The Wonderful Chemistry of Trifluoromethyl α‐Haloalkenyl Ketones

Abstract

Fluorinated α‐bromoenones have received considerable attention in the last decade. Their ability to react in 1.2‐ and 1.4‐addition modes, together with the presence of bromine, makes them valuable fluorinated building blocks in organic synthesis. This review focuses on the unusual and often unpredictable transformations of these compounds on treatment with nitrogen nucleophiles.

Assembly of Trifluoromethylated Morpholines through Cascade Reactions of Bromoenones with Secondary Amino Alcohols

“…The data obtained does not allow us to present a complete picture of the entire cascade of transformations. However, the results are consistent with the mechanism shown in Scheme , and do not contradict the previously proposed scheme for the assembly of carbocycles and heterocycles based on the reactions of CF 3 ‐bromenones 1 with mono‐ and bidentate nucleophiles . In fact, fluorinated bromoenones 1 can react as bielectrophiles with nucleophiles in both 1,2‐ and 1,4‐addition modes.…”

“…Finally, fluorinated α‐bromoenones react smoothly with β‐mercapto alcohols to give 1,4‐oxathianes in moderate yields; amino alcohols containing a primary amino group give morpholines and/or 1,4‐oxazepanes ― a previously unknown heterocyclic system ― in good to excellent yields and often with very high stereoselectivity . These nontrivial results motivated us to continue our efforts to develop elegant methods for the synthesis of fluorinated nitrogen heterocycles . In this paper, we discuss the synthesis of trifluoromethylated morpholines based on the reactions of CF 3 ‐bromoenones with amino alcohols containing a secondary amino group.…”

Brominated β-Alkoxyvinyl Trihalomethyl Ketones as Promising Synthons in Heterocyclic Synthesis

“…C2 is a highly electrophilic center because it is a carbonyl carbon attached to strongly electron-withdrawing CCl 3 or CF 3 groups. 10 The C3 and the oxygen atom of the carbonyl group are nucleophilic sites; while the trihalomethyl group provides important molecular properties of the products and, in some circumstances (e.g., CCl 3 in basic conditions), it can be eliminated in order to generate further functionalization. [11][12][13][14][15][16][17][18][19] By inserting the CH 2 Br electrophilic center, the reactivity towards nucleophiles, especially nitrogen nucleophiles, is highly affected, which means that it can experience competition reactions, that is, 1,4-addition at C4 and allylic nucleophilic substitution at C5.…”

One-Pot Metal-Free Synthesis of 3-CF3-1,3-Oxazinopyridines by Reaction of Pyridines with CF3CO-Acetylenes

“…α,β-Unsaturated CF 3 -ketones have been shown as versatile building blocks for the synthesis of various fluorinated heterocyclic compounds [36,37,38,39,40]. In a series of works, we have demonstrated a great potential of CF 3 -ynones in different heterocyclizations to prepare fluorinated derivatives of diazepines [41], pyrimidines [42], thiophenes [43], triazoles [44], pyrazoles [45,46,47].…”