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

Ilhyong Ryu*, Takahide Fukuyama, Mami Tojino, Yoshitaka Uenoyama, Yuka Yonamine, Nozomi Terasoma, Hiroshi Matsubara

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

29 Scopus citations


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. Coupled with the subsequent protodestannylation procedure (TMSCl plus MeOH), these reactions provide a useful entry to α-methylene lactams with incorporation of CO as a lactam carbonyl group. In cases where the amines do not have a substituent acting as a radical leaving group, a reaction course involving a 1,4-H shift is chosen so as to liberate tin radicals ultimately. Thus the proposed mechanism involves (i) nucleophilic attack of amine nitrogen onto a carbonyl group of α,β-unsaturated acyl radicals/α-ketenyl radicals via lone pair-π* interaction, which leads to zwitterionic radical species, (ii) the subsequent proton shift from N to O to give hydroxyallyl radicals, (iii) 1,4-hydrogen shift from O to C, and (iv) β-scission to give lactams with liberation of tin radicals. DFT calculations reveal that the 1,4-hydrogen shifts, the key step of the reaction mechanism, can proceed under usual reaction conditions. On the other hand, an SHi type reaction to give lactams may be the result of the β-scission of the similar zwitterionic radical intermediates. DFT calculations also predict that an SHi type reaction would result when the intermediate has a good (radical) leaving group such as a phenethyl group.

Original languageEnglish
Pages (from-to)3780-3786
Number of pages7
JournalOrganic and Biomolecular Chemistry
Issue number10
StatePublished - 21 May 2011

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