Oxyanionic assistance

Oxyanionic assistance to Cope rearrangements In the previous example, we utilized acceptor substituents to stabilize bond breaking in the TS. In this section, we will illustrate how to use donors to impose large effects on pericycUc reactions. 

Epoxidaiion of HPG. The reaction scheme for the epoxidation of HPG is shown in Figure 1. The generation of oxyanion II in toluene is assisted by (solid) KOH and QAS. II reacts rapidly with ECH to produce the 1,2-chlorohydrin of HPG, III. Dechlorohydrogenation of III proceeds immediately under the prevailing reaction conditions with formation of epoxide IV and KC1. The process can conveniently be monitored by HPLC. Completion is indicated when I is depleted. 

The "oxyanion hole." A third mechanism by which an enzyme can assist in a displacement reaction on a carbonyl group is through protonation of the carbonyl oxygen atom by an acidic group of the enzyme (Eq. 12-21). This will greatly increase the positive charge on the carbon atom making attack by a nucleophile easier and will also stabilize the tetrahedral... 

Stabilization of enolate anions generated from abstraction of a proton a to a carboxylate Hydrolysis, phosphoryl group transfer via hydrolytic nucleophilic substitution Stabilization of diverse oxyanion intermediates via metal-assisted catalysis Schiff base dependent formation of an electron sink ... 

What we found is that all metal ions catalyze P—O fission. Selective P—O fission by amines was increased from 80% to 100% in the presence of Mg2+ ion, which also enhanced the rate. Exclusive P—O fission also occurred in the attack by the oxyanion of PCA in the presence of Zn2+ ion. A plausible rationale is that such a path, which involves metal ion assistance in a pentacovalent intermediate as illustrated in Figure 12a, is energetically much more favorable than that of Sn2 displacement on sulfur. Conversely, if an enzyme that catalyzes the reaction of phosphosulfate is metal ion dependent, the reaction probably involves P—O fission, as suggested by Roy (4). 

Antibody esterase 48G7 was elicited against hapten 1 and effectively catalyzed the hydrolysis of the corresponding activated ester 2 (27). The X-ray crystal structure of this catalytic antibody Fab complexed with 1 revealed the corresponding stabilization of the oxyanion by a nearby cationic Arg residue (27, 38). Hydrogen bonds from the side chains of the adjacent amino acids His and Tyr serve to stabilize the polarized phosphoryl bonds of hapten 1 that would assist in forming the transition state of ester 2. Main-chain amide bonds from Tyr and Tyr also provide additional hydrogen-bond stabilization forces. 

In general terms, the crystallographic results show that lipases contain several distinct sites, each responsible for a specific function. The hydrolysis of the ester bond is accomplished by the catalytic triad, responsible for nucleophilic attack on the carbonyl carbon of the scissile ester bond, assisted by the oxyanion hole, which stabilizes the tetrahedral intermediates. The fatty acid recognition pocket defines the specificity of the leaving acid. There is also one or more interface activation sites, responsible for the conformational change in the enzyme. In this section the discussion is on the available structural data relevant to the function of all these sites. 

In this and subsequent studies, Gorenstein and coworkers proposed three successive incarnations of PAPH (Scheme 30 for [85] X = O). In the first, ring-flip must occur in order for the endocyclic app lone pairs to assist nucleophile entry and departure (Scheme 30a). Since attack of nucleophile on the axial isomer from the same direction will place an oxyanion in a high-energy apical position, it is argued that stereoelectronic assistance will favour reaction of the equatorial isomer (Gorenstein et ai, 1977a). 

The different solvents, additives, and cosolvents present in the reaction media can assist in the stabilization of the transition state and favor one facial preference for the approaching of the substrates as depicted in proposed transition state D [52b] (Fig. 2.10) for the 32-catalyzed Michael addition of ketones to nitrostyrene. In this case, a cooperative hydrogen-bond solvent participation (represented by H O) takes place resembling the oxyanion hole commonly found in enzymes for stabilizing transition states. It seems then very clear that intra- and intermolecular hydrogenbonding interactions play a key role in the organocatalytic cycle. 

Sol 10. (i) The l-alkenyl-4-pentyn-l-ol system (I) undergoes a microwave-assisted tandem oxyanionic 5-exo-dig addition reaction/Claisen rearrangement sequence to give cyclohept-4-enone derivative (II). 

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