with aqueous sodium bisulfite and subjected to Roush’s KF/
Celite protocol12 for removing residual tin. The resulting
semipurified material was subjected to carbamoylation13 to
afford the diastereomerically pure carbamate 8 in 78% yield
after recrystallization (two steps). Oxidative cleavage of the
benzyl ether protecting group gave hexynol 9 in 95% yield.
The tungsten-catalyzed cycloisomerization was slow relative
to the previously studied branched system;1a however, glycal
1014 was obtained in 72% yield after 6 h. Rhodium nitrene
insertion completed the synthesis, providing protected L-
daunosamine glycal 11 in five steps and 44% yield overall
from the lactic acid derivative (S)-7.
Similar schemes directed toward other 3,4-cis-3-amino
glycals would be successful only if the key functionalization
steps were regioselective, leading to insertion at the C3-H
bond. As there were no examples of the competition between
two activated but functionally different C-H bonds in
carbamate nitrogen insertion reactions,15 we examined the
regiochemistry in systems that would be informative and
suited to practical applications.
Scheme 1
and R to the pyranoside oxygen. However, only the C3-H
bond is sterically accessible to the reactive species. The clean
conversion of substrate 3 to the protected amino glycal 2
under the catalytic conditions of Du Bois was a gratifying
but not unexpected result.
In this communication, we disclose the extension of the
cycloisomerization/nitrene insertion approach to derivatives
of the unbranched amino sugar daunosamine. Furthermore,
we report that the Du Bois intramolecular rhodium carbamate
nitrene insertion8 is selective for allylic C-H bonds over
C-H bonds that are R to ether substituents. This selectivity
endows our approach to 3,4-cis-3-amino-3-deoxy glycals
with broad scope, permitting its application in the preparation
of protected glycals of ristosamine and saccharosamine as
well as to daunosamine.Of the 2,3,6-trideoxy-3-amino sugars,
Scheme 2
Figure 1.
branched and unbranched, daunosamine has received the
most attention from medicinal and synthetic chemists.
L-Daunosamine (4) is the glycosidic constituent of the
important anthracycline antitumor antibiotics daunorubicin
and doxorubicin.9
A protected daunosamine glycal is a valuable synthon.
Functionalized L-daunosamine glycals have been used to
glycosylate anthracyclinones in the synthesis of anthra-
cyclines and their analogues.4 Furthermore, protected D-
daunosamine glycals are potentially useful3 for the prepara-
tion of derivatives of D-ravidosamine (5), the sugar compo-
nent of ravidomycin.10
In light of the accessibility of the vancosamine synthon 2
by the nitrogen insertion approach, we initiated the synthesis
of the protected L-daunosamine glycal 11 by a similar
strategy. The Du Bois substrate 10 was prepared by a six-
step sequence from ethyl (S)-lactate in which the key step
was the diastereoselective addition of allenyl stannane 611
to aldehyde (S)-7.1a The crude reaction product was washed
D-Saccharosamine (12) is an element of the recently
isolated saccharomicin, an oligosaccharide antibiotic active
against multiply resistant strains of Staphylococcus aureus
and vancomycin-resistant enterococci.16 A synthesis of its
(11) Prepared from commercially available propargyl bromide by the
reported procedure: Tanaka, H.; Abdul Hai, A. K. M.; Ogawa, H.; Torii,
S. Synlett 1993, 11, 835.
(12) See the Supporting Information for: Scheidt, K. A.; Bannister, T.
D.; Tasaka, A.; Wendt, M. D.; Savall, B. M.; Fegley, G. J.; Roush, W. R.
J. Am. Chem. Soc. 2002, 124, 6981.
(13) Kocovsky, P. Tetrahedron Lett. 1986, 27, 5521.
(14) McDonald et al. have applied the cycloisomerization reaction to
the preparation of related 3-unsubstituted glycal derivatives. See: McDonald,
F. E.; Zhu, H. Y. H. J. Am. Chem. Soc. 1998, 120, 4246.
(15) Rh2(OAc)4-catalyzed sulfamate nitrogen insertion exhibits no prefer-
ence for ether CR-H, tertiary C-H, or benzylic C-H. However, the Rh2(O2-
CCPh3)4-catalyzed transformation favors insertion in the ether CR-H. See:
Fiori, K. W.; Fleming, J. J.; Du Bois, J. Angew. Chem., Int. Ed. 2004, 43,
4349.
(8) Espino, C. G.; Du Bois, J. Angew. Chem., Int. Ed. 2001, 40, 598.
(9) Monneret, C. Eur. J. Med. Chem. 2001, 36, 483.
(10) Futagami, S.; Ohashi, Y.; Imura, K.; Hosoya, T.; Ohmori, K.;
Matsumoto, T.; Suzuki, K. Tetrahedron Lett. 2000, 41, 1063.
(16) (a) Kong, F.; Zhao, N.; Siegel, M. M.; Janota, K.; Ashcroft, J. S.;
Koehn, F. E.; Borders, D. B.; Carter, G. T. J. Am. Chem. Soc. 1998, 120,
13301. (b) Singh, M. P.; Petersen, P. J.; Weiss, W. J.; Kong, F.; Greenstein,
M. Antimicrob. Agents Chemother. 2000, 44, 2154.
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Org. Lett., Vol. 7, No. 9, 2005