Challenges in the Highly Selective [3 + 1]-Cycloaddition of an Enoldiazoacetamide to Form a Donor–Acceptor <i>Cis</i>-Cyclobutenecarboxamide

• Main Authors: Sipak Joyasawal, Donghui Ma, Michael P. Doyle
• Format: Article
• Language: English
• Published: MDPI AG 2021-06-01
• Series: Molecules
• Subjects: donor–acceptor cyclobutenecarboxamide; [3 + 1]-cycloaddition reaction; 3-siloxy-2-diazo-3-butenamides; <i>Z</i>-γ-substituted metallo-enolcarbene; box ligands; copper(I)
• Online Access: https://www.mdpi.com/1420-3049/26/12/3520
• ISSN: 1420-3049

A substituted donor–acceptor cyclobutenecarboxamide is synthesized with modest enantiocontrol through a chiral copper(I) complex catalyzed [3 + 1]-cycloaddition reaction of α-acyl diphenylsulfur ylides with 3-siloxy-2-diazo-3-butenamides. With a methyl substituent on the 4-position of the 3-butenamide, the <i>cis</i>-vicinal-3,4-disubstituted cyclobutenecarboxamide is formed with >20:1 diastereocontrol. Donor-acceptor 3-methyl-2-siloxycyclopropenecarboxamide is rapidly formed from the reactant enoldiazoamide and undergoes catalytic ring opening to give only the <i>Z</i>-γ-substituted metallo-enolcarbene. Elimination from 3-siloxy-2-diazo-3-pentenamide to form the conjugated 3-siloxy-2,4-pentadienamide is competitive but minimized at low temperature.