Structural modification of carbohydrates via functionalised organolithium intermediates: EPC preparation of branched-chain functionalised sugars

Abstract

The reductive opening of epoxides 1, 9, 13 derived from d-glucose and 18 derived from d-fructose using lithium and a catalytic amount of 4,4′-di- tert-butylbiphenyl (DTBB) in THF at −78°C allows the formation of β-oxido organolithium derivatives ( 2, 10, 14 and 19), which, by reaction with different electrophiles [H 2O, D 2O, Me 3SiCl, PhCHO, Me 2CO, Et 2CO, (CH 2) 5CO, CO 2] at the same temperature yields, after hydrolysis with water, the expected branched-chain functionalised carbohydrates. An alternative route for compound 11, derived from the epoxide 9, consists of the deprotonation of the chlorohydrin 12 followed by the same protocol of lithiation-reaction with an electrophile. The application of this methodology to the oxetane 4 allows compound 6 to be obtained through the corresponding γ-functionalised organolithium intermediates 5. Finally, the addition of the dianions 25 (resulting from the DTBB-catalysed lithiation of phthalan and isochroman) to the ketones 8 and 23, derived from d-glucose and d-fructose, respectively, allowed the stereoselective functionalisation at the 3-position of the sugars, giving the corresponding diols 26 and 27, which can cyclise to the corresponding heterocycles 28 and 29, respectively, under Mitsunobu reaction conditions.