Horner–Wadsworth–Emmons reaction

Horner–Wadsworth–Emmons (HWE) reaction is a chemical reaction used in organic chemistry for the synthesis of alkenes. It is a modification of the Wittig reaction and is named after the chemists Leopold Horner, William S. Wadsworth, and William D. Emmons who developed the reaction in the 1950s and 1960s. The HWE reaction involves the reaction of a phosphonate ester with an aldehyde or ketone to produce an alkene and a phosphate ester as a byproduct.

Mechanism

The Horner–Wadsworth–Emmons reaction mechanism involves several key steps. Initially, the phosphonate ester is deprotonated by a strong base to form a phosphonate anion. This anion then attacks the carbonyl carbon of the aldehyde or ketone, forming a betaine intermediate. Subsequent elimination of the phosphate group leads to the formation of the alkene product. The choice of base and the substituents on the phosphonate ester can influence the stereochemistry of the resulting alkene, allowing for the synthesis of both E and Z isomers.

Variants

Several variants of the HWE reaction exist, including the Modified Horner–Wadsworth–Emmons reaction which uses different phosphorus reagents or conditions to improve the reaction's selectivity or yield. The Still–Gennari modification is one notable example, which employs fluorinated phosphonate esters to achieve high Z-selectivity in the synthesis of alkenes.

Applications

The Horner–Wadsworth–Emmons reaction is widely used in organic synthesis for the construction of carbon-carbon double bonds. It is particularly valuable in the synthesis of complex molecules such as natural products, pharmaceuticals, and polymers due to its versatility and the ability to control the stereochemistry of the alkene product. The reaction has been employed in the synthesis of various biologically active compounds and materials with specific optical or electronic properties.

Comparison with Wittig Reaction

While the HWE reaction is similar to the Wittig reaction in its outcome, it offers several advantages, including the use of less toxic and more stable phosphonate esters instead of phosphonium ylides. Additionally, the HWE reaction typically provides better control over the stereochemistry of the alkene product and often proceeds under milder conditions.

See Also

• Olefin Metathesis
• Julia–Lythgoe Olefination
• Tebbe reagent