Palladium-Mediated Cyclization on Carbohydrate Templates. 1. Synthesis of Enantiopure Bicyclic Compounds

Abstract

The bromo unsaturated carbohydrates 3a and 9 were prepared from ethyl 4,6-di-O-acetyl-2,3-dideoxy-d-erythro-hex-2-enopyranoside (1a) and (7) by deacetylation followed by monosilylation with TBDMSCl and then alkylation with BrCH2CBrCH2. The threo analogues 6 and 10 were obtained using the same methodology after inversion at C-4 via a Mitsunobu reaction. The N- and C-analogues 4b and 5 were prepared by palladium alkylation of the carbonate 2d with TsNHCH2CBrCH2 and (CO2Me)2CHCH2CBrCH2, respectively. Treatment of the unsaturated carbohydrates 3a and 9 with a catalytic amount of Pd(OAc)2/PPh3 in CH3CN/H2O in the presence of Bu4NHSO4 and NEt3 afforded the bicyclic compound 14a. The N- and C-analogues 14b and 14c were obtained using the same conditions and starting, respectively, from 4b and 5. On the other hand, treatment of the threo derivatives 6 and 10 under these conditions gave the furanic structure 15. In the case of compound 3a, performing the reaction in the presence of sodium formate yielded the bicyclic 2-deoxy carbohydrate 17.