Palladium-Catalyzed Carbonylative [5+1] Cycloaddition of N-Tosyl Vinylaziridines: Solvent-Controlled Divergent Synthesis of α,β- and β,γ-Unsaturated δ-Lactams

Abstract

A palladium-catalyzed carbonylative [5+1] cycloaddition of N-tosyl vinylaziridines with CO has been developed. This protocol affords an efficient and practical approach for solvent-controlled divergent synthesis of α,β-unsaturated δ-lactams in dimethylformamide and β,γ-unsaturated δ-lactams in tetrahydrofuran in good to excellent yields. Significantly, the step- and atom-economical reactions are more regioselective toward [5+1] cycloaddition than toward [3+1] cycloaddition.

Recent updates on vinyl cyclopropanes, aziridines and oxiranes: access to heterocyclic scaffolds

“…These aldehydes 81 underwent a facile Scheme 28 Synthesis of δ-lactams and δ-lactones by Li's approach. 66 Scheme 27 Synthesis of α,β-unsaturated-δ-lactams and lactones by Li's approach. 65 [3 + 3] cycloaddition reaction to accomplish an array of bi-and tri-heterocyclic scaffolds 83, 84-86 in a moderate yield (up to 73%).…”

“…In the presence of H 2 O, Int-II converts to Int-III , which upon migratory insertion delivers Int-IV , which upon reductive elimination followed by isomerization renders [5 + 1] cycloaddition product 77 with regeneration of the Pd(0) catalyst to continue the catalytic cycle. Later the same group 66 reported a Pd-catalyzed [5 + 1] cascade reaction by utilizing substituted vinyl aziridines 56 and CO gas to accomplish α,β-unsaturated δ-lactams 77 and β,γ-unsaturated δ-lactams 78 in a good-to-excellent yield ( 77 = up to 81% and 78 = up to 95%) by tuning the reaction with THF and DMF (Scheme 28). Sterically hindered vinyl aziridines 56f and 56h delivered [3 + 1] product 79a (33% yield) and 79b (35% yield) along with [5 + 1] cycloaddition product 78f (55% yield) and 78h (56% yield).…”

Palladium-Catalyzed Iodine Assisted Carbonylation of Indoles with ClCF2CO2Na and Alcohols

“…Song’s group developed an elegant Pd-catalyzed [4 + 1] annulation of 2-iodobiphenyls with ClCF 2 CO 2 Na . Additionally, we disclosed a Pd-catalyzed regioselective [5 + 1] annulation of vinyl aziridines/epoxides with ClCF 2 COONa . Inspired by employing difluorocarbene as carbonyl source − and the preiodination strategy of indoles, we herein developed a practical and efficient Pd-catalyzed, iodine-assisted carbonylation of indoles using ClCF 2 CO 2 Na and alcohols.…”

“…Based on the above-mentioned control experiments and previous literature reports, ,, a tentative mechanism was proposed, as shown in Scheme . Initially, 1a readily reacted with I 2 with the assistance of a base, leading to 3-iodo-1-methyl-indole 1a′ in a regioselective fashion.…”

“…Additionally, we disclosed a Pd-catalyzed regioselective [5 + 1] annulation of vinyl aziridines/epoxides with ClCF 2 COONa . Inspired by employing difluorocarbene as carbonyl source − and the preiodination strategy of indoles, we herein developed a practical and efficient Pd-catalyzed, iodine-assisted carbonylation of indoles using ClCF 2 CO 2 Na and alcohols. Significantly, our operationally simple and scalable carbonylation reaction displayed high regioselectivity and a great functional group tolerance.…”