The iodocyclization of unsaturated dihydroxysulfonamide derivatives. N- versus O-cyclization

Article abstract of DOI:10.1016/S0040-4039(00)01932-8

Iodocyclization of unsaturated dihydroxysulfonamide derivatives can lead to substituted monocyclic or bicyclic compounds depending on the hydroxy protecting groups and the electrophilic reagent used.

Full text of DOI:10.1016/S0040-4039(00)01932-8

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 251–254
The iodocyclization of unsaturated dihydroxysulfonamide
derivatives. N- versus O-cyclization
Janine Cossy,* Ludovic Tresnard, Damien Belotti and Domingo Gomez Pardo
Laboratoire de Chimie Organique, associe´ au CNRS, ESPCI, 10 rue Vauquelin, 75231 Paris Cedex 05, France
Received 30 September 2000; accepted 30 October 2000
Abstract—Iodocyclization of unsaturated dihydroxysulfonamide derivatives can lead to substituted monocyclic or bicyclic
compounds depending on the hydroxy protecting groups and the electrophilic reagent used. © 2000 Elsevier Science Ltd. All
rights reserved.
ent violation of Baldwin’s rules,3 as they are elec-
Electrophilic cyclizations are an attractive method for
trophile- rather than nucleophile-driven.4 Electrophilic
the formation of substituted 5- and 6-membered satu-
rated heterocyclic compounds.1 Substituted tetra-
hydrofurans can be obtained from homoallylic
alcohols2 by 5-endo-trig cyclizations despite the appar-
cyclizations of g,d-unsaturated alcohols as well as their
corresponding ethers can lead to the stereoselective
construction of substituted tetrahydrofurans.5 The po-
R2O
R2O
R1O
NHTs
E+
and / or
OR1
E
OR1
E
HN
Ts
A
N
O
Ts
C
B
Scheme 1.
4 steps
i, ii
OTBDPS
OTBDPS
OTBDPS
O
O
CO2H
O
N
H
N
N
Ts
Ts
(–)-1
(–)-2
(–)-3
iii
iv
OTBDPS
TBDMSO
HO
HN
Ts
HN
Ts
(–)-4
(+)-5
Scheme 2. Preparation of compounds (−)-4 and (+)-5. Reagents and conditions: i, LiHMDS, THF, −78°C; ii, allyl bromide, THF,
−78°C“rt (89%); iii, NaBH4, MeOH, rt (70%); iv, TBDMSCl, imidazole, CH2Cl2, 0°C“rt (78%).
Keywords: bicyclic heterocyclic compounds; cyclization; oxygen heterocycles; pyrrolidines; sulfonamides.
* Corresponding author. Fax: +33-1-40-79-46-60; e-mail: janine.cossy@espci.f
0040-4039/01/$ - see front matter © 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(00)01932-8

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J. Cossy et al. / Tetrahedron Letters 42 (2001) 251–254
tential of these electrophilic cyclizations was also used
to build substituted pyrrolidines6,7 and piperidines,8
respectively, from homoallylic tosylamides or d,o-unsat-
urated amines.
rt) or HBI (3 equiv., CH2Cl2, rt) produced two separa-
ble bicyclic compounds 8 and 9 (ratio 7:3) in similar
yields (NIS, yield: 48%; HBI, yield: 40%). The relative
stereochemistry in 8 and 9 was determined by NOE
experiments. Modification of the conditions, in the
electrophilic treatment of (+)-5, by replacing NIS by I2
in the presence of K2CO3 led to a mixture of the two
diastereomers 6 and 7 in 45% yield in a 7:3 ratio. We
have to point out that under these conditions a trace of
piperidine 10 was observed (ꢀ5%) (Scheme 3).
Here, we would like to report our preliminary studies
on the iodocyclization of dihydroxysulfonamide deriva-
tives of type A, which can lead either to substituted
tetrahydrofurans B and/or substituted piperidines C
(Scheme 1).
The required substrates (−)-4 and (+)-5 were efficiently
obtained, as outlined in Scheme 2, from L-pyroglu-
tamic acid. L-Pyroglutamic acid (−)-1 was transformed
to the N-tosyl lactam (−)-2 in four steps, following a
described procedure.9 After alkylation of (−)-2 with
allyl bromide (LiHMDS, THF, −78°C, de>96%, 89%
yield), the N-tosyllactam (−)-3 was reduced to the
monoprotected diol (−)-4 by NaBH4 (MeOH, rt, 70%
yield). Compound (−)-4 was converted to (+)-5 by
treatment with TBDMSCl (imidazole, CH2Cl2, 78%
yield).
The same diastereomeric ratio 6/7 (obtained from the
iodocyclization of (+)-5 or (−)-4) and 8/9 (obtained
from (+)-5) led us to speculate that the major isomer 6
should have a 2,4-cis relative stereochemistry. Depend-
ing on the source of electrophile, (+)-5 can be trans-
formed into monocyclic compounds 6/7 or bicyclic
compounds 8/9. According to these results, it seems
that the treatment of (+)-5 with I2 led to the iodonium
intermediate 12, which can be attacked by a silyl ether
to produce intermediate 13 and I−. The desilylation of
intermediate 13 by I−, liberated in the reaction media,
produced the observed tetrahydrofurans 6/7. When the
same protected dihydroxysulfonamide derivative (+)-5
was treated with NIS, the same intermediate 12 was
formed and the succinimide anion was liberated. This
succinimide anion is not nucleophilic enough to trans-
form 13 into 6/7 by desilylation. However, the tosy-
lamide group is able to attack intramolecularly the C-5
of intermediate 13 to produce the substituted N-to-
sylpyrrolidine 14. As an excess of NIS is present in the
reaction media, the N-tosylpyrrolidine 14 can react
Initially, we examined iodocyclization of hydroxysul-
fonamide (−)-4 by using N-iodosuccinimide (NIS, 3
equiv.) in dry CH2Cl2 at room temperature. This first
attempt led to the rapid formation of two inseparable
diastereomers 6 and 7 in 50% yield, in a ratio of 7:3.
When the electrophile bis(sym-collidine)iodine(I) hex-
afluorophosphate (HBI)10 was used, 6 and 7 were ob-
tained with the same ratio (7:3) but with lower yield
(25%). The treatment of the protected unsaturated di-
hydroxysulfonamide (+)-5 with NIS (3 equiv., CH2Cl2,
OTBDPS
OTBDPS
NIS, CH2Cl2, rt
OTBDPS
NHTs
NHTs
+
+
HO
HN
O
50%
(6/7=7/3)
O
I
I
Ts
(–)-4
6
7
HBI, CH2Cl2, rt
6
7
(–)-4
25%
(6/7=7/3)
OTBDPS
OTBDPS
NIS, CH2Cl2, rt
OTBDPS
NTs
NTs
+
TBDMSO
HN
O
O
48%
I
I
(8/9=7/3)
Ts
(+)-5
8
8
9
9
HBI, CH2Cl2, rt
(+)-5
+
40%
(8/9=7/3)
TBDMSO
I2, K2CO3,
CH2Cl2, rt
OTBDPS
I
OTBDPS
6 +
7
+
TBDMSO
N
HN
(45%)
Ts
Ts
(6/7=7/3)
(5%)
(+)-5
10
Scheme 3. Iodocyclizations.

J. Cossy et al. / Tetrahedron Letters 42 (2001) 251–254
253
(+)-5
2 or NIS
I
I
+
TBDMSO
I
O
O
N
–
OTBDPS
OTBDPS
13
TBDMSO
HN
N
Ts
12
Ts
14
I
OTBDPS
NHTs
NIS
TBDMSO
OTBDPS
+
H
O
N
+
I
I
Ts
O
TBDMS
15
13
I
O
I–
N
OTBDPS
–
TBDMSO
OTBDPS
OTBDPS
NHTs
I
+
N
NTs
O
O
I–
I
Ts
16
6 / 7
8 / 9
Scheme 4. Formation of 6/7 and 8/9.
OTBDPS
NHTs
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