Unexpected four-membered over six-membered ring formation during the synthesis of azaheterocyclic phosphonates: experimental and theoretical evaluation.
The cyclization of functionalized aminophosphonates is studied on both experimental and theoretical grounds. In a recently described route to phosphono-beta-lactams [Stevens C. V.; Vekemans, W.; Moonen, K.; Rammeloo, T. Tetrahedron Lett. 2003, 44, 1619], it was found that starting from an ambident allylic anion only four-membered rings were formed without any trace of six-membered lactams. New anion trapping experiments revealed that the gamma-anion is highly reactive in intermolecular reactions. Ab initio calculations predict higher reaction barriers for the gamma-anion due to restricted rotation about the C-N bond and due to highly strained transition states during ring closure. The sodium or lithium counterion, explicit dimethyl ether solvent molecules, and bulk solvent effects were properly taken into account at various levels of theory.
Van Speybroeck
Veronique
V
Center for Molecular Modeling, Ghent University, Proeftuinstraat 86, B-9000 Ghent, Belgium. veronique.vanspeybroeck@ugent.be
Moonen
Kristof
K
Hemelsoet
Karen
K
Stevens
Christian V
CV
Waroquier
Michel
M
D001372:Aza Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D003500:Cyclization; D008956:Models, Chemical; D008958:Models, Molecular; D015394:Molecular Structure; D063065:Organophosphonates / Q000138:chemical synthesis* / Q000737:chemistry*; D011789:Quantum Theory; D012995:Solubility; D013237:Stereoisomerism
D001372:Aza Compounds; D063065:Organophosphonates