Novel Methods for the Facile Construction of 3,3-Disubstituted and 3,3-Spiro-2H,4H-benzo[e]1,2-thiazine-1,1-diones: Synthesis of (11S,12R,14R)-2-Fluoro-14-methyl-11-(methylethyl)spiro[4H-benzo[e]-1,2-thiazine- 3,2′-cyclohexane]-1,1-dione, an Agent for the Electrophilic Asymmetric Fluorination of Aryl Ketone Enolates

Article abstract of DOI:10.1021/jo0055584

Novel methods for the facile construction of 3,3-disubstituted and 3,3-spiro 2H,4H-benzo[e][1,2]-thiazine-1,1-diones 8a-h are described. o-Methyl lithiation of N-Boc-o-toluenesulfonamide 6 followed by reaction with a variety of ketones gave the corresponding carbinol sulfonamides 7a-g, which underwent cyclization under acidic (methanesulfonic acid) or neutral (NaI/TMSCl/MeCN) conditions to afford the sultams 8a-h in high yields. The chiral spiro sultams 8g,h were subjected to FClO₃ fluorination to give the N-fluorosultams 11a,b, respectively, which were tested for electrophilic asymmetric fluorination of aryl ketone enolates. As a result, the N-fluorosultam 11a exhibited modest asymmetric inducing abilities with the highest ee, reaching 70% for enantioselective fluorination of the lithium enolate of 2-methyl-1-tetralone.