Mihai S. Viciu

Catalytic cross-coupling reactions mediated by palladium/nucleophilic carbene systems

Abstract In this mini-review, we present a summary of our recent work in the field of palladium-catalyzed cross-coupling reactions, with emphasis on the use of nucleophilic N-heterocyclic carbenes (NHC) as ancillary ligand. The palladium-mediated coupling reactions investigated include the Suzuki–Miyaura, Kumada–Tamao–Corriu, Heck, Sonogashira, Stille, Hiyama and aryl amination reactions.

10 Carbenes: reactivity and catalysis

Since the first report of a stable carbene by Arduengo in 1991, the use of N-heterocyclic carbenes (NHC) in organic synthesis has increased dramatically. This is principally due to their unique properties. NHC are known to form strong bonds to late transition metals since they are excellent σ-donors and possess (in general) minimal π-back donation capabilities. In view of this, NHCs have rapidly been used as a new class of ligand, capable of mimicking the well-known phosphines without the classical problems associated with phosphine use. The recent use of NHC is not restricted to catalysis using late transition metals, but they are also used as organic catalysts or as reactants in multi-component reactions, as is described in later sections of this report. Studies have shown that nucleophilic N-heterocyclic carbenes represent a very versatile class of ligands due to their interesting steric and electronic properties. These ligands have several advantages over the commonly utilized phosphines: (i) stabilizing effect, (ii) high thermal stability, (iii) resistance to dissociation from the metal center. Therefore an excess of the ligand is not required in order to prevent aggregation of the catalyst to yield bulk metal. As a consequence, an increasing number of catalytic reactions make use of nucleophilic carbenes as catalyst modifiers. Specific examples include the use of metal–carbene complexes in hydrosilylation, Ru-catalysed furan synthesis and olefin metathesis. In this report, attention will be focused on the latest highlights in the field of use of carbenes. Undoubtedly, NHC ligands are currently important in a wide range of reactions and the reader will find here a summary of current applications.

Lithium Diisopropylamide-Mediated Ortholithiation of 2-Fluoropyridines: Rates, Mechanisms, and the Role of Autocatalysis

Lithium diisopropylamide (LDA)-mediated ortholithiations of 2-fluoropyridine and 2,6-difluoropyridine in tetrahydrofuran at -78 °C were studied using a combination of IR and NMR spectroscopic and computational methods. Rate studies show that a substrate-assisted deaggregation of LDA dimer occurs parallel to an unprecedented tetramer-based pathway. Standard and competitive isotope effects confirm post-rate-limiting proton transfer. Autocatalysis stems from ArLi-catalyzed deaggregation of LDA proceeding via 2:2 LDA-ArLi mixed tetramers. A hypersensitivity of the ortholithiation rates to traces of LiCl derives from LiCl-catalyzed LDA dimer-monomer exchange and a subsequent monomer-based ortholithiation. Fleeting 2:2 LDA-LiCl mixed tetramers are suggested to be key intermediates. The mechanisms of both the uncatalyzed and catalyzed deaggregations are discussed. A general mechanistic paradigm is delineated to explain a number of seemingly disparate LDA-mediated reactions, all of which occur in tetrahydrofuran at -78 °C.

(N-Heterocyclic Carbene)-Metal Complexes and Their Application in Catalysis

This review covers recent advances (2009) in synthesis and catalytic activity of carbene metal complexes. Due to the wide variety of research interests in this field and the limited space of this account, a selection of the papers needed to be made focusing on a comprehensive coverage of recent trends and potential impact on catalysis.

Recent advances of metal–nucleophilic carbene complexes in catalysis

The field of nucleophilic carbenoid ligands in organometallic catalysis is continuously expanding with new chemical transformations and improved catalytic systems. This review highlights just few developments of the last year. Out of several hundred scientific papers that covered the subject last year, the authors limit themselves to the reports that present direct catalytic results and, at some extent, interesting stoichiometric reactions or mechanistic aspects with obvious applicability in catalysis.