Efficient Synthesis of 1H-Benzo[4,5]imidazo[1,2-c][1,3]oxazin-1-one Derivatives Using Ag2CO3/TFA-Catalyzed 6-endo-dig Cyclization: Reaction Scope and Mechanistic Study

Abstract

A small library of 1H-benzo[4,5]imidazo[1,2-c][1,3]oxazin-1-one derivatives was prepared in good to excellent yields, involving a Ag2CO3/TFA-catalyzed intramolecular oxacyclization of N-Boc-2-alkynylbenzimidazole substrates. In all experiments, the 6-endo-dig cyclization was exclusively achieved since the possible 5-exo-dig heterocycle was not observed, indicating the high regioselectivity of this process. The scope and limitations of the silver catalyzed 6-endo-dig cyclization of N-Boc-2-alkynylbenzimidazoles as substrates, bearing various substituents, were investigated. While ZnCl2 has shown limits for alkynes with an aromatic substituent, Ag2CO3/TFA demonstrated its effectiveness and compatibility regardless of the nature of the starting alkyne (aliphatic, aromatic or heteroaromatic), providing a practical regioselective access to structurally diverse 1H-benzo[4,5]imidazo[1,2-c][1,3]oxazin-1-ones in good yields. Moreover, the rationalization of oxacyclization selectivity in favor of 6-endo-dig over 5-exo-dig was explained by a complementary computational study.

Regioselective C6‐Arylation of Thieno[3,2‐c]pyrazole Heterocycles with Aryl Iodides

“…Next, the arylation of thieno[3,2-c]pyrazole 4 c was examined using a variety of silver salts, since, as we have demonstrated that the combination of TFA and Ag 2 CO 3 efficiently mediated an intramolecular annulation of N-Boc-2-alkynyl-4-bromo(alkynyl)-5methylimidazoles. [26] Although the reaction with AgNO 3 remained incomplete since only 50% of starting material was transformed to the desired compound 6 a, the arylations established with AgOMs, Ag 2 CO 3 and AgOAc gave satisfactory yields but without exceeding 78% of isolated C6-arylated product 6 a (Table 1, entries 10-13). Employing other acidic additives such as AcOH and PivOH instead of TFA did not appear to be beneficial for the arylation reaction, since the isolated yields of 6 a decreased to 83% and 52%, respectively (Table 1, entries 14-15).…”