N-vinyl-1,3-oxazolidine-2-thiones as dienophiles in inverse hetero-Diels-Alder reactions: New prospects for asymmetric induction

Article abstract of DOI:10.1055/s-2006-939722

Several N-vinyl-1,3-oxazolidine-2-thione (N-vinyl OZT) were conveniently used as new dienophiles in Eu(fod)₃-catalyzed reverse hetero-Diels-Alder reactions involving benzylidene pyruvic acid methyl ester. Simple chiral N-vinyl OZT analogues hom

Full text of DOI:10.1055/s-2006-939722

LETTER
1425
N-Vinyl-1,3-oxazolidine-2-thiones as Dienophiles in Inverse Hetero-
Diels–Alder Reactions: New Prospects for Asymmetric Induction
D
ienophiles in
é
Inverse
H
e
b
tero-Diels–A
a
lde
r
React
s
ions tien Tardy,a Arnaud Tatibouët,*a Patrick Rollin,a Gilles Dujardinb
ICOA UMR 6005 CNRS, Université d’Orléans, 45067 Orléans, France
Fax +33(2)38417281; E-mail: arnaud.tatibouet@univ-orleans.frUCO2M UMR 6011 CNRS, Université du Maine, 72085 Le Mans, France
Received 5 January 2006
With a view to exploring the potential of these N-vinyl
Abstract: Several N-vinyl-1,3-oxazolidine-2-thione (N-vinyl OZT)
cyclic thionocarbamates, we first selected the achiral
were conveniently used as new dienophiles in Eu(fod)3-catalyzed
reverse hetero-Diels–Alder reactions involving benzylidene pyru-
vic acid methyl ester. Simple chiral N-vinyl OZT analogues homo-
parent OZT 4a (R1 = R2 = H)7 together with representa-
tive chiral substituted OZTs 4b–h. These chiral N-vinyl
geneously led to moderate endo and facial diastereoselectivities, OZTs were efficiently prepared in 44–74% yields accord-
when compared to those obtained with the corresponding N-vinyl-
ing to the recently described two-step Michael addition–
reductive elimination sequence (Scheme 1, Table 1).6
1,3-oxazolidin-2-ones. In contrast, high diastereocontrols were
observed with a sugar-derived N-vinyl OZT.
Key words: oxazolidinethiones, hetero-Diels–Alder, enamide
SO2Ph
S
S
PhO2S
S
Na/Hg
PhSO2
NaH2PO4
BPSE
base
HN
R3
N
O
O
N
O
MeOH
N-Vinyloxazolidinones 1 were recently described as new
promising chiral dienophiles in inverse hetero-Diels–
Alder reactions towards activated 1-oxabutadienes, lead-
ing with high diastereocontrol to heteroadducts 2 under
Eu(fod)3-catalyzed conditions.1 An efficient route to
enantiopure N-(2-deoxyglycosyl)oxazolidinones 3 result-
ed from this approach. Compounds 3 appeared as the first
representatives of a new class of de novo synthesized 2-
deoxy N-glycosides bearing an amino acid derivative as
the aglycon. However, hydrolytic or reductive removal of
the carbamate moiety in 3 proved to be troublesome.2 For
that reason, we considered that extending the scope of the
hetero-Diels–Alder reactions to other relevant enamides
such as N-vinyl-1,3-oxazolidine-2-thiones (N-vinyl OZT)
4 would be of much interest.3 OZT heterocycles are useful
synthons that can be specifically functionalized4 and
moreover, they are emerging as new chiral auxiliaries
with high potential in chirality transfer.5 Our laboratory
has developed an efficient process based on a two-step se-
quence using the BPSE [1,2-bis(phenylsulfonyl)ethylene]
methodology, which has shown a great efficiency on sim-
ple, chiral and carbohydrate-derived OZTs (Figure 1).6,7
R3
R3
R2
R1
R2
R1
R1
R2
Scheme 1
Table 1 Preparation of Chiral N-Vinyl OZTs 4b–e
N-Vinyl OZT
R1
R2
R3
Overall yield
(%)a
4b (4R)
4c (4S)
4d (4R)
4e (4S)
4f (4R)
4g (4S,5R)
4h
Et
H
H
H
H
H
Ph
H
H
64
74
65
51
44
69
64
Bn
Bn
Ph
Ph
Me
Me
H
H
H
H
H
Me
a After purification over silica gel.
Compounds 4 were reacted with benzylidenepyruvic acid
methyl ester 5 (Scheme 2). Under the standard conditions
previously used with N-vinyloxazolidinone 1 [refluxing
cyclohexane, catalyst: 5 mol% Eu(fod)3],8 N-vinyl OZT
4a was smoothly converted in 56% yield into the hetero-
adduct 6a with a moderate endo-selectivity (entry 1).
Under similar conditions, the chiral N-vinyl OZTs 4b–h
exhibited a fair reactivity, giving rise to adducts 6b–h in
consistently good yields (75–87%, entries 2–7). Steric
hindrance encountered in 4g (entry 8) caused a consider-
able lowering of the yield but without interfering much in
the stereochemical outcome.
Ot-Bu
R
X
O
O
HO
HO
N
O
N
N
O
O
MeO
O
O
R2
R1
O
R2
R2
R1
R1
1: X = O
4: X = S
2
3
Figure 1
The observed stereoselectivities with these new chiral
dienophiles proved not to be higher than those observed in
oxazolidinone series. After careful identification of cis-
SYNLETT 2006, No. 9, pp 1425–1427
Advanced online publication: 22.05.2006
DOI: 10.1055/s-2006-939722; Art ID: D00206ST
© Georg Thieme Verlag Stuttgart · New York
0
1.
0
6.
2
0
0
6

1426
S. Tardy et al.
LETTER
O
R
O
O
O
S
O
O
O
O
O
N
HN
O
O
MeO
+
O
O
S
O
Ph
R3
N
S
O
O
R2
H
R1
Eu(fod)3
5 mol%
S
6a–h exo (I–II)
1) (E)-BPSE
2) Na/Hg 6%
N
O
+
77%
O
89%
MeO
R3
O
cyclohexane
reflux
R
R1
R2
O
O
O
S
O
5
4a–h
O
O
O
O
N
O
MeO
O
O
R3
O
N
S
O
S
O
R1
R2
N
6a–h endo (I–II)
7b
7a
Scheme 2
5, Eu(fod)3, 5 mol%
cyclohexane
reflux
20%
yield
60%
yield
and trans-isomers by NMR, the endo-selectivities of the
cycloadditions were evaluated to range around 4:1, and
the facial selectivity for endo-adducts did not exceed 3:1.
O
O
O
O
O
O
O
O
O
O
S
When compared to the results obtained with type-2 ad-
ducts (Figure 1, R = Ph),1 such a stereochemical outcome
seems to indicate that the nature of the cyclic moiety of the
dienophile (carbamate versus thionocarbamate) would
significantly influence both stereochemical parameters of
the hetero-cycloaddition by a favorable versus disfavor-
able interaction with the lanthanide salt in the transition
state (Table 2).
N
MeO2C
O
N
O
O
O
S
Ph
Ph
8
CO2Me
>98:2
9
endo/exo
endo I/endo II 90:10
95:5
endo/exo
endo I/endo II 77:23
Scheme 3
The vinyl bis-sulfone methodology has also proven effi-
cient for the N-vinylation of complex bicyclic thiono-
carbamates such as branched, fused and spiranic sugar-
derived OZTs.9 The chiral spiro N-vinyl OZT 7 was thus
conveniently prepared from D-glucose in its two epimeric
forms (7a,b) and tested in the cycloaddition study
(Scheme 3).
This enhanced facial diastereoselectivity compares well
with previous results observed in the use of carbohydrate-
based vinyl ethers as chiral dienophiles towards hetero-
dienes related to 5 under similar conditions.12 The effi-
cient chiral transfer in the synthesis of 8 could mainly be
attributed to the specific architecture of the 1,2:5,6-di-O-
isopropylidene-a-D-glucofuranose moiety. In these cases,
Heterocycloaddition of 7b and heterodiene 5 proceeded in the chirality is anchored on carbon 5 of the OZT while
low yields, albeit with a high endo-selectivity, whereas fa- with classical oxazolidinones, oxazolidinethiones and
cial selectivity remained moderate (77:23) in the range of thiazolidinethiones carbon 4 is the chirality center en-
previous values. On the contrary, reacting 7a with 5 gave countered. Those first results open the development of
a remarkably good yield of the desired heteroadduct 8 well-defined spiro-carbohydrate templates towards im-
with a high selectivity for the endo-diastereomer in addi- proved auxiliaries for chirality transfer.
tion to a very good (90:10) facial selectivity.10,11
Table 2 Eu(fod)3-Catalyzed Heterocycloaddition of N-Vinyl OZTs 4a–e with 5
Entry
4
R1
H
R2
H
R3
H
Time (h)
48
6
Yield (%) endo/exo
endo I/endo II exo I/exo II
1
2
3
4
5
6
7
8
4a
6a
6b
6c
6d
6e
6f
56
75
78
87
75
82
77
20
86:14
78:22
81:19
86:14
80:20
75:25
89:11
70:30
–
–
4b (4R)
4c (4S)
4d (4R)
4e (4S)
4f (4R)
4g (4S,5R)
4h
Et
H
H
48
72:28
71:29
27:73
74:26
72:28
54:46
–
74:26
100:0
0:100
84:16
61:39
75:25
–
Bn
Bn
Ph
Ph
Me
H
H
H
48
H
H
48
H
H
48
H
H
48
Ph
Me
H
48
6g
6h
Me
48
a After purification over silica gel.
Synlett 2006, No. 9, 1425–1427 © Thieme Stuttgart · New York

LETTER
Dienophiles in Inverse Hetero-Diels–Alder Reactions
1427
JAB = 12.8 Hz, J2ax¢-3¢ = J2ax¢-1¢ = 11.3 Hz, 1 H, H2ax¢), 2.36
Acknowledgment
(ddt, JAB = 12.8 Hz, J2eq¢-3¢ = 6.3 Hz, J2eq¢-1¢ = J2eq¢-4¢ = 1.8 Hz,
1 H, H2eq¢), 3.38 (d, JAB = 10.0 Hz, 1 H, H7b), 3.79 (s, 3 H,
H7¢), 3.80–4.00 (m, 2 H, H6b, H3¢), 4.17–4.80 (m, 4 H, H4, H5,
H6a, H7a), 4.38 (d, J2-1 = 3.5 Hz, 1 H, H2), 5.70 (d, J1-2 = 3.5
Hz, 1 H, H1), 6.20 (t, J4¢-3¢ = J4¢-2eq¢ = 1.6 Hz, 1 H, H4¢), 6.29
(dd, J1¢-2ax¢ = 11.3 Hz, J1¢-2eq¢ = 1.8 Hz, 1 H, H1¢), 7.18–7.41
(m, 5 H, H-arom.) ppm. 13C NMR (CDCl3): d = 25.1, 26.6,
26.8, 31.1 (CH3), 34.4 (C-2¢), 38.6 (C-3¢), 47.0 (C-7), 52.4
(C-7¢), 68.2 (C-6), 73.2 (C-5), 77.4 (C-4), 83.5 (C-3), 83.9
(C-2), 88.3 (C-1¢), 103.2 (C-1), 110.5, (CIV-iPrd), 114.4
(C-4¢), 114.9 (CIV-iPrd), 127.2 (C-o¢), 127.5 (C-p¢), 129.1
(C-m¢), 142.0 (C-n¢), 144,0 (C-5¢), 162.4 (C-6¢), 186.8 (C=S)
ppm. MS (IS): m/z = 548.5 [M + H]+.
We thank Teddy Chapin for his helpful contribution.
References and Notes
(1) Gaulon, C.; Dhal, R.; Chapin, T.; Maisonneuve, V.;
Dujardin, G. J. Org. Chem. 2004, 69, 952.
(2) Gaulon, C.; Dhal, R.; Chapin, T.; Dujardin, G. unpublished
results.
(3) (a) OZTs can readily be transformed into oxazolines using
Raney Ni® (see ref. 3b) and further hydrolysed. Up to 74%
of chemical transformation was attained on model
compounds. Current explorations in our laboratory indicate
possible removal of the anomeric OZT moiety through a
transglycosylation reaction which will be disclosed in due
time. (b) Gosselin, G.; Bergogne, M.-C.; de Rudder, J.; De
Clerq, E.; Imbach, J.-L. J. Med. Chem. 1986, 29, 203.
(4) (a) Girniene, J.; Apremont, G.; Tatibouët, A.; Sackus, A.;
Rollin, P. Tetrahedron 2004, 60, 2609; and references cited
therein. (b) Girniene, J.; Tatibouët, A.; Sackus, A.; Yang, J.;
Holman, G. D.; Rollin, P. Carbohydr. Res. 2003, 338, 711.
(5) (a) Velazquez, F.; Olivo, H. F. Curr. Org. Chem. 2002, 6, 1.
(b) Jalce, G.; Seck, M.; Franck, X.; Hocquemiller, R.;
Figadère, B. J. Org. Chem. 2004, 69, 3240. (c) Crimmins,
M. T.; McDougall, P. J. Org. Lett. 2003, 5, 591.
(6) Chéry, F.; Desroses, M.; Tatibouët, A.; De Lucchi, O.;
Rollin, P. Tetrahedron 2003, 59, 4563.
(7) Girniene, J.; Tardy, S.; Tatibouët, A.; Sackus, A.; Rollin, P.
Tetrahedron Lett. 2004, 45, 6443.
(8) Gaulon, C.; Gizecki, P.; Dhal, R.; Dujardin, G. Synlett 2002,
952.
(9) Tardy, S.; Tatibouët, A.; Rollin, P. unpublished results.
(10) Compound 8 endo I: [a]D20 +50 (c 1.0, CHCl3). 1H NMR
(CDCl3): d = 1.33, 1.36, 1.47 (3 s, 12 H, CH3), 1.85 (dt,
(11) Compound 8 endo II: [a]D20 –26 (c 0.5, CHCl3). 1H NMR
(CDCl3): d = 1.17, 1.37, 4.41, 1.62 (4 s, 12 H, CH3), 1.86 (dt,
JAB = 12.8 Hz, J2ax¢-3¢ = J2ax¢-1¢ = 11.3 Hz, 1 H, H2ax¢), 2.37
(ddt, JAB = 12.8 Hz, J2eq¢-3¢ = 6.5 Hz, J2eq¢-1¢ = J2eq¢-4¢ = 1.8 Hz,
1 H, H2eq¢), 3.69 (d, JAB = 10.3 Hz, 1 H, H7b), 3.82 (s, 3 H,
H7¢), 3.90–4.00 (m, 4 H, H3¢, H5, H7a, H6b), 4.09 (dd, JAB = 7.3
Hz, J6a-5 = 2.8 Hz, 1 H, H6a), 4.17 (d, J4-5 = 8.5 Hz, 1 H, H4),
4.59 (d, J2-1 = 3.5 Hz, 1 H, H2), 5.71 (d, J1-2 = 3.5 Hz, 1 H,
H1), 6.21 (t, J4¢-3¢ = J4¢-2eq¢ = 1.6 Hz, 1 H, H4¢), 6.32 (dd,
J
1¢-2ax¢ = 11.3 Hz, J1¢-2eq¢ = 1.8 Hz, 1 H, H1¢), 7.18–7.40 (m,
5 H, H-arom.) ppm. 13C NMR (CDCl3): d = 25.4, 26.6, 27.0,
31.1 (CH3), 33.7 (C-2¢), 38.6 (C-3¢), 46.6 (C-7), 52.5 (C-7¢),
68.6 (C-6), 73.9 (C-5), 77.4 (C-4), 84.0 (C-2), 84.2 (C-3),
88.3 (C-1¢), 103.2 (C-1), 110.6, (CIV-iPrd), 114.8 (C-4¢,
CIV-iPrd), 127.2 (C-o¢), 127.5 (C-p¢), 129.1 (C-m¢), 142.0
(C-n¢), 143.8 (C-5¢), 162.4 (C-6¢), 186.2 (C=S) ppm. MS
(IS): m/z = 548.5 [M + H]+.
(12) Hughes, K. D.; Hguyen, T.-L. N.; Dyckman, D.; Dulay, D.;
Boyko, W. J.; Giuliano, R. M. Tetrahedron: Asymmetry
2005, 16, 273.
Synlett 2006, No. 9, 1425–1427 © Thieme Stuttgart · New York