Visible-Light-Enabled Dual-Catalysis Approach to Stereoselective [2+2] Cycloaddition of Erlenmeyer-Plöchl Azlactones

Author(s)

Marra, Isabella F. S. ; Silva, Larissa P. ; De Castro, Pedro P. ; Flores, Leona S. ; De Oliveira, Kleber T. ; De Souza, Paulo E. N. ; Neto, Brenno A. D. ; Dos Santos, Helio F. ; Amarante, Giovanni W.

• Document type: Journal article
• Source: ASIAN JOURNAL OF ORGANIC CHEMISTRY; v. 13, n. 11, p. 9-pg., 2024-10-18.

Abstract

Visible-light-driven dual catalysis was employed to stereoselectively produce densely substituted cyclobutanes from Erlenmeyer-Pl & ouml;chl azlactones. The single-step preparation of non-natural amino acid dimers containing the cyclobutane moiety was achieved through a synergy between iridium photocatalysis and catalytic nickel(II) triflate as a Lewis acid. The desired 1,2-(zeta)-Z,E-isomers were isolated in good yields and with high regio- and diastereoselectivity (in all cases, >19 : 1 d.r.). To the best of our knowledge, this is the first report of direct access to truxinic acid analogues using azlactones. Control experiments, EPR reaction monitoring, and DFT calculations suggest that the presence of a Lewis acid, combined with the use of powerful blue LEDs, plays a crucial role in the reactivity of this reaction. (AU)

• FAPESP's process: 23/04020-8 - APIs synthesis using enabling technologies: approaches involving electrosynthesis and photocatalysis under continuous flow conditions
• Grantee: Kleber Thiago de Oliveira
• Support Opportunities: Regular Research Grants
• FAPESP's process: 21/13924-2 - Development of novel continuous flow approaches towards the preparation of pharmaceuticals: Axitinib, Lacosamide, Pioglitazone and Rosiglitazone
• Grantee: Pedro Pôssa de Castro
• Support Opportunities: Scholarships in Brazil - Post-Doctoral