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Contra-Thermodynamic Halolactonization Of Lactam-Tethered 5-Aryl-4(E)-Pentenoic Acids For The Flexible And Stereocontrolled Synthesis Of Fused Lactam-Halolactones, Timothy K. Beng, Claire Borg, Morgan J. Rodriguez
Contra-Thermodynamic Halolactonization Of Lactam-Tethered 5-Aryl-4(E)-Pentenoic Acids For The Flexible And Stereocontrolled Synthesis Of Fused Lactam-Halolactones, Timothy K. Beng, Claire Borg, Morgan J. Rodriguez
All Faculty Scholarship for the College of the Sciences
Halolactonization of alkenoic acids enables the construction of oxygen-heterocycles via intramolecular halonium-induced nucleophilic addition. Although the literature is currently inundated with halolactonizations of 5-aryl-4(E)-pentenoic acids that predictably afford the 6-endo cyclization adducts, methods that reliably alter the innate regioselectivity bias to instead deliver the thermodynamically less favored 5-exo cyclization products are relatively rare. Here, we attempt to bridge this gap and have found mild conditions for contra-thermodynamic halolactonization of lactam-tethered 5-aryl-4(E)-pentenoic acids that lead to the formation of trans-fused lactam-γ-lactones. The natural proclivity for these 5-aryl-4(E)-pentenoic acids to undergo 6-endo cyclization is overridden and 5-exo-trig cyclization predominates. The success of …
Stereocontrolled Access To Δ-Lactone-Fused-Γ-Lactams Bearing Angular Benzylic Quaternary Stereocenters, Timothy K. Beng, Morgan J. Rodriguez, Claire Borg
Stereocontrolled Access To Δ-Lactone-Fused-Γ-Lactams Bearing Angular Benzylic Quaternary Stereocenters, Timothy K. Beng, Morgan J. Rodriguez, Claire Borg
All Faculty Scholarship for the College of the Sciences
C-fused γ-lactam-lactones are resident in several bioactive molecules, including anticancer agents such as omuralide. In this embodiment, we report mild conditions for the catalytic halolactonization of lactam-tethered 5-aryl-4(E)-pentenoic acids. The use of dichloromethane as the solvent and Ph3PS as the catalyst led to predominant 6-endo-trig cyclization and furnished the trans-fused-γ-lactam-δ-lactones. The transformation is modular, regioselective, chemoselective, and diastereoselective. The γ-lactam-δ-lactones bear angular quaternary benzylic stereocenters, which is noteworthy since the presence of a quaternary carbon in bioactive small molecules often promotes an element of conformational restriction that imparts potency, selectivity, and metabolic stability. The …