Isophthalic Acid–Derived Dicarbothioamides as Novel Metal-Free Catalysts in Hydrogen Bond–Promoted Reactions

Abstract

The synthesis of N,N′-diaryl-1,3-benzene-dicarbothioamides was accomplished in only two steps with good yields, and their ability to act as hydrogen-bond donors in Diels–Alder reactions was evaluated. These new organocatalysts were indeed able to promote the cycloaddition of cyclopentadiene to α,β-unsaturated aldehydes. In the attempt to control the absolute stereochemistry of the reaction, chiral catalysts were also prepared by simple condensation of isophthalic acid and α-amino acid derivatives. Molecular mechanics calculations were performed to elucidate the mode of action of these metal-free catalytic systems and to find a rationale for the achieved enantioselectivity.

Keywords:

• Carbothioamides
• C–C bond formation
• cycloaddition
• hydrogen bond
• organocatalysis

ACKNOWLEDGMENTS

This work was supported by Ministero Istruzione, Università e Ricerca (MIUR) (Rome) within the national project “Nuovi metodi catalitici stereoselettivi e sintesi stereoselettiva di molecole funzionali.”

Notes

^a Determined by ¹H NMR and confirmed after chromatographic purification after 72 h at 25°C.

^b Determined by ¹H NMR and confirmed by HPLC analysis.

^a Determined by ¹H NMR and confirmed after chromatographic purification after 72 h without any solvent.

^b Determined by ¹H NMR.

^c Determined by GC on chiral stationary phase (Agilent HP-chiral) t _{major exo}  = 59.1 min, t _{min exo}  = 59.6 min, t _{major endo}  = 60.6 min, t _{min endo}  = 62.2 min.