Double-metal-catalyzed coupling

The last decade has witnessed the application of 1-halogenoacetylenes as crucial intermediates for the synthesis of increasingly complex structures, especially in natural product chemistry. In pheromone synthesis it is essential to create double-bond systems diastereoselec-tively, and a route often taken consists in the preparation of a suitable alkyne precursor which is then converted into the final olefin by various addition reactions (catalytic hydrogenation, metalation, etc.). For the construction of the alkyne precursor to the pheromone, 1-bromo-(94) and 1-iodoalkynes (95) have been particularly valuable since they can easily be subjected to metal-catalyzed coupling reactions [105]. For ocample, the unsaturated ester 163, which is a sex attractant of Lepidoptera (moths and butterflies), has been prepared by first converting the terminal acetylene 160 into its 1-iodo derivative 161. This is subsequently hydrogenated... 

Nanostructured Carbon Materials for Catalysis 24 Heterocycles from Double-Functionalized Arenes Transition Metal Catalyzed Coupling Reactions 25 Asymmetric Functionalization of C—H Bonds... 

Heterocycles from Double-Functionalized Arenes Transition Metal Catalyzed Coupling Reactions... 

The method enables conversion of substituted alkynes to (fc)-2-methyl-1 -alkenylalumi-num species, and, by subsequent iodinolysis, to the corresponding iodoalkenes with retention of the double-bond configuration. Depending on the substitution pattern of the starting alkyne, many useful products emerge from this reaction, which themselves can serve as building blocks for transition metal-mediated or -catalyzed coupling reactions [59—62]. 

The increased development of transition metal-catalyzed cross-coupling methods to form C-C bonds has served as an impetus to find methods to synthesize 3-halochromones and 3-haloflavones. The synthesis of 3-halochromones and flavones can be achieved with the addition of halogens across the double bond of the pyrone ring by reaction with a halogenating reagent (e.g., Br2) followed by spontaneous, or base-induced, elimination (Scheme 48). Synthesis of these important compounds has been recently reviewed <2003RCR489>. 

The optional site selective metallation of fluorotoluenes158 with the superbasic mixture of butyllithium and potassium fert-butoxide has been applied to the synthesis of the anti-inflammatory and analgesic drug Flurbiprofen.171 3-Fluorotoluene is selectively metallated in the 4-position with LIC-KOR in THF at — 75 °C to afford, after reaction with fluorodimethoxyborane and hydrolysis, the corresponding boronic acid in 78% yield. A palladium-catalyzed coupling with bromobenzene gives the 2-fluoro-4-methylbiphenyl in 84% yield. This four-step sequence can also be contracted to a one-pot procedure with an overall yield of 79%. A double metallation with the superbasic mixture lithium diisopropylamide/potassium tert-butoxide (LIDA-KOR)172 173 is then required to produce flurbiprofen. 

In the last years transition metal-silyl complexes have received special attention for several reasons [1, 2], On the one hand, they are assumed to be important intermediates in catalytic processes [2] (transition metal-catalyzed hydrosilylation reaction, dehydrogenative coupling of silanes to polysilanes, etc.), on the other metal-substituted silanes show special properties, which can be tuned systematically by judicious choice of the metal and its ligands [3] Furthermore, silylenes (silanediyls) are stabilized by unsaturated transition metal fragments leading to metal-silicon double-bonds [4]. In the light of a possible application in MOCVD processes some of these complexes are of interest as potential single-source precursors for the manufacture of thin silicide films [5]. 

With the success of transition-metal-catalyzed aryl-aryl cross-coupling reactions through C-H activation of one of the coupling partners, obviously, a more economic and attractive alternative is the coupling reaction via double C-H activation of two arenes, neither of which needs to be preactivated (Scheme 5). However, the development of such a process is very challenging because many difficulties remain to be solved. For instance, the control of selectivity when two coupling partners have more than one type of aromatic C-H bond is a challenge. 

In cases where the Pd- or Ni-catalyzed cross-coupling reactions of alkenylalu-minum and alkenylzirconium derivatives are sluggish, addition of Zn salts (e.g., ZnCl2 and ZnBr2) has significantly accelerated these reactions in many cases (double metal... 

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