Highly functionalized, enantiomerically pure furo[ x, y- c]pyrans via alkylidenecarbenes derived from sugar templates: synthesis and mechanism study via computational chemistry

Abstract

The new method for the generation of alkylidenecarbenes based on the reaction of trimethylsilylazide/Bu 2SnO with α-cyanomesylates has been applied to readily available sugar derivatives for the synthesis of highly functionalized, enantiomerically pure furo[ x, y- c]pyrans. The furo[ x, y- c]pyran heterocyclic ring system is present in a number of natural or non-natural products of biological interest such as the miharamycins, and deserve particular attention. The scope and extent of the present new methodology has been investigated by systematic modification of the starting sugar precursor ( d-glucose, d-galactose, etc.) in the hexo-α(β)- d-pyranoside forms, bearing also different O-protecting groups, the effect of the absolute configuration of the substituent at the anomeric position, the location (C-2, -3 and -4) of the alkylidenecarbene species on the pyran nucleus, as well as the substitution (H or Ph) at the ‘carbon donor’ in the 1,5 C–H bond insertion process. In overall, using these key 1,5 C–H bond insertion reactions a simple protocol results for the synthesis of the furo[ x, y- c]pyrans, difficult to be prepared by other methodologies, from moderate to good yields. To examine the reactivity of the alkylidenecarbene, we have undertaken a systematic investigation of the insertion reactions of various alkylidenecarbene derivatives into C–H bonds using density functional theory.