Conspectus
Transition
metal hydride catalyzed functionalization of remote and proximal olefins
has many advantages over conventional cross-coupling reactions. It
avoids the separate, prior generation of stoichiometric amounts of
organometallic reagents and the use of preformed organometallic reagents,
which are sometimes hard to access and may compromise functional group
compatibility. The migratory insertion of metal hydride complexes
generated in situ into readily available alkene starting
materials, the hydrometalation process, provides an attractive and
straightforward route to alkyl metal intermediates, which can undergo
a variety of sequential cross-coupling reactions. In particular, with
the synergistic combination of chain-walking and cross-coupling chemistry
of nickel, NiH-catalyzed functionalization of remote and proximal
olefins has undergone particularly intense development in the past
few years. This Account aims to chronicle the progress made in this
arena in terms of activation modes, diverse functionalizations, and
chemo-, regio-, and enantioselectivity.
We first provide a brief
introduction to the general reaction mechanisms. Taking remote hydroarylation
as an example, the four oxidation states of Ni have allowed us to
develop two different reaction strategies to form the final product:
a Ni(I)-H/X-Ni(II)-H platform that relies on stoichiometric reductants
and a Ni(I/II/III) cycle and a redox-neutral functional group or FG-Ni(II)-H
platform that reacts with an alkene substrate and forms the migratory
products via a Ni(0/II) pathway. We also demonstrate that diverse
functionalization, including general C–C bond-forming reactions
and the more challenging C–N/C–S bond-forming reactions
could be realized. Moreover, the employment of appropriate chiral
ligands has allowed us to successfully realize the corresponding asymmetric
hydrofunctionalization reactions of olefins, including hydroalkylation,
hydroarylation, hydroalkenylation, hydroalkynylation, and hydroamination.
Interestingly, the enantio-determining step could be enantioselective
hydronickelation, selective oxidative addition, or selective reductive
elimination. To realize more challenging asymmetric migratory hydrofunctionalization,
we have developed a general ligand relay catalytic strategy with a
combination of two simple ligands, the first for chain-walking and
the second for asymmetric coupling. This novel strategy avoids the
design of a single, possibly structurally complex chiral ligand to
promote both steps of chain-walking and asymmetric coupling. In addition,
the success of multicomponent hydrofunctionalization provides a convenient
approach to gain simple access to complex molecules. Finally, alkyl
halides could be used as olefin precursors to undergo a variety of
reductive migratory cross-electrophile coupling reactions. Applications
of these remote hydrofunctionalization reactions are also discussed.
We hope this Account will inspire future development in the field
to overcome key challenges, including conceptually new catal...