Mechanistic Studies of the Palladium-Catalyzed Desulfinative Cross-Coupling of Aryl Bromides and (Hetero)Aryl Sulfinate Salts

Pyridine and related
heterocyclic sulfinates have recently emerged
as effective nucleophilic coupling partners in palladium-catalyzed
cross-coupling reactions with (hetero)­aryl halides. These sulfinate
reagents are straightforward to prepare, stable to storage and coupling
reaction conditions, and deliver efficient reactions, thus offering
many advantages, compared to the corresponding boron-derived reagents.
Despite the success of these reactions, there are only scant details
of the reaction mechanism. In this study, we use structural and kinetic
analysis to investigate the mechanism of these important coupling
reactions in detail. We compare a pyridine-2-sulfinate with a carbocyclic
sulfinate and establish different catalyst resting states, and turnover
limiting steps, for the two classes of reagent. For the carbocyclic
sulfinate, the aryl bromide oxidative addition complex is the resting
state intermediate, and transmetalation is turnover-limiting. In contrast,
for the pyridine sulfinate, a chelated Pd­(II) sulfinate complex formed
post-transmetalation is the resting-state intermediate, and loss of
SO2 from this complex is turnover-limiting. We also investigated
the role of the basic additive potassium carbonate, the use of which
is crucial for efficient reactions, and deduced a dual function in
which carbonate is responsible for the removal of free sulfur dioxide
from the reaction medium, and the potassium cation plays a role in
accelerating transmetalation. In addition, we show that sulfinate
homocoupling is responsible for converting Pd­(OAc)2 to
a catalytically active Pd(0) complex. Together, these studies shed
light on the challenges that must be overcome to deliver improved,
lower temperature versions of these synthetically important processes.