Stereoelectronic effects in pentacoordinate intermediates and acceleration of nucleophilic substitution at phosphorus

Gregory R.J. Thatcher, E. S. Krol, Dale R. Cameron

Research output: Contribution to journalArticlepeer-review

16 Scopus citations


Hydroxide-dependent hydrolysis of triesters of phosphonoformic acid (PFA) via P-O bond cleavage proceeds at rates 103-106 times greater than hydrolysis of simple phosphonates. The means by which an α-carbonyl substituent elicits such a rate enhancement has been examined using ab initio calculations. Model compounds have been derived, from full geometry optimization at the RHF/6-31G*//6-31G* level, of (a) the tetracoordinate ground state PFA triesters (4, RPO3Me2; R = CHO) and simple phosphonate esters (4, R = CF2H, CH3), and (b) pentacoordinate intermediates for hydrolysis of these triesters (5, RPO4H3-; 6, RPO4HMe2 -, R = CHO, CO2H and 5, 6, R = CF2H, CH 3, respectively). Intramolecular charge-transfer interactions have been quantified employing natural bond orbital analysis, including calculation of molecular energies on deletion of each individual interaction. These molecular orbital calculations demonstrate significant stabilizing, intramolecular charge-transfer interactions, including internal hydrogen bonding and np(O)→π* (C=O) charge transfer in the pentacoordinate state. The n→π* stabilization contributes 4-10 kcal mol-1 to the stabilization of these intermediates in the gas phase. It is suggested that such charge-transfer stabilization in the pentacoordinate intermediates and transition states for hydrolysis of PFA triesters contributes to the observed rate enhancement. In contrast, these calculations show no evidence for the stereoelectronic effect (akin to the generalized anomeric effect) proposed by Gorenstein and Taira for pentacoordinate phosphoranes and suggested also to lead to large rate enhancements for nucleophilic substitution at phosphorus. Calculations on models [7, RC(O)CO3HMe-, R = H, OH] for tetrahedral intermediates in oxalate ester hydrolysis demonstrate a greatly diminished intramolecular np(O)→π*(C=O) charge-transfer stabilization. This is in accord with rate data on carboxylate ester hydrolysis.

Original languageEnglish (US)
Pages (from-to)683-690
Number of pages8
JournalJournal of the Chemical Society, Perkin Transactions 2
Issue number4
StatePublished - 1994
Externally publishedYes

ASJC Scopus subject areas

  • General Chemistry


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