Terminal oxidants, addition with

Ruthenium-catalyzed oxidative coupling of 2-aryl-substituted indoles and pyrroles with a variety of alkynes to generate structural analogs of bioactive marine alkaloids was reported (Eq. (7.26)) [34]. Ambient air was used as the terminal oxidant together with the addition of cocatalytic amounts of Cu(OAc)2 H2O in this transformation. The annulation reactions favored the electron-deficient alkyne and the more acidic C-H bond. Mechanistic experiments showed that the catalytic process took place via a concerted, acetate-assisted deprotonative metalation step. 

The most general methods for the syntheses of 1,2-difunctional molecules are based on the oxidation of carbon-carbon multiple bonds (p. 117) and the opening of oxiranes by hetero atoms (p. 123fl.). There exist, however, also a few useful reactions in which an a - and a d -synthon or two r -synthons are combined. The classical polar reaction is the addition of cyanide anion to carbonyl groups, which leads to a-hydroxynitriles (cyanohydrins). It is used, for example, in Strecker s synthesis of amino acids and in the homologization of monosaccharides. The ff-hydroxy group of a nitrile can be easily substituted by various nucleophiles, the nitrile can be solvolyzed or reduced. Therefore a large variety of terminal difunctional molecules with one additional carbon atom can be made. Equally versatile are a-methylsulfinyl ketones (H.G. Hauthal, 1971 T. Durst, 1979 O. DeLucchi, 1991), which are available from acid chlorides or esters and the dimsyl anion. Carbanions of these compounds can also be used for the synthesis of 1,4-dicarbonyl compounds (p. 65f.). 

Alkynes undergo stoichiometric oxidative reactions with Pd(II). A useful reaction is oxidative carboiiyiation. Two types of the oxidative carbonyla-tion of alkynes are known. The first is a synthesis of the alkynic carbox-ylates 524 by oxidative carbonylation of terminal alkynes using PdCN and CuCh in the presence of a base[469], Dropwise addition of alkynes is recommended as a preparative-scale procedure of this reation in order to minimize the oxidative dimerization of alkynes as a competitive reaction[470]. Also efficient carbonylation of terminal alkynes using PdCU, CuCI and LiCi under CO-O2 (1 I) was reported[471]. The reaction has been applied to the synthesis of the carbapenem intermediate 525[472], The steroidal acetylenic ester 526 formed by this reaction undergoes the hydroarylalion of the triple bond (see Chapter 4, Section 1) with aryl iodide and formic acid to give the lactone 527(473],... 

In Grignard reactions, Mg(0) metal reacts with organic halides of. sp carbons (alkyl halides) more easily than halides of sp carbons (aryl and alkenyl halides). On the other hand. Pd(0) complexes react more easily with halides of carbons. In other words, alkenyl and aryl halides undergo facile oxidative additions to Pd(0) to form complexes 1 which have a Pd—C tr-bond as an initial step. Then mainly two transformations of these intermediate complexes are possible insertion and transmetallation. Unsaturated compounds such as alkenes. conjugated dienes, alkynes, and CO insert into the Pd—C bond. The final step of the reactions is reductive elimination or elimination of /J-hydro-gen. At the same time, the Pd(0) catalytic species is regenerated to start a new catalytic cycle. The transmetallation takes place with organometallic compounds of Li, Mg, Zn, B, Al, Sn, Si, Hg, etc., and the reaction terminates by reductive elimination. 

The decarbonylation-dehydration of the fatty acid 887 catalyzed by PdCl2(Ph3P)2 fO.Ol mol%) was carried out by heating its mixture with acetic-anhydride at 250 C to afford the terminal alkene 888 with high selectivity and high catalyst turnover number (12 370). The reaction may proceed by the oxidative addition of Pd to the mixed anhydride[755]. 

Complex [(CXI )Ir(/j,-pz)(/i,-SBu )(/j,-Ph2PCH2PPh2)Ir(CO)] reacts with iodine to form 202 (X = I) as the typical iridium(II)-iridium(II) symmetrical species [90ICA(178)179]. The terminal iodide ligands can be readily displaced in reactions with silversalts. Thus, 202 (X = I), upon reaction with silver nitrate, produces 202 (X = ONO2). Complex [(OC)Ir(/i,-pz )(/z-SBu )(/i-Ph2PCH2PPh2)Ir(CO)] reacts with mercury dichloride to form 203, traditionally interpreted as the product of oxidative addition to one iridium atom and simultaneous Lewis acid-base interaction with the other. The rhodium /i-pyrazolato derivative is prepared in a similar way. Unexpectedly, the iridium /z-pyrazolato analog in similar conditions produces mercury(I) chloride and forms the dinuclear complex 204. 

The introduction of chlorinated porphyrins (10) allowed for hydrogen peroxide to be used as terminal oxidant [62], These catalysts, discovered by Mansuy and coworkers, were demonstrated to resist decomposition, and efficient epoxidations of olefins were achieved when they were used together with imidazole or imidazo-lium carboxylates as additives, (Table 6.6, Entries 1 and 2). 

The observation that addition of imidazoles and carboxylic acids significantly improved the epoxidation reaction resulted in the development of Mn-porphyrin complexes containing these groups covalently linked to the porphyrin platform as attached pendant arms (11) [63]. When these catalysts were employed in the epoxidation of simple olefins with hydrogen peroxide, enhanced oxidation rates were obtained in combination with perfect product selectivity (Table 6.6, Entry 3). In contrast with epoxidations catalyzed by other metals, the Mn-porphyrin system yields products with scrambled stereochemistry the epoxidation of cis-stilbene with Mn(TPP)Cl (TPP = tetraphenylporphyrin) and iodosylbenzene, for example, generated cis- and trans-stilbene oxide in a ratio of 35 65. The low stereospecificity was improved by use of heterocyclic additives such as pyridines or imidazoles. The epoxidation system, with hydrogen peroxide as terminal oxidant, was reported to be stereospecific for ris-olefins, whereas trans-olefins are poor substrates with these catalysts. 

The addition of acetic acid (0.5 equiv. to the substrate) to the catalyst system led to increased activity (doubling of yield) by maintaining the selectivity with 1.2 equiv. H2O2 as terminal oxidant. Advantageously, the system is characterized by a certain tolerance towards functional groups such as amides, esters, ethers, and carbonates. An improvement in conversions and selectivities by a slow addition protocol was shown recently [102]. For the first time, a nonheme iron catalyst system is able to oxidize tertiary C-H bonds in a synthetic applicable and selective manner and therefore should allow for synthetic applications [103]. 

The coupling of terminal alkynes with aryl or alkenyl halides catalysed by palladium and a copper co-catalyst in a basic medium is known as the Sonogashira reaction. A Cu(I)-acetylide complex is formed in situ and transmetallates to the Pd(II) complex obtained after oxidative addition of the halide. Through a reductive elimination pathway the reaction delivers substituted alkynes as products. 

The proposed reaction mechanism (Scheme 7-2) comprises (1) oxidative addition of ArSH to RhCl(PPh3)3 to give Rh(H)(Cl)(SPh)(PPli3)n, (2) coordination ofalkyne to the Rh complex, (3) ris-insertion of alkyne into the Rh-H bond with Rh positioned at terminal carbon and H at internal carbon, (4) reductive elimination of 16 from the Rh(III) complex to regenerate the Rh(I) complex. 

This reaction typifies the two possibilities of reaction routes for M-catalyzed addition of an S-X (or Se-X) bond to alkyne (a) oxidative addition of the S-X bond to M(0) to form 94, (b) insertion of alkyne into either the M-S or M-X bond to provide 95 or 96 (c) C-X or C-S bond-forming reductive elimination to give 97 (Scheme 7-21). Comparable reaction sequences are also discussed when the Chalk-Harrod mechanism is compared with the modified Chalk-Harrod mechanism in hydrosily-lations [1,3]. The palladium-catalyzed thioboratiori, that is, addition of an S-B bond to an alkyne was reported by Miyaura and Suzuki et al. to furnish the cis-adducts 98 with the sulfur bound to the internal carbon and the boron center to the terminal carbon (Eq. 7.61) [62]. 

There are a number of procedures for coupling of terminal alkynes with halides and sulfonates, a reaction that is known as the Sonogashira reaction.161 A combination of Pd(PPh3)4 and Cu(I) effects coupling of terminal alkynes with vinyl or aryl halides.162 The reaction can be carried out directly with the alkyne, using amines for deprotonation. The alkyne is presumably converted to the copper acetylide, and the halide reacts with Pd(0) by oxidative addition. Transfer of the acetylide group to Pd results in reductive elimination and formation of the observed product. 

Olefin hydrocarbonylation can be used in conjunction with oxidative addition to prepare indanones and cyclopentenones, but the reaction is limited to terminal alkenes.243... 

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