Dynamic Cross‐Exchange in Halophosphonium Species: Direct Observation of Stereochemical Inversion in the Course of an S_N2 Process

Abstract

The complex fluxional interconversions between otherwise very similar phosphonium bromides and chlorides R PX X (R=Alk, Ar, X=Cl or Br) were studied by NMR techniques. Their energy barriers are typically ca. 11 kcal mol , but rise rapidly as bulky groups are attached to phosphorus, revealing the importance of steric factors. In contrast, electronic effects, as measured by Hammett analysis, are modest (ρ 1.46) but still clearly indicate negative charge flow towards phosphorus in the transition state. Most significantly, detailed analysis of the exchange pathways unequivocally, and for the first time in any such process, shows that nucleophilic attack of the nucleophilic anion on the tetrahedral centre results in inversion of configuration.

Mechanisms and Beyond: Elucidation of Fluxional Dynamics by Exchange NMR Spectroscopy

“…Having established predominantly steric control in model process 173 a$173 b,N ikitin, Gilheany and colleagues developed the more general mixed-halogen cross-exchange methodology. [84] In as eries of P-stereogenic XPS 174 a-h (Scheme 55) with variable para-substituents,t he rate of exchange was monitored by 31 P- 31 PEXSY at À50 8C. The Hammett plot demonstrated good linearity with ap ositive reaction parameter (1 = 1.46 AE 0.15)-ac onfirmation of associative attack on the positively chargedp hosphonium centre.…”

“…Having established predominantly steric control in model process 173 a ↔ 173 b , Nikitin, Gilheany and colleagues developed the more general mixed‐halogen cross‐exchange methodology . In a series of P‐stereogenic XPS 174 a – h (Scheme ) with variable para ‐substituents, the rate of exchange was monitored by 31 P‐ 31 P EXSY at −50 °C.…”

Nucleophilic Substitution (SN2): Dependence on Nucleophile, Leaving Group, Central Atom, Substituents, and Solvent

“…Bulky substituents had a destabilizing effect on the central TC, thereby raising the barrier and eventually resulting in a labile TS. In a follow‐up study, Gilheany and co‐workers again turned to NMR techniques and this time measured the dynamic exchange of two different halogens at a tetrahedral phosphorus center . The free‐energy barrier of activation was calculated to be around 11 kcal mol −1 for the triphenyl halophosphonium salt and was found to increase rapidly as the steric bulk increased from Me, Et, iso ‐propyl, tert ‐butyl, to other sterically bulky groups.…”

One-Electron-Addition to Pentavalent Phosphorus with the Phosphorus-Chlorine Bond as Acceptor Introducing a Fundamental Distinction in Substitution Mechanism between S<sub>N</sub>2(P) and S<sub>N</sub>2(C)

“…The increase of the P-Cl bond is 0.47 Å and for the dissociation of Cl − 0.57 Å is requested which is in accordance with the favored electron-addition at 2R, 4S, 5R stereoisomer of 2-chloro-3,4 dimethyl-5-phenyl-1,3,2oxazaphospholidine-2-sulphide with regards to its 2S, 4S, 5R stereoisomer as shown in Figure 1. A related example can be given for the electron capture of an x-irradiated single crystal di(pentavalent-phosphine) disulphide [9] as: The sum of the spin densities of phosphorus is 0.816 (0.840), 0.870, and 0.830 with corresponding R(n) values of 1.23 (5), 1.23 (7), 1.23 (9), and 1.23 (6). The first two values correspond with two sets of the R = Me precursors with P-P distances of 2.245 and 2.165 Å, respectively.…”

“…Recently, a study of Nikitin et al [6] was published on the direct observation of the stereochemical inversion of phosphorus in an S N 2(P) reaction via a trigonal bipyramidal (TBP) geometry based on the conventional mechanism. The fluxional interconversions between otherwise very similar bromides and chlorides [R 3 P + -X] X − (R = Alkyl, Aryl; X = Cl, Br) were studied with NMR techniques.…”