Nucleophilic substitution at a vinylic carbon

Nucleophilic substitution at a vinylic carbon is difficult (see p. 433), but many examples are known. The most common mechanisms are the tetrahedral mechanism and the closely related addition-elimination mechanism. Both of these mechanisms are impossible at a saturated substrate. The addition-elimination mechanism has... 

In an earlier chapter, we dealt with SN2 reactions in aliphatic compounds. In that chapter it was stated that the normal nucleophilic pathway could not operate at carbon centres that were unsaturated, because of the impossibility of inversion of the configuration of the carbon involved. This does not mean that nucleophilic substitution at a vinyl carbon is impossible if it is to occur, however, then there must be a different pathway by which it must proceed. 

While the major use for palladium catalysis is to make carbon-carbon bonds, which are difficult to make using conventional reactions, the success of this approach has recently led to its application to forming carbon-heteroatom bonds as well. The Overall result is a nucleophilic substitution at a vinylic or aromatic centre, which would not normally be possible. A range of aromatic amines can be prepared direcdy from the corresponding bromides, iodides, or triflates and the required amine in the presence of palladium(O) and a strong alkoxide base. Similarly, lithium thiolates couple with vinylic triflates to give vinyl sulfides provided lithium chloride is present. 

The Sn2 reaction involves the attack of a nucleophile from the side opposite the leaving group and proceeds with exclusive inversion of configuration in a concerted manner. In contrast to the popular bimolecular nucleophilic substitution at the aliphatic carbon atom, the SN2 reaction at the vinylic carbon atom has been considered to be a high-energy pathway. Textbooks of organic chemistry reject this mechanism on steric grounds [175]. 

To sum up, nucleophilic substitution at an olefinic carbon (at any rate, at the sharply electrophilic one, as in 3-substituted vinyl aryl ketones) involves addition of a nucleophile followed by formation of the PhC(0)CHCHXY anion, whose fate depends on the rate at w hich the group X leaves the molecule. If X leaves the molecule as soon as Y" attacks,... 

The stereochemical course of nucleophilic substitution reactions is best illustrated by reference to substitution at a saturated carbon atom. The underlying principles of these reactions are fundamental to an understanding of the more complex stereochemistry of iSn reactions on steroids, carbohydrates and vinyl compounds which are considered in detail in the relevant sections below. 

All the mechanisms so far discussed take place at a saturated carbon atom. Nucleophilic substitution is also important at trigonal carbons, especially when the carbon is double bonded to an oxygen, a sulfur, or a nitrogen. Nucleophilic substitution at vinylic carbons is considered in the next section at aromatic carbons in Chapter 13. 

Similar qualitative relationships between reaction mechanism and the stability of the putative reactive intermediates have been observed for a variety of organic reactions, including alkene-forming elimination reactions, and nucleophilic substitution at vinylic" and at carbonyl carbon. The nomenclature for reaction mechanisms has evolved through the years and we will adopt the International Union of Pure and Applied Chemistry (lUPAC) nomenclature and refer to stepwise substitution (SnI) as Dn + An (Scheme 2.1 A) and concerted bimolecular substitution (Sn2) as AnDn (Scheme 2.IB), except when we want to emphasize that the distinction in reaction mechanism is based solely upon the experimentally determined kinetic order of the reaction with respect to the nucleophile. 

The ab initio MO calculations of vinyl-AModane indicate that the a orbital for the Cvinyl-I bond is lower in energy than the n orbital for chloro(divinyl)-A3-iodane, the a orbital (1.81 eV) for the Cvinyl-I apical bond is the LUMO, and the 7i orbital (3.34 eV) of the apical vinyl group is the third lowest vacant orbital (LUMO + 2) [183,184]. The low-lying o orbital is an important feature of the vinyl-A3-iodanes and makes the bimolecular nucleophilic substitution (SN2) at the vinylic carbon possible. 

The last two examples in Table 8.5 have the leaving group bonded to an. s/r-hybridized carbon, either a vinylic carbon or an aromatic carbon. Under normal conditions, both of these types of compounds are inert to nucleophilic substitution reactions because of the stronger C—L bond, the difficulty in forming carbocations at s/r-hybridized carbons, and the extra steric hindrance to approach of the nucleophile from the side opposite the leaving group. (Under particularly favorable circumstances, SN1 reactions of these compounds can be forced to occur.)... 

Modena and co-workers examined the relevance of the symmetry of the lowest unoccupied molecular orbital (LUMO) of the electrophile in substitutions at vinyl carbon of thiirene <1995JA2297>. The computational levels included 3-21G //3-21G, 6-31G //3-21G, and 6-311G //3-21G. In attack at the vinyl carbon of a thiirenium ion, for example, the thiirenium ion is the electrophile and the attacking nucleophile is a neutral species with a lone pair, or an anion. It was found that in cases where the first vacant a- and n-levels differ in energy by more than 0.01 hartree, there is a good correspondence between the symmetry of the lowest unoccupied orbital and the stereochemical... 

Towards electrophiles, the reactivity of vinylsilanes is similar to that of the corresponding alkene. However, incorporating a silicon substituent at the vinylic carbon of a ir-nucleophile markedly affects the cyclization outcome. Specifically, iminium ion-vinylsilane cyclizations occur cleanly to substitute, preferentially with retention of double-bond configuration, the iminium ion carbon for the silyl substituent. Both endocyclic and exocyclic modes of intramolecular electrophilic substitution have been demonstrated (Scheme 35). 

The lack of reactivity observed for vinyl chloride and chlorobenzene are a reflection of the high energy pathway required for nucleophilic substitution at vinylic and aromatic carbons. Vinyl and phenyl carbonium ions have been observed, but their formation requires very reactive leaving groups, such as trifluoro-methanesplfonate. 

For trisubstituted olefins, the nucleophile attacks predominantly at the less substituted end of the allyl moiety, e.g. to afford a 78 22 mixture of 13 and 14 (equation 7). Both the oxidative addition of palladium(O) and the subsequent nucleophilic attack occur with inversion of configuration to give the product of net retention7. The synthesis of the sex pheromone 15 of the Monarch butterfly has been accomplished by using bis[bis(l,2-diphenylphosphinoethane)]palladium as a catalyst as outlined in equation 87. A substitution of an allyl sulfone 16 by a stabilized carbon nucleophile, such as an alkynyl or vinyl system, proceeds regioselectively in the presence of a Lewis acid (equation 9)8. The... 

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