ORGANIC
LETTERS
2006
Vol. 8, No. 5
1007-1009
New One-Carbon Degradative
Transformation of
Alcohols
â-Alkyl-â-azido
Qiu-Hua Fan, Nan-Ting Ni, Qin Li, Li-He Zhang, and Xin-Shan Ye*
The State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical
Sciences, Peking UniVersity, Xue Yuan Road #38, Beijing 100083, China
Received January 24, 2006
ABSTRACT
A new transformation of 2-azido-1-hydroxy-containing compounds to nitriles with one carbon less than the starting materials by oxidation was
reported. The reaction can be performed under mild conditions.
Nitriles have proven to be versatile building blocks in organic
synthesis.1 They undergo a variety of synthetically useful
transformations such as reduction, alkylation of their imino
enolates, enzymatic hydrolysis to acids or amides by nitrile
hydratase,2 and Ritter reaction.3 Functionalized nitriles such
as ketonitriles are important synthetic intermediates. Meth-
odologies for the synthesis of ketonitriles include the
Beckmann fragmentation of cyclic R-hydroxy oximes4 and
the cleavage of trisubstituted cyclic olefins with (diacetoxy-
iodo)benzene (DIB)/(TMS)N3. Alternatively, Pb(OAc)4/
(TMS)N3,5 CAN/NaN3,6 or photooxygenation in the presence
of NaN3/Cu(OTf)27 can achieve the same results. On the other
hand, highly functionalized aldononitriles have found wide-
spread applications as chiral synthons in the preparation of
polyhydroxypiperidines (1,5-iminoalditols) and polyhydroxy-
pyrrolidines (1,4-iminoalditols); the latter are glycosidase
inhibitors.8 Several approaches to aldononitriles from car-
bohydrates have been described in the literature, including
the direct addition of HCN to aldoses (Fischer-Killiani
cyanohydrin synthesis),9 the dehydration of aldose oximes,9b,10
the reaction of N-bromoglycosylimines with Zn/Ag graph-
ite,11 and the alkoxyl radical fragmentation of reducing
sugars.12 Herein, we now disclose a novel oxidative trans-
(5) (a) Zbiral, E.; Nestler, G.; Kischa, K. Tetrahedron 1970, 26, 1427-
1434. (b) Zbiral, E.; Nestler, G. Tetrahedron 1970, 26, 2945-2951. (c)
Ehrenfreund, J.; Zbiral, E. Tetrahedron 1972, 28, 1697-1704. (d) Hugl,
H.; Zbiral, E. Tetrahedron 1973, 29, 759-767.
(6) Nair, V.; Rajan, R.; Balagopal, L.; Thomas, S.; Narasimlu, K.
Tetrahedron Lett. 2002, 43, 8971-89074.
(7) Shimizu, I.; Fujita, M.; Nakajima, T.; Sato, T. Synlett 1997, 887-
888.
(1) (a) The Chemistry of the Cyano Group; Rappoport, Z., Ed.;
Interscience: New York, 1970. (b) Arseniyadis, S.; Kyler, K. S.; Watt, D.
S. In Organic Reactions; Dauben, W. G., Ed.; John Wiley: New York,
1984; Vol. 31, pp 1-374.
(2) (a) Brennam, B. A.; Alms, G.; Nelson, M. J.; Durney, L. T.; Scarrow,
R. C. J. Am. Chem. Soc. 1996, 118, 9194-9195. (b) Taylor, S. K.; Chmiel,
H. H.; Simons, L. J.; Vyvyan, J. R. J. Org. Chem. 1996, 61, 9084-9085.
(c) Maddrell, S. J.; Turner, N. J.; Kerridge, A.; Willetts, A. J.; Crosby, J.
Tetrahedron Lett. 1996, 37, 6001-6004.
(3) Ritter, J. J.; Minieri, P. P. J. Am. Chem. Soc. 1948, 70, 4045-4048.
(4) (a) Magyar, A.; Schonecker, B.; Wolfling, J.; Schneider, G.; Gunther,
W.; Gorls, H. Tetrahedron: Asymmetry 2003, 14, 2705-2715. (b) Ho, T.-
L.; Gorobets, E. Tetrahedron 2002, 58, 4969-4973. (c) Martinez, A. G.;
Vilar, E. T.; Fraile, A. G.; Cerero, S. M.; Maroto, B. L. Eur. J. Org. Chem.
2002, 781-783. (d) Tokic-Vujosevic, Z.; Cekovic, Z. Synthesis 2001, 2028-
2034. (e) Biju, P. J.; Laxmisha, M. S.; Rao, G. S. R. S. J. Chem. Soc.,
Perkin Trans. 1 2000, 4512-4519. (f) Pejanovic, V. M.; Petrovic, J. A.;
Csanadi, J. J.; Stankovic, S. M.; Miljkovic, D. A. Tetrahedron 1995, 51,
13379-13384.
(8) (a) Lillelund, V. H.; Jensen, H. H.; Liang, X.; Bols, M. Chem. ReV.
2002, 102, 515-553. (b) Stu¨tz, A. E. Iminosugars as Glycosidase
Inhibitors: Nojirimycin and Beyond; Wiley-VCH: Weinheim, 1999.
(9) (a) Hough, L.; Richardson, A. C. In The Carbohydrates. Chemistry
and Biochemistry; Pigman, W., Horton, D., Eds.; Academic Press: San
Diego, 1972; Vol. IA, pp 118-120. (b) McGinnis, G. D. Carbohydr. Res.
1982, 108, 284-292.
(10) See, for example: (a) Chen, C. C.; McGinnis, G. D. Carbohydr.
Res. 1981, 90, 127-130. (b) Ermert, P.; Vasella, A. HelV. Chim. Acta 1991,
74, 2043-2053. (c) Dorsey, A. D.; Barbarow, J. E.; Trauner, D. Org. Lett.
2003, 5, 3237-3239. (d) Molina, P.; Alajarin, M.; Vilaplana, M. J. Synthesis
1982, 1016-1017. (e) Attanasi, O.; Palma, P.; Serra-Zanetti, F. Synthesis
1983, 741-742.
(11) Fu¨rstner, A.; Praly, J.-P. Angew. Chem., Int. Ed. Engl. 1994, 33,
751-753.
10.1021/ol0601996 CCC: $33.50
© 2006 American Chemical Society
Published on Web 02/10/2006