β-Trifluoromethylated enones as trifluoromethylated synthons in asymmetric catalysis

Abstract

Trifluoromethylated organic molecules are ubiquitous in pharmaceutics, materials science, and agrochemicals. In the past few decades, great efforts have been devoted to the development of convenient and efficient strategies for...

Transition-Metal-Free Hydrodefluoroamination of Trifluoromethyl Enones for the Synthesis of α-Fluoroenamides

“…By leveraging sequential carbonyl reduction, hydrodefluorination, and defluoroamination steps in one pot, the capability of the cascade to exclusively form α-fluoroenamides in moderate to good yields with moderate E -selectivity and good functional group tolerance through two C­(sp 3 )-F bond activations is demonstrated. Impressively, our method efficiently bypassed various previously reported competitive side reactions, including 1,4-addition ( I ), hydrodefluorination ( II ), hydroamination ( III ), hydrosilylation ( III ), defluorodiamination (Scheme B, a), defluoroamination ( IV ), and defluorosilylation ( IV ) (Scheme B, c). The configuration, unsaturated alkenyl motif, and auxiliary function of a carbonyl group in CF 3 -alkenes are all crucial for modulating the inherent reactivity and selectivity.…”

“…Based on mechanistic verification experiments and literature reports, − a plausible reaction mechanism is depicted in Scheme . Initially, the selective defluorinative multihydrogenation of β-CF 3 -enones with PhSiH 3 occurs through a sequence of carbonyl reduction (via OH-containing trifluoromethyl alkene A ) and downstream hydrodefluorination (via intermediate B ), leading to hydroxyl-containing gem -difluoroalkene C (pathway a).…”

“…The desired product, 4-(1 H -benzo­[ d ]­imidazol-1-yl)-4-fluoro-1,3-diphenylbut-3-en-1-ol ( 3aa ), was successfully obtained in 79% yield with a Z / E ratio of 1/9 in the presence of Cs 2 CO 3 (2.5 equiv) in THF at 50 °C for 12 h (entry 1). A slight enhancement of the product yield to 81% was observed by increasing the reaction temperature to 70 °C, whereas room temperature (25 °C) resulted in poor transformation along with the formation of various byproducts − (entries 2–3). Following a systematic solvent screen (entries 4–8), MeCN emerged as the optimal choice, affording α-fluoroenamide 3aa with 91% yield with Z / E = 1/12 selectivity (entry 5).…”