Palladium-Catalyzed Synthesis of α‑Carbonyl-α′-(hetero)aryl Sulfoxonium Ylides: Scope and Insight into the Mechanism

Despite recent advances, a general method for the synthesis
of
α-carbonyl-α′-(hetero)­aryl sulfoxonium ylides is
needed to benefit more greatly from the potential safety advantages
offered by these compounds over the parent diazo compounds. Herein,
we report the palladium-catalyzed cross-coupling of aryl bromides
and triflates with α-carbonyl sulfoxonium ylides. We also report
the use of this method for the modification of an active pharmaceutical
ingredient and for the synthesis of a key precursor of antagonists
of the neurokinin-1 receptor. In addition, the mechanism of the reaction
was inferred from several observations. Thus, the oxidative addition
complex [(XPhos)­PhPdBr] and its dimer were observed by 31P­{1H} NMR, and these complexes were shown to be catalytically
and kinetically competent. Moreover, a complex resulting from the
transmetalation of [(XPhos)­ArPdBr] (Ar = p-CF3–C6H4) with a model sulfoxonium
ylide was observed by mass spectrometry. Finally, the partial rate
law suggests that the transmetalation and the subsequent deprotonation
are rate-determining in the catalytic cycle.