A Ruthenium‐(Ph‐BPE) Catalyst for Asymmetric Alkynylation of Fluoral: Enantioselection From 1 of 12 Fluxional Stereogenic‐at‐Ruthenium Complexes

An iodide-bound ruthenium catalyst derived from RuHCl(CO)(PPh3)3 and (S,S)-Ph-BPE catalyzes highly enantioselective alkynylations of terminal alkynes 1a–1y with fluoral hydrate 2a and related α,α-difluoro-aldehydes 4a–4f. The ruthenium-(Ph-BPE)-catalyst is air- and water-tolerant, operates in the absence of exogenous base, and is chemoselective for alkynylation of fluorinated aldehydes in the presence of aromatic aldehydes. Calculations of the 12 possible stereogenic-at-metal ruthenium-(Ph-BPE) acetylide complexes bound by fluoral reveal that 2 of the 12 octahedral complexes comprise 99.9% of the Boltzmann population, yet, in a Curtin-Hammett-type scenario, the less stable of these two diastereomers dominates the kinetics of carbonyl addition. Fuzzy bond order (FBO) analysis of formyl-hydrogen bonds to iodide versus chloride in the transition states for fluoral addition reveals that the C–H···I hydrogen bonds are stronger due to iodide's greater size and polarizability, which, in part, accounts for the enhanced enantioselectivities of the iodide-bound catalyst.