Catalytic Asymmetric Construction of CF3-Substituted Chiral sp3 Carbon Centers

Abstract

Due to the unique steric and electronic nature of fluorine atom, organofluorine compounds have received significant attention in fields of pharmaceuticals and agrochemicals. In particular, the CF3 group is most frequently occurring in biologically active compounds. However, compared to aryl- and alkenyl-CF3 molecules, the synthesis, particularly, catalytic enantioselective synthesis of sp3 carbon-based alkyl-CF3 molecules still remains a great challenge in spite of their high potential in medicinal application. This short review focuses on recent advances in this research fields: the reported strategies are categorized according to reaction types as well as starting substrates, and chiral catalysts, substrate scope, and reaction mechanisms are briefly summarized.

Ni-Catalyzed Reductive Dibenzylation of Trifluoromethylalkenes for CF3-Containing All-Carbon Quaternary Center Construction

“…In this regard, 3,3,3-trifluoropropene derivatives that are easily accessible from inexpensive feedstock chemicals should be promising candidates (Scheme A-d), although the facile β-F elimination, to some extent, hinders their potential application for the straightforward assembly of CF 3 -bearing skeletons . Notwithstanding the pitfall of β-F elimination, catalytic hydro/borofunctionalization of 3,3,3-trifluoropropene derivatives with F retention have witnessed exciting progress under the catalysis of Cu, Co, photocatalyst, base, and Brønsted acid during the past several years. In this vein, Ni catalysis has also proved applicable for the hydroalkylation reaction, as reported recently by our group (Scheme B-a) .…”

Chiral Trifluoromethylated Enamides: Synthesis and Applicability

“…[58][59][60] Additionally, the construction of CF3-substituted chiral sp 3 -carbon centers remains a difficult synthetic task despite the high potential of fluorinated motifs in medicinal chemistry. 61,62 Thus, efficient asymmetric methodologies to access such…”

SCpRh(III)-Catalyzed Asymmetric C–H Trifluoromethylalkylation of N-Methoxybenzamides with β-Trifluoromethyl-α,β-Unsaturated Ketones

“…The trifluoromethyl group is an important structural motif in pharmaceutical and agrochemical molecules because of its beneficial effect on the physicochemical and biological properties of organic compounds . Therefore, the synthesis of CF 3 -containing molecules, especially in an enantioselective manner, has been of growing interest. , In the past decades, numerous asymmetric reactions have been reported by exploiting either trifluoromethyl reagents or prochiral trifluoromethylated building blocks . Among these reactions, the installation of trifluoromethylated stereogenic carbon centers by direct transformation of C–H bonds proves to be an atom-economical approach.…”