Synthesis of highly functionalized pyrrolidines via a selective iodide-mediated ring expansion of methylenecyclopropyl amides.
This manuscript describes a highly selective iodide-mediated, tandem Mannich/cyclization to afford trans-2,3-disubstituted pyrrolidines from methylenecyclopropyl amides in good to excellent yields and selectivities. The reaction scope has been drastically expanded to include a wide array of aromatic, heteroaromatic and alpha,beta-unsaturated imines, as well as a variety of methylenecyclopropyl amides. Additionally, mechanistic studies were carried out to ascertain the nature of the ring-opening/ring-closing mechanism using deuterated substrates. Results from these studies indicate that the primary mechanism is an S(N)2/S(N)2 ring opening/ring closing and that iodine- or iodide-mediated isomerization of the iodo enolate is likely occurring.
Davenport Research Laboratories, Department of Chemistry, University of Toronto, 80 St. George Street, Toronto, Ontario, Canada M5S 3H6.
Mark E
ME
Scott
Mark
M
Lautens
D000577:Amides / Q000737:chemistry*; D003500:Cyclization; D003521:Cyclopropanes / Q000737:chemistry*; D003903:Deuterium; D007097:Imines / Q000737:chemistry; D007454:Iodides; D007536:Isomerism; D011759:Pyrrolidines / Q000138:chemical synthesis*
D000577:Amides; D003521:Cyclopropanes; D007097:Imines; D007454:Iodides; D011759:Pyrrolidines; C067351:cyclopropylamine; D003903:Deuterium