G. Trewartha et al. / Tetrahedron Letters 46 (2005) 3553–3556
Table 1. Synthesis of 2-nitroalkyl and 2-oximinoalkyl glycosides
3555
Acknowledgements
Entry
Pyranose
Reagenta
Product (%)
a:b Ratio
We thank AstraZeneca and the EPSRC for their gener-
ous support of this project, GlaxoSmithKline for the
generous endowment (to A.G.M.B.), the Royal Society
and the Wolfson Foundation for a Royal Society—
Wolfson Research Merit Award (to A.G.M.B.), and
the Wolfson Foundation for establishing the Wolfson
Centre for Organic Chemistry in Medical Science at
Imperial College London.
1
2
3
4
5
6
7
8
9
10
2
3
4
5
6
7
8
13
6
6
24
24
24
24
24
24
24
24
25
26
14 (56)
15 (65)
16 (44)
17 (51)
18 (48)
19 (52)
20 (63)
21 (55)
22 (69)
23 (62)
4:1
b
—
b
—
3:1
b
—
b
—
b
—
3:1
b
—
b
—
a Glycosidation using nitrocyclohexene 24, or nitrosoalkenes generated
in situ from the oximes 25 or 26.
b Ratios not determined.
References and notes
1. (a) Schmidt, R. R. In Comprehensive Organic Synthesis;
Trost, B. M., Fleming, I., Winterfeldt, E., Eds.; Pergamon:
Oxford, 1991; Vol. 6, pp 33–64; (b) Toshima, K.; Tatsuta,
K. Chem. Rev. 1993, 93, 1503.
The 2-nitrocyclohexyl glycosidations were extended to
related reactions using the labile nitrosoalkenes derived
from the a-chloro-ketoximes 25 and 26, by desilylation
and chloride elimination in situ (Table 1, Scheme 2).
The required oximes 25 and 26 were, respectively, pre-
pared from the corresponding a-chloro-ketones and
O-(t-butyldimethylsilyl)hydroxylamine.19 Sequential addi-
tion of n-butyllithium (at À10 ꢁC) and tetrabutylammo-
nium fluoride in THF to pyranose 6 and oxime 25 gave
the corresponding glycoside 22 (69%) as a mixture of
isomers. In the same way,20 pyranose 6 and oxime 26
were converted into the glycoside 23 (62%), also as a
mixture of isomers
2. Isolation: (a) Matsumoto, N.; Tsuchida, T.; Maruyama,
M.; Sawa, R.; Kinoshita, N.; Homma, Y.; Takahashi, Y.;
Iinuma, H.; Naganawa, H.; Sawa, T.; Hamada, M.;
Takeuchi, T. J. Antibiot. 1996, 49, 953; Structure deter-
mination; (b) Matsumoto, N.; Tsuchida, T.; Maruyama,
M.; Kinoshita, N.; Homma, Y.; Iinuma, H.; Sawa, T.;
Hamada, M.; Takeuchi, T. J. Antibiot. 1999, 52, 269; (c)
Matsumoto, N.; Tsuchida, T.; Nakamura, H.; Sawa, R.;
Takahashi, Y.; Naganawa, H.; Iinuma, H.; Sawa, T.;
Takeuchi, T.; Shiro, M. J. Antibiot. 1999, 52, 276;
Synthetic studies including the Danishefsky synthesis of
the aglycone: (d) Cox, C.; Danishefsky, S. J. Org. Lett.
2000, 2, 3493; (e) Cox, C.; Danishefsky, S. J. Org. Lett.
2001, 3, 2899; (f) Deville, J. P.; Behar, V. Org. Lett. 2002,
4, 1403; (g) Kelly, T. R.; Xu, D.; Martinez, G.; Wang, H.
Org. Lett. 2002, 4, 1527; (h) Cox, C. D.; Siu, T.;
Danishefsky, S. J. Angew. Chem., Int. Ed. 2003, 42,
5625; (i) Siu, T.; Cox, C. D.; Danishefsky, S. J. Angew.
Chem., Int. Ed. 2003, 42, 5629; (j) Kelly, T. R.; Cai, X.; Tu,
B.; Elliott, E. L.; Grossmann, G.; Laurent, P. Org. Lett.
2004, 6, 4953.
O
O
O
O
O
Me
O
O
O
O
O
OTBS
27
28
3. For examples of glycosylation of acyloins see; (a) Hashim-
oto, S.; Yanagiya, Y.; Honda, T.; Ikegami, S. Chem. Lett.
1992, 1511; (b) Roush, W. R.; Briner, K.; Kesler, B. S.;
Murphy, M.; Gustin, D. J. J. Org. Chem. 1996, 61, 6098.
4. (a) Mukaiyama, T.; Murai, Y.; Shoda, S. Chem. Lett.
1981, 431; (b) Schmidt, R. R. Angew. Chem., Int. Ed. Engl.
1986, 25, 212; (c) Barrett, A. G. M.; Bezuidenhoudt, B. C.
B.; Melcher, L. M. J. Org. Chem. 1990, 55, 5196.
5. (a) Noland, W. E. Chem. Rev. 1955, 55, 137; (b) Shinada,
T.; Yoshihara, K. Tetrahedron Lett. 1995, 36, 6701, and
references cited therein.
6. Wehrli, P. A.; Schaer, B. J. Org. Chem. 1977, 42, 3956.
7. Ram, S.; Ehrenkaufer, R. E. Tetrahedron Lett. 1984, 25,
3415.
8. (a) Berner, O. M.; Tedeschi, L.; Enders, D. Eur. J. Org.
Chem. 2002, 1877; (b) Barrett, A. G. M. Chem. Soc. Rev.
1991, 20, 95; (c) Barrett, A. G. M.; Graboski, G. G. Chem.
Rev. 1986, 86, 751; (d) Gilchrist, T. L. Chem. Soc. Rev.
1983, 53.
Finally, a representative 2-nitroalkyl glycoside 21 was
converted into the corresponding 2-oxoalkyl glycoside
27 (50%, a:b 3:1) using an oxidative Nef reaction with
potassium permanganate, potassium hydroxide and
magnesium sulfate in methanol.21 Secondly, the
2-oximinoalkyl glycoside 22 was converted into the
corresponding 2-oxoalkyl glycoside 28 (71%) using
manganese dioxide in hexane5 and was obtained as a
mixture of isomers. These oxidative conversions are rel-
evant to the synthesis of the keto glycoside unit of lac-
tonamycin 1.
In conclusion we have developed novel glycosylation
strategies for the preparation of 2-nitroalkyl, 2-oxi-
minoalkyl and 2-oxoalkyl glycosides, through the conju-
gate addition of anomeric alkoxides to nitro- or
nitrosoolefins. This methodology has been applied to a
range of pyranose sugars affording the desired addition
products in good yields and, in several cases, with prom-
ising levels of a-diastereoselectivity. Further work con-
cerned with the formation of O-glycosides through the
conjugate addition of anomeric alkoxides will be re-
ported in due course.
9. (a) Kamimura, A.; Sasatani, H.; Hashimoto, T.; Kawai,
T.; Hori, K.; Ono, N. J. Org. Chem. 1990, 55, 2437; (b)
Barrett, A. G. M.; Lebold, S. A. J. Org. Chem. 1990, 55,
3853; (c) Barrett, A. G. M.; Weipert, P. D.; Dhanak, D.;
Husa, R. K.; Lebold, S. A. J. Am. Chem. Soc. 1991, 113,
9820; (d) Duffy, J. L.; Kurth, J. A.; Kurth, M. J.
Tetrahedron Lett. 1993, 34, 1259.
10. (a) Lubineau, A.; Beinayme, H.; Le Gallic, J. Chem.
Commun. 1989, 1918; (b) Buchanan, D. J.; Dixon, D. J.;