Oxides, metal catalyzed arylation

As a matter of fact the photochemically generation of the triplet phenyl cation is synthetically equivalent to activation by metal catalysis that likewise produces a sort of phenyl cation complexes to the metal by oxidative addition of the aryl halide and elimination of the halide anion (see above). In fact, a photochemical parallel has been found for most type of metal catalyzed arylations, via reactions that occur from the same or similar reagents. 

An only partial execution of the aryl-aryl bridging approach at each second phenylene-phenylene linkage gives rise to PR PFs have been first synthesized by Yoshino [29,30] by the oxidative coupling of 9,9-dialkylfluorene monomers with FeCls- However, these initial products were characterized by an ill-defined chemical structure since the coupling did not proceed regioselectively at the 2- and 7-positions of the fluorene core. Later on, more effective transition metal-catalyzed aryl-aryl coupling methods have been also applied for the PF synthesis. 

In biatyl synthesis, although transition metal catalyzed aryl-aryl crosscoupling reactions have been widely exemplified using Suzuki-type reactions, CDC reactions between sp C-H bonds leading to sp C-C bonds are scarce. In 2010, Katsuki reported an enantioselective CDC reaction between two naphthol moieties catalyzed by a chiral iron(salan) complex under aerobic oxidative conditions (Scheme 4.23). Using 4 mol% of the iron(salan) complex 23-A as the catalyst in toluene at 60 °C for 48 h, two different 2-naphthols were coupled and the cross-coupled derivatives were isolated with moderate yields (44-70%) and good ee (87-95%). It must be pointed out that the homocoupling derivatives are also obtained in low yields. 

In contrast to the asymmetric procedures discussed above, the metal-catalyzed oxidation of alkyl aryl sulphides by t-butylhydroperoxide carried out in a chiral alcohol gives rise to chiral sulphoxides of low optical purity290 (e.e. 0.6 9.8%). Similarly, a very low asymmetric induction was noted when prochiral sulphides were oxidized by sodium metaperiodate in chiral alcohols as solvents291. 

Enantiomerically pure sulfoxides play an important role in asymmetric synthesis either as chiral building blocks or stereodirecting groups [156]. In the last years, metal- and enzyme-catalyzed asymmetric sulfoxidations have been developed for the preparation of optically active sulfoxides. Among the metal-catalyzed processes, the Kagan sulfoxidation [157] is the most efficient, in which the sulfide is enantioselectively oxidized by Ti(OzPr)4/tBuOOH in the presence of tartrate as chirality source. However, only alkyl aryl sulfides may be oxidized by this system in high enantiomeric excesses, and poor enantioselectivities were observed for dialkyl sulfides. 

By far the most common way for organic molecules to enter late transition metal catalyzed reactions is oxidative addition. In this process a low valent palladium(O)3 or nickel(O) atom inserts into a carbon-heteroatom bond, usually of an aryl halide or sulfonate (Figure 1-2). The formation of the carbon-metal bond is accompanied by an increase in the oxidation number of the metal by 2. There are a series of factors determining the speed of the process. 

Yamaguchi, S. Ohno, S. Tamao, K. Palla-dium(II)-catalyzed oxidative homocoupling of aryl—metal compounds using acrylate dibromide derivatives as effective oxidants. Synlett 1997, 1199-1201. 

Among the most important reactions in organic synthesis are those that form carbon-carbon bonds. Classically this was accomplished using base-catalyzed reactions such as the aldol, Claisen, and Knoevenagel condensation reactions. Modem versions of these reactoins often display remarkable stereoselectivity.1 Unfortunately, many types of carbon atoms cannot be joined together by these reactions, for example, an aryl carbon to another aryl carbon. It took the development of transition metal-catalyzed reactions before new types of carbon-carbon and carbon-heteroatom bonds could be created. Of particular note in this regard are the reactions catalyzed by palladium, usually in its 0 or +2 oxidation state.2,3,4,5... 

Hexamethylditin is a suitable reagent for Pd-catalyzed metallation of aryl-halides to furnish aryltin compounds that in turn can react in Stille couplings with aryl halides to form biaryl derivatives. Hitchcock and coworkers [ 126] have shown that 2-pyridyl triflate and (hetero)aryl bromides can be coupled to 2-(hetero)aryl pyridines 174 in moderate to good yields (Scheme 66). The underlying principle of this heterocoupling of two aryl (pseudo)hahdes is the selective stannylation of the triflate that is undergoing a faster oxidative addition to the Pd(0) complex than the bromide. 

In the area of metal catalyzed asymmetric sulfoxidation there is still much room for improvement. The most successful examples involve titanium tartrates, but at the same time often require near stoichiometric quantities of catalysts [301, 302]. Recently, this methodology has been successfully used for the production of (S)-Omeprazole by AstraZeneca [303] (see Fig. 4.110). A modified Kagan-pro-cedure [302] was applied, using cumene hydroperoxide as the oxidant. Another example is the sulfoxidation of an aryl ethyl sulfide, which was in development by Astra Zeneca as a candidate drug for the treatment of schizophrenia. In this case the final ee could be improved from 60% to 80% by optimising the Ti tar-trate ratio [304]. 

The metal catalyzed reaction with ammonia or amines likely proceeds by the SNAr mechanism. This reaction, with phase-transfer catalysis, has been used to synthesize triarylamines. Copper ion catalysts (especially cuprous oxide or iodide) also permit the Gabriel synthesis (10-41) to be applied to aromatic substrates. Aryl bromides or iodides are refluxed with potassium phthalimide and... 

Scheme 7 displays a possibility of the synthesis of chiral 2-arylpropionic acids via the oxidative tranformation of (7 )-3-aryl-l-butenes. The requisite chiral olefins may be obtained by transition metal-catalyzed asymmetric coupling between a benzylic Grignard reagent and vinyl bromide (93 % optical yield) [28] or, more attractively, asymmetric hydrovinylation of an aromatic olefin with ethylene. The asymmetric combination of styrene and ethylene, giving the adduct 25 in 95 % ee, has been performed on a 10-kg scale with a dinuclear Ni catalyst formed from ( -allyl)NiCl2 and a unique chiral dimeric aminophosphine obtainable from (/ )-myrtenal and (5)-l-phenylethylamine [7a],... 

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