Vinylic carbon, nucleophilic substitution

Pd(II) compounds coordinate to alkenes to form rr-complexes. Roughly, a decrease in the electron density of alkenes by coordination to electrophilic Pd(II) permits attack by various nucleophiles on the coordinated alkenes. In contrast, electrophilic attack is commonly observed with uncomplexed alkenes. The attack of nucleophiles with concomitant formation of a carbon-palladium r-bond 1 is called the palladation of alkenes. This reaction is similar to the mercuration reaction. However, unlike the mercuration products, which are stable and isolable, the product 1 of the palladation is usually unstable and undergoes rapid decomposition. The palladation reaction is followed by two reactions. The elimination of H—Pd—Cl from 1 to form vinyl compounds 2 is one reaction path, resulting in nucleophilic substitution of the olefinic proton. When the displacement of the Pd in 1 with another nucleophile takes place, the nucleophilic addition of alkenes occurs to give 3. Depending on the reactants and conditions, either nucleophilic substitution of alkenes or nucleophilic addition to alkenes takes place. 

Unlike elimination and nucleophilic substitution reactions foimation of oigano lithium compounds does not require that the halogen be bonded to sp hybndized carbon Compounds such as vinyl halides and aiyl halides m which the halogen is bonded to sp hybndized carbon react m the same way as alkyl halides but at somewhat slowei rates... 

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... 

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. 

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... 

The nucleophilic substitution on poly(vinyl chloroformate) with phenol under phase transfer catalysis conditions has been studied. The 13c-NMR spectra of partly modified polymers have been examined in detail in the region of the tertiary carbon atoms of the main chain. The results have shown that the substitution reaction proceeds without degradation of the polymer and selectively with the chloroformate functions belonging to the different triads, isotactic sequences being the most reactive ones. 

Moreover it has been shown that PV0CC1 prepared by free-radical polymerization of vinyl chloroformate (V0CC1) is an atactic polymer having a Bernouillian statistical distribution as expected (J[9). In order to extend our studies on the chemical modification of PV0CC1, the stereoselective character of the nucleophilic substitution of the chloroformate units with phenol has been examined by the study of the 13c-NMR spectra of partly modified polymers in the region of the aliphatic methine carbon atoms. The results obtained in this field are presented here. 

Compound 874, as a representative of derivatives with an electron-withdrawing substituent at C-[1 of the vinyl group, is easily prepared by elimination of one benzotriazole from 2,2-/fo(benzotriazol-l-yl)ethyl methyl ketone 873. The stereoselective elimination catalyzed by NaOH gives exclusively the (E) isomer of derivative 874. Addition of nucleophiles to the double bond of vinyl ketone 874 followed by elimination of benzotriazole leads to a,P unsaturated ketones 875. Amines used as nucleophiles do not need any catalysis, but reactions with carbon and sulfur nucleophiles require addition of a base. The total effect is nucleophilic substitution of the benzotriazolyl group at the i-carbon of orji-iinsaturatcd ketone (Scheme 142) <1996SC3773>. 

The attack of the nucleophile on the acceptor-substituted allene usually happens at the central sp-hybridized carbon atom. This holds true also if no nucleophilic addition but a nucleophilic substitution in terms of an SN2 reaction such as 181 — 182 occurs (Scheme 7.30) [245]. The addition of ethanol to the allene 183 is an exception [157]. In this case, the allene not only bears an acceptor but shows also the substructure of a vinyl ether. A change in the regioselectivity of the addition of nucleophilic compounds NuH to allenic esters can be effected by temporary introduction of a triphenylphosphonium group [246]. For instance, the ester 185 yields the phos-phonium salt 186, which may be converted further to the ether 187. Evidently, the triphenylphosphonium group induces an electrophilic character at the terminal carbon atom of 186 and this is used to produce 187, which is formally an abnormal product of the addition of methanol to the allene 185. This method of umpolung is also applicable to nucleophilic addition reactions to allenyl ketones in a modified procedure [246, 247]. 

Nucleophilic substitutions at vinylic carbon atoms usually proceed with retention of con-flguration. See, for example G. Modena, Ace. Chem. Res. 4, 73 (1971). Rationales have been proposed by W. D. Stohrer, Tetrahedron Lett., 207 (1975) S. I. Miller, Tetrahedron 33, 1211 (1977)... 

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. 

Unsaturated fluorinated compounds are fundamentally different from those of hydrocarbon chemistry. Whereas conventional alkenes are electron rich at the double bond, fluoroal-kenes suffer from a deficiency of electrons due to the negative inductive effect. Therefore, fluoroalkenes react smoothly in a very typical way with oxygen, sulfur, nitrogen and carbon nucleophiles.31 Usually, the reaction path of the addition or addition-elimination reaction goes through an intermediate carbanion. The reaction conditions decide whether the product is saturated or unsaturated and if vinylic or allylic substitution is required. Highly branched fluoroalkenes, obtained from the fluoride-initiated ionic oligomerization of tetrafluoroethene or hexafluoropropene, are different and more complex in their reactions and reactivities. 

The HDO and isomerization reactions were previously described as bimolecular nucleophilic substitutions with allylic migrations-the so-called SN2 mechanism (7). The first common step is the fixation of the hydride on the carbon sp of the substrate. The loss of the hydroxyl group of the alcohols could not be a simple dehydration -a preliminar elimination reaction- as the 3-butene-l-ol leads to neither isomerization nor hydrodehydroxyl at ion (6). The results observed with vinylic ethers confirm that only allylic oxygenated compounds are able to undergo easily isomerization and HDO reactions. Moreover, we can note that furan tetrahydro and furan do not react at all even at high temperature (200 C). 

Scheme 9.14 Stereoconvergence in nucleophilic substitutions at vinylic carbon.

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]. 

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. 

Alkenyl(phenyl)iodonium salts are highly reactive in vinylic nucleophilic substitution reactions because of the excellent leaving group ability of the phenyliodonium moiety. Only a few examples of non-catalytic alkenylation of carbon nucleophiles are known [50,51]. In most cases these reactions proceed with predominant retention of configuration via the addition-elimination mechanism or ligand coupling on the iodine [42,50]. 

The selectivity of the alkenylation reactions and the yields of products can be dramatically improved by carrying out the reaction of alkenyliodonium salts with carbon nucleophiles in the presence of transition metal compounds in stoichiometric or catalytic amounts. Thus, the reactions of bicycloalkenyldiiodo-nium salts 62 with cyanide anion or with alkynyllithium in the absence of transition metals are non selective and lead to a wide spectrum of products, while the same reactions in the presence of the equimolecular amount of copper(I) cyanide afford the respective products of vinylic nucleophilic substitution in good yields (Scheme 29) [52,53]. 

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