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.
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 FClO(3) 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.
Liu
Z
Z
Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University, Sugitani 2630, Toyama 930-0194, Japan.
Shibata
N
N
Takeuchi
Y
Y
D000890:Anti-Infective Agents / Q000138:chemical synthesis*; D003500:Cyclization; D013141:Spiro Compounds / Q000138:chemical synthesis*; D013449:Sulfonamides / Q000138:chemical synthesis*; D013843:Thiazines / Q000138:chemical synthesis*
C416983:2-fluoro-14-methyl-11-(methylethyl)spiro(4H-benzo(e)-1,2-thiazine-3,2'-cyclohexane)-1,1-dione; D000890:Anti-Infective Agents; D013141:Spiro Compounds; D013449:Sulfonamides; D013843:Thiazines