Diastereoselective addition of planar N-heterocycles to vinyl sulfone-modified carbohydrates: a new route to isonucleosides

Abstract

Michael-type addition reactions of planar N-heterocycles at the C-2 positions of vinyl sulfone-modified carbohydrates provide an efficient and general route for the carbon–N-heterocycle bond formation. Therefore, the addition pattern of planar heterocycles, such as imidazole, triazole, thymine, and adenine to 3-C-phenylsulfonyl-hex-2-enopyranosides (1α/1β) and 3-C-p-toluenesulfonyl-pent-2-enofuranosides (2α/2β) was studied for developing a general methodology for the synthesis of new classes of isonucleosides possessing a carbon–N-heterocycle linkage at C-2 positions of furanosyl and pyranosyl sugars. To a great extent, the anomeric configurations of the starting vinyl sulfones play crucial roles in deciding the diastereoselectivity of addition of heterocycles. However, the trityl protected 3-C-p-toluenesulfonyl-hex-2-enopyranosides (33α/33β) were judged to be more practical starting materials for desulfonylation and deprotection for the synthesis of a new class of thymine and adenine deoxyisonucleosides.