Regioselective O/C phosphorylation of α-chloroketones: a general method for the synthesis of enol phosphates and β-ketophosphonates via Perkow/Arbuzov reaction

Abstract

A highly regioselective O/C phosphorylation of α-chloroketones with trialkyl phosphites was developed in the preparation of enol phosphates and β-ketophosphonates.

Synthesis of β‐Chloro‐α‐hydroxyphosphonates through Triethylamine‐Catalyzed Pudovik Reaction

“…Since our previous research has shown that solvent-free conditions could highly benefit to the Perkow regioselectivity, [28] we then inferred that it might also be applicable to the Pudovik reaction involving similar carbonyl additon by phosphite. Therefore, dimethyl phosphite (1 a) and 2-chloroacetophenone (2 a) were Initially chosen as a model substrate for the optimization of the solvent-free reaction conditions (Table 1).…”

“…Encouraged by our previous success in regiospecific O/Cphosphorylation progress about the Perkow/Arbuzov reaction, [28] we then turned into the control of Pudovik/ Arbuzov/Perkow reactions. Herein, we wish to report an efficient Et 3 N-catalyzed solvent-free synthesis of β-chloro-αhydroxyphosphonates under mild conditions.…”

Synthesis of enol phosphates directly from ketones via a modified one-pot Perkow reaction

“…To date, numerous methods to synthesize EPs have been reported which can be broadly categorized as follows: (1) the earliest recorded and still extensively used Perkow reaction between α-haloketones and phosphites; 15 (2) the phosphorylation of in situ generated enolate of ketones by various kinds of metalation process; 16 (3) other approaches such as hydrophosphoryloxylation of alkynes, 17 tandem reaction of α-aryloxyacetophenones, 18 and so on. 19 However, whilst the classical Perkow reaction is much limited by the availability of the toxic and lachrymatory α-haloketones and the lack of effective regio- and stereocontrol, the non-Perkow methods always suffer from harsh reaction conditions including use of strong bases (mostly metallic) and unstable phosphorochloridates some of which are generally inconvenient to prepare such as P–C and/or P–N containing materials.…”