Carbonyl complexes thioesters, formation

The latter carbonylation involves the formation of PtH(SR)(PPh3)2 by the oxidative addition of RSH to the zero-valent platinum complex. A possible pathway may include the CO insertion into the S-Pt bond of PtH(SR)(PPh3)2. Then, acylplatination of alkynes generates p-thiocarbonyl-substituted vinylplatinum intermediate, which undergoes reductive elimination to give the a,p-unsaturated thioesters with regeneration of the catalyst. 

Stavropoulos et al. [162] synthesized the methyl, carbonyl, hydride, and acetyl coordinated complexes of the compound shown in Scheme 8 as models of a possible pathway to the formation of a thioester. The tripodal ligands N(CH2CH2SR)3 are biologically relevant in using N and S coordination. Further, the sequence of reactions... 

Another example of the activation of a hydroxy acid was described by Rastetter and Phillion [60] First the 0-protected hydroxyacid 68 reacts with a thiol group containing crown ether 67. Then the resulting thioester 69 reacts with potassium mrt-butoxide to give the alkoxide. At the same time a complexation of the potassium ion by the [18]crown-6 part of the molecule occurs. Thus, the alkoxide ion comes close to the carbonyl group of the molecule, so that nucleophilic attack leading to ring formation is facilitated (cooperation of dilution principle, template effect, and ion pair interaction). 

The reaction is effective with electron-rich carbonyls such as trimethylsilyl esters and thioesters, as Table 20 indicates. Lactones ate substrates for alkylidenation however, hydroxy ketones are formed as side products, and yields are lower than with alkyl esters. Amides are also effective, but form the ( )-isomer predominantly. This method has been applied to the synthesis of precursors to spiroacetals (499) by Kocienski (equation 115). ° The reaction was found to be compatible with THP-protected hy- oxy groups, aromatic and branched substituents, and alkene functionality, although complex substitution leads to varying rates of reaction for alkylidenation. Kocienski and coworkers found the intramolecular reaction to be problematic. As with the CrCb chemistry, this reaction cannot be used with a disubstituted dibromoalkane to form the tetrasubstituted enol ether. Attempts were made to apply this reaction to alkene formation by reaction with aldehydes and ketones, but unfortunately the (Z) ( )-ratio of the alkenes formed is virtu ly 1 1. ... 

The formation of macrolides from co-alkoxy-thioester derivatives of crown ethers (82) and Bu O has been studied. The role of the crown ether is to provide stabilization of the transition state for the attack of the alkoxide ion on the carbonyl group of the thioester by placing the carbonyl oxygen adjacent to the complexed ion. ... 

In addition, reductive elimination of palladium and nickel complexes to form esters (Equations 8.67 and 8.68), amides, and tiiioesters has been reported. -" The reductive eliminations of esters and amides were observed during mechanistic studies on the palladium-catalyzed formation of esters and amides from aryl halides, carbon monoxide, and alcohols or amines. This catalytic process is presented in Qiapter 17 (carbonylation processes). The reductive elimination of thioesters from nickel complexes were studied, in part, to understand the C-S bond-forming process of acetyl coenzyme A synthase. Prior to this work, an iron-mediated synthesis of p-lactams had been reported that appears to occur by reductive elimination to form the amide C-N bond of the lactam. ... 

Metal complexes are known to insert CO into carbon-sulfur bonds [118], even catalytically [119], Stoichiometric precedents exist for the formation offhioesters from nickel-alkyls, CO, and thiols [120], For example, NiMe2(bipy) reacts with thiols to afford mefhylnickel(ll) fhiolates, which carbonylate to afford acetyl-nickel(ll) fhiolates. These acetylnickel(II) thiolates reductively eliminate fhioester in the presence of CO [121], More biologically relevant is the reactivity of nickel acyls toward fhiolates, which gives fhe thioester concomitant with reduction to Ni(0) (Eq. 12.10) [122]. Thiolates are known to reduce Ni(II) to Ni(0) under an atmosphere of CO [123]. 

The free energy of the transfer reaction is a function of pH, because in addition to the carboxyl groups the carbonyl group of acetoacetate thioester can ionize (as an enol). Since this ionization is favored by alkaline media, the equilibrium is somewhat shifted towards acetoacetyl CoA formation at higher pH values. The reaction favors succinyl CoA formation at all pH values studied, however (Fo at pH 7.0 = +3470 cal.). Another factor that influences the apparent equilibrium of the transferase is the presence of Mg++. This ion forms a complex with the /3-ketothioester. The enzyme has been assayed by measuring the appearance of the absorption band of the j8-ketothioester at 303 m/ , where simple thioesters do not absorb. This band is shifted slightly and the extinction coefficient greatly increased by Mg++, which has therefore been added to assay systems to increase the sensitivity. CoA transferase does not require Mg" for activity, however. 

In the case of thiols (RSH), the corresponding hydrothiocarbonylation takes place successfully at the terminal double bond, as shown in Scheme 11.8 [11]. A possible pathway is as follows (1) formation of an H-Pd-SR species via oxidative addition of H -S R to Pd(0) (2) coordination of the allene double bond and subsequent insertion into a Pd-H bond to form an allypalladium complex intermediate (3) CO insertion resulting in the formation of an acylapalladium carbonyl species and (4) reductive elimination affording the thioester derivates. 

The serine proteases catalyze a nucleophilic displacement reaction of a group attached to a carbonyl carbon—such groups comprising esters, thioesters, and amides. The reaction carried out by this class of enzymes is essentially an acyl transfer in which the substrate binds to the enzyme, forming the noncovalent Michaelis complex, followed by the formation of a covalent bond between the carbonyl carbon of the... 

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