Ring-opening reactions of semicyclic NO-acetals possessing an exocyclic nitrogen atom with silicon-based nucleophiles (silyl enol ethers, ketene silyl acetals, allylic silanes, and trimethylsilyl cyanide) were systematically studied for the first time. It was found that the reactions were effectively catalyzed by a Lewis acid, trimethylsilyl trifluoromethanesulfonate (TMSOTf), to afford 1,4- and 1,5-amino alcohols in high yields. In reactions of 3-oxygen functionalized semicyclic N,O-acetals, high 1,2-syn-diastereoselectivity was obtained. By H-1 NMR experiment, the formation of the O-trimethylsilylated ring-opened product was observed as the initial product. Furthermore, the epimerization between the diastereomers of a 3-benzyloxy semicyclic N,O-acetal suggested the transient formation of an acyclic iminium ion species as a reactive intermediate. It was also found that 3-acetoxy and 3-benzyloxy N,O-acetals showed a tendency for the larger nucleophile to provide higher syn-selectivity, while 3-tert-butyldiphenylsilyloxy NO-acetals showed the opposite tendency. These stereochemical outcomes can be rationalized by assuming four transition state models for the acyclic iminium ion intermediate. The synthetic utility of the reaction has been demonstrated in the diastereoselective synthesis of piperidine alkaloids, (+)-isofebrifugine and (+/-)-sedacryptine.