An expedient route to heterocycles through α-arylation of ketones and arylamides by microwave induced thermal S_RN1 reactions

Abstract

Quick reaction by microwave irradiation promotes nucleophilic substitution by thermally induced electron transfer mechanism and allows to synthesize deoxibenzoin and indol heterocycles derivates by inter or intramolecular ring closure.

Anions involved in the initiation of the thermally induced SRN1 reaction for α-arylation of ketones

“…A more thorough analysis can be found in from Soria-Castro et al ref. 7. Compound 3n-p synthesized with 5 eq.…”

“…Recently, we reported reactions of PhI (or ArX) with acetophenone enolates, founding good yield of dehalogenation and moderate yields of the expected product ($50% 3a-h) 7 A minor substituent effects on the substrate was detected (Table 1, 3a vs. 3b-g), except when the p-nitro-iodobenzene was used, with 19% yield (Table 1, 3h). In addition, when any substituent was located in the aryl ring of the acetophenone, lower yields were found with a stronger effect for electro-withdrawing groups (Table 1, 3i-l).…”

“…6 Recently we reported the aarylation of aromatic ketones and acetamides at moderate temperatures applying microwave heating for the thermally induced S RN 1 reaction, with yields $50% of the expected substitution product (Scheme 1A). 7 On the other hand, the reaction induced by microwave offers advantages such as simplicity, shorter reaction times (1 min of microwave irradiation compared to 120 minutes under photoirradiation). It is also compatible with different substituent and shows a better performance for intramolecular cyclization reactions to get indole derivatives (Scheme 1B).…”

“…In previous studies, different derivatives of the nucleophile acetophenone substituted at aryl moiety were also used ( Table 1, R 3 ). 7 However, questions remain about the process of initiation of the chain reaction. There is a great interest in determining which of the species present in the reaction mixture are involved in the initiation step.…”

Transition‐Metal‐Free α‐Arylation of Enolizable Aryl Ketones and Mechanistic Evidence for a Radical Process

“…Whereas transition‐metal‐catalyzed processes are now commonly employed, methods for the arylation of ketone enolates by radical nucleophilic aromatic substitution (S RN 1), first reported as early as 1970, are seldom used 6. These reactions can proceed in the presence of iron or samarium catalysts7 or without transition metals by photochemical,8 thermal,9 or microwave‐induced thermal10 activation. However, these methods have not found widespread use in organic synthesis, probably because of substrate‐scope limitations.…”