A construction of 4,4-spirocyclic γ-lactams by tandem radical cyclization with carbon monoxide.

A straightforward synthesis of 4,4-spirocyclic indol γ-lactams by tandem radical cyclization of iodoaryl allyl azides with CO was achieved. The reaction of iodoaryl allyl azides, TTMSS and AIBN under CO pressure (80 atm) in THF at 80 °C gave the desired 4,4-spirocyclic indoline, benzofuran, and oxindole γ-lactams in moderate to good yields.

Radical carbonylation of ω-alkynylamines leading to α-methylene lactams. Synthetic scope and the mechanistic insights.

Tin hydride mediated radical carbonylation and cyclization reaction was investigated using a variety of ω-alkynyl amines as substrates. In this reaction α-methylene and α-stannylmethylene lactams having five to eight membered rings were obtained as principal products. In cases where the nitrogen has a substituent capable of giving stable radicals, such as an α-phenethyl group, the lactam ring formation again took place with extrusion of an α-phenethyl radical.

Synthesis of lactams by radical substitution reaction of alpha,beta-unsaturated acyl radicals at amine nitrogen.

[reaction: see text] Substitution at nitrogen by alpha,beta-unsaturated acyl radicals took place accompanied by elimination of an alpha-phenethyl radical. This reaction led to the development of a new carbonylative annulation method for five- to seven-membered ring lactams.

CO-trapping reaction under thermolysis of alkoxyamines: application to the synthesis of 3,4-cyclopenta-1-tetralones.

[reaction: see text] An efficient one-pot sequence comprising a PRE-mediated radical 5-exo-cyclization, a radical carbonylation, a nitroxide trapping reaction, and a subsequent acid-catalyzed Friedel-Craft-type acylation provides a new entry into 3,4-cyclopenta-1-tetralones. Eight examples are presented.

Intramolecular nucleophilic carbonyl trapping of alpha-ketenyl radicals by an amino group.

Free-radical carbonylation of omega-alkynylamines with tributyltin hydride gives a mixture of alpha-methylene lactams and alpha-stannylmethylene lactams. Nucleophilic addition of an internal amino group to the carbonyl group of alpha-ketenyl radicals is proposed as the cyclization step. The subsequent unusual 1,4-H shift from the resulting 1-hydroxyallyl radical, followed by elimination of the beta-tributyltin radical leads to the formation of alpha-methylene lactams.