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.