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Aryl-aryl bond formation one century after the discovery of the Ullmann reaction.

The biaryl structural motif is a predominant feature in many pharmaceutically relevant and biologically active compounds. As a result, for over a century 1 organic chemists have sought to develop new and more efficient aryl -aryl bond-forming methods. Although there exist a variety of routes for the construction of aryl -aryl bonds, arguably the most common method is through the use of transition-metalmediated reactions. 2-4 While earlier reports focused on the use of stoichiometric quantities of a transition metal to carry out the desired transformation, modern methods of transitionmetal-catalyzed aryl -aryl coupling have focused on the development of high-yielding reactions achieved with excellent selectivity and high functional group tolerance under mild reaction conditions. Typically, these reactions involve either the coupling of an aryl halide or pseudohalide with an organometallic reagent (Scheme 1), or the homocoupling of two aryl halides or two organometallic reagents. Although a number of improvements have developed the former process into an industrially very useful and attractive method for the construction of aryl -aryl bonds, the need still exists for more efficient routes whereby the same outcome is accomplished, but with reduced waste and in fewer steps. In particular, the obligation to use coupling partners that are both activated is wasteful since it necessitates the installation and then subsequent disposal of stoichiometric activating agents. Furthermore, preparation of preactivated aryl substrates often requires several steps, which in itself can be a time-consuming and economically inefficient process.

http://aether.cmi.ua.ac.be/artikels/Artikels%20Gitte/Artikels/Reviews/Heck-Type-lautens.pdf

Aryl-aryl bond formation by transition-metal-catalyzed direct arylation.

The direct functionalization of C-H bonds in organic compounds has recently emerged as a powerful and ideal method for the formation of carbon-carbon and carbon-heteroatom bonds. This Review provides an overview of C-H bond functionalization strategies for the rapid synthesis of biologically active compounds such as natural products and pharmaceutical targets.

C-H bond functionalization: emerging synthetic tools for natural products and pharmaceuticals

Native wood celluloses can be converted to individual nanofibers 3–4 nm wide that are at least several microns in length, i.e. with aspect ratios >100, by TEMPO (2,2,6,6-tetramethylpiperidine-1-oxyl radical)-mediated oxidation and successive mild disintegration in water. Preparation methods and fundamental characteristics of TEMPO-oxidized cellulose nanofibers (TOCN) are reviewed in this paper. Significant amounts of C6 carboxylate groups are selectively formed on each cellulose microfibril surface by TEMPO-mediated oxidation without any changes to the original crystallinity (∼74%) or crystal width of wood celluloses. Electrostatic repulsion and/or osmotic effects working between anionically-charged cellulose microfibrils, the ζ-potentials of which are approximately −75 mV in water, cause the formation of completely individualized TOCN dispersed in water by gentle mechanical disintegration treatment of TEMPO-oxidized wood cellulose fibers. Self-standing TOCN films are transparent and flexible, with high tensile strengths of 200–300 MPa and elastic moduli of 6–7 GPa. Moreover, TOCN-coated poly(lactic acid) films have extremely low oxygen permeability. The new cellulose-based nanofibers formed by size reduction process of native cellulose fibers by TEMPO-mediated oxidation have potential application as environmentally friendly and new bio-based nanomaterials in high-tech fields.

TEMPO-oxidized cellulose nanofibers

Isolation and synthesis of biologically active carbazole alkaloids

Publisher Summary This chapter updates the directed ortho metalation (DoM) reaction of pyridines, quinolines, pyrimidines, pyrazines, and pyridazines. Various directed metalation group (DMGs) (halo, NHCOR and NHC02R, OR and OCONR2, 2-oxazolino, CONHR, CONR2, and masked RCHO and RCOR, SO2NR2) have been described, with major emphasis given to the metalation of halo pyridines, an area in which selectivity and mechanistic aspects have been extensively studied. Reactions of powerful alkyllithiums with halo pyridines, quinolines, and diazines may lead to nucleophilic substitution (by addition-elimination or hetaryne mechanisms), ring opening, halogen-scrambling, and coupling reactions that compete with the desired DoM process. Lithiation chemistry of bare pyridines and pyridine N-oxides is presented, followed by the use of the DoM strategy for the synthesis of natural products and biologically active molecules. The exploration of DoM chemistry in haloheteroaromatics is valuable for two reasons: (a) halo derivatives can be readily prepared from accessible amino, hydroxy, and, at times, unsubstituted systems, and (b) halogens can be subsequently induced to undergo a variety of funcionalizations via addition-elimination, metal-halogen exchange, and cross coupling reactions. Some of these transformations are more facile than in the aromatic series. Thus, DoM tactics may lead to diverse substituted heteroaromatics, which can be difficult to obtain by more classical means.

Directed Metalation of Pi-Deficient Azaaromatics: Strategies of Functionalization of Pyridines, Quinolines, and Diazines

Pyridylmagnesium chlorides from bromo and dibromopyridines by brominemagnesium exchange: A convenient access to functionalized pyridines

The first deprotonations of oxazole and benzoxazole using lithium magnesates are described. The reactions occurred in tetrahydrofuran at room temperature using 1/3 equiv of lithium tributylmagnesate. As 2-lithiooxazole and 2-lithiobenzoxazole, lithium tri(2-oxazolyl)magnesate and lithium tri(2-benzoxazolyl)magnesate very rapidly and completely isomerized to the more stable 2-(isocyano)enolate and 2-(isocyano)phenolate type structures, respectively, a result shown by NMR analysis. The isolation of 2-substituted oxazoles and benzoxazoles in medium to good yields after electrophilic trapping was interpreted in two ways:  (1) the equilibration between the open and closed structures is faster than the trapping of the open isomers, and the closed isomers are more reactive than the open ones, or (2) the open isomers react with electrophiles in a intramolecular Passerini type reaction. The nonreactivity of the 2-(isocyano)enolate type structure toward anisaldehyde in the absence of lithium bromide makes the intra...

Francis Marsais

Papers

Directed Metalation of Pi-Deficient Azaaromatics: Strategies of Functionalization of Pyridines, Quinolines, and Diazines

Pyridylmagnesium chlorides from bromo and dibromopyridines by brominemagnesium exchange: A convenient access to functionalized pyridines

Deprotonation of Benzoxazole and Oxazole Using Lithium Magnesates

Metallation regioselective en serie pyridinique: Synthese originale d'amino-2 aroyl-3 pyridines

Regioselective palladium-catalyzed phenylation of ethyl 4-oxazolecarboxylate