Nucleophilic substitution anchimeric assistance

As shown by the relative rates of methanolysis of thioethers PhS(CH2)nCl (Scheme 4.50), the same substrate can react with or without neighboring-group participation, depending on the nucleophile and on the reaction conditions. Under conditions which favor bimolecular substitution, anchimeric assistance by neighboring groups is observed only rarely. 

Within the past several years, we have examined the synthesis and reactions of several classes of polymers related to PECH. We have adopted three simple approaches to the preparation of polymeric substrates more reactive than PECH toward nucleophilic substitution. We have i). removed the 8-branch point by extension of the side chain, ii). replaced the chloride leaving group by a more reactive bromide and iii). replaced the backbone oxygen atom by a sulfur atom that offers substantial anchimeric assistance to nucleophilic... 

An Sn2 reaction with anchimeric assistance (via formation of a bicyclic aziridinium ion intermediate) has been proposed for the nucleophilic substitution of trans-2-substituted 3-piperidinol mesylates by nitrogen nucleophiles with retention of trans... 

Substitution of complexed dienols (244) or dienol acetates with carbon or heteroatom nucleophiles, in the presence of a Lewis acid, occurs with retention of configuration (Scheme 69). (Alkyl aluminum reagents act as both nucleophile and Lewis acid in this process). This reaction is believed to proceed via stereospecific ionization, with anchimeric assistance from the iron, to generate the transoid pentadienyl cation (247) followed by attack of the weak nucleophile on the face opposite to iron. The cross-conjugated pentadienyl cation can also be generated the substitution of (2-acetoxymethyl-l,3-butadiene)Fe(CO)3 (193) has previously been discussed (Section 6.1.1). 

The rate of nucleophilic substitution at positions ft to selenium is greatly enhanced. This anchimeric assistance has been ascribed to neighboring group participation with formation of the corresponding seleniranium ion in the ratedetermining step as shown in Equation (11). 

Acid mediated elimination of cyclic (dienyl ether)- and (dienol)Fe(CO)2L complexes leads to the formation of (cyclodienyl)Fe(CO)2L cations (equation 26 and 27) . Protonation of (pentadienol)- or (pentadienyl ether)Fe(CO)3 complexes generates the corresponding (pentadienyl)Fe(CO)3+ cations 167 (Scheme 41). Lillya and coworkers have demonstrated that ionization of the hydroxyl substituent occurs with anchimeric assistance from iron, and that isomerization of the initially generated transoid pentadienyl cation 168 to the more stable cisoid cation occurs with retention of configuration about the Cl—C2 bond . The in situ generated transoid pentadienyl cations may also undergo reaction with heteroatom, hydride or carbon nucleophiles to afford substituted ( , -diene)Fe(CO)3 products (169) . Acyclic (pcntadicnyl)MCp cations (M = Rh, Ir) may be prepared by acidic dehydration of (dienol)MCp complexes. ... 

The use of 2,3-dichloropropene as an acetonyl equivalent is essentially limited to those cases where enolates are used as nucleophiles, since clean chlorovinyl-to-acetyl conversion with Hg(OAc)2 and HCOOH requires anchimeric assistance by a y- or 5-carbonyl group. To circumvent this difficulty, 2-alkoxyallyl electrophiles have been used in Pd-catalyzed aryl-allyl coupling.The products can then be readily hydrolyzed to give a-aryl-substituted acetones (Scheme 61). Further details of this reaction are presented in Sect. III.2.9. 

The nucleophilic hydroxyl oxygen of the carboxylic anion, generated by deprotonatlon of the carboxylic acid, undergoes a nucleophilic substitution reaction with the alkyl chloride formed In the previous step (with anchimeric assistance of the SMe group) to give the ester product. 

Summary This is an example of anchimeric assistance (also called neighbouring group participation) in nucleophilic substitution reactions... 

The above constants are usually only used in discussions of nucleophilic substitution reactions at saturated carbon. In other reactions a quantity known as the effective molarity is frequently used as a measure of anchimeric assistance. This can be determined only if the rate constant for an analogous intermolecular reaction has been measured. Consider two analogous reactions, one intramolecular [Eq. (10)] and one intermolecular [Eq. (11)]. These are, respectively, first- and second-order pro-... 

Mechlorethamine is a "nitrogen mustard" that reacts with nucleophiles in the same way as sulfur mustard, via two successive substitution reactions. The first reaction is an intramolecular S 2 process involving anchimeric assistance from the nitrogen atom the second reaction is another Sn2 process involving attack of an external nucleophile ... 

Keywoids Anchimeric assistance. Carbohydrates, Deamination, Fragmentation, Group migration, Neighbouring group participation. Nucleophilic substitution. Rearrangement, Ring contraction, Sulfonate displacement... 

Anchimeric assistance , which results - via formation of positively charged cyclic intermediates (route b or b ) - either in (an enhanced rate of) direct substitution by the external nucleophile under retention of configuration [route (b + c) or (b + c ), symbol AS] or nucleophilic migration of the neighbouring group and entry of the external nucleophile at the vicinal position with configurational inversion at both ends [route (b + d) or (b -I- d )> symbol MS]. 

AIS (anchimerically assisted substitution, by another internal nucleophilic group, with retention of configuration at the position of the original activation)... 

MIS (substitution by migration of the first participating group and entry of another internal nucleophilic atom at the position where the group having lent anchimeric assistance departs, with inversion of configuration at both centres involved)... 

In the absence of a good nucleophile, the involvement of an NG capable of participation becomes dominant. Starting from a vicinal trans disposition of LG and NG in the educt, besides anchimerically assisted substitution with retention of configuration (AS[3,NG-2], entry 8) and group migration (MS[3,NG-2], entry 8), participation of NGs of the complex (ISC[3,NG-2], entries 7 [54b], 11 and 12 [47], (ISC[3,NG-4] -I- Hy), entry 14 [55]) as well as the simple type (IS [3,0-2], entry 5 [49]) have been observed. In some instances, e.g., for the results shown in entry 6 [48], discrimination between an (Sn2 -l-AcM) and an (ISC -i- Hy) mechanism cannot be made. Of special interest is an unusual triflate rearrangement , reported by Binkley [55] during his efforts to... 

---