Potassium tert‐Butoxide‐Catalyzed Synthesis of α‐Methylene‐β‐Lactams from Propiolamides

Abstract

We reported herein the regio-and stereoselective synthesis of α-methylene-β-lactams via a 4-exo-dig-cyclization of N-benzyl-N-methyl-propiolamides catalyzed by a base. The experimental evidence suggests that this transformation proceeds via a concerted ionic cyclization with a carbon nucleophilic addition to the carbon-carbon triple bond, followed by protonation of the vinyl species promoted by tert-butanol. The obtained αmethylene-β-lactams were suitable substrates for the Heck coupling conditions affording the corresponding products via carbon-carbon bond formation.

Stereoselective synthesis of β-lactams: recent examples

“…Zeni and coworkers described a stereo- and regioselective base-catalyzed intramolecular cyclization of N -benzyl- N -methyl-propiolamides 96 to form α-methylene-β-lactam compounds 97 employing potassium tert -butoxide as the base and dimethylsulfoxide as the solvent. 67 The target lactams were obtained in yields up to 87% observing high selectivity for the 4- exo -dig cyclization over the 5- endo -dig process. The highest yields were observed when aryl motifs having electron-donating substituents in the para position were employed.…”

Roles of Alkali Metals tert‐Butoxide as Catalysts and Activators in Organic Transformations

“…Using a similar catalytic approach with a combination of t BuOK/DMSO, Claus and co‐workers have reported 4‐exo‐dig‐cyclization of substituted‐propionamides 10 to synthesize the different substituted derivatives of α ‐methylene‐ β ‐lactams 11 (Scheme 10). [18] To achieve the required cyclization, 30 mol% of KO t Bu has been shown to be most effective and they have proved this methodology to be efficient by synthesizing diversely substituted β ‐lactams through different propiolamides.…”