[reaction: see text] Two strategies were tried to synthesize 3'-deoxy-3'-difluoromethyl azanucleosides. After the failure of the first route, the key intermediate 12 from trans-4-hydroxyproline 7 in 8 steps was stereoselectively prepared. The alcohol 12 was subjected to selective protection, oxidation, and difluoromethylenation to afford the fluorinated compound 18, whose hydrogenation was then systematically investigated. After a series of transformations of protecting groups, the resultant compounds 22 and 23 were oxidized to the desired lactams 24 and 25, which were successfully utilized to synthesize our target molecules, 3'-deoxy-3'-difluoromethyl azanucleosides 33, 34a, 34b, and 35.