Microfluidic light-driven synthesis of tetracyclic molecular architectures

• Published in: Beilstein journal of organic chemistry Vol. 14; no. 1; pp. 2418 - 2424
• Main Authors: Mateos, Javier, Meneghini, Nicholas, Bonchio, Marcella, Marino, Nadia, Carofiglio, Tommaso, Companyó, Xavier, Dell'Amico, Luca
• Format: Journal Article
• Language: English
• Published: Germany Beilstein-Institut zur Föerderung der Chemischen Wissenschaften 17.09.2018; Beilstein-Institut
• Subjects: [4 + 2] photoenol; Biological activity; Chemistry; Chromatography; cycloaddition; Decomposition; flow chemistry; Intermediates; Letter; Light; Methods; microfluidic photoreactor; Microfluidics; photoredox catalysis; Productivity; synthetic photochemistry; synthetic photochemistry; microfluidic photoreactor; photoredox catalysis; cycloaddition; [4 + 2] photoenol; flow chemistry
• ISSN: 1860-5397; 2195-951X; 1860-5397
• DOI: 10.3762/bjoc.14.219

Herein we report an effective synthetic method for the direct assembly of highly functionalized tetracyclic pharmacophoric cores. Coumarins and chromones undergo diastereoselective [4 + 2] cycloaddition reactions with light-generated photoenol intermediates. The reactions occur by aid of a microfluidic photoreactor (MFP) in high yield (up to >98%) and virtually complete diastereocontrol (>20:1 dr). The method is easily scaled-up to a parallel setup, furnishing 948 mg of product over a 14 h reaction time. Finally, a series of manipulations of the tetracyclic scaffold obtained gave access to valuable precursors of biologically active molecules.