Replacement of Alcoholic Hydroxyl Groups by Halogens and Other Nucleophiles via Oxyphosphonium Intermediates

Abstract

The Michaelis–Arbuzov reaction involves the formation of dialkyl alkylphosphonates by heating alkyl halides with trialkyl phosphites, via an intermediate phosphonium salt. In recent years it has been found that phosphonium salts can be formed by reaction of a variety of trivalent phosphorus compounds with oxidizing electrophiles, and that the resulting phosphonium intermediates can be trapped with an alcohol to form alkoxyphosphonium cations. These cations can then undergo nucleophilic displacements, either with their own counterions or with added nucleophiles. This chapter is limited to species formed in situ from trivalent phosphorus compounds and various oxidants. The most commonly used trivalent phosphorus compounds are triphenyl phosphite, triphenylphosphine, and tris(dimethylamino)phosphine. The most commonly used oxidants are molecular halogens, alkyl halides, carbon tetrahalides, N ‐haloamides, N ‐haloamines, and diethyl azodicarboxylate (DEAD). Other oxidants that have been used include mercuric salts, peroxides, dithioesters, and sulfenamides. The more common combinations of phosphorus(III) compounds and oxidants are summarized. The replacement of hydroxyl groups by halogen, the most common use of oxyphosphonium intermediates, is the principal subject of this chapter. However, the replacement of hydroxyl groups by oxygen, nitrogen, sulfur, and carbon nucleophiles is also discussed. This review is restricted to alcoholic hydroxyl groups, and does not include a discussion of carboxylic hydroxyl groups. The principal combinations covered are triphenylphosphine–diethyl azodicarboxylate, triphenyl phosphite–methiodide, triphenylphosphine–halogen, triphenylphosphine–tetrahalomethane, triphenylphosphine–N‐haloimide, and tris(dimethylamino)phosphine–tetrahalomethane. Some of these combinations have been discussed in recent reviews.

O-alkylhydroxylamines as rationally-designed mechanism-based inhibitors of indoleamine 2,3-dioxygenase-1

“…The O-alkylhydroxylamine derivatives were synthesized from the analogous alcohol through a one pot process involving the Mitsunobu reaction with N-hydroxyphthalimide 27 and subsequent deprotection of the phthalimide group with hydrazine (Scheme 1) 28 . The O-alkyl hydroxylamines were purified and isolated as their hydrochloride salts.…”

Chemical Space Exploration of Oxetanes

“…Then a crossed Cannizzaro reaction was performed [21], reacting the aldehydes with formaldehyde in concentrated basic conditions, obtaining the 1,3-diol derivatives 4a-c. For the synthesis of the oxetanes applying strategy 1, we used the concept of hydroxyl replacement via oxyphosphonium salts, in which phosphonium salts can also be formed by reaction of different trivalent phosphorus compounds with oxidizing electrophiles, like the tris(dimethylamino)phosphine-carbon tetrachloride component system. The produced phosphonium intermediates can be trapped with an alcohol to form alkoxyphosphonium salts, which can then undergo nucleophilic displacement [22]. Based on the works of Castro and Selve [23], the dialkyloxetanes 5a-c were obtained in good yields (Scheme 1).…”

Viscosity, Degree of Polymerization, Water Uptake, and Water Solubility Studies on Experimental Dichloro-BisGMA-Based Dental Composites

“…The chemical structure of the monomer under investigation, dCl-BisGMA, was reported elsewhere [2]. The substitution generally occurs through a catalytic Appel reaction with an SN2 mechanism, resulting in an inverted configuration [15,22,23] (Figure 1). Al-Odayni et al [2] reported some of the monomer physicochemical properties, including viscosity and biocompatibility.…”