Mizoroki–Heck Cyclizations of Amide Derivatives for the Introduction of Quaternary Centers

Abstract

We report the non-decarbonylative Mizoroki–Heck reactions of amide derivatives. The transformation relies on the use of nickel catalysis and proceeds using sterically hindered tri- and tetrasubstituted olefins to give products containing quaternary centers. The resulting polycyclic or spirocyclic products can be obtained in good yields. Moreover, a diastereoselective variant of this methodology demonstrates its value for accessing adducts bearing vicinal, highly substituted sp3 stereocenters. Our results demonstrate that amide derivatives can be used as building blocks for the assembly of complex scaffolds.

Recent Advances in the Metal‐Catalyzed Activation of Amide Bonds

“…In 2017, the intramolecular variant of the Mizoroki-Heckr eactionw as developedb yG arg and coworkers to afford ar ange of 2-indanone derivatives (Scheme 31). [69] The transformation was facilitated by [Ni(cod) 2 ]a st he catalyst, NHC as al igand,N aOtBu as ab ase, and tert-amyl alcohol as an additive in toluene at 60 8C. The reaction followed the classical mechanism, which comprised oxidative addition, olefin coordination, insertion, and b-hydride elimination steps to afford the quaternaryc arbon center.…”

Nickel‐Catalyzed Domino Heck‐Type Reactions Using Methyl Esters as Cross‐Coupling Electrophiles

“…In 2017, the groups of Garg and Stanley independently reported the trapping of amide‐derived acyl‐Ni intermediates intramolecularly by the insertion of a tethered allyl fragment, a step which is generally proposed to be energetically downhill . Sequential β‐hydride elimination or intermolecular transmetallation with an organoboron nucleophile forms the corresponding Mizoroki–Heck or Suzuki–Miyaura products, respectively (Scheme C).…”

Palladium‐Catalyzed Decarboxylative Cross‐Couplings of 1‐Boc‐3‐iodoazetidine: Regioselective Access to 2‐Alkynylazetidines, 3‐Alkynylazetidines and 3‐Vinylazetidines

“…Previous works established that the intermediate of Pd or Ni occurred migratory insertion could offer the potential opportunity to develop a new class of alkene functionalization reactions . Buchwald described a selective preparation of branched or linear products from the secondary alkylzinc reagents with aryl bromides or aryl chlorides by using a new CPhos ligand supported catalyst system to control the rates of reductive elimination versus β‐hydride elimination‐reinsertion (Scheme , a) .…”