Stereochemistry nucleophilic substitution, retention

As previously mentioned, the nucleophilic substitution on the Mo complex 71 most likely occurs with retention of configuration based on the stereochemistry outcomes of the product and 71. The retention-retention mechanism was confirmed with labeling experiments in collaboration with Professor Lloyd-Jones, as shown in Scheme 2.25 [27]. 

Chiral sulfonium ylides have been known for some 30 years, and their stereochemistry and properties have been studied.15 Optically active selenonium ylides were obtained by reacting selenoxides with 1,3-cyclohexanedione under asymmetric conditions by Sakaki and Oae in 1976 for the first time,16 and also optically resolved by fractional recrystallization of the diastereomeric mixtures in the early 1990s.17 In 1995, optically active selenonium ylides 6 were obtained in over 99% de by nucleophilic substitution of optically active chloroselenurane or selenoxide with active methylene compounds with retention of configuration.18 The absolute configurations were determined by X-ray analysis of one... 

In Section II,B we reported significant data concerning the influence of the solvation in the case of nucleophilic substitutions by alkoxides at Si—OMe, Si—F, and Si—SMe bonds (55). The most important fact that emerges from these data is that the stereochemistry changes from retention to inversion when the alcohol content of the medium is increased. We propose the following analysis ... 

Another important argument is provided by the stereochemistry of substitution reactions at silicon. In the optically active complex 6 nucleophilic substitution by H, OH-, or OMe- occurs with inversion of configuration at silicon, while retention was observed with the related... 

The Mitsunobu reaction is one of the staple reactions for clean nucleophilic substitution with inversion of configuration. It came as a surprise, therefore, to find that a Mitsunobu reaction on atlyEic alcohol 143,1 [Scheme 8 143) using terf-butyl 2-(trimethylsilyl)ethylsulfonylcarbamate (143.2) as the nucleophile occurred with retention of configuration.320 The unusual stereochemistry was explained by a double inversion process in which neighbouring group participation first leads to the intermediate 1433. A subsequent second nucleophilic substitution by 1433 then gave the product 143.4 in 86% yield ... 

Reference has already been made (p. 47) to the unusual retention of configuration in nucleophilic substitutions of 3j0-substituted-A -steroids (i). The stereochemistry of substitution is controlled by participation of the sr-electrons of the C(5) C(6) bond in a unimolecnlar solvolysis at C(S), to give, as the primary product, a mesomeric carbonium ion commonly represented by the non-classical structure (2) [19,20], although this is probably an over-simplification (see below). Carbonium ions related to the structure (2) are well-known outside the... 

On occasion, a molecule undergoing nucleophilic substitution may contain a nucleophilic group that participates in the reaction. This is known as the neighboring group effect and usually is revealed by retention of stereochemistry in the nucleophilic substitution reaction or by an increase in the rate of the reaction. 

Palladium-catalyzed displacement reactions with carbon nucleophiles are not only regioselective but also highly stereoselective. In the first step, displacement of the leaving group by palladium to form the 7i-allylpalladium complex occurs from the less hindered face with inversion. Subsequent nucleophilic substitution of the intermediate 7t-allylpalladium complex with soft nucleophiles such as amines, phenols, or mal-onate-type anions also proceeds with inversion of the stereochemistry. The overall process is a retention of configuration as a result of the double inversion. 

Micellar control of the stereochemistry of nucleophilic substitution reactions was first recognized in die nitrous acid deamination of 2-aminooctanel91 Below the CMC of 2-octylammonium perchlorate, 2-octanol is formed with the inversion stereochemistry normally expected in the deamination of a 2-aminoalkane. With increasing concentration the percentage of inversion decreases to zero, after which retention of configuration occurs. The observed stereochemistry was demonstrated to... 

The stereochemistry of the direct attack can be expected to resemble the corresponding reactions at a saturated carbon (Sections 5.1.1.1 and 5.1.1.2)—inversion for nucleophilic substitution, and retention, or perhaps occasionally inversion, for electrophilic substitution. In practice, SN2 reactions at trigonal carbon are rare,503 and their stereochemistry, where inversion is known,504 barely established. Electrophilic attack, like the reactions of vinyllithium reagents with protons, aldehydes and carbon dioxide, takes place invariably... 

The TT electrons of carbon-carbon double bonds can also become involved in nucleophilic substitution reactions. This participation can facilitate the ionization step if it leads to a carbocation having special stability. Solvolysis reactions of the syn and anti isomers of 7-norbornenyl tosylates provide some dramatic examples of the influence of participation by double bonds on reaction rates and stereochemistry. The anfi-tosylate is more reactive by a factor of about 10 than the saturated analog toward acetolysis. The reaction product, anft -7-acetoxynorbornene, is the product of retention of configuration. These results can be explained by participation of the tt electrons of the double bond to give the ion 3, which is stabilized by delocalization of the positive charge. ... 

All these reactions are nucleophilic substitutions at a carbon adjacent to oxygen as shown, the nature of X and Y, their degree of protonation, deprotonation or metal coordination, and the stereochemistry of the reaction (retention or inversion), varying with the individual process. 

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