Structure–activity relationship of dihydroimidazo-, dihydropyrimido, tetrahydrodiazepino-[2,1-b]-thiazoles, and -benzothiazoles as an acylation catalyst

Dramatic Acceleration of an Acyl Transfer-Initiated Cascade by Using Electron-Rich Amidine-Based Catalysts

“…7 As expected, derivatives of DHPB bearing electron-donating substituents on the benzene ring (12b−e) produced strongly negative values. More interestingly, bicyclic isothioureas 17a and 18a disclosed recently by Okamoto et al 8 displayed considerably higher intrinsic Lewis basicities than DHPB itself and were further enhanced by substitution on the phenyl group (17b−d, 18b−d). Finally, the highest Lewis basicity was predicted for DHIP 19the very first ABC that served as the starting point for designing this whole class of catalysts.…”

“…These results were all the more remarkable given the fact that catalysts 17a−c and 18a performed slower than DHPB 12a in the acylation of 1phenylethanol with anhydrides in Okamoto's study. 8 Finally, DHIP 19 displayed catalytic activity comparable to the fastest bicyclic isothioureas (entry 14). This was in sharp contrast to its poor performance in the acetylation of alcohols observed in our early studies: several hundred times slower than DHPB!…”

“…Bicyclic isothioureas 17 and 18 (entries 6–13) were even more activemuch more than DHPB derivatives with similar computed acylation enthalpies (see, e.g., 17a and 18a vs 12d or 17d and 18d vs 12e ). These results were all the more remarkable given the fact that catalysts 17a – c and 18a performed slower than DHPB 12a in the acylation of 1-phenylethanol with anhydrides in Okamoto’s study . Finally, DHIP 19 displayed catalytic activity comparable to the fastest bicyclic isothioureas (entry 14).…”

Organocatalytic Enantioselective Synthesis of α-Fluoro-β-amino Acid Derivatives

“…Other achiral Lewis base catalysts were examined briefly. Both electron-poor ( 11b ) and electron-rich ( 11c ) derivatives of DHPB produced lower conversion (entries 8 and 9). DMAP 12 was slightly more effective than DHPB 11a (entry 10).…”

A Scalable, Chromatography-Free Synthesis of Benzotetramisole

“…Recently, Okamoto and co-workers reported a conceptually different four-step synthesis of BTM starting from o-bromoaniline. 16 Although (R)-and (S)-4 are now commercially available (ca. £ 90/1 g), 17 the need for multi-gram quantities of racemic and enantiopure BTM (4) to support our investigations into its use in catalysis motivated the development of a scalable, operationally simple synthesis.…”