400 MHz): 8.05–7.97 (m, 1H), 7.55–
7.61 (m, 4H), 4.40 (q, 2H, J = 7.2), 1.40 (t, 3H, J = 7.2), 1.33 (s,
9H). 13C-NMR (CD2Cl3, 100 MHz): 173.9, 166.3, 136.1, 132.2,
130.6, 130.0, 129.1, 127.5, 62.1, 58.1, 22.1, 14.1. MS (DCI,
NH3): 315 (MNH4+). IR (ATR, cmÀ1): 3068, 2971, 1710, 1688,
1428, 1278, 1247, 1062, 885, 805, 703. MP: 129–131 8C.
1.6.1. (S)-methylbenzyl 2-(t-butane sulfinylcarbamoyl)-1-
benzoate 18
The title product is a white solid isolated as a mixture of
the two diastereoisomers (0.97 g, 52%).
1.5. Addition of chiral amines to t-butane
sulfinylphthalimide, general procedure
1H-NMR (CD2Cl2, 400 MHz): 8.03 (d, 2 Â 1H, J = 7.2 Hz),
7.67–7.32 (m, 2 Â 8H), 6.10 (q, 2 Â 1H, J = 6.6 Hz), 1.70 (d,
2 Â 3H, J = 6.6 Hz), 1.26 (s, 2 Â 9H). 13C-NMR(CD2Cl2,
100,6 MHz): 141.5, 141.4, 136.4, 136.3, 132.4, 132.4,
130.3, 128.5, 128.4, 128.0, 127.9, 127.8, 126.2, 126.1,
125.8, 74.2, 57.1, 22.0, 21.9, 21.8. MS (DCI): 374 (MH+), 391
(MNH4+). IR (cmÀ1 Hz): 3067, 2978, 1717, 1687, 1416,
1265, 1057, 760, 736, 697.
To a solution of t-butane sulfinylphthalimide in 15
volumes of dichloromethane is added one equivalent of the
chiral amine. The solution is heated under reflux for 16 h,
concentrated to dryness and purified by flash chromato-
graphy (eluent DCM/i-PrOH: 95/5).
1.5.1. 2-(2-(N-t-butane sulfinyl)N-acetyl)-N-((R)-1-
phenylethyl)benzamide 16
1.6.2. Diacetone-D-glucose 2-(t-butane sulfinylcarbamoyl)-
1-benzoate 19
The title product is a white solid isolated as a mixture of
the two diastereoisomers (1.74 g, 91%).
1H-NMR (CD2Cl2, 400 MHz): 7.92–7.76 (m, 2H), 7.54–
7.50 (m, 6H), 7.45–7.39 (m, 8H), 7.35–7.31 (m, 2H), 7.14–6.89
The title product is a white solid isolated as a mixture of
the two diastereoisomers (0.67 g, 43%).
1H-NMR (CD2Cl2, 400 MHz): 7.92–7.83 (m, 2 Â 1H),
6.78–6.57 (m, 3 Â 2H), 6.01 (d, 1H, J = 3.6 Hz), 5.98 (d, 1H,

A. Honraedt et al. / C. R. Chimie 16 (2013) 350–357
357
References
J = 3.6 Hz), 5.42–5.41 (m, 2 Â 1H), 4.75 (d, 1H, J = 3.6 Hz),
4.72 (d, 1H J = 3.6 Hz), 4.36–4.27 (m, 2 Â 2H), 4.14–4.01 (m,
2 Â 2H), 1.55 (s, 2 Â 3H), 1,42 (s, 2 Â 3H), 1.35 (s, 2 Â 3H),
1,31 (s, 2 Â 3H), 1.29 (s, 2 Â 9H). 13C-NMR (CD2Cl2,
100,6 MHz): 136.3, 136.2, 135.0, 132.6, 132.4, 132.1,
130.6, 130.5, 130.0, 128.0, 127.9, 123.9, 112.2, 112.1,
109.3, 109.2, 105.4, 105.3, 83.1, 82.9, 79.7, 79.6, 77.6, 77.5,
72.6, 72.5, 67.1, 67.0, 57.6, 57.4, 26.6, 26.5, 26.4, 26.0, 23.0,
22.0, 21.9. MS (DCI): 529 (MNH4+). HRMS (DCI): calculated
for C24H33NO9S: 512,1954, found: 519,1977. IR (cmÀ1 Hz):
2986, 1729, 1689, 1371, 1260, 1064, 1017, 843, 736, 705.
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Acknowledgements
The authors are very much thankful to Minakem
´
´ ´
holding (A.H. & G.C.), to the Conseil regional Midi-Pyrenees
(G.C.) for PhD fundings, to Minakem for generous sponsor-
ship and to the CNRS and the University of Toulouse for
their support.