Nickel‐Catalyzed Regioselective Alkenylarylation of γ,δ‐Alkenyl Ketones via Carbonyl Coordination

Abstract

We disclose a nickel‐catalyzed reaction, which enabled us to difunctionalize unactivated γ,δ‐alkenes in ketones with alkenyl triflates and arylboronic esters. The reaction was made feasible by the use of 5‐chloro‐8‐hydroxyquinoline as a ligand along with NiBr2⋅DME as a catalyst and LiOtBu as base. The reaction proceeded with a wide range of cyclic, acyclic, endocyclic and exocyclic alkenyl ketones, and electron‐rich and electron‐deficient arylboronate esters. The reaction also worked with both cyclic and acyclic alkenyl triflates. Control experiments indicate that carbonyl coordination is required for the reaction to proceed.

Cobalt-Catalyzed C(sp2)–C(sp3) Suzuki–Miyaura Cross-Coupling Enabled by Well-Defined Precatalysts with L,X-Type Ligands

“… ,, Another class of ligand that exhibited promising performance was 8-hydroxyquinoline (QNOL), which gave the desired product ( 3a ) in up to 42% UPLC-MS area (Table ). Notably, this class of ligands likely forms “L,X-type” interactions where deprotonation of the phenol generates an anionic donor ( vide infra ). Related N , O ligands such as amino alcohols have also been successful in nickel-catalyzed Suzuki–Miyaura arylation reactions of unactivated alkyl electrophiles …”

Access to dialkylated allylic stereogenic centers by Ni-catalysed enantioselective hydrovinylation of unactivated alkenes

“…Accordingly, b-vinyl acids and ketones as well as g-vinyl amines and alcohols were obtained in good yields (69-84%) with good levels of enantioselectivity (87-91%). Moreover, a-alkylated carboxylic acid bearing acidic a-proton (11) was obtained in 73% yield with 90% ee by C]C cleavage.…”

Selective Three-Component Reductive Alkylalkenylation of Unbiased Alkenes via Carbonyl-Directed Nickel Catalysis

“…Catalytic three-component dicarbofunctionalization (DCF) reactions of olefins stand for a powerful approach to access functionalized molecules with the spontaneous installation of two different carbon fragments from readily available starting materials. − However, efforts to explore their enormous synthetic potentials have often been hampered by the challenges associated with the regioselective control, particularly in the cases of electronically unbiased alkenes. Accordingly, a coordination strategy with pendant functional groups to stabilize transient metallacyles has been recently adopted, enabling excellent regioselective control in three-component DCFs of electronically unbiased alkenes. − With regard to carboalkenylation reactions, ,,,− Engle and Giri , groups independently utilized amino-quinoline and carbonyl as directing groups to develop Pd- and Ni-catalyzed three-component aryl-alkenylation of unbiased alkenes (Figure A). However, such a coordination strategy brings a new challenge to the stereoselective control of the newly formed allylic stereogenic centers. − Recently, several groups reported three-component DCFs of electronically unbiased alkenes with two electrophiles via nickel-catalyzed cross-electrophile strategy, in which a number of directing groups were also utilized to control regioselectivity (Figure B). − Specifically, our group reported a Ni-catalyzed asymmetric three-component reductive 1,2-alkylarylation of unbiased alkenes with (hetero)­aryl halides and alkyl iodide in the presence of Mn (Figure B) .…”