β‐Trifluoromethyl α,β‐unsaturated Ketones: Efficient Building Blocks for Diverse Trifluoromethylated Molecules

Abstract

The trifluoromethyl (CF 3) group is an advantageous structural motif in various biologically active molecules as well as materials, which is depicted by steadily increasing demand from the industries involved in drug discovery, agrochemicals and material development. β-trifluoromethyl α,βunsaturated carbonyl compounds constitute a very efficient building blocks as starting material in the synthesis of fluorinated molecules. Their usage for the synthesis of various heterocycles and organic molecules bearing stereogenic carbon containing CF 3 motif has received significant attention during the recent times. This review provides the existing methods for the synthesis of β-substituted trifluoromethyl-α,β-unsaturated ketones and the efforts made by researchers for the synthetic development through various reactions by employing them as synthetic building blocks for trifluoromethylated organic scaffolds.

Recent advances in transition-metal catalyzed directed C–H functionalization with fluorinated building blocks

“…Thus recently, efforts from the scientific community have resulted in the design of several elegant and efficient methods to synthesize diverse organofluorine scaffolds using fluorinated building blocks. [38][39][40][41][42][43][44] Moreover, C-H functionalization via C-H activation under transition-metal catalysis [45][46][47][48] has tremendously gained a lot of attention in the recent past as it has the potential to transform an unreactive C-H bond ubiquitously present in all organic molecules. In particular, directing group assisted C-H activation has enabled the synthesis of complex molecular frameworks including various C-C and C-heteroatom connections.…”

“…experiments revealed that the LUMO energy level of the fluorinated α,β-unsaturated carbonyl compound was lower than that of the non-fluorinated one which indicates the feasibility for higher reactivity of these fluorinated building blocks. [196][197][198][199] To this end, for the first time, Yu et al, in 2016, showed the conjugate addition of β-CF 3 enone 283 with arenes under Rh(III) catalysis and redox neutral conditions. Pyridine 282 as a directing group was used for the reaction to obtain the conjugated trifluoromethyl alkylated compounds 284 in good to high yields as shown in Scheme 52.…”

“…Thus recently, efforts from the scientific community have resulted in the design of several elegant and efficient methods to synthesize diverse organofluorine scaffolds using fluorinated building blocks. 38–44…”

Rh(III)-Catalyzed Annulation of 2-Biphenylboronic Acid with Diverse Activated Alkenes

“…Enones have exhibited high activity in C–H activation chemistry, and CF 3 -substituted enones are particularly reactive and have been widely used in transition-metal-catalyzed coupling reactions, affording diverse cyclic or noncyclic skeletons. − This class of substrate can readily undergo insertion. The cascade addition process together with other transformations can lead to cyclic and spirocyclic products .…”

α-Trifluoromethyl Carbanion-catalyzed Intermolecular Stetter Reaction of Aromatic Aldehydes with 2-Bromo-3,3,3-trifluoropropene: Synthesis of β-Alkoxyl-β-trifluoromethylated Ketones

“…However, these Stetter reactions limited to the generation and transformation of stabilized carbanion intermediates. In sharp contrast, unstable carbanion intermediates, such as the highly unstable trifluoromethyl carbanion intermediates, involved Stetter reactions that have never been reported, which might become a direct route to access useful β-trifluoromethylated ketones …”