Alkynes intramolecular reactions, with arenes

Reactions of acylpalladium complexes involving acylpalladation with arenes or formally equivalent processes have been much less exploited compared with those involving acylpalladation with alkenes or alkynes discussed in the previous section, and to the best of our knowledge, their examples are limited to intramolecular reactions. A few reactions that may include the intramolecular acylmetallation with arenes are known in the case of a rhodium catalyst, but the products are limited to a narrow range of compounds such as indenones.t In contrast, the Pd-catalyzed carbonylation of 3-arylaUyl acetates or hahdes, most typically cinnamyl acetate, involving intramolecular acylpalladation with arenes results in the construction of 1-naphthol, which is a hiding member of cyclic aromatic ketones. The outline of the conversion is sketched in Scheme 1. In fact, this type of carbonylation-cyclization reaction (cyclocarbonylation) can be applied to the synthesis of a variety of fused aromatics, which is summarized in the following subsection. 

In our attempt to extend the coupling reaction of arenes with alkenes to the coupling with alkynes, as shown in Scheme 4, it was found that the reaction of arenes with ethyl propiolate in TFA (trifluoroacetic acid) gave addition products instead of a coupling product [3]. This addition reaction has been extended to various alkynes and various arenes and also to intramolecular reactions for synthesis of heterocycles such as coumarins, quinolines, and thiocoumarins. 

Arenes, especially electron-rich ones, have been found to react with alkynes in the presence of Pd(ll) or Pt(ll) species in a mixed solvent containing CF3COOH (Eq. 81) [158-160]. The intramolecular reaction is also possible (Eq. 82). The mechanism proposed for the reaction involves aromatic pallada-tion to form arylpalladium species as in Fujiwara-Moritani reaction, insertion of an alkyne, and protonolysis of the resulted vinylpalladium intermediate. 

From a synthetic point of view, bond forming steps are the most important reactions of radical ions [202]. Several principle possibilities have been described in Section 8.1 and are summarized in Scheme 52. Many carbo- and heterocyclic ring systems can be constructed by (inter- and intramolecular) radical addition to alkenes, alkynes, or arenes. Coupling of carbonyl radical anions leads to pinacols either intra-or inter-molecular which can be further modified to give 1,2-diols, acyloins or alkenes. Radical combination reactions with alkyl radicals afford the opportunity to synthesize macrocyclic rings. These radical ion-radical pairs can be generated most efficiently by inter- or intramolecular photoinduced electron transfer. 

Domino or cascade reactions provide valuable approaches, especially to various carbo- and heterocyclic systems with three, four, or even more annelated rings. The Heck reaction has successfully been employed in various inter-inter-, intra-inter-, inter-intra-, as well as all-intramolecular reaction cascades, hi this section, the termination of these processes by alkenes, arenes, and related ir-bond systems such as alkynes and allenes will be described. A cascade Heck reaction is considered to consist of an oxidative addition of a heteroatom-carbon bond to palladium (starter), carbopalladation of a nonaromatic carbon-carbon double or triple bond without immediate dehydropalladation (relay), one, two, or more fimher car-bopalladation(s) of a carbon-carbon double or triple bond, and eventually ensuing dehydropalladation. Crucial for a cascade reaction of this kind to occur is the blockage or retardation of a dehydropalladation at one of the intermediate stages by using 1,1-disubsti-tuted alkenes and appropriately substimted cycloalkenes, bicycloalkenes, or alkynes as relays since they give kinetically stable alkyl- or alkenylpalladium intermediates, respectively. 

Denmark pursued intramolecular alkyne hydrosilylation in the context of generating stereodefined vinylsilanes for cross-coupling chemistry (Scheme 21). Cyclic siloxanes from platinum-catalyzed hydrosilylation were used in a coupling reaction, affording good yields with a variety of aryl iodides.84 The three steps are mutually compatible and can be carried out as a one-pot hydro-arylation of propargylic alcohols. The isomeric trans-exo-dig addition was also achieved. Despite the fact that many catalysts for terminal alkyne hydrosilylation react poorly with internal alkynes, the group found that ruthenium(n) chloride arene complexes—which provide complete selectivity for trans-... 

At the beginning of the new millennium, Hashmi et al. presented a broad research study on both intramolecular and intermolecular nucleophilic addition to alkynes and olefins [18]. One of the areas covered by these authors was the isomerization of co-alkynylfuran to phenols [19]. After that, Echavarren and coworkers identified the involvement of gold-carbene species in this type of process, thus opening a new branch in gold chemistry [20]. And subsequently, Yang and He demonstrated the initial activation of aryl —H bonds in the intermolecular reaction of electron-rich arenes with O-nucleophiles [21, 22]. 

Cyclization of dienynes.1 This Ni(0) catalyst in combination with a triarylphos-phite, particularly tri-o-biphenyl phosphite, permits intramolecular cycloaddition at 25° of [4+2] dienynes, in which the diene and the alkyne are separated by 3- and 4-atom units. This reaction is a useful route to products containing a cyclohexadiene group, which are oxidized to an arene by DDQ. 

A final type of oxidative carbon-carbon bond forming dearomatization process involves electrophile-induced dearomatization. The most common variant of this reaction entails activation of an alkyne or alkene moiety with an electrophilic halide source to initiate intramolecular dearomatization accompanied by formal arene oxidation (Scheme 15.26) [72]. Proper positioning of an electron-donating methoxy group is crucial for success of this transformation. Other examples of halocyclization-dearomatization reactions involving appropriately substituted arenes tethered to alkynes and alkenes have been reported, along with an intramolecular Pummerer-type dearomatization initiated by an electrophilic thionium ion [73, 74]. 

The Lewis acid-mediated [4+2] cycloaddition of conjugated enynes with alkynes affords arenes however, it is limited to the intramolecular cycloaddition [44]. The use of transition metal complexes realizes the catalytic intermolecular variants. The first example was reported in the paUadium(O)-catalyzed homo-[4+2] cycloaddition of monosubstituted conjugated enynes giving substituted styrenes (Scheme 21.38) [45]. Importantly, this reaction proceeded with definite regioselectivity. 

In 2014, Rh(III)-catalyzed intramolecular annulation of alkyne-tethered acetanilides for the synthesis of fused tricyclic indoles 3 via C-H activation was developed by the groups of Liu, Jia, and Li [6a-c]. The reactions have a good substrate scope, utilize molecular oxygen as the cooxidant, and proceed with complete regioselectivity. It is interesting to note that only the sterically hindered ortho-C-H bond of the arene moiety participated in C-C bond formation (Eq. (5.3)). Similarly, the cyclization of anilides with allyl carbonates also proceeded to form 2-substituted indoles 4 (Eq. (5.4)) [6d]. 

In 2006, Liu and coworkers reported a gold-catalyzed intramolecular cycloaddition of diynes with tethered arenes 118 to synthesize l,3-dihydroindeno[2,l-c]pyran or 2,3-dihydro-l//-indeno[2,l-c]pyridinederivatives 120 (Scheme 12.52) [56]. On the basis of deuterium labeling, they believed that the first reaction step is the intramolecular arylation of one alkyne to form vinylgold(I) intermediate 119,... 

---