Synthesis of 4-membered ring alkaloid analogues via intramolecular [2+2] cycloaddition involving keteniminium salt intermediates

• Published in: Tetrahedron letters Vol. 58; no. 30; pp. 2904 - 2909
• Main Authors: Kolleth, Amandine, Lumbroso, Alexandre, Tanriver, Gamze, Catak, Saron, Sulzer-Mossé, Sarah, De Mesmaeker, Alain
• Format: Journal Article
• Language: English
• Published: OXFORD Elsevier Ltd 26.07.2017; Elsevier
• Subjects: [2+2]Cycloaddition; Aminocyclobutane; Chemistry; Chemistry, Organic; Cyclobutane iminiums; DFT calculations; Keteniminium salts; Physical Sciences; Science & Technology; Cyclobutane iminiums; [2+2]Cycloaddition; Aminocyclobutane; Keteniminium salts; DFT calculations; ELECTROPHILIC REARRANGEMENTS; ENTRY; AMINO; DENSITY FUNCTIONALS; SOLUTES; OLEFINS; CYCLIZATION; AMIDES
• ISSN: 0040-4039; 1873-3581
• DOI: 10.1016/j.tetlet.2017.06.033

[Display omitted] •Straightforward method for the synthesis of 4-membered ring alkaloid analogues via intramolecular [2+2] cycloadditions.•Keteniminium salt cyclization in which an alkene is linked by the nitrogen atom follow by a diastereoselective reduction.•Competition reaction as well as DFT calculation have been done to confirm and explain experimental observation. We have developed a very straightforward method for the synthesis of 4-membered ring alkaloid analogues via intramolecular [2+2] cycloadditions. This involves the cyclization of a keteniminium salt in which an alkene is linked by the nitrogen atom, and where, the resulting cyclobutane iminium is reduced in a diastereoselective manner. Competition reactions have been performed to fully understand the features of this sequence. Moreover, DFT calculations have verified that the [2+2] cycloaddition step is driven by kinetic and not thermodynamic factors confirming all the experimental observations.