Enantioselective Synthesis of 2, 3‐Dihydrofurocoumarins by Squaramide‐Catalyzed Michael Addition/Cyclization of 4‐Hydroxycoumarins with β‐Nitrostyrenes. Issue 5 (5th February 2018)

• Record Type: Journal Article
• Authors: Modrocká, Viktória; Veverková, Eva; Baran, Rastislav; Šebesta, Radovan
• Is Part Of: ChemistrySelect. Volume 3:Issue 5(2018)
• Page Start: 1466
• Page End: 1471
• Publication Date: 2018-02-05
• Subjects: coumarin -- Michael addition -- nitroalkene -- organocatalysis -- squaramide; Chemistry -- Periodicals; 540.5
• DOI: 10.1002/slct.201800147
• Languages: English
• ISSNs: 2365-6549

Abstract

Abstract: This work describes the enantioselective synthesis of chiral 2, 3‐dihydrofurocoumarins by squaramide‐catalyzed Michael addition of 4‐hydroxycoumarins to β‐nitrostyrenes, followed by a cyclization reaction. A coumarin moiety is present in many chiral bioactive compounds, but the organocatalysis has still not reached its full potential in the synthesis of chiral coumarins. Here, we used squaramide catalysts comprising two chiral units, ( S )‐phenylethylamine and cyclohexane‐1, 2‐diamine. These catalysts showed high reactivity and enantioselectivity in this transformation. Following this procedure, we prepared a series of 2, 3‐dihydrofurocoumarin derivatives in 47‐93% yields and enantiomeric purities in the range of 78‐94% ee. Polystyrene‐immobilized squaramide catalyst performed well for the initial two reaction cycles but then slowly degraded. The absolute configuration of 2, 3‐dihydrofurocoumarin products was determined by the comparison of the experimental and density functional theory‐calculated electronic circular dichroism spectra. Abstract : Squaramide catalyst comprising two chiral elements, phenylethylamine and 2‐(piperidin‐1‐yl)cyclohexan‐1‐amine, effectively catalyzes Michael addition followed by a cyclization reaction of 4‐hydroxycoumarins with nitroalkenes. This transformation affords chiral 2, 3‐dihydrofuro[3, 2‐c]‐coumarin derivatives in good yields and enantiomeric purities. Immobilized squaramide catalyst was effective for two reaction cycles. Absolute configurations of furocoumarin products were determined by comparison of DFT calculated ECD with experimental ones.