Transnitrilation from Dimethylmalononitrile to Aryl Grignard and Lithium Reagents: A Practical Method for Aryl Nitrile Synthesis
详细信息 查看全文
- 作者：Jonathan T. Reeves ; Christian A. Malapit ; Frederic G. Buono ; Kanwar P. Sidhu ; Maurice A. Marsini ; C. Avery Sader ; Keith R. Fandrick ; Carl A. Busacca ; Chris H. Senanayake
- 刊名：Journal of the American Chemical Society
- 出版年：2015
- 出版时间：July 29, 2015
- 年：2015
- 卷：137
- 期：29
- 页码：9481-9488
- 全文大小：646K
- ISSN：1520-5126
文摘
An electrophilic cyanation of aryl Grignard or lithium reagents, generated in situ from the corresponding aryl bromides or iodides, by a transnitrilation with dimethylmalononitrile (DMMN) was developed. DMMN is a commercially available, bench-stable solid. The transnitrilation with DMMN avoids the use of toxic reagents and transition metals and occurs under mild reaction conditions, even for extremely sterically hindered substrates. The transnitrilation of aryllithium species generated by directed ortho-lithiation enabled a net C鈥揌 cyanation. The intermediacy of a Thorpe-type imine adduct in the reaction was supported by isolation of the corresponding ketone from the quenched reaction. Computational studies supported the energetic favorability of retro-Thorpe fragmentation of the imine adduct.