[2537-48-6] · C6H12NO3P · Diethyl Cyanomethylphosphonate · (MW 177.14)
(modified Wittig reagent,
Wadsworth-Emmons modification, producing a,b-unsaturated nitriles as products from reaction with aldehydes and ketones)
Physical Data: bp 101-102 °C/0.4 mmHg; d 1.095 g cm-3.
Solubility: sol THF, DME, methylene chloride.
Form Supplied in: oil; widely available.
Preparative Methods: prepared by the Michaelis-Arbuzov reaction1 utilizing Triethyl Phosphite and a haloacetonitrile.2 More recently, a preparation was reported utilizing Trimethyl Phosphite and Chloroacetonitrile.3 Thus a mixture of the two reagents was heated at 140-150 °C for 18 h under nitrogen to give a 75% yield of the closely related dimethyl cyanomethylphosphonate. Alternatively, Acetonitrile is treated with 2 equiv of Lithium Diisopropylamide in THF at -78 °C followed by diethyl chlorophosphate (Diethyl Phosphorochloridate) to provide a 47% yield of diethyl cyanomethylphosphonate.4
Handling, Storage, and Precautions: corrosive.
The most common use of the reagent is the preparation of a,b-unsaturated nitriles from ketones or aldehydes. The stereochemistry of the a,b-unsaturated nitriles is variable, depending on the substrate5 and the reaction conditions.6 Pasto reported a (Z)-favored alkenation on 3-hydroxy-3-methylbutanal (eq 1).7 In contrast, Paquette reported the alkenation shown in eq 2 where the (E)-isomer predominates.8
Sodium Hydride in THF or DME is the most popular base-solvent combination used to effect the Horner-Emmons reaction with diethyl cyanomethylphosphonate. Other useful but less popular conditions include: phase transfer,9 polymer bound diethyl cyanomethylphosphonate,10 and electrochemical methods.11 A vast array of other reaction conditions have been reported in the literature.12
Cyano-substituted cyclopropanes can be prepared by the reaction between diethyl cyanomethylphosphonate and epoxides (eq 3).2
Diethyl cyanomethylphosphonate anions react with aryl iodides in the presence of copper(I) to give a-arylated alkanenitriles (eq 4).13
Nitrones react with diethyl cyanomethylphosphonate to yield aziridines (eq 5).14
Syntex Technology Center, Boulder, CO, USA