Synthesis of highly functionalized chiral nitriles by radical fragmentation of beta-hydroxy azides. Convenient transformation of aldononitriles into 1,4- and 1,5-iminoalditols

8 pages, 2 tables, 5 schemes.-- PMID: 15549818 [PubMed].-- Printed version published Nov 26, 2004.

Supporting information available: Detailed experimental procedures and spectral and analytical data for several compounds.-- Available at: http://pubs.acs.org/doi/suppl/10.1021/jo049026p

The synthesis of highly functionalized nitriles by an alkoxyl radical fragmentation of cyclic β-hydroxy azides is described. The alkoxyl radicals were generated by reaction of the alcohols with (diacetoxyiodo)benzene and iodine under mild conditions compatible with the presence of sensitive substituents and the protective groups most frequently used in carbohydrate chemistry. To explore the scope and limitations of this methodology, experiments were carried out using a variety of β-hydroxy azides of the carbohydrate (1−6, 33, and 41), monoterpenoid (21 and 22), and steroid (23−25) families of natural products. Of special interest are the aldopentonitriles (15−18, 34, and 42) and aldotetrononitriles (19 and 20) synthesized from the corresponding 2-azido-2-deoxycarbohydrates. To demonstrate the versatility of these aldononitriles as chiral synthons, 1,4-imino-1-deoxysugar (37) and 1,5-imino-1-deoxysugar (43) analogues of the polyhydroxypyrrolidine and -piperidine types were prepared.

This work was supported by the Investigation Programme Nos. BQU2000-0650, BQU2001-1665, and PPQ2000-0728 of the Dirección General de Investigación Científica y Técnica, Spain. C.R.-F. thanks the Dirección General de Investigación del Gobierno de Canarias for a fellowship.