Nucleophilic Substitution at Heteroatoms—Identity Substitution Reactions at Phosphorus and Sulfur Centers: Do They Proceed in a Concerted (SN2) or Stepwise (A–E) Way?

Abstract

The mechanisms of three selected identity substitution reactions at phosphorus and sulfur occurring with stereospecific inversion have been investigated using density functional theory (DFT). The first identity reaction between methoxyl anion and methyl ethylphenylphosphinate 1 reported in 1963 has been shown to proceed in a stepwise fashion according to the addition–elimination (A–E) mechanism involving formation of a pentacoordinate phosphorus intermediate (TBI-1). In contrast, the results of DFT studies of the identity chloride exchange reaction in (ethoxy)ethylphosphonochloridothionate 3 in acetone solution provided evidence that it proceeds synchronously according to the classical Ingold’s SN2-P mechanism. DFT calculations of the methoxyl–methoxy exchange reaction at sulfur in methyl p-toluenesulfinate 4 catalyzed by trifluoroacetic acid in methanol revealed that it proceeds stepwise (A–E mechanism), involving the formation of the high-coordinate sulfurane intermediate. In both identity transesterification reactions, 1 and 4, the transiently formed trigonal bipyramidal intermediates with the two methoxyl groups occupying apical positions (TBI-1 and TBI-4) have higher free energy barriers for the Berry-type pseudorotation than those for direct decomposition to starting phosphinate and sulfinate ensuring stereospecific inversion of configuration at the phosphinyl and sulfinyl centers. Thus, the DFT method proved its usefulness in the distinction between both mechanisms that are often indistinguishable by kinetic measurements.

Nucleophilic Substitution at Tricoordinate Sulfur—Alkaline Hydrolysis of Optically Active Dialkoxysulfonium Salts: Stereochemistry, Mechanism and Reaction Energetics

“…More information on this type of identity substitution reactions at S and P may be found in our recent paper [ 9 ].…”

“…A solution of this fundamental question was especially interesting for the identity substitution reactions at the chiral phosphorus and sulfur atoms. Taking advantage of the results of theoretical studies on substitution reactions at heteroatoms (P, S, Si) in simple achiral model compounds [ 5 , 6 , 7 , 8 ], we performed [ 9 ] the DFT calculations for the three symmetrical displacement reactions in the optically active phosphorus and sulfur compounds, as shown below ( Figure 1 ).…”

“…The kinetic measurements provided direct evidence that each elementary substitution step in these reactions occurs with a full inversion of configuration at the phosphorus and sulfur [ 10 , 11 , 12 ]. Now it has been found [ 9 ] that the methoxy–methoxy exchange reactions in phosphinate 4 and sulfinate 6 proceed in a stepwise fashion via the corresponding P V -phosphorane and S IV -sulfurane, respectively. The latter intermediates with the two methoxy groups in apical positions are the most stable, do not undergo pseudorotation and decompose directly to the starting compounds 4 and 6 , but with opposite configurations at P and S. On the other hand, the chloride–chloride exchange at phosphorus in 5 is a typical concerted S N 2-P process.…”

Nucleophilic Substitution at Phosphorus Centres – Old and Recent Studies and a Final Solution of Mechanistic and Related Stereochemical Problems

“…The outcome of our DFT calculation carried out for the identity transesterification reaction under discussion and the energetic profile obtained for this reaction (Figure 4) clearly demonstrates that it proceeds according to the stepwise AÀ Emechanism involving trigonal bipyramidal intermediate (TBPI) with the methoxy groups occupying apical positions. [23] This intermediate is most stable and undergoes direct stabilization to the enantiomeric phosphinate with inversion of configuration at P.…”