Palladium-Mediated Cyclization on Carbohydrate Templates. 2. Synthesis of Enantiopure Tricyclic Compounds

Abstract

The bromo substituted unsaturated carbohydrates 3a−f were prepared from 3,4,6-tri-O-acetyl-d-glucal by Ferrier reaction with the appropriate allylic or homoallylic alcohol, deacetylation followed by monosilylation with TBDMSCl, and then alkylation with BrCH2CBrCH2. The N- and C-analogues 4a,b were synthesized by palladium alkylation of the intermediate carbonate with TsNHCH2CBrCH2 and (MeO2C)2CHCH2CBrCH2, respectively. Treatment of the unsaturated carbohydrates 3a, 4a, and 4b with a catalytic amount of Pd(OAc)2/PPh3 in CH3CN/H2O, in the presence of Bu4NHSO4 and NEt3, afforded the tricyclic compounds 5, 6, and 7, respectively. Under the same conditions, the analogue tricyclic compounds 8, 9, and 10 were formed starting from 3b−d. In the case of compounds 3e and 3f, the formation of the bicyclic glucal 11 via an already described β-alkoxyelimination was only observed. Moreover, trapping of the σ-alkylpalladium intermediate obtained from 3e with an external nucleophile yielded the 2-deoxy carbohydrate 12 and the 2,3-unsaturated sugar 13, using respectively sodium formate and sodium tetraphenylborate.