Deracemization of Binaphthyl by Suzuki Diarylation: The Role of Electronic and Steric Effects.

We report a Suzuki 2,2'-diarylation of the racemic 2,2'-diiodo-1,1'-binaphthyl which proceeds with deracemization via a pallada(IV)cyclic intermediate, induced by a simple chiral ligand─BINAP [2,2'-bis(diphenylphosphino)-1,1',-binaphthyl]. A systematic study of the reaction scope, using 45 arylboronic acids, reveals that the diarylated product is formed when - and/or -substituted phenylboronic acids are functionalized with a substituent with the Hammett constant from -0.5 to +0.4. Multiparametric analysis accounting for the effect of geometry on the reactivity using Boltzmann-weighted Sterimol parameters and electronic effects described by Hammett descriptors shows that the enantioselectivity depends on steric effects only, with enhanced enantioselectivity observed for substituents with a larger length, , and reduced for substituents with a larger maximum width, . We show that careful tuning of these parameters, with the aid of the presented mathematical model, can lead to excellent enantioselectivity. Additional factors that are investigated and found to affect the stereoselective course of the reaction include the reaction temperature, palladium source, palladium to ligand ratio, and the type of boronic acid derivative. During the chromatographic separation of diarylated products on an achiral silica gel, we observed a rare phenomenon: the diarylated products undergo self-disproportionation of enantiomers, with the major enantiomer being eluted first.