The Horner-Wadsworth-Emmons reaction

Question 1

Describe the key features of the HWE rxn

Answer 1

1 - driving force is formation of P=O. 2 - works best with phosphonates with alpha-anion stabilising substituent e.g. R= CO2R, CN, SO2Ph, Ph etc. 3 - a-phosphonate anions more Nu- than phosphonium ylids (pentavalent P cannot stabilise charge as well) so can use less reactive aldehydes and ketones and milder conditions. 4 - typical bases: NaH, KH, alkoxides, NaNH2. 5 - dialkyl phosphate salt byproduct water soluble so facilitates work up.

Question 2

Describe the addition of phosphonate anions to carbonyls

Answer 2

THERMODYNAMIC control (c.f. Wittig). Forms more stable trans oxaphosphetane. Stereoselectivity determined by initial condensation rxn and degree of equilibration. Stereoselectivity of addition modulated by varying alkoxy substituents on phosphate.

Question 3

How are phosphonates formed?

Answer 3

Arbusov rxn. Heat trialkylphosphite and alkyl halide in absence of solvent. Driving force is formation of strong P=O.