Substitution at vinyl carbon

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 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)... 

Scheme 9.14 Stereoconvergence in nucleophilic substitutions at vinylic carbon.

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... 

Substitution at the Carbon—Chlorine Bond. Vinyl chloride is generally considered inert to nucleophilic replacement compared to other alkyl halides. However, the chlorine atom can be exchanged under nucleophilic conditions in the presence of palladium [7440-05-3] Pd, and certain other metal chlorides and salts. Vinyl alcoholates, esters, and ethers can be readily produced from these reactions. 

In order to strengthen evidence in favour of the proposition that concerted inplane 5n2 displacement reactions can occur at vinylic carbon the kinetics of reactions of some /3-alkyl-substituted vinyliodonium salts (17) with chloride ion have been studied. Substitution and elimination reactions with formation of (21) and (22), respectively, compete following initial formation of a chloro-A, -iodane reaction intermediate (18). Both (17) and (18) undergo bimolecular substitution by chloride ion while (18) also undergoes a unimolecular (intramolecular) jS-elimination of iodoben-zene and HCl. The [21]/[22] ratios for reactions of (18a-b) increase with halide ion concentration, and there is no evidence for formation of the -isomer of (Z)-alkene (21) iodonium ion (17d) forms only the products of elimination, (22d) and (23). 

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. 

Even with these developments, the synthetic potential of acetoacetic ester was still not completely exhausted. Notice in the transformations that not all four of the carbon atoms of this reagent are used. In the concluding step of the synthesis, the COOEt or CH3CO group is usually removed as if it were simply an extraneous pendant. The strive to find a 100% utilization of the acetoacetic ester carbon skeleton was realized with the development of a method for substitution at vinylic positions with the use of cuprate reagents (Section 2.12). It turns out that a similar reaction can be carried out with the enol esters of 1,3-dicarbonyl compounds. 

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. 

A precursor of methyl vinyl ketone, 4-(trimethylamino)-2-butanone, was used as the reagent in the early examples of the reaction. This compound generates methyl vinyl ketone in situ, by p elimination. Other a,)8-unsaturated enones can be used, but the reaction is somewhat sensitive to substitution at the -carbon, and adjustment of the reaction conditions is necessary. Entry 4 in Scheme 2.6 is an example of use of a -substituted enone. 

Before we discuss specific nucleophiles, leaving groups, and transformations, we should be clear about what this type of reaction will not do. Substituents attached to sp or sp carbon atoms cannot be substituted in this way. S l is precluded by the instability of sp or sp cations. 5 2 is impossible because backside attack is inhibited by the n-system. Thus, in Figure 9.29, only the allylic or benzylic halides are substituted. This is not to say that replacement of vinyl or aryl halides is impossible—simply that it does not happen in the same way, or under the same conditions (see Sections 13.4 and 23.6.3), as substitution at sp carbon atoms. 

Additional chemical stability can be given to PPVs by substitution at the vinyl-ene carbons. Thus, CN-PPV and PPV-DP are more stable than their parent polymers [173]. Carter et al. [172] showed that a random copolymer of PPV containing non-conjugated segments is considerably more stable to photooxidation than the fully conjugated polymer. Of course, the electrical and optical properties are also altered by these substitutions. 

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 electron-transfer-induced cyclization of homochrysanthemol proceeds via a flve-membered transition state, from intramolecular substitution at the quaternary cyclopropane carbon, to generate the flve-membered cyclic ethers (69) and (70). In contrast, the intramolecular photo-induced cyclization of chrysanthemol goes via a six-membered transition state involving attack at the terminal vinyl carbon. 

An example of C—Si bond formation concludes this overview of carbon heteroatom bond formation. Reflux of bromide 62 in benzene and in the presence of small amounts of (TMS)3SiH and AIBN afforded the silabicycle 63 in 88 % yield (Reaction 7.64) [76]. The key step for this transformation is the intramolecular homolytic substitution at the central silicon atom, which occurred with a rate constant of 2.4 x 10 s at 80 °C (see also Section 6.4). The reaction has also been extended to the analogous vinyl bromide (Reaction 7.65) [49]. 

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