Orientation of nucleophilic attacks

The orientation of nucleophilic attack on a fluoroolefin is influenced also by the presence on the fluoroolefin of electron-withdrawing functional groups that stabilize the intermediate carbanion. Thus nucleophilic attack tends to be oriented... 

The reactivity and orientation of nucleophilic attack on fluoroolefins are determined by the stability of the possible carbamon intermediates Fluoroolefins react regioselectively with nucleophiles so as to maximize the number of fluorines (3 to the electron-rich carbon in the transition state The reactivities increase in the order CF2=CF2 < CF2=CFCF3 CF2=C(CF3)2 and CF2=CF2 < CF2=CFC1 < CF2=CFBr, and nucleophdes attack exclusively at the CF2= end of these olefins [129,141] The regiochemistry of nucleophilic attack normally is predictable, but the product distribution arising from addition and addition-elimination pathways depends upon the olefin, nucleophile, and reaction conditions (equations 13-15) The various factors that control product distributions have been reviewed [142,143 144]... 

The orientation of nucleophilic attacks in equation (1) is usually regulated by the substituents on the alkyne. As a guide, molecular orbital (MO) charge distributions for several mono- and disubstituted acetylenes are given in Figure 6 Where... 

One other point regarding nucleophilic substitution, in particular orientation therein, must be mentioned. It has been suggested that orientation of nucleophilic attack upon pyridinium salts may be connected with the ability of the nucleophile to form a charge-transfer complex with the pyridinium ring nucleophiles which should easily form charge-transfer complexes will add at C(4), whilst others will add at 0(2) " How far this is true is not known, and indeed we know little about the role of charge-transfer complexes in substitution processes in general (see p. 281). 

The changes of stereochemistry in these systems are due to changes in the preferred direction of nucleophilic attack upon a carbocationic intermediate or a related ion pair. These results therefore indicate that the substrates or reaction intermediates have preferred orientations at the micellar surface. 

Figure 8.3 Stereochemistry of nucleophilic attack by HO- on the coordinated ethylene. /ratramolecular and i rarermolecular reactions should give cis and Irans orientations °f Pd-C and C-O bonds, respectively. D labeling helps to identify the stereochemistry of addition.

As in the case of the base-catalyzed hydrolysis, the observed rate constant for the reaction of ester 9c in the presence of amine 5a was found to decrease with increasing concentration of CTAB. Using equation (28), the second order rate constants for the aminolysis and those for the alkaline hydrolysis were calculated as a function of CTAB concentration and were found to be decreased by factors of 30-6 and 13-3, respectively, by micellar CTAB. These results can be interpreted by an explanation analogous to that for the alkaline hydrolysis in the absence of amines. However, the magnitude of the inhibition for the aminolysis (30-6) as compared to that for the hydroxide ion-catalyzed hydrolysis (13-3) is not readily explicable. It is conceivable, however, that deep penetration of ester into the micelle could result in an environment for the ester group in which the amino group is either not suitably oriented for nucleophilic attack or is excluded to a greater extent than water and hydroxide ion. 

Simulations of the native form of carboxypetidase A indicate that the zinc bound water forms a hydrogen bond with the carboxyl group of Glu270, positioning the water in a seemingly optimal orientation for nucleophilic attack on the substrate (Stote and Karplus 1995). A similar result, whereby the zinc plays a role in orienting residues important for the catalysis, was observed in the simulations of another zinc containing enzyme, carbonic anhydrase (Stote and Karplus 1995). The zinc also provides... 

The representations of nucleophilic attack on formaldehyde as involving the carbonyl LUMO and electrophilic attack on ethene as involving the HOMO also make a prediction about the trajectory of the approach of the reagents. The highest LUMO density is on carbon and it is oriented somewhat away from the oxygen. On the other hand, the ethene HOMO is the tt orbital, which has maximum density at the midpoint above and below the molecular plane. Calculations of the preferred direction of attack of electrophilic and nucleophilic reagents are in accord with this representation, as shown below. ... 

The TT-electron density refers to the electron density at a given carbon atom obtained by summing the contributions from all the filled molecular orbitals. Electrophilic attack occurs where this density is highest, and nucleophilic attack where it is lowest tt-electron densities are not dominant in determining the orientation of homolytic substitution. 

The effect of conformation on reactivity is intimately associated with the details of the mechanism of a reaction. The examples of Scheme 3.2 illustrate some of the w s in which substituent orientation can affect reactivity. It has been shown that oxidation of cis-A-t-butylcyclohexanol is faster than oxidation of the trans isomer, but the rates of acetylation are in the opposite order. Let us consider the acetylation first. The rate of the reaction will depend on the fiee energy of activation for the rate-determining step. For acetylation, this step involves nucleophilic attack by the hydroxyl group on the acetic anhydride carbonyl... 

The rate-determining expulsion of bromide ion through a bridged intermediate requires an anti orientation of the two bromides. The nucleophilic attack of iodide at one bromide enhances its nucleophilicity and permits formation of the bridged ion. The stereochemical preference in noncyclic systems is also anti, as indicated by the fact that /neso-stilbene... 

The fluoroxy reagents react readily with activated aromatic systems (Table 1) to give moderate yields of fluoroaromatic compounds. The fluorine atom shows a preference for ortho orientation because of complexation between the fluoroxy reagent and the ring substituent [75, 22] Nucleophilic attack by the substrate on... 

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