科里-富克斯反應

科里-富克斯反應，又稱拉米雷斯-科里-富克斯反應，指醛與四溴化碳和三苯基膦反應，發生一碳同系化生成二溴烯烴，然後再用正丁基鋰處理而得到末端炔烴。^[1]^[2]^[3]

反應由美國化學家艾里亞斯·詹姆斯·科里和菲利普·L·富克斯的名字命名。與早期Desai等^[4]製取二溴烯烴的方法相比，鋅粉的加入促進了葉立德中間體的生成，從而減少了三苯基膦的用量，分離更易，產率更高。對於敏感的底物，需用三乙胺代替鋅才能取得較好的效果。^[5]

選用適宜的鹼，可使反應也可停在1-溴代炔一步。溴代炔和末端炔烴是有機合成中很有用的官能團。^[6]

近來工業界發展了三氯乙酸的等價合成方法，解決了大量合成中副產物三苯基氧膦的難處理問題，使反應用於大規模的製備。^[7]

反應機理

目前普遍接受的機理為，首先三苯基膦親核進攻四溴化碳奪取一個溴離子，生成鏻離子，它受到同時生成的溴仿負離子的親核取代，形成二溴亞甲基磷葉立德。之後與維蒂希反應類似，二溴亞甲基碳與醛羰基進行親核加成，形成的兩性中間體環化為氧磷雜環丁烷，進一步消除為三苯基氧膦和二溴烯烴。

科里-富克斯反應的機理一

二溴烯烴與正丁基鋰交換為鋰代二溴烯烴，它發生β-消除生成溴代末炔。溴代末炔與正丁基鋰再交換為末炔鋰，末炔鋰最後經水或鹵代烴等親電試劑處理，得末端炔或內炔。

科里-富克斯反應的機理二

參見

參考資料

^ Corey, E. J.; Fuchs, P. L. A synthetic method for formyl → ethynyl conversion (RCHO → RCCH or RCCR′). Tetrahedron Lett. 1972, 13 (36): 3769–3772. doi:10.1016/S0040-4039(01)94157-7.
^ Mori, M.; Tonogaki, K.; Kinoshita, A. "Synthesis of 1,3-Dienes from Alkynes and Ethylene: Acetic Acid 2-Methylene-3-phenethylbut-3-enyl Ester （頁面存檔備份，存於互聯網檔案館）". Organic Syntheses, Vol. 81, p.1 (2005).
^ Marshall, J. A.; Yanik, M. M.; Adams, N. D.; Ellis, K. C.; Chobanian, H. R. "Generation of Nonracemic 2-(t-Butyldimethylsilyloxy)-3-butynyllithium from (S)-Ethyl Lactate （頁面存檔備份，存於互聯網檔案館）". Organic Syntheses, Vol. 81, p.157 (2005).
^ N. B. Desai, N. McKelvie. A New Synthesis of 1,1-Dibromoölefins via Phosphine-Dibromomethylenes. the Reaction of Triphenylphosphine with Carbon Tetrabromide. J. Am. Chem. Soc. 1962, 84 (9): 1745–1747. doi:10.1021/ja00868a057.
^ D. Grandjean, P. Pale and J. Chuche. An improved procedure for aldehyde-to-alkyne homologation via 1,1-dibromoalkenes; synthesis of 1-bromoalkynes. Tetrahedron Letters. 1994, 35 (21): 3529–3530. doi:10.1016/S0040-4039(00)73227-8.
^ Craig M. Williams and Lewis N. Mander. Bridgehead Arylation: A Direct Route to Advanced Intermediates for the Synthesis of C-20 Diterpene Alkaloids. Org. Lett. 2003, 5 (19): 3499–3502. doi:10.1021/ol0353060.
^ Zhe Wang, Silvio Campagna, Kaihong Yang, Guoyou Xu, Michael E. Pierce, Joseph. M. Fortunak, and Pat. N. Confalone. A Practical Preparation of Terminal Alkynes from Aldehydes. J. Org. Chem. 2000, 65 (6): 1889–1891. doi:10.1021/jo9916582.

[1] Corey, E. J.; Fuchs, P. L. A synthetic method for formyl → ethynyl conversion (RCHO → RCCH or RCCR′). Tetrahedron Lett. 1972, 13 (36): 3769–3772. doi:10.1016/S0040-4039(01)94157-7.

[2] Mori, M.; Tonogaki, K.; Kinoshita, A. "Synthesis of 1,3-Dienes from Alkynes and Ethylene: Acetic Acid 2-Methylene-3-phenethylbut-3-enyl Ester （頁面存檔備份，存於互聯網檔案館）". Organic Syntheses, Vol. 81, p.1 (2005).

[3] Marshall, J. A.; Yanik, M. M.; Adams, N. D.; Ellis, K. C.; Chobanian, H. R. "Generation of Nonracemic 2-(t-Butyldimethylsilyloxy)-3-butynyllithium from (S)-Ethyl Lactate （頁面存檔備份，存於互聯網檔案館）". Organic Syntheses, Vol. 81, p.157 (2005).

[4] N. B. Desai, N. McKelvie. A New Synthesis of 1,1-Dibromoölefins via Phosphine-Dibromomethylenes. the Reaction of Triphenylphosphine with Carbon Tetrabromide. J. Am. Chem. Soc. 1962, 84 (9): 1745–1747. doi:10.1021/ja00868a057.

[5] D. Grandjean, P. Pale and J. Chuche. An improved procedure for aldehyde-to-alkyne homologation via 1,1-dibromoalkenes; synthesis of 1-bromoalkynes. Tetrahedron Letters. 1994, 35 (21): 3529–3530. doi:10.1016/S0040-4039(00)73227-8.

[6] Craig M. Williams and Lewis N. Mander. Bridgehead Arylation: A Direct Route to Advanced Intermediates for the Synthesis of C-20 Diterpene Alkaloids. Org. Lett. 2003, 5 (19): 3499–3502. doi:10.1021/ol0353060.

[7] Zhe Wang, Silvio Campagna, Kaihong Yang, Guoyou Xu, Michael E. Pierce, Joseph. M. Fortunak, and Pat. N. Confalone. A Practical Preparation of Terminal Alkynes from Aldehydes. J. Org. Chem. 2000, 65 (6): 1889–1891. doi:10.1021/jo9916582.

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