is generally preferred to secondary C-H bonds, and electron-
donating groups activate the R-C-H bond toward insertion.3c,5
In connection with our studies on carbohydrate mimics,6
we recently applied the Du Bois reaction to C-glycoside 1
and obtained spiranic oxathiazolidine 2 by regiospecific
insertion into the pseudoanomeric C-H bonds (Scheme 1).5
3 to PhI(OAc)2, MgO, and 5 mol % of Rh2(OAc)4 in
dichloromethane. Surprisingly, no product corresponding to
the formation of a six- or five-membered ring was observed.
The only insertion product isolated was the oxathiazepane
derivative 4 produced in 67% yield (Table 1). Structural
evidence for 4, which corresponds to the insertion product
at C-6, was obtained unambiguously by X-ray crystal-
lographic analysis (Figure 2).7 To the best of our knowledge,
Scheme 1
Quite unexpectedly, this reaction was found to be strongly
dependent on the anomeric configuration since no insertion
product could be isolated from the pseudo-R-epimer of 1.
To evaluate the potential of this methodology for the
synthesis of original imino-C-glycosides, we first performed
a model study from piperidine 3, obtained in two steps from
2-piperidinemethanol (Table 1, entry 1). Amination of the
Figure 2. Perspective ORTEP view of compound 4.
4 is the first seven-membered ring ever obtained by way of
Du Bois reaction.8
Table 1. Study of the Influence of Various Structural
Parameters in Rh-Catalyzed C-H Insertion of Sulfamate Estersa
To rationalize this unexpected result, we decided to study
the influence of diverse structural parameters (Table 1).
Addition of an electron-donating or a strong electron-
withdrawing substituent on the phenyl group of the N-
benzenesulfonylpiperidine decreased the yield but did not
change the regioselectivity of the insertion process (entries
2 and 3). Ring size was found to play a key role since no
trace amount of an oxathiazepane product could be detected
from pyrrolidine 9. Compound 10 corresponding to the open-
chain imine form of the C-2 insertion product was isolated
in 29% yield from 9 (entry 4). The nature of the endocyclic
heteroatom was also found to be critical. Du Bois reaction
performed from pyran and furan derivatives 11 and 13 led
(3) (a) Espino, C. G.; Wehn, P.; Chow, M. J.; Du Bois, J. J. Am. Chem.
Soc. 2001, 123, 6935. (b) Espino, C. G.; Du Bois, J. Angew. Chem., Int.
Ed. 2001, 40, 598. (c) Fiori, K. W.; Flemming, J. J.; Du Bois, J. Angew.
Chem., Int. Ed. 2004, 43, 4349.
(4) For examples of related work, see: (a) Breslow, R.; Gellman, S. H.
J. Am. Chem. Soc. 1983, 105, 6728. (b) Fruit, C.; Mu¨ller, P. HelV. Chim.
Acta 2004, 87, 1607. (c) Liang, J.-L.; Yuan, S.-X.; Huang, J.-S.; Yu, W.-
Y. Che, C.-M. Angew. Chem., Int. Ed. 2002, 41, 3465. (d) Lebel, H.; Huard,
K.; Lectard, S. J. Am. Chem. Soc. 2005, 127, 14198. (e) Cui, Y.; He, C.
Angew. Chem., Int. Ed. 2004, 43, 4210. (f) Liang, C.; Robert-Peillard, F.;
Fruit, C.; Mu¨ller, P.; Dodd, R. H.; Dauban, P. Angew. Chem., Int. Ed. 2006,
45, 4641.
(5) Toumieux, S.; Compain, P.; Martin, O. R. Tetrahedron Lett. 2005,
46, 4731.
(6) For selected references, see: (a) Godin, G.; Compain, P.; Masson,
G.; Martin, O. R. J. Org. Chem. 2002, 67, 6960. (b) Godin, G.; Compain,
P.; Martin, O. R. Org Lett. 2003, 5, 3269. (c) Compain, P.; Martin, O. R.;
Boucheron, C.; Godin, G.; Yu, L.; Ikeda, K.; Asano, N. ChemBioChem
2006, 7, 1356.
a Reaction conditions: CH2Cl2, 40 °C, 4-24 h, substrate/PhI(OAc)2/
MgO/Rh2(OAc)4 1:1.1:2.3:0.05. b Isolated yield. c Compound 14 was ob-
tained along with 22% of the corresponding spiranic cyclized product.
(7) Crystallographic data for structure 4 have been deposited with the
Cambridge Crystallographic Data Centre as supplementary publication no.
CCDC 605300.
(8) For the synthesis of oxathiazepanes by way of PhIdO-mediated
copper-catalyzed aziridination of unsaturated sulfamates, see: (a) Duran,
F.; Leman, L.; Ghini, A.; Burton, G.; Dauban, P.; Dodd, R. H Org Lett.
2002, 4, 2481. (b) Duran, F. J.; Ghini, A.; Dauban, P.; Dodd, R. H.; Burton,
G. J. Org. Chem. 2005, 70, 8613.
C-3 position would open the way to a general synthesis of
imino-C-glycoside analogues of hexosamine whereas nitro-
gen atom insertion at C-2 would yield a functionalized
piperidine containing an aminal structure that could serve
as surrogate iminium ions. We thus submitted test substrate
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Org. Lett., Vol. 8, No. 20, 2006