Synthesis of Highly Functionalized Chiral Nitriles by Radical Fragmentation of β-Hydroxy Azides. Convenient Transformation of Aldononitriles into 1,4- and 1,5-Iminoalditols

Abstract

The synthesis of highly functionalized nitriles by an alkoxyl radical fragmentation of cyclic beta-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 beta-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.

Furanosyl Oxocarbenium Ion Conformational Energy Landscape Maps as a Tool to Study the Glycosylation Stereoselectivity of 2‐Azidofuranoses, 2‐Fluorofuranoses and Methyl Furanosyl Uronates

“…We therefore took a different approach to generate the 2‐azidoxyloside (Scheme C). Thus, glycal 49 was functionalised by azidophenylselenation with TMSN 3 and N ‐(phenylseleno)phthalimide to give the desired 2‐azidoxyloside 50 with good diastereoselectivity ( xylo / lyxo 9:1) . Oxidative hydrolysis of the selenophenyl group by aqueous NIS then gave lactol 44 .…”

Synthesis of the enantiomers of XYLNAc and LYXNAc: comparison of β-N-acetylhexosaminidase inhibition by the 8 stereoisomers of 2-N-acetylamino-1,2,4-trideoxy-1,4-iminopentitols

“…Base catalysed epimerizations of α-azidolactones are common. 52,53 Protection of base-sensitive alcohols under neutral conditions by heating with diphenyldiazomethane gave the corresponding benzhydryl ethers in high yields. 54 Reaction of 36L with diphenyldiazomethane in toluene gave the benzhydryl protected lactone 41L (75%).…”

Polyvalent iodine in organic chemistry: Recent developments, 2002–2005

“…The reaction, triggered by an alkoxyl radical generated in situ by the reaction of alcohol with the iodine reagent in the presence of iodine under mild conditions, can also be extended to β-hydroxy azides belonging to the terpenic and steroid families of natural products [124] (Scheme 81).…”