|
The Horner–Wadsworth–Emmons reaction (or HWE reaction) is a chemical reaction used in organic chemistry of stabilized phosphonate carbanions with aldehydes (or ketones) to produce predominantly E-alkenes.〔Wadsworth, W. ''Org. React.'' 1977, ''25'', 73. 〕 In 1958, Leopold Horner published a modified Wittig reaction using phosphonate-stabilized carbanions.〔Leopold Horner; Hoffmann, H. M. R.; Wippel, H. G. ''Ber.'' 1958, ''91'', 61–63.〕〔Horner, L.; Hoffmann, H. M. R.; Wippel, H. G.; Klahre, G. ''Ber.'' 1959, ''92'', 2499–2505.〕 William S. Wadsworth and William D. Emmons further defined the reaction.〔Wadsworth, W. S., Jr.; Emmons, W. D. ''J. Am. Chem. Soc.'' 1961, ''83'', 1733. ()〕〔Wadsworth, W. S., Jr.; Emmons, W. D. ''Organic Syntheses'', Coll. Vol. 5, p.547 (1973); Vol. 45, p.44 (1965). ((Article ))〕 In contrast to phosphonium ylides used in the Wittig reaction, phosphonate-stabilized carbanions are more nucleophilic but less basic. Likewise, phosphonate-stabilized carbanions can be alkylated. Unlike phosphonium ylides, the dialkylphosphate salt byproduct is easily removed by aqueous extraction. Several reviews have been published.〔Wadsworth, W. S., Jr. ''Org. React.'' 1977, ''25'', 73–253. (Review)〕〔Boutagy, J.; Thomas, R. ''Chem. Rev.'' 1974, ''74'', 87–99. (Review, )〕〔Kelly, S. E. ''Comp. Org. Syn.'' 1991, ''1'', 729–817. (Review)〕〔B. E. Maryanoff; Reitz, A. B. ''Chem. Rev.'' 1989, ''89'', 863–927. (Review, )〕〔Bisceglia, J. A., Orelli, L. R. ''Curr. Org. Chem.'' 2012, 16, 2206-2230 (Review)〕〔Bisceglia, J. A., Orelli, L. R. ''Curr. Org. Chem.'' 2015, 19, 744-775 (Review)〕 ==Reaction mechanism== The Horner–Wadsworth–Emmons reaction begins with the deprotonation of the phosphonate to give the phosphonate carbanion 1. Nucleophilic addition of the carbanion onto the aldehyde 2 (or ketone) producing 3a or 3b is the rate-limiting step.〔Larsen, R. O.; Aksnes, G. ''Phosphorus Sulfur'' 1983, ''15'', 218–219.〕 If R2 = H, then intermediates 3a and 4a and intermediates 3b and 4b can interconvert with each other.〔Lefèbvre, G.; Seyden-Penne, J. ''J. Chem Soc., Chem. Commun.'' 1970, 1308–09.〕 The final elimination of 4a and 4b yield (''E'')-alkene 5 and (''Z'')-alkene 6. The ratio of alkene isomers 5 and 6 is dependent upon the stereochemical outcome of the initial carbanion addition and upon the ability of the intermediates to equilibrate. The electron-withdrawing group (EWG) alpha to the phosphonate is necessary for the final elimination to occur. In the absence of an electron-withdrawing group, the final product is the α-hydroxyphosphonate 3a and 3b.〔Corey, E. J.; Kwiatkowski, G. T. ''J. Am. Chem. Soc.'' 1966, ''88'', 5654–56. ()〕 However, these α-hydroxyphosphonates can be transformed to alkenes by reaction with diisopropylcarbodiimide.〔Reichwein, J. F.; Pagenkopf, B. L. ''J. Am. Chem. Soc.'' 2003, ''125'', 1821–24. ()〕 抄文引用元・出典: フリー百科事典『 ウィキペディア（Wikipedia）』 ■ウィキペディアで「Horner–Wadsworth–Emmons reaction」の詳細全文を読む スポンサード リンク
|