Cyclative cleavage carbon nucleophiles

The final example in this section features a rare instance where the electrophilic center is s -hybridized carbon, as most cyclative cleavages involve the attack of carbonyl derivatives. Oxazolidinones are formed cyclatively18 by the displacement of a sulfonate ester by an acylsulfonamide (Fig. 5). In a variant19 of this cyclization, a quasi-meso bis-sulfonate partitions into a pair of quasi-enantiomeric sulfonates, one resin bound and the other cleaved, depending on the direction of intramolecular cyclization. The resin-bound enantiomer can then be displaced by an external nucleophile. 

Metallacyclic complexes play an important role as reactive intermediates in catalytic cycles initiated by homogeneous transition-metal complexes. Thus, metallacyclobutanes are discussed as intermediates in alkene metathesis, isomerization of strained cyclopropane compounds and many other reactions. On the other hand, numerous examples of isolable me-tallacyclobutane complexes have been reported. These can be formed by different routes such as carbon-carbon bond cleavage of cyclopropane compounds (A), cyclometallation via C — H bond cleavage (B), nucleophilic addition to allyl complexes (C), rearrangement of metallacyc-lopentanes (D) or transmetalation of 1,3-dimetallalated carbon chains (E). ... 

There follows cleavage of acetyl-CoA from the end of the chain via a reverse Claisen reaction (see Box 10.15). This requires use of a molecule of coenzyme A as nucleophile, with the loss of the enolate anion of acetyl-CoA as leaving group. The net result is production of a new fatty acyl-CoA that is two carbons shorter than the original, and a molecule of acetyl-CoA that can be metabolized via the Krebs cycle. 

Carbon-carbon bond formation by reductive elimination from Ni, Pd, or Pt complexes is widespread. In many cases it is presumed to occur as the final step in a catalytic cycle, whereby the organic product is expelled from the metal center, but in others it is a well-defined, mechanistically studied reaction. Elimination takes place from Ni, Pd, and Pt complexes in their - - 2 or + A oxidation states, and it may be promoted by thermolysis, by photolysis, or by nucleophilic attack at the metal center. The reaction may proceed by heterolytic or homolytic metal-carbon bond cleavage, reductive elimination, or dinuclear elimination, and more than one mechanism may operate. 

Fats are metabolized down to a thioester called acetyl Co A. Acetyl Co A enters the citric acid cycle and eventually is converted to two molecules of carbon dioxide. The cleavage step in metabolizing long-chain fatty acids is the reverse of the Claisen reaction of the previous section. A thiol group attached to the enzyme is the nucleophile for general base-catalyzed addition, starting the reverse Claisen. 

Fig. 2. Schematic diagram of the catalytic mechanism of 20S proteasomes. A proton transfer from the hydroxyl group of Thrl of /3 subunits to its own terminal amino group initiates the nucleophilic attack (I). As a result of the nucleophilic addition to the carbonyl carbon of the scissile peptide bond, a tetrahedral intermediate is formed (II). By an N—O acyl rearrangement, an ester is formed (the acyl enzyme) and the amino-terminal cleavage product is released (III). Finally, hydrolysis of the acyl enzyme yields the carboxyl-terminal cleavage product and frees the enzyme for another reaction cycle (IV).

The subsequent coordination and insertion of CO into the metal-alkyl bond leads to a hable acyl complex. Finally, hydrolysis of the acyl complex with the nucleophile NuH gives off the corresponding carboxylic acid or carboxylic acid derivative and completes the catalytic cycle. Presumably, the acyl cleavage takes place by a nucleophilic attack on the carbonyl carbon of the acyl group. 

Macrocyclic polyamine Zn +-complexes not only were used as carbonic anhydrase models. They were also shown to promote hydrolytic cleavage of phosphate esters and in particular phosphate diesters as present in DNA. In Figure 3, the catalytic cycle for monometallic activation is shown. Dissociation of a metal-bound water molecule provides a metal hydroxide species, which nucleophilically attacks the phosphorus center of a phosphate diester, whereby finally the aUcoxide gets released and the product is formed. 

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