Asymmetric Synthesis of Phosphine Oxides with the Arbuzov Reaction

Abstract

The Arbuzov reaction of (5S,6S)-dimethoxy-2-phenyl-1,3,2-dioxaphosphacycloheptane with various alkyl halides produced acyclic phosphinates in a moderate to high diastereomer excess. The same reaction of (1S,7S)-9,9-dimethyl-4-phenyl-3,5,8,10,4-tetraoxaphosphabicyclo[5.3.0]decane with the alkyl halides needed the more vigorous reaction conditions and gave phosphinates in a low diastereomer excess. These phosphinates were converted into optically active phosphine oxides.

Asymmetric Electrophilic Reactions in Phosphorus Chemistry

“…(33) The Michaelis-Arbuzov reaction is one of the most universal methods for the formation of carbon-phosphorus bonds. The classical Michaelis-Arbuzov reaction consists in the alkylation of trivalent phosphorus acid esters with alkyl halides to form derivatives of the corresponding pentavalent phosphorus acids containing a new P-C bond: phosphonates, phosphinates or tertiary phosphine oxides (Equation 34) [49][50][51][52][53][54]. The stereochemistry of this reaction is of particular interest, the research results of which have not been fully generalized, although intensive studies were carried out.…”

“…In the next stage, the intramolecular nucleophilic attack of a halide ion to the carbon atom of alkoxy group afforded an alkyl halide and phosphine oxide. The Michaelis-Arbuzov reaction of chiral phosphinites with alkyl halides proceeds stereospecifically with complete retention of absolute configuration at the phosphorus atom (Equation (35)) [49][50][51]. 35The reaction of trialkylphosphites containing chiral alkoxy groups stereospecifically led to the formation of chiral alkyl halides with the inverted configuration [50].…”

“…These phosphinates were converted into optically active phosphine oxides by reaction with Grignard reagents as shown in Equation 43 The Michaelis-Arbuzov reaction of (5S, 6S)-dimethoxy-2-phenyl-1,2,3-dioxaphosphacycloheptane with various alkyl halides led to the formation of corresponding phosphinates with a satisfactory enantiomeric excess. These phosphinates were converted into optically active phosphine oxides by reaction with Grignard reagents as shown in Equation 43 [49].…”

“…This phosphinate was introduced into the Grignard reaction resulted in the tertiary (R)-phosphinates. Thus, the stereospecific Michaelis-Arbuzov reaction of the geometric isomer of 2-methoxy-5-tert-butyl-1,1,3,2-dioxaphosphorinan with the alkyl halide X-R 1 led to the formation of chiral tertiary phosphine oxides (Scheme 6) [49].…”

Cyclic tri- and Pentavalent Amidoesters and Diamides with a Stereogenic Phosphorus Atom in Asymmetric Synthesis: Part I: Stoichiometric Reagents

“…Among a few protocols leading to optically active phosphine oxides and phosphinates based on asymmetric synthesis which have been worked-up [10][11][12][13][14][15][16][17][18][19] since the classical works of Mislow et al [20][21] one can apply an approach proposed by Juge based on a Arbusov rearrangement of diasteromerically pure 2-phenyl-1,3,2-oxazaphospholidine (2R,4S, 5R)-3 which was prepared by the reaction of achiral bis-(diethylamino)phenylphosphine 1 with L-ephedrine 2 (Scheme 1) [22]. Its reaction with alkyl halides gave the phosphinamides 4a-d by the Arbusov rearrangement with retention of configuration at the phosphorus atom and stereoselectivity which depends on the steric requirements of the alkyl group and reaction conditions (de from 0 to 85%).…”