How Does an Earth-Abundant Copper-Based Catalyst Achieve Anti-Markovnikov Hydrobromination of Alkynes? A DFT Mechanistic Study

The first catalytic
hydrohalogenation of alkynes was recently achieved
using a copper­(I) N-heterocyclic carbene (NHC) complex, and the reaction
was found to be syn and anti-Markovnikov selective. The present work
is a density functional theory (DFT) computational study (B3LYP and
M06) on the detailed mechanism of this remarkable catalytic reaction.
The reaction begins with a phenoxide additive turning over the precatalyst
(NHC)­CuCl into (NHC)­Cu­(OAr), which subsequently transmetalates with
the hydride source Ph2SiH2 to deliver the copper­(I)
hydride complex (NHC)­CuH. (NHC)­CuH undertakes hydrocupration of the
substrate RCCH via alkyne coordination and subsequent migratory
insertion into the Cu–H bond, forming (E)-(NHC)­Cu­(CHCHR).
The migratory insertion step determines the syn selectivity because
it occurs by a concerted pathway, and it also determines the anti-Markovnikov
regioselectivity that arises from the charge distributions across
the Cu–H and CC bonds. The brominating agent (BrCl2C)2 uses the bromonium end to attack the Cu-bound
vinylic carbon atom of (E)-(NHC)­Cu­(CHCHR),
leading to the final (E)-alkenyl bromide product
(E)-RHCCHBr, as well as the copper­(I) alkyl
complex (NHC)­Cu­(CCl2CBrCl2), which undergoes
β-bromide elimination to give the catalyst precursor (NHC)­CuBr
for the next cycle. (NHC)­CuBr reacts with the phenoxide to regenerate
the active catalyst (NHC)­Cu­(OAr). The computational results rationalize
the experimental observations, reveal new insights into the mechanism
of the Cu­(I)-catalyzed hydrobromination of alkynes, and have implications
for other catalytic functionalization reactions of alkynes involving
active [Cu]–H intermediates.