A Ni-catalyzed enantioselective
reductive diarylation of activated
alkenes by domino cyclizative/cross-coupling of two aryl bromides
is developed. This reaction proceeds under very mild conditions and
shows broad substrate scope, without requiring the use of preformed
organometallic reagents. Moreover, this approach provides direct access
to various bis-heterocycles bearing all-carbon quaternary centers
in synthetically useful yields (up to 81%) with excellent enantioselectivity
(>30 examples, 90–99% ee).
The restricted availability, expense and toxicity of precious metal catalysts such as rhodium and palladium challenge the sustainability of synthetic chemistry. As such, nickel catalysts have garnered increasing attention as replacements for enyne cyclization reactions. On the other hand, bridged tricyclo[5.2.1.0 1,5 ]decanes are found as core structures in many biologically active natural products; however, the synthesis of such frameworks with high functionalities from readily available precursors remains a significant challenge. Herein, we report a nickel-catalyzed asymmetric domino cyclization reaction of enynones, providing rapid and modular synthesis of bridged tricyclo[5.2.1.0 1,5 ]decane skeletons with three quaternary stereocenters in good yields and remarkable high levels of regio-and enantioselectivities (92-99% ee).
Transition-metal-catalytic domino
reactions represent important
advances in synthetic organic chemistry. Their development benefits
synthesis by providing highly efficient and step-economical methods
to complex molecules with impressive selectivity. Herein, a Ni-catalyzed
domino reductive cyclization of acrylamides with alkynyl bromides
is reported, enabling rapid assembly of a range of substituted 2,3-fused
cyclopentannulated indolines. Preliminary mechanistic studies revealed
that tricyclic indolines are afforded through a highly regioselective
migratory insertion of 1,3-diynes, which are formed from the homocoupling
of alkynyl bromides, into the in situ generated σ-alkyl-Ni(II)
species, followed by nucleophilic addition of the resulting alkenyl
nickel to unactivated amides. Most importantly, a highly regio- and
enantioselective reductive cyclization of acrylamides and internal
alkynes has also been developed. This transformation takes place under
mild conditions with high efficiency, providing a rapid access to
structurally diverse cyclopentannulated indolines in synthetically
useful yields with high regioselectivity (>20/1) and enantioselectivity
(27 examples, 82–96% ee).
Spirocycles play an important role in drug discovery and development owing to their inherent three-dimensionality and structural novelty. Despite the recent significant progress, the straightforward catalytic asymmetric assembly of spirocyclic scaffolds with multiple stereocenters from readily available starting materials remains a formidable challenge. Herein, we develop an unprecedented nickel-catalyzed one-pot synthesis of enantioenriched spiroindanones from easily available 1,6-enynes and oformylarylboronic acids. The reaction proceeds smoothly under redox-neutral conditions, without the need for an additional hydrogen donor, and features a broad substrate scope and excellent regio-, enantio-, and diastereoselectivity.
A Ni-catalyzed enantioselective reductive aryl-alkenylation of alkenes for the synthesis of functionalized oxindoles is developed. With this method, a concise formal synthesis of (+)-physovenine and (+)-physostigmine has been completed.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.