Intramolecular nucleophilic displacement of halogen by phosphinate and thiophosphinate anions: relative rates of formation of five- and six-membered rings 1

Thiophosphinic Acids: Historic Overview and Recent Advances in their Synthesis and Applications

“…In 1999 Harger synthesized thiophosphinic acid 32 [9] to study the subsequent cyclization process. Hydrolysis of phosphinate 30 (prepared by an Arbusov reaction between diethoxyphenyl phosphine PhP(OEt) 2 and 1,4-chlorobromobutane) using 37% HCl at 120 o C gave phosphinic acid 31.…”

Cover Picture: Catalytic Molecular Logic Devices by DNAzyme Displacement (ChemBioChem 7/2014)

“…In an S N 2 process it is perhaps not surprising that the cyclization occurs more rapidly for the thiophosphonate than for the phosphonate 20. The difference in the rates of formation of the five‐ and the six‐membered cycles 22a and 22b , respectively (Scheme ), from the starting chloro thiophosphinate derivatives 21 ( k 5 / k 6 ) in CH 2 Cl 2 at 35 °C was calculated to be 30‐fold 21. This preference for the five‐membered product over the normally favored six‐membered form can be attributed to the longer lengths of P–S and S–C bonds, which thus create a bond angle (P–S–C) that is more accommodating than that in the oxygen counterpart.…”

Reactivity of ω-hydroxyalkylphosphinic Anilides in Cyclisation by Intramolecular Displacement of the Aniline Moiety

“…On completion the solution was washed with very dilute aqueous HCl and NaHCO 3 and the identity of the cyclic product 2 (n = 0 or 1) was confirmed spectroscopically: m/z (ES) 183 (n = 0) or 197 (n = 1) (M+H + ), δ P (CDCl 3 ) 57.8 (n = 0) or 37.9 (n = 1), δ H (CDCl 3 ) as previously described for products obtained from 1 (n = 0, 1). 4 In one case (n = 1) the spectra included signals attributable to the byproduct, probably the ester 7 (n = 1), δ P (CDCl 3 ) 28.5; m/z (ES) 366, 368 (M+H + ), δ H (CDCl 3 ) 4.04 (s, OCOCH 2 Cl).…”

“…Ester hydrolysis involving intramolecular nucleophilic catalysis by the phosphonate dianion 2 is only 1.5 times faster when the cyclic anhydride intermediate is five-membered rather than six; 3 also, the rate of formation of the cyclic phosphinate 2 from 1 by nucleophilic substitution (Scheme 1) is only 4.3 times greater when n = 0 than when n = 1. 4 We hoped to clarify this apparent anomaly by looking again at the formation of 2 but with the nucleophile and leaving group transposed. The structure of the product dictates that the nucleophile be an OH group (or O -) while the need to avoid premature cyclisation restricts the choice of leaving group.…”

“…Such values are not far removed from the values (∼ 10 2 ) generally seen for cyclisation reactions, 1 but they are much greater than the value of 4.3 (in CH 2 Cl 2 ) found previously for the base-induced cyclisation of the bromo compound 1 (n = 0, 1). 4 Since the two types of cyclisation give the same product 2, however, the anomalously small k 5 /k 6 ratio in one case cannot just be a reflection of strain in the product. The probable transition states 9 and 10 for the two types of cyclisation are not the same but they are rather similar, yet only in the case of 10 does ∆G ‡ show the normal sensitivity to chain length (k 5 >> k 6 ).…”