Stereochemistry of electrophilic substitution

Lithiated allyl carbamates stereochemistry of electrophilic substitution... 

Organometallic reagents in /3-lactam chemistry 88T5615. Stereochemistry of electrophilic substitution in /3-lactams 90KGS1155. /3-Lactam antibiotics (see Section II,D,3,c). 

The stereochemistry of electrophilic substitutions of a-lithio sulfoxides had previously been studied by a number of groups, albeit using only acyclic sulfoxides, and it was thought that the electrophiles used in these studies (D2O, Mel, CO2, Mc2CO) quenched the equilibrium between diastereoisomeric lithiated intermediates, and hence reflected the stabilities of the corresponding carbanions [84]. However, such interpretations do not account for many experimental discoveries when Mel and D2O were used, and consequently Marquet proposed... 

The effects of electrophiles and solvents on the stereochemistry of electrophilic substitution of a lithium carbanion generated from (5, )-l-phenylbut-2-en-l-yl diiso-propylcarbamate have been examined using various acids and carbon electrophiles. The stereochemical outcomes have been described in terms of the existence of an equilibrium involving a solvent-separated ion pair and three different kinds of contact ion pairs in which the ligand coordinated to the lithium atom differs. 

Vinylsilanes react readily with a range of electrophiles to give products of substitution (1). The overall stereochemistry of such substitution will depend on a number of factors, including the stereochemistry of addition and subsequent elimination when 1,2-adducts are discrete species. However, the regiochemistry of substitution is normally unambiguous, the -effect ensuring that carbonium-ion development on attack by the electrophile will occur at the carbon terminus remote, i.e. /3, to silicon ... 

The possibility of electrophilic substitution at saturated carbon as an independent mechanism was considered by Hughes and Ingold2 in 1935, but this mechanism was not kinetically demonstrated with metal alkyls as substrates until 1955, when Winstein and Traylor3 published their results on the acetolysis of dialkylmercurys. At about the same time, stereochemical studies on electrophilic substitutions at saturated carbon were commenced by Winstein and by Reutov, again using alkylmercury compounds as substrates. Notable studies on the kinetics and stereochemistry of substitution at saturated carbon have been carried out by Ingold and his co-workers and by Reutov and his co-workers. Ingold4... 

The stereospecificity of deprotonation of ketone NA -dialkylhydrazones is less defined because of the problem of making unambiguous stereochemical assignments. However, based on the observed stereoselectivity of electrophilic substitutions on these anions, on chemical shift data and on analogies to enolate chemistry, it appears that ( )c—c stereochemistry again predominates, at least with LDA de-protonations. ... 

Neutral Complexes. Interaction of acetylacetone and hydrous Rh2G3 gives the trisacetylacetonate, which has been resolved into enantiomeric forms. It undergoes a variety of electrophilic substitution reactions of the coordinated ligand, such as chlorination. The stereochemistry and racem-ization of the cis- and trans-isomers of the unsymmetrical trifluoroacetyl-acetonate have been studied by nmr spectroscopy the compound is extremely stable to isomerization. 

The stereochemistry of electrophilic addition to norbornenes and norbomadienes is very interesting" . As these reactions form on intermediate carbocations, there arises, just as for the solvolysis of 2-substituted norbornanes and norbornenes, the question of the nature of these ions — classical or nonclassical. The electrophilic addi-... 

No gas-phase reactions of electrophilic substitution have been known so far, while the formation of the transition state structure of Eq. (5.9) in solution is greatly (often decisively) affected by medium factors, the specific solvation and the nucleophilic catalysis. Even though the true structure of a transition state of the Se2 reaction is much more complicated than XXIV, this structure correctly reflects the stereochemistry of substitution at the tetrahedral carbon atom, namely, the retention of configuration of the carbon atom bonds observed experimentally in most Se2 reactions (the Se2 rule. Ref. [1]). 

The stereochemistry of the carboxylation of 4-substituted ( + )-(/ S)-fra ,v-1-(4-mcthylphcnyl-sulfinylmethyl)cyclohexane after metalation with methyllithium and quenching with carbon dioxide was reported64. The results listed in Table 1 show that the d.r. of around 75 25 under kinetic control changes to 25 75 under thermodynamic control. This is the result of the equilibration of the two diastereomeric metalated species. As shown by the experiment in hexamethylphosphoric Iriamide (IIMI A) (d.r. = 57 43 under kinetic control) an electrophilic assistance of the lithium cation to the electrophilic approach is probably involved. 

As the o-complexes in these azo coupling reactions are steady-state intermediates (Wheland intermediates, named after Wheland s suggestion in 1942), their stereochemistry cannot be determined directly. Bent structures like that in Figure 12-6 can, however, be isolated in electrophilic substitutions of 1,3,5-triaminobenzene... 

Clearly, a study of the stereochemistry can distinguish between Se2 (back) on the one hand and Se2 (front) or Ssi on the other. Many such investigations have been made. In the overwhelming majority of second-order electrophilic substitutions, the result has been retention of configuration or some other indication of frontside attack, indicating an Se2 (front) or SeI mechanism. For example, when cis-l was treated with labeled mercuric chloride, the 2 produced was 100% cis. The bond between the mercury and the ring must have been broken (as well as the other Hg—C... 

Reactivity toward nucleophiles and comparison with other electrophilic centers 152 Paths for nucleophilic substitution of sulfonyl derivatives 156 Direct substitution at sulfonyl sulfur stereochemistry 157 Direct substitution at sulfonyl sulfur stepwise or concerted 158 The elimination-addition path for substitution of alkanesulfonyl derivatives 166 Homolytic decomposition of a-disulfones 172 10 Concluding remarks 173 Acknowledgement 174 References 174... 

Organosulfur chemistry is presently a particularly dynamic subject area. The stereochemical aspects of this field are surveyed by M. Mikojajczyk and J. Drabowicz. in the fifth chapter, entitled Qural Organosulfur Compounds. The synthesis, resolution, and application of a wide range of chiral sulfur compounds are described as are the determination of absolute configuration and of enantiomeric purity of these substances. A discussion of the dynamic stereochemistry of chiral sulfur compounds including racemization processes follows. Finally, nucleophilic substitution on and reaction of such compounds with electrophiles, their use in asymmetric synthesis, and asymmetric induction in the transfer of chirality from sulfur to other centers is discussed in a chapter that should be of interest to chemists in several disciplines, in particular synthetic and natural product chemistry. 

A similar reaction pathway was found for the Sn2 substitution of an epoxide with a lithium cuprate cluster [124]. In contrast to that in the MeBr reaction, the stereochemistry of the electrophilic carbon center is already inverted in the transition state, providing the reason for the preferred trans-diaxial epoxide-opening widely observed in synthetic studies. The TS for the Sn2 reaction of cyclohexene oxide is shown in Eq. 10.12. 

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