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. 2023 Sep 1;25(34):6380-6384.
doi: 10.1021/acs.orglett.3c02390. Epub 2023 Aug 23.

Cobalt-Catalyzed Aerobic Aminocyclization of Unsaturated Amides for the Synthesis of Functionalized γ- and δ-Lactams

Manuel Freis  1 , Moritz Balkenhohl  1 , David M Fischer  1 , Tony Georgiev  1 , Roman C Sarott  1 , Erick M Carreira  1
Affiliations

Cobalt-Catalyzed Aerobic Aminocyclization of Unsaturated Amides for the Synthesis of Functionalized γ- and δ-Lactams

Manuel Freis et al. Org Lett. .

Abstract

We report the cobalt-catalyzed aminocyclization of unsaturated N-acyl sulfonamides in the presence of oxygen to provide γ- and δ-lactam aldehydes. Use of an optically active cobalt catalyst resulted in the formation of enantiomerically enriched γ-and δ-lactam alcohols. The γ-lactam aldehydes and alcohols obtained were elaborated into useful building blocks.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Scheme 1
Scheme 1. Biologically Active γ- and δ-Lactams and Aminocyclization of Unsaturated Amides
Scheme 2
Scheme 2. Prior Work: Cyclization of Unsaturated N-Acyl Sulfonamides and Unsaturated N-Aryl Amides
Scheme 3
Scheme 3. Substrate Scope for the Cobalt-Catalyzed Aminocyclization of Unsaturated N-Acyl Sulfonamides
Scheme 4
Scheme 4. Substrate Scope of the Cobalt-Catalyzed Aminocyclization with Subsequent Reduction
Enantiomeric ratios were determined via chiral HPLC or SFC by comparison with racemic samples (see SI). For the enantioenriched reaction it was found, that catalyst C2 required higher catalyst loadings of 20 mol %. Reaction conditions: (b) 55 °C, 2 h; (c) 55 °C, 48 h. (d) e.r. of the major diastereomer.
Scheme 5
Scheme 5. Selected Derivatization of γ-Lactam Aldehydes and Alcohols
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