posted on 2024-02-29, 17:36authored byConnor
P. Delaney, Andrew F. Zahrt, Vincent M. Kassel, Scott E. Denmark
The structure of the diol from which
an arylboronic ester
is derived
dramatically influences the rate of transmetalation in the Suzuki-Miyaura
cross-coupling reaction. Some esters undergo transmetalation more
than 20 times faster than the parent arylboronic acid. Herein, investigations
into the influence of arylboronic ester ring size and steric properties
on the mechanism of transmetalation in the Suzuki-Miyaura reaction
are described. Both factors impact the propensity of an arylboronic
ester to bind to a dimeric palladium hydroxide complex. The reaction
of hindered arylboronic esters derived from 1,2-diols (1,3,2-dioxaborolanes)
with palladium hydroxide dimers to form a complex incorporating a
Pd–O–B linkage is thermodynamically favorable, but the
barrier to coordination is often higher than the barrier to arene
transfer. In contrast, the analogous reaction between arylboronic
esters derived from 1,3-diols (1,3,2-dioxaborinanes) and palladium
hydroxide dimers is thermodynamically unfavorable, as 1,3,2-dioxaborinanes
exhibit decreased electrophilicity compared to esters derived from
1,2- or 1,4-diols. These factors also influence the barrier of the
arene transfer step, and in many cases, arylboronic esters that do
not easily form Pd–O–B linked complexes undergo transmetalation
faster than those that do because of hyperconjugative stabilization
of the arene transfer transition state.