Neighboring-group participation in nitrile-forming Beckmann fragmentation reactions: Synthesis of enantiopure (E)-2,3-Di-O-substituted-5-methoxy-pent-4-enenitriles and their conversion into pyranosylamines

The selective Beckmann fragmentations of multifunctionalised ketoximes have been proven to proceed effectively to give the corresponding nitriles. The chiral (E)-1,3,4-tri-O-substituted-6-methoxy-hex-5-en-2-one oxime derivatives, available from glycals and glycosyl glycals, gave enantiopure (E)-2,3-di-O-substituted-5-methoxypent-4-enenitriles by treatment with mesyl chloride and triethylamine. The C1-C2 heterolytic fragmentation was completely controlled and directed by the adjacent C1 ether oxygen, which generates a carbonium-oxonium ion as an active electrofugal group. Unexpectedly, the C3 heteroatom did not assist the cleavage reaction and products derived from C2-C3 fragmentation were never detected. The excellent regio- and stereospecificity of the fragmentation reaction, based on the stereochemical outcome, are discussed. A simple synthetic approach to some pyranosylamines is also described. ((C) Wiley-VCH Verldg GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004).