Fe-catalyzed Decarbonylative Alkylative Spirocyclization of N-Arylcinnamamides: Access to Alkylated 1-Azaspirocyclohexadienones

Abstract

For the convenient introduction of simple linear/branched alkyl groups into biologically important azaspirocyclohexadienones, a practical Fe-catalyzed decarbonylative cascade spiro-cyclization of N-aryl cinnamamides with aliphatic aldehydes to provide alkylated 1-azaspiro-cyclohexadienones was developed. Aliphatic aldehydes were oxidative decarbonylated into primary, secondary and tertiary alkyl radicals conveniently and allows for the subsequent cascade construction of dual C(sp3)-C(sp3) and C=O bonds via radical addition, spirocyclization and oxidation sequence.

Recent Advances in the Construction of Spiro Compounds via Radical Dearomatization

“…After that, the same group demonstrated another alkyl and cyanoalkyl radicals induced spirocyclization and dearomatization of N ‐phenyl‐cinnamamides with TBPB or DTBP promotion, which was coupled with oxidative C( sp 3 )−H bond functionalization of simple alkanes [32b,c] . A short time later, the group of Yang extended this cascade spirocyclization and dearomatization to the DTBP‐promoted decarbonylative reaction of aliphatic aldehydes (Scheme 17c) [31g] …”

Strategies and methodologies for the construction of spiro-γ-lactams: an update

“…The iron-catalyzed decarbonylative alkylative spirocyclization of N-phenylcinnamamides 185 with aliphatic aldehydes 103 afforded 3-alkyl-spiro--lactams 186 in moderate to good yields (42-72%) (Scheme 41). 66 This synthesis shows good functional group tolerance, allowing the use of substrates bearing a 2-naphthalenyl and 2-furanyl at the β-position of the unsaturated amide and a wide array of aliphatic aldehydes. The generation of alkyl radicals was rationalized by considering an oxidative decarbonylation of aliphatic aldehydes promoted by a Fe(acac)2/DTPB catalytic system.…”