Isoxazole Functionalization Technologies Enable Construction of Tetracycline Derivatives

Synthesis of 3,4,5‐Trisubstituted Isoxazoles from Morita–Baylis–Hillman Acetates by an NaNO2/I2‐Mediated Domino Reaction

“…Isoxazoles,aprivileged class of five-member nitrogen heterocycles,occupy an important place in organic chemistry because of their wide applications in pharmaceuticals,b iologically active molecules,advanced organic materials,and as intermediates in organic synthesis. [1][2][3][4][5] Owing to this ubiquity, their preparation has received remarkable attention and there are already scores of elegant methods which are general, regioselective,a nd high yielding. [6] As summarized by Carreira et al, [6m] the classical routes to isoxazole derivatives involve condensations with hydroxylamine,c yclization of ketoxime dianions,a nd propargylic oximes,a sw ell as 1,3dipolar cycloaddition reactions.Unfortunately,these methods were inefficient for the synthesis of 3-nitroisoxazoles,w hich are potent antimicrobials.…”

Palladium‐Catalyzed Direct CH Arylation of Isoxazoles at the 5‐Position

“…Fore xample,w ith the monodentate PPh 3 ,a nd the somewhat flexible 1,2-bis(diphenylphosphino)ethane (dppe), 3aa was obtained in 35 and 46 %yields,respectively (entries 7and 8). [16] Fluoro,c hloro,a nd bromo substituents at the para position of iodoarenes 2b-d remained intact throughout the CÀCb ond-forming process (entries [3][4][5]. Additive salts were found to have al arge impact on the reaction efficiency( entries [12][13][14][15].…”

Palladium‐Catalyzed Direct CH Arylation of Isoxazoles at the 5‐Position

“…Substituting the iodide 2a for the corresponding bromide 2a' ' furnished only 26 %yield of 3aa,thus indicating low reactivity of the C(sp 2 )ÀBr bond under these reaction conditions (entry 2). [16] Fluoro,c hloro,a nd bromo substituents at the para position of iodoarenes 2b-d remained intact throughout the CÀCb ond-forming process (entries [3][4][5]. Reaction with iodobenzene (2e)s imply gave the phenylated isoxazole 3ae in 77 %yield (entry 6).…”