Arenes ketones, cyclic

The transformation is selective for the formation of C-2 substituted chromones and is tolerant toward a number of functional groups including nitro, free hydroxyl, acetyl, triflates, trifluoromethyl, and halogens (Scheme 24.41). The Backvall group subsequently reported a similar transformation that enabled the Pd-catalyzed coupling of arenes with cyclic saturated ketones [37]. 

One may well ask why the isomerization of alkenes discussed in the preceding section requires a sensitizer. Why cannot the same result be achieved by direct irradiation One reason is that a tt — tt singlet excited state (5,) produced by direct irradiation of an alkene or arene crosses over to the triplet state (Ij) inefficiently (compared to n —> it excitation of ketones). Also, the Si state leads to other reactions beside isomerization which, in the case of 1,2-diphenyl-ethene and other conjugated hydrocarbons, produce cyclic products. For example, cw-l,2-diphenylethene irradiated in the presence of oxygen gives phenanthrene by the sequence of Equation 28-8. The primary photoreaction is cyclization to a dihydrophenanthrene intermediate, 6, which, in the presence of oxygen, is converted to phenanthrene ... 

Arene activation by metal complexation is not always necessary for the cyclisation of samarium ketyls on to aromatic systems. Studies carried out by Reissig demonstrated the utility of these reactions for the synthesis of a wide variety of polycyclic systems, although yields and stereoselectivities depend highly on the substrate structure.68 One well-behaved system is represented by the cyclic y-naphthyl ketones 50-54, which cyclise with excellent diaster-eocontrol, thereby incorporating four- to eight-membered rings into the tetracyclic structures 55-59 (Scheme 5.38).68 Tetracyclic product 56 (n = 1) is of particular interest because of its steroid-like structure. 

Cyclic ketals of acetophenone can be prepared directly under basic conditions by the reaction of aryl triflates, bromides or iodides with hydroxyatkyl vinyl ethers in the presence of a catalytic amount of palladium(II) acetate and 1,3-bis(diphenylphosphino)propane (DPPP).84 The example illustrated in Scheme 2.39 is noteworthy since a protected methyl ketone was appended to an arene in the presence of a reactive aldehyde functionality. 

The Michael addition of malonates to cyclic enones, catalyzed by chiral Ru(77 -arene)(p-toluenesulfonyl-l,2-diamine), has been performed to afford the adduct with excellent enantiomeric excess [91,92]. A related catalyst was designed to perform sequentially the Michael addition to cyclic enone and the enantioselective hydrogenation of the ketone. Thus, the chiral ruthenium catalyst B containing trans hydride and borohydride ligands was able to enan-tioselectively (96% ee) promote the Michael addition of malonate to cyclo-hexenone. Further in situ catalytic hydrogenation (400 psi H2) was performed and led to excellent diastereoselectivity transicis 30/1 [93] (Scheme 43). 

The Friedel-Crafts alkylation of arenes with lactones provides a convenient method for the synthesis of arylalkanoic acids. However, depending on the nature of the arene, catalyst, temperature and reaction time, the resulting arylalkanoic acids can undergo partial or complete cyclization to the corresponding cyclic ketones (Scheme 10). Equations (65) to (68) show examples of Friedel-Crafts alkylations using lactones as the alkylating agents." "" ... 

Dihydroxy allenes are generated from ketoenes and ethynyl epoxides. a,P-Epoxy ketones undergo reductive cleavage but the P-hydroxy ketones thus obtained can react further, for example with an e, -double bond to give cyclic 1,3-diols. Note that the double bond does not have to be activated, and furthermore, a silylalkyne moiety and a tricarbonylchromium-complexed arene can play the same role, although in the latter case the net result is a cine-substitution. 

In the literature there are reactions of DMC with what would be considered ambident nucleophiles. For instance, indole is an ambident nucleophile. Using various organic chemistry procedures, reactions can either occur at the nitrogen or the conjugated arene carbon." In the field of DMC chemistry, Shieh and co-workers were able to selectively methylate the nitrogen using DABCO as a catalyst in contrast to other systems that effected carboxymethylation at the same nucleophilic centre. " Also cyclic ketones have been successfully reacted witli DMC to produce acyclic diesters via carboxymethylation at the alpha carbon. In these examples, however, the ambidenticity of these systems toward DMC has not been shown (Scheme 12). Only activation of one of tlie two centres has occurred. 

Good yields of cyclic aryl ketones are achieved with arenes, provided they are not very electron deficient. For example, the cycloacylation of arylpropanoic acids can be performed in the presence of scandium triflate as Lewis acid to give indanones in good yields with electron-rich aromatic substrates, whereas lower yields are obtained with very electron-deficient ones. The reaction can also be performed in the presence of protic acid thus, 3-(3,5-dibromophenyl)propanoic acid is directly converted into... 

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. 

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