DFT studies on Palladium/Xiao-Phos-catalyzed asymmetric arylation of
secondary phosphine oxides
Abstract
Asymmetric arylation of secondary phosphine oxides (SPOs) is a potential
strategy to obtain P-chiral compounds, and has developed rapidly
since the first report in 2016. However, the mechanism is still
ambiguous and few DFT studies have been published so far in this field.
Taking palladium/Xiao-Phos-catalyzed asymmetric arylation of SPOs as
model, our DFT mechanism studies allows the updating of the catalytic
cycle. Tautomerization of SPOs occurs first to initiate the downstream
arylation transformations. DFT computations show that
Pd/X1-catalyzed H2O-assisted tautomerization is
more favored, and the resulting intermediate with trivalent SPO fragment
enters the downstream arylation directly. Meanwhile, reductive
elimination is both the rate- and enantioselectivity-determining step in
the whole catalytic cycle. Bonding and IGMH analysis on the TSs
of reductive elimination indicate that, the difference in non-bonding
interactions between X1 and substrates mainly determines the
enantioselectivity. This work not only provides deeper insights into the
self-adaptive property of SadPhos ligands but also offers valuable
guidance for future related studies of SPOs.