Alkynes transformations, benzene

Part A Reactions with [bis(trifluoroacetoxy)iodo]benzene. Transformations of Alkynes. Transformations of Ketones. Phenolic Oxidation. Oxidation of Nitrogen Compounds. Transfomration of Sulfur Compounds. Miscellaneous Transformations. 

Transition-metal-catalyzed intermolecular [2+2+2] cyclotrimerization of alkynes to benzenes has been extensively studied with several catalyst systems involving palladium, cobalt, nickel, rhodium, and other transition metals. This methodology can be applied to the preparation of polysubstituted benzenes. The major challenge of this transformation is control of regioselectivity of unsymmetrical alkynes, particularly in the cross-cyclotrimerization of two or three alkynes. 

In addition to the reaction of vinylcarbene complexes with alkynes, further synthetic procedures have been developed in which Fischer-type carbene complexes are used for the preparation of benzenes. Most of these transformations are likely to be mechanistically related to the Dbtz benzannulation reaction, and can be rationalized as sequences of alkyne-insertions, CO-insertions, and electrocycli-zations. A selection of examples is given in Table 2.18. Entry 4 in Table 2.18 is an example of the Diels-Alder reaction (with inverse electron demand) of an enamine with a pyran-2-ylidene complex (see also Section 2.2.7 and Figure 2.36). In this example the adduct initially formed eliminates both chromium hexacarbonyl ([4 -I- 2] cycloreversion) and pyrrolidine to yield a substituted benzene. 

The activation barrier for the oligomerization of alkynes may be overcome thermally or catalytically. Because the classical thermal transformation of ethyne into benzene in a hot tube is rather ineffective (47), more emphasis has been placed on working out catalytic routes for the synthesis of linear oligomers, cyclooligomers, and polymers. Transition metal compounds have proved to act as effective catalysts in homogeneous as well as in heterogeneous processes (48). 

The formation of benzene (or substituted benzene derivatives) is a common transformation catalyzed by numerous homogeneous and heterogeneous metal catalysts, mainly Co, Rh, Pd, and Ni.63-69 Even highly crowded molecules, such as hexaisopropylbenzene, could be synthesized in the presence of metal carbonyls such as [Co(CO)4]2.70 A very simple catalyst system, Me3SiCl and Pd on carbon in refluxing tetrahydrofuran, has been shown to transform symmetrical alkynes into hexaalkylbenzenes in excellent yield.71... 

This mechanism is supported by the transformation of preformed metallacyclo-pentadienes with alkynes,73,76-78 and labeling experiments79 that excluded the involvement of cyclobutadiene intermediates. It also accounts for the observation that terminal alkynes yield 1,2,4- (and 1,3,5-) trisubstituted benzene derivatives as the main product but not 1,2,3 derivatives. In contrast with this picture in cyclotrimerization with PdCl2-based catalysts, stepwise linear insertion of alkynes takes place without the involvement of palladacyclopentadiene.80... 

The other major dehalogenation pathway involves elimination of two halogens, leaving behind a pair of electrons that usually goes to form a carbon-carbon double bond. Where the pathway involves halogens on adjacent carbons, it is known as vicinal dehalogenation or reductive -elimination. The major pathway for reductive transformation of lindane involves vicinal dehalogenation, which can proceed by steps all the way to benzene (28). Recently, data has shown that this pathway not only can convert alkanes to alkenes, but can produce alkynes from dihaloalkenes (29). 

Thiepins sometimes undergo sulfur extrusion even during their preparation. Thus, thiepins 55 accessible from thiophenes 52 and alkynes 53 either slowly eliminate sulfur to form the corresponding benzene derivatives 56 (in some cases, even at -30°C) or they can be transformed to 56 by heating... 

A double furanoid Schiff base has been transformed into its benzene analog (Scheme 6) by means of maleic anhydride39 more generally and more directly alkynes are employed for this purpose (see below). 

The most popular Pd-catalyzed method for the production of furans and benzofurans involves reactions of alkynols. Acyclic alkynols are converted into furans, while benzene substituted alkynols are transformed into benzofurans. The use of this strategy is widespread for the synthesis of benzofurans however, it is occasionally used for the syntheses of furans. For example, intramolecular alkoxylation of alkyne 189 proceeds via an alkenylpalladium complex and subsequent carbonylation to form furan 190 [156, 157]. In addition, 3 -hydroxyalkyl-benzo[/)J furans were prepared by Bishop et al. via a Pd-catalyzed heteroannulation of silyl-protected alkynols with 2-iodophenol in a fashion akin to the Larock indole synthesis [158]. In a related series of experiments, Qing demonstrated that alkynes 191 could be efficiently converted into furans 192 [159]. 

The more complex [2 -f 2 + 2] cycloisomerization reaction of acetylene units is also catalyzed by transition metal-alkyne n complexation and can be readily utilized for the synthesis of a variety of polysubstimted benzene derivatives in a straightforward manner (10, 352, 353). Recently, this methodology has been applied to the cyclization of 15-membered, nitrogen-containing di- and triacetylenic macrocycles. Upon coordination with Pd(0) to the triacetylenic macrocycle at ambient temperature, the ti-coordinated Pd(0) complex results. Subsequent refluxing of this species in toluene promotes cycloisomerization to the hexasubstituted arene (354) (Scheme 28). The Rh(I) [e.g., RhCl(CO)(PPh3)2] complex also catalyzes these same transformations in high (>80%) yields. 

In order to further explore the reactivity of the homobimetallic ruthenium complexes, the reaction of 4 with terminal alkynes was investigated. Thus, when phenylacetylene or ferf-butylacetylene was added to a solution of complex 4 in CH2CI2 or benzene, the rapid and quantitative formation of the corresponding rathenium- vinylidene complexes, 8 and 9, respectively, was observed (13). The formation of 8 and 9 can be rationalised by the displacement of the ethylene ligand by the respective acetylene followed by an alkyne-to-vinylidene transformation. 

Suzuki-Miyaura cross-coupling polymerization of 1,4-bis((Z)-2-bromovinyl)benzenes with aryl-bis-boronic acids. The interest has been in an alternative approach, where rather than building a PPV with a pre-ordained stereochemistry, a postpolymerization yyn-selective reduction on a poly(phenylene ethynylene) (PPE) is used [125]. This scheme has the advantage that high molecular weight PPEs can be synthesized using either Pd-catalysis or alkyne metathesis. This route could also potentially allow for the access to an additional array of PPVs that are uniquely accessible from PPEs. The transformation of the triple bonds in PPEs and other acetylene building blocks to alkenes has considerable potential. 

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