Department of Chemistry, University of Florida, Gainesville, Florida 32611-7200, USA.
J Org Chem. 2011 May 6;76(9):3450-6. doi: 10.1021/jo200423y. Epub 2011 Apr 12.
The Friedel-Crafts reactions of 2,2-difluorocyclopropanecarbonyl chloride with various arenes did not lead to the straightforward formation of the expected aryl 2,2-difluorocyclopropyl ketones. Instead the reactions proceeded, to various degrees depending on the reactivity of the arene, via an apparent rearrangement of the initially formed acylium ion to form novel aryl 3-chloro-3,3-difluoropropyl ketones. The ring-opened product was formed exclusively, and therefore the reaction may be synthetically useful when relatively unreactive arene substrates such as benzene, toluene, and p-xylene are used. No conditions were found where ring-intact products could be formed exclusively when using substituted benzenes as substrates, with the very reactive substrate thiophene being most selective in that regard, favoring ring intact product 3 with a selectivity of 98:2. The regioselectivity of ring-opening was examined and compared with other related systems computationally.
2,2-二氟环丙甲酰氯与各种芳基的 Friedel-Crafts 反应并没有直接生成预期的芳基 2,2-二氟环丙基酮。相反，反应会根据芳环的反应性以不同程度进行，通过最初形成的酰基阳离子的明显重排形成新型芳基 3-氯-3,3-二氟丙基酮。仅形成开环产物，因此当使用相对不活泼的芳基底物（如苯、甲苯和对二甲苯）时，该反应可能具有合成用途。在使用取代苯作为底物时，没有发现可以排他性地形成完整环产物的条件，其中非常活泼的底物噻吩在这方面最具选择性，有利于环完整产物 3，选择性为 98:2。还通过计算考察了开环的区域选择性，并与其他相关体系进行了比较。
