FAM‐Ag‐catalyzed asymmetric synthesis of heteroaryl‐substituted pyrrolidines

• Published in: Chirality (New York, N.Y.) Vol. 33; no. 8; pp. 465 - 478
• Main Authors: Beksultanova, Nurzhan, Gözükara, Zeynep, Araz, Mihrimah, Bulut, Merve, Polat‐Çakır, Sıdıka, Aygün, Muhittin, Dogan, Özdemir
• Format: Journal Article
• Language: English
• Published: HOBOKEN Wiley 01.08.2021; Wiley Subscription Services, Inc
• Subjects: Acrylics; Acrylonitrile; Asymmetric synthesis; Asymmetry; Catalysts; Chemical synthesis; Chemistry; Chemistry, Analytical; Chemistry, Medicinal; Chemistry, Organic; chiral FAM ligands; chiral metal catalyst; Crystallization; Cycloaddition; heteroaryl‐substituted pyrrolidines; Life Sciences & Biomedicine; Ligands; Methanol; Pharmacology & Pharmacy; Physical Sciences; Science & Technology; Stereochemistry; Substitutes; substituted pyrrolidines; asymmetric synthesis; SELF-DISPROPORTIONATION; ENANTIOMERS; AZOMETHINE YLIDES; chiral metal catalyst; chiral FAM ligands; heteroaryl‐ DERIVATIVES; ENANTIOSELECTIVE 1,3-DIPOLAR CYCLOADDITION
• ISSN: 0899-0042; 1520-636X
• DOI: 10.1002/chir.23320

New derivatives of FAM (ferrocenyl aziridinyl methanol) ligands NFAM1–4 (naphthyl ferrocenyl aziridinyl methanol) and CFAM1–4 (cyclohexyl ferrocenyl aziridinyl methanol) were synthesized to form a small ligand library and used as chiral catalysts with AgOAc for the asymmetric synthesis of heteroaryl‐substituted pyrrolidines by the 1,3‐dipolar cycloaddition (1,3‐DC) reaction of azomethine ylides. 2‐Thienyl, 2‐furyl, 2‐, 3‐, and 4‐pyridyl aldimines were prepared and used with N‐methylmaleimide, dimethyl maleate, tert‐butyl acrylate, methyl acrylate, and acrylonitrile to form the corresponding heteroaryl‐substituted pyrrolidines. 1,3‐DC reactions yielded the expected cycloadducts in up to 89% yield and up to 76% ee that could be increased up to 95% ee upon crystallization. New chiral ligands NFAM1–4 and CFAM1–4 were fully characterized, and their absolute stereochemistry was determined by single‐crystal X‐ray analysis. New FAM ligands were synthesized and used as chiral catalysts for the asymmetric synthesis of heteroaryl‐substituted pyrrolidines.