CF₃-Substituted semisquarate: a pluripotent building block for the divergent synthesis of trifluoromethylated functional molecules

Abstract

The first synthesis of a CF3-substituted semisquarate was accomplished via nucleophilic trifluoromethylation using CF3SiMe3 and subsequent rhenium-catalyzed allylic alcohol rearrangement. The short-step skeletal-divergent synthesis of trifluoromethylated functional molecules was successfully achieved using the CF3-substituted semisquarate as the platform.

Cs2CO3-Initiated Trifluoro-Methylation of Chalcones and Ketones for Practical Synthesis of Trifluoromethylated Tertiary Silyl Ethers

“…Notably, we recently found that the alkylidenecyclobutenone 1k [ 54 ] was a highly reactive compound and could be easily used in ring-opening and ring expansion with Grignard reagents, organolithium species, primary amines, and water [ 55 ], in which the four-membered ring was easily broken by the nucleophilic reagent. Interestingly, we found that the four-membered ring was stable in the trifluoromethylation reaction [ 56 ] and the desired products 5j or 5k were isolated in promising yields. The structure of the novel compound 5k was unambiguously confirmed by X-ray diffraction analysis ( Figure 1 ).…”

FeCl2-Mediated Rearrangement of Allylic Alcohols

“…2 A rhenium-assisted rearrangement has also been used in the synthesis of semisquarates. 18 Trifluoroacetic acid has also been used to isomerize allylic alcohols, and this method has been applied to the synthesis of valerenic acid, which binds to both the GABA A and 5-HT 5A receptors, and is used as a treatment of insomnia. 19 Acid-assisted allylic alcohol rearrangement was also used in the synthesis of two quinolone natural products isolated from Pseudonocardia sp.…”

Divergent Total Synthesis of Atisane‐Type Diterpenoids

“…A divergent synthesis is a strategy aiming to improve the efficiency of chemical synthesis and generate a library of natural compounds from one common versatile synthetic intermediate with a set of reactions. This strategy is rather popular in modern organic synthesis as it permits rapid divergence to a large number of new compounds . Abad's group, Baran's group, and Liu's group have reported the efficient divergent total synthesis of atisane‐type diterpenoids.…”