Enantioselective Suzuki Cross-Couplings of Unactivated 1‑Fluoro-1-haloalkanes: Synthesis of Chiral β‑, γ‑, δ‑, and ε‑Fluoroalkanes

The incorporation of fluorine atom into a stereogenic center is a highly challenging transformation with current methodologies offering access mainly to chiral α- and β-fluoroalkanes. In this article, the development of a novel general approach to construct β-, γ-, δ-, and ε- fluoroalkanes with good enantioselectivity is described. Different directing groups, such as benzyl, ketone, and sulfonyl, were shown to give good enantioselectivity under Suzuki cross-coupling conditions in the presence of a Ni catalyst and chiral diamine ligand. It includes the first examples of enantioselective synthesis of chiral fluorine-containing centers at as distant as δ or ε positions from the functional groups

Efficient Synthesis of Secondary Alkyl Fluorides via Suzuki Cross-Coupling Reaction of 1‑Halo-1-fluoroalkanes

Organofluorine compounds have found extensive applications in various areas of science. Consequently, the development of new efficient and selective methods for their synthesis is an important goal in organic chemistry. Here, we present the first Suzuki cross-coupling reaction which utilizes dihalo compounds for the preparation of secondary alkyl fluorides. Namely, an unprecedented use of simple 1-halo-1-fluoroalkanes as electrophiles in C_sp³-C_sp³ and C_sp³-C_sp² cross-couplings allows for the formal site-selective incorporation of F-group in the alkyl chain with no adjacent activating functional groups. Highly effective approach to the electrophilic substrates, 1-halo-1-fluoroalkanes, via iododecarboxylation of the corresponding α-fluorocarboxylic acids is also presented. The conceptually new route to organofluorides was used for the facile preparation of biomedically valuable compounds. In addition, we demonstrated that an asymmetric version of the developed reaction for the stereoconvergent synthesis of chiral secondary alkyl fluorides is feasible

Synthesis of Quaternary 3,3-Disubstituted 2‑Oxindoles from 2‑Substituted Indole Using Selectfluor

A facile method to construct quaternary 3,3-disubstituted 2-oxindole from 2-substituted indole without a catalyst in mild conditions is developed. A mechanistic study suggests that an iminium-intermediate-triggered 1,2-rearrangement is involved, and a trace amount of water is required for subsequent oxidation

Enantioselective Bromolactonization of Deactivated Olefinic Acids

A novel enantioselective bromolactonization of α,β-unsaturated ketones using bifunctional amino-urea catalysts has been developed. The scope of the reaction is evidenced by 23 examples of halolactones bearing various functionalities with up to 99% yield and 99:1 er. Unlike typical urea catalysts that require electron-deficient substituents to enhance the hydrogen bond strength, it is interesting to realize that electron-rich ureas are essential for high enantioselectivity in this case. Moreover, experimental data reveals that the halolactone compounds exhibit considerable anti-inflammatory effects on LPS-induced RAW 264.7 cells