Department of Chemistry, Northeast Normal University, Changchun, 130024, China.
Department of Chemistry, University of Pavia, Viale Taramelli 12, 27100, Pavia, Italy.
Nat Commun. 2022 Jul 25;13(1):4280. doi: 10.1038/s41467-022-31976-z.
The C-F bond cleavage and C-C bond formation (i.e., carbodefluorination) of readily accessible (per)fluoroalkyl groups constitutes an atom-economical and efficient route to partially fluorinated compounds. However, the selective mono-carbodefluorination of trifluoromethyl (CF) groups remains a challenge, due to the notorious inertness of C-F bond and the risk of over-defluorination arising from C-F bond strength decrease as the defluorination proceeds. Herein, we report a carbene-initiated rearrangement strategy for the carbodefluorination of fluoroalkyl ketones with β,γ-unsaturated alcohols to provide skeletally and functionally diverse α-mono- and α,α-difluoro-γ,δ-unsaturated ketones. The reaction starts with the formation of silver carbenes from fluoroalkyl N-triftosylhydrazones, followed by nucleophilic attack of a β,γ-unsaturated alcohol to form key silver-coordinated oxonium ylide intermediates, which triggers selective C-F bond cleavage by HF elimination and C-C bond formation through Claisen rearrangement of in situ generated difluorovinyl ether. The origin of chemoselectivity and the reaction mechanism are determined by experimental and DFT calculations. Collectively, this strategy by an intramolecular cascade process offers significant advances over existing stepwise strategies in terms of selectivity, efficiency, functional group tolerance, etc.
易于获得的（全）氟烷基的 C-F 键断裂和 C-C 键形成（即碳脱氟）是部分氟化化合物的原子经济性和有效途径。然而，由于 C-F 键的显著惰性以及随着脱氟进行 C-F 键强度降低而导致的过度脱氟风险，三氟甲基 (CF) 基团的选择性单碳脱氟仍然是一个挑战。在此，我们报告了一种卡宾引发的重排策略，用于氟烷基酮与β,γ-不饱和醇的碳脱氟反应，以提供骨架和官能团多样化的α-单-和α,α-二氟-γ,δ-不饱和酮。反应从氟烷基 N-三氟甲磺酰腙形成银卡宾开始，然后β,γ-不饱和醇进行亲核攻击，形成关键的银配位氧鎓叶立德中间体，通过 HF 消除选择性地触发 C-F 键断裂，并通过原位生成的二氟乙烯基醚的 Claisen 重排形成 C-C 键。通过实验和 DFT 计算确定了化学选择性和反应机制的起源。总的来说，这种通过分子内级联过程的策略在选择性、效率、官能团耐受性等方面相对于现有逐步策略有显著的进步。
