Control of the Dual Reactivity (Iminium-Dienamine) of β‑Arylmethyl α,β-Unsaturated Aldehydes in Organocatalytic 1,3-Dipolar Cycloadditions with N‑Benzoyl C,N-Cyclic Azomethine Imines

• Published in: Journal of organic chemistry 2014-11, Vol.79 (21), p.10417-10433
• Main Authors: Izquierdo, Cristina, Esteban, Francisco, Parra, Alejandro, Alfaro, Ricardo, Alemán, José, Fraile, Alberto, Ruano, José Luis García
• Format: Article
• Language: English
• Subjects: Aldehydes - chemistry; Azo Compounds - chemistry; Cycloaddition Reaction; Imines - chemistry; Ions - chemistry; Isoquinolines - chemistry; Models, Molecular; Molecular Structure; Thiosemicarbazones - chemistry
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo5018519

1,3-Dipolar cycloadditions of C,N-cyclic azomethine imines with α,β-unsaturated aldehydes can be performed with complete control of the regio-, exo-, and enantioselectivity under aminocatalytic conditions. The so far never studied competence of the iminium-dienamine reactivity inherent to β-alkyl α,β-unsaturated aldehydes was studied, which was possible by allowing achievement of complete control of the chemoselectivity in reactions of the β-arylmethyl derivatives with azomethine imines by using different additives and organocatalysts, whose role has been rationalized by DFT calculations and chemical proofs. Thus, it has been possible to selectively obtain the pyrazolidines resulting from both the attack to the C2–C3 (via iminium) and the C3–C4 (via dienamine) bonds at the starting enals, which can be used as precursors of interesting tetrahydroisoquinolinic compounds.