Transition metal-catalyzed reactions, aryne

In 1953, Robert s experiments on the conversion of C-labeled chlorobenzene with KNH2 into aniline gave strong support to the intermediacy of ortho-benzyne in this and related reactions. Additional direct evidence for the existence of ortho-benzyne was provided by the observation of its IR spectrum, sohd-state dipolar NMR spectrum, and NMR in a molecular container, and by UV photoelectron spectroscopy. Even at low temperatures, arynes are extraordinary reactive. The reactions of arynes can be divided into three groups (i) pericyclic reactions, (ii) nucleophilic additions, and (iii) transition-metal catalyzed reactions. The pericyclic reactions can be divided into several categories such as Diels-Alder reactions, [2-f2] cycloadditions, 1,3- and l,4-dipolar cycloadditions, and the ene reactions. Arynes react with practically aU kinds of nucleophiles. More recently, the transition-metal catalyzed reactions of arynes have been studied, in particular those involving palladium. 

The reactions of arynes can be divided into three groups (i) pericyclic reactions, (ii) nucleophilic additions, and (iii) transition-metal catalyzed reactions. 

Finally, transition metal-catalyzed reactions of arynes have been explored as a useful method for the construction of a wide variety of carbo- and heteocycles. These reactions include cyclotrimerization of arynes, cocyclization of arynes with alkynes or alkenes, and carbopaUadation of arynes with Pd-complexes. Moreover, some insertion reactions of arynes into a-bonds are also catalyzed by metal complexes. 

This chapter deals with advances in the synthetic application of the transition-metal-catalyzed reactions of arynes or o-QDMs, except for the cycloaddition of arynes, which was described in earlier chapters. Because arynes and o-QDMs, which can be regarded as dearomatized reactive intermediates, are utilized for the construction of aromatic skeletons via the reactions discussed herein, this chapter is entitled Dearomatization-Aromatization Sequence. ... 

Just as in aryl halides, the halogen can be replaced by hydrogen and by a metal, or be involved in transition metal-catalyzed processes (covered in Section 3.2.3.11.2). Three of the mechanisms of such nucleophilic substitutions are familiar from benzene chemistry via arynes, SrnI processes, and Pd(0)-catalyzed sequences. However, of the two further mechanisms of nucleophilic replacement, the ANRORC (Addition of Micleophile, Ring Opening, Ring Closure) is unique to heterocycles, and Sae reactions occur only with strongly activated benzenoid systems. 

In the last two decades transition metal catalyzed cyclization/annulation reactions have also been reported. In most cases alkynes are cyclized within a biphenyl-containing substrate. Different modes of action for the transition metal can be distinguished. In the first case the metal undergoes an oxidative addition into an aryl-halogen bond and then performs the carbometallation of the alkyne. Here, an example by Larock and coworkers is presented, in which an in situ formed aryne species is cyclized with an iodo biaryl substrate 136 (Scheme 34) [89]. 

The strained nature of the aryne triple bond results in an easily accessible LUMO and so, arynes are excellent electrophiles that react with different anionic or neutral nucleophilic species. This low-lying LUMO also makes arynes prone to participate in a variety of pericyclic reactions. In addition, arynes are also able to undergo interesting transition metal-catalyzed processes. The increased availability of functionalized aryne precursors as well as the possibility of generating arynes under reagent-free conditions is allowing the development of new aryne-mediated synthetic strategies and the discovery of new reactivity patterns, which will expand the repertoire of chemistry that is actually possible with arynes. 

The reactions between benzotriafulvenes and transition metals (Pt and Rh) afford metallacyclobutane derivatives 41 as stable crystalline compounds in good yields. Recently, Huang developed the highly regioselective palladium-catalyzed [i+2] cycloaddition reactions of 34 (R = Ph) with arynes or alkynes to provide fluorene 42 and rndene derivatives 43, respectively (Scheme 6.4) [24]. 

In this chapter we described [2 + 2 + 2] and related cycloaddition reactions using palladium, iron, manganese, rhenium, and other transition metals. Palladium complexes are able to catalyze [2 + 2 + 2] and related cycloaddition reactions, which proceed via cascade-type mechanism or metallacycle intermediates. It is worthy of note that arynes are suitable substrates for this palladium catalysis. Iron complexes are promising catalysts for practical [2 + 2 + 2] cycloaddition reactions, owing to their low cost and nontoxicity, although both catalytic activity and substrate scope are not satisfactory. Manganese and rhenium complexes allow the use of 3-keto esters as a cycloaddition partner. To realize the practical process and broaden the product scope, further development of new transition-metal catalysts is expected in this research field. 

Some palladium-catalyzed reactions of organotins, such as carbostannylations, are not related to the Stille cross-coupling. The history of the transition-metal-cata-lyzed carbostarmylation [148] began with alkynylstannylation of alkynes catalyzed by a palladium-iminophosphine complex [149]. Thus, alkynylstannanes added to a carbon-carbon triple bond of various acetylenes, conjugated ynoates and propar-gyl amines and ethers in the presence of a catalytic amount of a palladium-iminophosphine complex [150]. The reaction also proceeded with arynes to afford ortho-substituted arylstannanes, which could further be converted into 1,2-substituted arenes via carbon-carbon bond-forming reactions [151]. 

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