定义Definition
HWE 反应是稳定化的膦酸酯碳负离子（如 (EtO)₂P(O)CH⁻CO₂Et）与醛或酮反应，高选择性地生成 E-α,β-不饱和酯（或酮、腈）的烯化反应，副产物为水溶性磷酸二烷基酯盐。
The HWE reaction olefinates aldehydes or ketones with stabilised phosphonate carbanions such as (EtO)₂P(O)CH⁻CO₂Et, giving mainly E-α,β-unsaturated esters (or ketones, nitriles); the dialkyl phosphate by-product is water-soluble.
与维蒂希反应比较Compared with the Wittig reaction
膦酸酯负离子比磷叶立德亲核性更强、碱性更弱，能与位阻酮反应；E-选择性高；副产物易用水洗去，无三苯基氧膦分离难题。膦酸酯可由阿尔布佐夫反应方便制备。
Phosphonate anions are more nucleophilic and less basic than phosphorus ylides, react with hindered ketones and give high E-selectivity; the by-product washes out with water, avoiding Ph₃PO. Phosphonates are easily made by the Arbuzov reaction.
变体Variants
施蒂尔–根纳里（Still–Gennari）改良用双（三氟乙基）膦酸酯和 KHMDS/18-冠-6，得到 Z-烯烃；安藤（Ando）试剂也给出 Z-选择性。马萨穆内–鲁什条件（LiCl/DBU）适合碱敏感底物。
The Still–Gennari modification (bis(trifluoroethyl) phosphonates, KHMDS/18-crown-6) and Ando’s reagents give Z-alkenes; Masamune–Roush conditions (LiCl/DBU) suit base-sensitive substrates.
由来Origin
霍纳于 1958 年报道膦氧化物变体，沃兹沃思与埃蒙斯于 1961 年系统发展了膦酸酯版本。
Horner reported the phosphine-oxide variant in 1958; Wadsworth and Emmons developed the phosphonate version in 1961.
反应Reactions
NaH 或 DBU/LiCl，THF，0 °C 至室温
NaH or DBU/LiCl in THF at 0 °C to room temperature
碱夺取膦酸酯 α-H 生成碳负离子。
Base removes the α-H of the phosphonate.
加成到醛羰基形成 β-氧负离子中间体。
Addition to the aldehyde gives a β-alkoxide.
经氧磷杂环丁烷消除磷酸酯盐得 E-烯烃。
Elimination through an oxaphosphetane gives the E-alkene.
高 E 选择性。
High E selectivity.
反应机理图Mechanism
红色弯箭头表示一对电子的移动方向：从电子来源（孤对电子或化学键）指向电子去向。Red curly arrows show where an electron pair moves: from its source (lone pair or bond) to its destination.
膦酸酯碳负离子进攻醛羰基
The phosphonate carbanion attacks the aldehyde
烷氧负离子进攻磷，经四元环中间体消除
The alkoxide attacks P; a four-membered intermediate then fragments
(E)-α,β-不饱和酯；磷酸盐副产物溶于水，易分离
(E)-α,β-Unsaturated ester; the phosphate by-product washes out with water
年表Timeline
- 1958
霍纳报道
Horner’s report
- 1961
沃兹沃思与埃蒙斯发展膦酸酯烯化
Wadsworth and Emmons develop phosphonate olefination
- 1983
施蒂尔–根纳里 Z-选择性改良
Still–Gennari Z-selective modification