Base Catalyzed Nucleophilic Displacement Reactions of Pentacovalent Phosphorus.

摘要

Pentaoxyphosphoranes are studied as intermediates or activated states in nucleophilic displacement reactions at pentacovalent phosphorus. The work concentrated on the synthesis and structural characterization of cyclic oxyphosphoranes and their role in reaction mechanisms of cyclic AMP with phosphodiesterases and protein kinases. Both experimental and ab-initio calculations support mechanistic schemes for inversion of caMP by phosphodiesterases which position the ring axial equatorially in a trigonal bipyramid (TBP) and argue against retention mechanisms for the action of caMP with protein kinases involving a covalently bound intermediate with the ring located diequatorially. Active site constraints, i.e., hydrogen bonding, electronegativity, steric, and ring strain, were used in synthesizing new oxyphosphorane model intermediates. Rings varying in size from five- to eight-membered prefer apical-equatorial sites of a TBP. Variable temperature NMR and single crystal X-ray diffraction gave energy barriers for ring interchange and solid state molecular structures, respectively.