Transition‐Metal‐Free Formal Sonogashira Coupling and α‐Carbonyl Arylation Reactions

Transition‐metal‐free formal Sonogashira coupling and α‐carbonyl arylation reactions have been developed. These transformations are based on the nucleophilic aromatic substitution (S_NAr) of β‐carbonyl sulfones to electron‐deficient aryl fluorides, producing a key intermediate that, depending on the reaction conditions, gives the aromatic alkynes or α‐aryl carbonyl compounds. The development of these reactions is presented and, based on investigations under basic and acidic conditions, mechanisms have been proposed. To develop the formal Sonogashira coupling further, a milder, two‐step protocol is also disclosed that expands the reaction concept. The scope of these reactions is demonstrated for the synthesis of Sonogashira and α‐carbonyl arylated products from a range of electron‐deficient aryl fluorides with a variety of functional groups and aryl‐, heteroaryl‐, alkyl‐, and alkoxy‐substituted sulfone nucleophiles. These transition‐metal‐free reactions complement the metal‐catalyzed versions in terms of substitution patterns, simplicity, and reaction conditions.     

Palladium‐Catalyzed Insertion of α‐Diazoesters into Vinyl Halides To Generate α,β‐Unsaturated γ‐Amino Esters

As easy as 1, 2, 3 : A palladium‐catalyzed three‐component coupling generates α,β‐unsaturated γ‐amino acids in a single step (see scheme). The reaction is believed to involve migration of a vinyl substituent to a highly electrophilic palladium carbene. Unlike previous synthetic approaches, this synthesis provides access to γ‐amino acids with non‐natural side chains.

     

Synthesis of Nickel(II) Azacorroles by Pd‐Catalyzed Amination of α,α′‐Dichlorodipyrrin NiII Complex and Their Properties

Synthesis of nickel(II) complexes of meso‐aryl‐substituted azacorroles was performed by Buchwald–Hartwig amination of a dipyrrin Ni^II complex with benzylamine through C? N and C? C coupling. The highly planar structure of Ni^II azacorroles was elucidated by X‐ray diffraction analysis. ¹H NMR analysis and nucleus independent chemical shift (NICS) calculation on Ni^II azacorrole revealed its distinct aromaticity with [17]triaza‐annulene 18π conjugation. In addition, acylation of azacorrole selectively afforded N‐ and C‐acylated azacorroles depending on the reaction conditions, showing the dual reactivity of azacorroles.     

Gas‐Phase Energetics of Reductive Elimination from a Palladium(II) N‐Heterocyclic Carbene Complex

Energy‐resolved collision‐induced dissociation experiments using tandem mass spectrometry are reported for an phenylpalladium N‐heterocyclic carbene (NHC) complex. Reductive elimination of an NHC ligand as a phenylimidazolium ion involves a barrier of 30.9(14) kcal mol^?1, whereas competitive ligand dissociation requires 47.1(17) kcal mol^?1. The resulting three‐coordinate palladium complex readily undergoes reductive C? C coupling to give the phenylimidazolium π complex, for which the binding energy was determined to be 38.9(10) kcal mol^?1. Density functional calculations at the M06‐L//BP86/TZP level of theory are in very good agreement with experiment. In combination with RRKM modeling, these results suggest that the rate‐determining step for the direct reductive elimination process switches from the C? C coupling step to the fragmentation of the resulting σ complex at low activation energy.     

Pd‐NHC‐Catalyzed Direct Arylation of 1,4‐Disubstituted 1,2,3‐Triazoles with Aryl Halides

A highly efficient method for the synthesis of unsymmetrical multi‐substituted 1,2,3‐triazoles via a direct Pd‐NHC system catalyzed C(5)‐arylation of 1,4‐disubstituted triazoles, which are readily accessible via "click" chemistry has been developed. It is important to note that C? H bond functionalizations of 1,2,3‐triazoles with a variety of differently substituted aryl iodides and bromides as electrophiles can be conveniently achieved through this catalytic system at significantly milder reaction temperatures of 100°C under air.