Regioselective N-vinylation of cyclic thionocarbamates through a vinyl bis-sulfone methodology

Article abstract of DOI:10.1016/j.tetlet.2004.06.124

A vinyl bis-sulfone Michael type approach towards heteroatom vinylation was applied on nitrogen derivatives. Cyclic thionocarbamates - mainly 1,3-oxazolidine-2-thiones- were converted into their N-vinyl counterparts; the procedure proved particularly efficient in the case of carbohydrate-derived complex structures.

Full text of DOI:10.1016/j.tetlet.2004.06.124

Tetrahedron
Letters
Tetrahedron Letters 45 (2004) 6443–6446
Regioselective N-vinylation of cyclic thionocarbamates
through a vinyl bis-sulfone methodology
a
a,
b
Jolanta Girniene,a,b Sebastien Tardy, Arnaud Tatiboue¨t, Algirdas Sackus and
*
´
ˇ
Patrick Rollina,
*
a
´
´
´
ICOA––UMR 6005, Universite d’Orleans, BP 6759, F-45067 Orleans, France
bDepartment of OrganicChemistry, Kaunas University of Technology, LT-3028 Kaunas, Lithuania
Received 10 June 2004; revised 28 June 2004; accepted 29 June 2004
Available online 20 July 2004
Abstract—A vinyl bis-sulfone Michael type approach towards heteroatom vinylation was applied on nitrogen derivatives. Cyclic
thionocarbamates––mainly 1,3-oxazolidine-2-thiones––were converted into their N-vinyl counterparts; the procedure proved partic-
ularly efficient in the case of carbohydrate-derived complex structures.
Ó 2004 Published by Elsevier Ltd.
1,2-Bis-(phenylsulfonyl)ethylidene (BPSE) is recognized
as a useful reagent in organic synthesis, in particular
for cycloadditions1 or Michael type reactions.2 In recent
years, our group has developed a broad study of BPSE
and its application in carbohydrate chemistry.3 A dou-
ble Michael addition on BPSE involving a carbohydrate
partner led to the formation of a phenylsulfonylethylid-
ene (PSE) acetal, a new protective device in carbohy-
drate chemistry,4 with promising properties owing
especially to its remarkable resistance against acidic
media. Further studies were centered on the selective
opening of PSE acetals under reductive desulfonylation
conditions, to produce vinyl ethers.5 A parallel study on
selective mono-Michael additions on BPSE of both hydr-
oxyl and thiol groups was also performed with the aim
of producing––after reductive desulfonylation––vinyl
ethers and vinyl sulfides connected to mono-saccharide
templates (Scheme 1).6
OH
OH
PhSO2
PhSO2
PhSO2
O
O
(BPSE)
ROH
PhSO2
RO
RO
Scheme 1. Vinyl ether formation starting with BPSE.
been occasionally synthesized on complex templates
and mostly applied in biopolymer development.8 Simple
N-vinylated derivatives have been prepared following
various pathways through elimination processes,9 cata-
lytic transetherification,10 acetylene addition,11 Curtius
rearrangement,12 enamine acylation,13 copper- or palla-
dium-mediated vinyl transfer.14 The Peterson-type
In asymmetric synthesis, vinyl ethers are useful synthons
for the development of stereoselective cycloadditions.7
Our two-step process is both efficient and smooth
enough to be applied to complex structures like saccha-
ridic compounds. In contrast with O-vinyl derivatives,
N-vinyl amide- or carbamate-type structures have only
approach to enamides developed by Furstner et al.15 is
¨
also worth mentioning. Developing a convenient new
methodology to introduce a vinyl group on nitrogen is
nevertheless attractive with respect to enamine chemi-
stry and its chiral applications. This preliminary report
delivers preliminary results about the extension of our
vinyl bis-sulfone methodology to the synthesis of N-vinyl-
ated cyclic thionocarbamates.
Keywords: Oxazolidinethione; Oxazinethione; Carbohydrate; BPSE;
N-Vinylation.
*
Corresponding authors. Tel.: +33-(0)-2-38494854; fax: +33-(0)-
238417281; e-mail: arnaud.tatibouet@univ-orleans.fr
0040-4039/$ - see front matter Ó 2004 Published by Elsevier Ltd.
doi:10.1016/j.tetlet.2004.06.124

6444
J. Girniene et al. / Tetrahedron Letters 45 (2004) 6443–6446
A number of naturally-occurring 1,3-oxazolidine-2-thi-
ones (OZT) originate from important vegetable metabo-
lites known as glucosinolates;16 various aspects of the
chemical behaviour of such OZT have been previously
investigated in our group.17 In other respects, carbohy-
drate-based OZT are readily obtainable through con-
densation of thiocyanic acid with free sugars: such
more complex chiral OZT have proven useful in elabo-
rating a range of biologically relevant molecules.18
1,3-oxazine-2-thione19 3 and finally sugar-derived thio-
nocarbamates 4–8 (Table 1).18b,21
Condensation of Michael acceptors on a five-membered
ring lactam has previously been attempted by Knapp
and Levorse,22 using sodium hydride as a base. Unfortu-
nately, in our case those conditions proved unsuccessful.
Screening miscellaneous basic reagents––triethylamine,
pyridine, diisopropylethylamine (DIEA), DBU––all-
owed us to establish optimized conditions for condens-
ing BPSE on the cyclic thionocarbamates 1–8: a
combination of DIEA and the phase transfer agent
Bu4NBr in DMF afforded 70–90% yields of the N-phen-
ylsulfonylvinyl derivatives 9–16, respectively (Table 1).23
Our vinylation process was tested on a selection of both
simple and more complex OZT (Scheme 2). The Michael
type addition on BPSE was applied to parent OZT19 1,
epi-goitrin20 2 (an enantiopure derivative), tetrahydro-
As expected from previous studies,17a N-regioselectivity
was observed, no trace of isomeric 2-phenylsulfonylvin-
ylthio-derivative A (Scheme 3) could be detected in the
reaction medium using our protocol. Furthermore, the
addition–elimination process leading to 9–16 was
stereospecific, in harmony with previous results from
our laboratory and the formerly postulated mecha-
nism.6,7 However, for compounds 7 and 8, S-phenyl-
sulfonylvinyl derivatives (A) could be detected when
reduced time conditions (1.5h) were applied. In the spe-
cific case of oxazinethione 8, a complete S-selectivity was
observed after 1.5h, producing a 75% isolated yield of
the S-vinylated isomer of 16. In contrast, applying the
general protocol23 only gave N-selectivity and com-
pound 16 was obtained in 72% yield. These results sug-
gested a Michael type addition on sulfur for the first
stage then an S to N transfer of the vinylsulfone residue
during the mechanism process (Scheme 3).
S
S
S
Na/Hg
BPSE
base
NaH2PO4
SO2Ph
O
N
O
NH
O
N
MeOH
Scheme 2. Two-step sequence to N-vinyl OZT.
Table 1. N-vinylsulfones and N-vinyl derivatives
OZT
N-phenylsulfonyl
vinyl OZT
N-vinyl OZT
S
O
9 (80%)
17 (86%)b
NH
S
1
O
NH
10 (93%)
18 (75%)b
The previously established sodium amalgam reduction
conditions5a,6a were implemented to desulfonylate the
N-phenylsulfonylvinyl derivatives in order to produce
the corresponding N-vinylated compounds. When
applied to the simplest structures 9–11, reduction at
room temperature failed to deliver the expected N-vinyl
derivatives. However by lowering the temperature, the
N-vinyl OZT 17 was obtained in good yield whereas
precursor 11 mainly returned oxazinethione 3 together
with a disappointing 13% yield of N-vinyl oxazinethione
19.
2
S
O
NH
11 (91%)
12 (91%)
13 (70%)
14 (72%)
19 (13%)b
20 (76%)a
21 (98%)a
22 (96%)a
3
O
H
N
TBDMSO
S
O
TBDMSO
4
OBn
O
O
H
N
TBDMSO
TBDMSO
S
O
Extension of the reduction procedure24 to heavier carbo-
hydrate-based structures 12–15 produced the corre-
sponding N-vinylated OZT 20–23 in 64–98% yields
(Table 1); in the case of oxazinethione 16, degradation
was mostly observed in the course of the reductive proc-
ess. This final result points out the patent unstability of
N-vinyl oxazinethiones 19 and 24 as compared with
N-vinyl OZT 20–22, for which no degradation was
observed even at room temperature.
5
OBn
H
N
TBDMSO
S
O
TBDMSO
6
H
N
S
S
O
23 (64%)b
O
O
15 (98%)
16 (72%)
O
BnO
7
H
N
O
S to N
S
S
O
O
N
BPSE
base
24b
BnO
migration
BnO
SO2Ph
S
O
O
NH
O
N
8
SO2Ph
A
a Reaction performed at rt.
b Reaction performed at ꢀ30 °C for less than 1h.
Scheme 3. Tentative mechanism.

J. Girniene et al. / Tetrahedron Letters 45 (2004) 6443–6446
6445
Rollin, S.; Palmieri, S. Tetrahedron: Asymmetry 1999,
10, 4775–4780, and references cited therein.
17. (a) Gueyrard, D.; Grumel, V.; Leoni, O.; Palmieri, S.;
Rollin, P. Heterocycles 2000, 52, 827–843; (b) Gueyrard,
D.; Leoni, O.; Palmieri, S.; Rollin, P. Tetrahedron:
Asymmetry 2001, 12, 337–340.
18. (a) Girniene, J.; Gueyrard, D.; Tatiboue¨t, A.; Sackus, A.;
Rollin, P. Tetrahedron Lett. 2001, 42, 2977–2980; (b)
Girniene, J.; Tatiboue¨t, A.; Sackus, A.; Yang, J.; Holman,
G. D.; Rollin, P. Carbohydr. Res. 2003, 338, 711–719.
In summary, we have disclosed a simple, smooth and
effective two-step sequence based on our vinyl bis-sulf-
one methodology to produce N-vinylated OZT: (i) regio-
selective Michael-type N-phenylsulfonylvinylation; (ii)
chemoselective reduction. The enantiopure substrates
of type 18 and 20–23 are currently tested in stereoselec-
tion transfer through cycloaddition processes and palla-
dium-catalyzed reactions.
19. Fulo¨p, F.; Csirinyi, G.; Bernath, G. Synthesis 1985,
¨
1149–1151.
Acknowledgements
20. Leoni, O.; Marot, C.; Rollin, P.; Palmieri, S. Tetrahedron:
Asymmetry 1994, 5, 1157–1160.
The authors wish to thank EGIDE for a fellowship
(J.G.), Elena Cabianca for technical skill and Prof. O.
21. Girniene, J.; Apremont, G.; Tatiboue¨t, A.; Sackus, A.;
Rollin, P. Tetrahedron 2004, 60, 2609–2619.
`
De Lucchi (Universita CaÕ Foscari di Venezia) for fruit-
ful discussions.
22. Knapp, S.; Levorse, A. T. J. Org. Chem. 1988, 53,
4006–4014.
23. General protocol for the Michael addition: a 0.2M DMF
solution of the thionocarbamate (1equiv) was prepared
under Ar in anhydrous conditions. After cooling at 0°C,
DIEA (2equiv) then E-BPSE (1equiv) were added
together with 0.1equiv of Bu4NBr. After a slow return
to room temperature and overnight stirring, the solution
was extracted with CH2Cl2, washed with water, dried over
MgSO4. Removing the solvent and chromatography of the
residue afforded the desired E-compound. Fully satisfac-
tory spectroscopic data were obtained for all new com-
pounds. Selected data for compound 9: mp=57–59 °C; 1H
NMR (250MHz, CDCl3): d (ppm) 3.84–4.00 (m, 2H, H-4a
and -4b); 4.62–4.77 (m, 2H, H-5a and -5b); 5.95 (d, 1H,
Jvic =13.5Hz, H-20); 7.47–7.65 (m, 3H, meta, para-H–
PhSO2); 7.80–7.95 (m, 2H, ortho-H–PhSO2); 8.35 (d, 1H,
H-10). 13C NMR (62.89MHz, CDCl3): d (ppm) 45.6 (C-4);
References and notes
1. (a) De Lucchi, O.; Lucchini, V.; Pasquato, L.; Modena, G.
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Lucchi, O.Paquette, L. A., Ed.; Encyclopedia of Reagents
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1, pp 547.
2. (a) Cossu, S.; De Lucchi, O.; Pasetto, P. Angew. Chem.,
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dron Lett. 2000, 41, 2357–2360.
4. Chery, F.; Rollin, P.; De Lucchi, O.; Cossu, S. Synthesis,
2001, 286–292, and references cited therein.
´
´
0
*
67.9 (C-5); 113.1 (C-2 ); 127.2 (2 CH–ortho-PhSO2); 129.4
*
(2 CH–meta-PhSO2); 133.4 (CH–para-PhSO2); 136.7 (C-
´
5. (a) Cabianca, E.; Chery, F.; Rollin, P.; Cossu, S.; De
Lucchi, O. Synlett 2001, 1962–1964; (b) Cabianca, E.;
10); 141.1 (CIV–PhSO2); 187.0 (C@S). MS (IonsprayÒ) m/z:
270 (M+H)+; 292 (M+Na)+. Selected data for compound
13: [a]D ꢀ88 (c 1.02, CHCl3). 1H NMR (250MHz,
CDCl3): d (ppm) ꢀ0.12, ꢀ0.07, 0.07, 0.11 (4s, 12H,
CH3Si); 0.78, 0.85 (2s, 18H, (CH3)3C); 3.37 (dd, 1H,
J6b,5 =6.6Hz, Jgem =11.0Hz, H-6b); 3.47 (dd, 1H,
J6a,5 =4.4Hz, H-6a); 3.53 (d, 1H, Jgem =11.0Hz, H-1b);
3.88 (d, 1H, H-1a); 3.99–4.06 (m, 1H, H-5); 4.38 (d, 1H,
Jgem =12.3Hz, CH2–Ph); 4.46 (dd, 1H, J4,3 =1.9Hz, H-4);
4.49 (d, 1H, CH2–Ph); 4.86 (d, 1H, H-3); 6.70 (d, 1H,
Jvic =14.1Hz, H-20); 7.15–7.24 (m, 2H, H–Ar); 7.28–7.38
(m, 3H, H–Ar); 7.46–7.65 (m, 3H, meta, para-H–PhSO2);
´
Chery, F.; Rollin, P.; Tatiboue¨t, A.; De Lucchi, O.
Tetrahedron Lett. 2002, 43, 585–587.
´
6. (a) Chery, F.; Desroses, M.; Tatiboue¨t, A.; De Lucchi, O.;
Rollin, P. Tetrahedron 2003, 59, 4563–4572; (b) Cabianca,
´
E.; Tatiboue¨t, A.; Chery, F.; Pillard, C.; De Lucchi, O.;
Rollin, P. Tetrahedron Lett. 2003, 44, 5723–5725.
´
7. Desroses, M.; Chery, F.; Tatiboue¨t, A.; De Lucchi, O.;
Rollin, P. Tetrahedron: Asymmetry 2002, 13, 2535–2539.
8. (a) He, W.; Gonsalves, K. E.; Pickett, J. H.; Halberstadt,
C. Biomacromolecules 2003, 4, 75–79; (b) Theodoridis, G.
Tetrahedron Lett. 1998, 39, 9365–9368; (c) Ciapetti, P.;
Taddei, M. Tetrahedron 1998, 54, 11305–11310; (d) Abele,
E.; Dzenitis, O.; Rubina, K.; Lukevics, E. Chem. Hetero-
cycl. Compd. 2002, 38, 682–685; (e) Bogdal, D.; Jaskot, K.
Synth. Commun. 2000, 30, 3341–3352.
9. (a) Ishibashi, H.; Kato, I.; Takeda, Y.; Kogure, M.;
Tamura, O. Chem. Commun. 2000, 1527–1528; (b) Gau-
lon, C.; Dhal, R.; Dujardin, G. Synthesis 2003, 2269–2272.
10. Dalpozzo, R.; De Nino, A.; Maiuolo, L.; Procopio, A.;
Romeo, R.; Sindona, G. Synthesis 2002, 172–174.
7.86–7.92(m, 2H, ortho-H–PhSO2); 8.02(d, 1H, H-1 ). 13C
0
NMR (62.89MHz, CDCl3) d: (ppm) ꢀ5.5, ꢀ5.4, ꢀ4.9,
ꢀ4.8 (CH3Si); 17.9, 18.2(( CH3)3C); 25.7, 25.8 ((CH3)3C);
61.0 (C-6); 66.6 (C-1); 73.7 (CH2–Ph); 76.1 (C-4); 88.8 (C-
5); 91.7 (C-3); 100.8 (C-2); 116.2 (C-20); 127.5, 127.7,
*
128.4, 128.8 (CH–Ar); 129.4 (2 CH–meta-PhSO2); 133.4
(C-10); 136.6 (CIV–Ar);141.4 (CIV–PhSO2); 185.4 (C@S).
MS (IonsprayÒ) m/z 706.5 (M+H)+. IR (NaCl) m 1748
(C@S), 1625 (C@C), 1384, 1145 (SO2) cmꢀ1
.
24. General protocol for reductive desulfonylation. The N-
vinylsulfone (1equiv) was dissolved in THF–MeOH (1:1
v/v). NaH2PO4 (25equiv) and Na/Hg 5% (25equiv) were
added and the solution stirred at room temperature until
completion of the reaction. The heterogeneous solution
was filtered, extracted with CH2Cl2, washed with water,
dried over K2CO3; removing the solvent in vacuo afforded
the N-vinyl derivative, which was pure enough for further
uses. Selected data for compound 21: [a]D ꢀ97 (c 1.0,
11. Reppe, W. Liebigs Ann. Chem. 1956, 601, 81–104.
12. Govindan, C. K. Org. Process Res. Dev. 2002, 6, 74–77.
13. Garcia, A.; Rodriguez, D.; Castedo, L.; Saa, C.; Domin-
guez, D. Tetrahedron Lett. 2001, 42, 1903–1905.
14. (a) Shen, R.; Porco, J. A., Jr. Org. Lett. 2000, 2,
1333–1336; (b) Brice, J. L.; Meerdink, J. E.; Stahl, S. S.
Org. Lett. 2004, 6, 1845–1848.
15. Furstner, A.; Brehm, C.; Cancho-Grande, Y. Org. Lett.
¨
2001, 3, 3955–3957.
1
CHCl3). H NMR (250MHz, CDCl3): d (ppm) 0.03, 0.10,
16. See for example: (a) Daubos, P.; Grumel, V.; Iori, R.;
Leoni, O.; Palmieri, S.; Rollin, P. Ind. Crops Prod. 1998, 7,
187–193; (b) Leoni, O.; Bernardi, R.; Gueyrard, D.;
0.12(3s, 12H, CH 3Si); 0.86, 0.87 (2s, 18H, (CH3)3C); 3.40
(dd, 1H, J6b,5 =8.2Hz, Jgem =10.7Hz, H-6b); 3.51–3.60 (m,

6446
J. Girniene et al. / Tetrahedron Letters 45 (2004) 6443–6446
1H, H-6a); 3.55 (d, 1H, Jgem =10.4Hz, H-1b); 3.98–4.10
(m, 2H, H-1a, H-5); 4.43–4.62 (m, 3H, CH2–Ph, H-4); 4.78
15.9, 16.3 ((CH3)3C); 23.7, 23.9 ((CH3)3 C); 59.5 (C-6);
64.5 (C-1); 71.5 (CH2–Ph); 74.4 (C-4); 86.9 (C-5); 89.0 (C-
3); 99.9 (C-2); 101.4 (C-20); 125.9, 126.1, 126.8 (CH–Ar);
127.5 (C-10); 135.1 (CIV–Ar); 183.8 (C@S). MS (Ion-
sprayÒ) m/z: 566,0 (M+H)+; 588,0 (M+Na)+. IR (NaCl):
0
0
0
0
0
(dd, 1H, J2 Z, 2 E =0.9Hz, J2 Z,1 =9.4Hz, H-2 ); 4.84–4.88
=16.3Hz, H-20); 6.86
20E,10
(m, 1H, H-3); 5.20 (dd, 1H, J
(dd, 1H, H-10); 7.22–7.41 (m, 5H, H–Ar). 13C NMR (62.89
MHz, CDCl3): d (ppm) ꢀ7.3, ꢀ7.2, ꢀ6.8, ꢀ6.7 (CH3Si);
1642(C @C), 1748 (C@S), 2949 (@CH2) cmꢀ1
.