Diastereoselective synthesis of fluorinated piperidine quinazoline spirocycles as iNOS selective inhibitors

A diastereoselective synthesis of fluoropiperidine quinazoline spirocycles has been developed through a silyl triflate mediated intermolecular coupling of difluorobenzamidine and racemic N-protected 3-fluoropiperidine dimethyl ketals or piperidones. Combination of the silyl reagents together with Lewis acids (such as BF3·OEt2, ZnCl2, InCl3, etc.) accelerated the coupling reaction to afford the desired fluorospirocycles in good yields (40-83%) and high diastereoselectivity. A ratio of the two diastereoisomers of up to 10:1 in favor of the desired isomer can be achieved.