Neighboring groups

Neighboring group participation (a term introduced by Winstein) with the vacant p-orbital of a carbenium ion center contributes to its stabilization via delocalization, which can involve atoms with unshared electron pairs (w-donors), 7r-electron systems (direct conjugate or allylic stabilization), bent rr-bonds (as in cyclopropylcarbinyl cations), and C-H and C-C [Pg.150]

Under superacidic, low nucleophilicity so-called stable ion conditions, developing electron-deficient carbocations do not find reactive external nucleophiles to react with thus they stay persistent in solution stabilized by internal neighboring group interactions. 

In cases of more effective 7t-electron donor or tz-donor neighboring groups, as is the case in forming /3-phenylethyl (studied by Don Cram from UCLA Nobel Prize in chemistry, 1987) or /3-halogen bridged species, these have sufficient electrons to form 2e-2c bonds (with some intermediate delocalization). 

In some cases where there is a neighboring group participation effect, aldehydes are formed. The a-vinyl group in the / -lactam 29 is mainly oxidized to aldehyde 30[83],... 

Figure 5.1 The reaction of A and B groups at the ends of two different chains. Note that rotations around only a few bonds will bring A and B into the same cage of neighboring groups, indicated by the broken line enclosure.

The preparation of polyacrylamides and postpolymeri2ation reactions on polyacrylamides are usually conducted ia water. Reactions on the amide groups of polyacrylamides are often more compHcated than reactions of simple amides because of neighboring group effects. Reaction rates, for example, can differ considerably. 

In the presence of sulfide or sulfhydryl anions, the quinonemethide is attacked and a benzyl thiol formed. The P-aryl ether linkage to the next phenylpropane unit is broken down as a result of neighboring-group attack by the sulfur, eliminating the aryloxy group which becomes reactive phenolate ion (eq. 2). If sulfide is not present, a principal reaction is the formation of the stable aryl enol ether, ArCH=CHOAr. A smaller amount of this product also forms in the presence of sulfhydryl anion. 

Some cleavage takes place even if the phenoHc hydroxyl is blocked as an ether link to another phenylpropane unit and quinonemethide formation is prevented. If the a- or y-carbon hydroxyl is free, alkaH-catalyzed neighboring-group attack can take place with epoxide formation and P-aryloxide elimination. In other reactions, blocked phenoHc units are degraded if an a-carbonyl group is present. 

The pify of the leaving group and the hydrophobe chain length can dramatically affect the efficiency of the perhydrolysis reaction. Additionally, the stmcture of the acid portion of the precursor can affect the yield and sensitivity of the reaction to pH. The mono-4-hydroxybenzenesulfonic acid ester of a-decylsuccinic acid (13) undergoes extremely efficient perhydrolysis at much lower pHs than other peracid precursors, eg, decanoyloxybenzene sulfonate (14). This may be because of the neighboring group participation of the adjacent carboxylate as shown in Table 2 (115). 

When a molecule that is a substrate for nucleophilic substitution also contains a group that can act as a nucleophile, it is often observed that the kinetics and stereochemistiy of nucleophilic substitution are strongly affected. The involvement of nearby nucleophilic substituents in a substitution process is called neighboring-group participation ... 

A classic example of neighboring-group participation involves the solvolysis of compounds in which an acetoxy substituent is present next to a carbon that is undergoing nucleophilic substitution. For example, the rates of solvolysis of the cis and trans isomers of 2-acetoxycyclohexyl p-toluenesulfonate differ by a factor of about 670, the trans compound being the more reactive one ... 

In contrast to the usual behavior, replacement of the mesyl group in 2 O mesyl-3-diallylaminodeoxy-a-D-altropyranoside by treatment with triethylamine trihydrofluonde leads to, because of neighboring-group participation, the fluori-nated product with retention of configuration [45] (equation 33)... 

On the other hand, as a result of participation of a neighboring group, complete or predominant retention of configuration takes place in many reactions of hy-droxylic compounds with DAST A number of examples have been reported in the field of steroids [727, 729], m the conversion of vitamins D into fluoro vitamins D [745], and in the fluormation of liquid crystals [146] (equation 72]... 

Hydrolytic cleavage of single carbon-fluorine bonds generally requires activation by a neighboring group such as a carbonyl, sulfonyloxy, or olefinic bond or a negatively substituted aromatic group. 

Series 7 gives a linear plot with p = —5.27, consistent with the S l mechanism. Series 8, however, shows a discontinuity, which Gassmann and Fentiman interpreted as a change in mechanism. Compounds in series 8 are capable of intramolecular assistance (neighboring group participation) by electron donation from the double bond to stabilize the cation, as in 9. 

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