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

The reductive opening of epoxides 1, 9, 13 derived from D-glucose and 18 de rived from D-fructose using lithium and a catalytic amount of 4,4'-di-tert- butylbiphenyl (DTBB) in THF at -78 degrees C allows the formation of beta-o xido organolithium derivatives (2, 10, 14 and 19), which, by reaction with different electrophiles [H2O, D2O, Me3SiCl, PhCHO, Me2CO, Et2CO, (CN2)(5)CO , CO2] at the same temperature yields, after hydrolysis with water, the exp ected 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 wi th an electrophile. The application of this methodology to the oxetane 4 al lows compound 6 to be obtained through the corresponding gamma-functionalis ed organolithium intermediates 5. Finally, the addition of the dianions 25 (resulting from the DTBB-catalysed lithiation of phthalan and isochroman) t o the ketones 8 and 23, derived from D-glucose and D-fructose, respectively , allowed the stereoselective functionalisation at the 3-position of the su gars, giving the corresponding diols 26 and 27, which can cyclise to the co rresponding heterocycles 28 and 29, respectively, under Mitsunobu reaction conditions. (C) 2000 Elsevier Science Ltd. All rights reserved.