Domino Pd⁰‐Catalyzed C(sp³)–H Arylation/Electrocyclic Reactions via Benzazetidine Intermediates

Abstract

The Pd -catalyzed C(sp )-H arylation of 2-bromo-N-methylanilides leads to unstable benzazetidine intermediates that rearrange to benzoxazines through 4π electrocyclic ring-opening and 6π electrocyclization. The introduction of a bulky, non-activatable amide group on the nitrogen atom was key to favor the challenging reductive elimination step and disfavor undesired reaction pathways.

Benzazetidines and Related Compounds: Synthesis and Potential

“…The presence of these groups disfavors undesired reaction pathways. The benzazetidine ring was never observed, even at short reaction times . Performing the reaction at lower temperatures only resulted in incomplete conversion.…”

“…Recently, Baudoin and co‐workers considered an alternative synthesis of benzazetidine through a Pd 0 ‐catalyzed intramolecular C(sp 3 )−H arylation from easily accessible 2‐bromo‐ N ‐methylanilides (Scheme ) . This approach was initially reported by Ohno et al.…”

Stereoselective synthesis and applications of spirocyclic oxindoles

“…Inspired by Overman's study of asymmetric Heck cyclisations to spirocyclic oxindoles, 80 Sunoj and Kundig developed a Pd-catalysed enantioselective C-H arylation reaction to afford oxindole lic cascade reaction. 82,83 Xu could form the same unsubstituted cyclobutane, as well as 5-and 6-membered analogues, in an intramolecular 1,5-HAT using aryl iodides by visible light photoredox catalysis. 84 Gouverneur recently developed a silyl radical-mediated hydrosulfamoylation using sulfonyl chlorides and could effect a cascade spirocyclisation (Giese-type addition followed by aryl C-H transfer) from cyclobutene 15, albeit with only poor diastereoselectivity (Scheme 16).…”

Site-selective functionalization of remote aliphatic C–H bonds via C–H metallation

“…In 2016, Baudoin and co-workers reported intramolecular C(sp 3 )–H alkenylation of N , N -disubstituted bromoamides. 35 a The competitive generation of γ- and β-lactams arising from 6- and 5-membered palladacycles was investigated ( Scheme 17a ). While N-tert -butyl- N -methyl substrate 50a afforded exclusively γ-lactam 51a in high isolated yield (92%), the N -isopropyl- N -methyl substrate 50b gave a low yield of γ-lactam 51b (38%) with a small amount of β-lactam 52b (11%).…”