Explain Horner Wadsworth Emmons reaction.
Answers
Horner-Wadsworth-Emmons Reaction
"Olefin Synthesis with Organic Phosphonate Carbanions," J. Boutagy and R. Thomas, Chem. Rev. 1974, 74, 87. "Synthetic Applications of Phosphoryl Stabilized Anions," W. S. Wadsworth, Jr. Org. React. 1977, 25, 73. "Wadsworth-Emmons Reaction Revisited," W. J. Stec, Acc. Chem. Res. 1983, 16, 411. "Vinylphosphonates in Organic Synthesis," Minami, T.; Motoyoshiya, J. Synthesis 1992, 333. Minami, T.; Okauchi, T.; Kouno, R. α-Phosphonovinyl Carbanions in Organic Synthesis. Synthesis 2001, 349-57. "Stereocontrol in Organic Synthesis Using the Diphenylphosphoryl Group," Clayden, J.; Warren, S. Angew. Chem. Int. Ed. Engl. 1996, 35, 241-70.
The HWE reaction is the reaction of a carbonyl compound with an α-metalated phosphonate to give an alkene. The reaction is usually used when the nucleophilic carbon bears a strong anion stabilizing group (CO2Me, COMe, COH, CN, SO2R, SOR, vinyl, phenyl). Like the analogous Wittig reagents, the metalated phosphonates tend to give trans olefins if the substituents on phosphorus are simple alkoxy groups, and if lithium or sodium counterions are used. They can become cis-selective if non-coordinating cations (e.g., K+ - 18-crown-6) or electron withdrawing substituents on the phosphonate ester groups are used (e.g. CF3CH2O- or ArO).
In the absence of a carbanion-stabilizing group on the anionic carbon the elimination reaction to form the double bond becomes very slow. Apparently the transition state for the syn-elimination resembles the carbanion formed by cleavage of the P-C bond:
Metalated phosphonates are substantially more reactive than analogous Wittig reagents, and will react with ketones as well as aldehydes. This can be predicted from the much higher basicity of phosphonates. Stabilized Wittig reagents react only with aldehydes.