Vinyl substrates, reaction

Of course, we have seen (p. 430) that SnI reactions at vinylic substrates can be accelerated by a substituents that stabilize that cation, and that reactions by the tetrahedral mechanism can be accelerated by P substituents that stabilize the carbanion. Also, reactions at vinylic substrates can in certain cases proceed by addition-elimination or elimination-addition sequences (pp. 428, 430). 

Esters of inorganic acids, including those given above and others, can be hydrolyzed to alcohols. The reactions are most successful when the ester is that of a strong acid, but it can be done for esters of weaker acids by the use of hydroxide ion (a more powerful nucleophile) or acidic conditions (which make the leaving group come off more easily). When vinylic substrates are hydrolyzed, the products are aldehydes or ketones. 

This mechanism is the same as the simple electrophilic one shown on page 970 except that the charges are reversed (lUPAC An- -Ae or A +Ah). When the alkene contains a good leaving group (as defined for nucleophilic substitution), substitution is a side reaction (this is nucleophilic substitution at a vinylic substrate, see p. 428). 

Scheme XI. Possible Reaction Paths of Vinyl Substrates.

Examples of the behavior of other substituted vinyl substrates upon exposure to the action of trifluoroacetic acid and triethylsilane are known. For example, -butyl vinyl ether, when reacted at 50° for 10 hours, gives -butyl ethyl ether in 80% yield (Eq. 65).234 In contrast, -butyl vinyl thioether gives only a 5% yield of n-butyl ethyl sulfide product after 2 hours and 15% after 20 horns of reaction.234 It is suggested that this low reactvity is the result of the formation of a very stable sulfur-bridged carbocation intermediate that resists attack by the organosilicon hydride (Eq. 66). 

An application of Stille couplings to the solid phase using a traceless A-glycerol linker with 2-stannylindoles has been developed [177]. Only a few examples of the use of 3-stannylindoles in Stille reactions have been described. Ortar and co-workers prepared 169 and 170 and effected Pd-catalyzed cross coupling reactions with several aryl, heteroaryl, and vinyl substrates (bromides, iodides, triflates) to give the expected products 171 in high yields [178]. Enol triflates behave exceptionally well under the Ortar conditions, e.g., 172 to 173. 

A series of pyrido[2,3-rf pyrimidine-2,4-diones bearing substituents at C-5 and/or C-6 were synthesized using palladium-catalyzed coupling of uracil derivative 417 with vinyl substrates or allyl ethers to give the regioisomeric mixtures of 418/419 and 420/421, respectively. The ratio of the isomeric structures was dependent on the substituent R. In the case of the reaction with -butyl vinyl ether, only the product 419 was obtained. However, the reactions with acrylonitrile, ethyl acrylate, 2-trifluoromethylstyrene, and 3-nitrostyrene afforded only 418. Also, reaction with allyl phenyl ether gave only 420. The key intermediate 417 was prepared by the reaction of 6-amino-l-methyluracil with DMF-DMA (DMA = dimethylacetamide), followed by N-benzylation with benzyl chloride and vinyl iodination with iV-iodosuccinimide (NIS) (Scheme 15) <2001BML611>. 

Such an intermediate can also stabilize itself by combining with a positive species. When it does, the reaction is nucleophilic addition to a G=C double bond (see Chapter 15). It is not surprising that with vinylic substrates addition and substitution often compete. For chloroquinones, where the charge is spread by resonance, tetrahedral intermediates have been isolated 220... 

We will now consider successively the different reactions (4) and (5) of this reaction scheme in order to examine what is their relative importance for obtaining block or graft copolymers. Initially it was admitted that the graft copolymers were produced only by reaction (4b), considering that in the competition between monomer and substrate for primary initiator radicals the addition of vinyl monomers [reaction (2)] is much easier than the abstraction of an atom of another molecule [reaction (4 a)]. This assumption is based on the higher value of the activation energy for a chain transfer reaction than for a monomer addition, at least in the case of saturated molecules (88). 

The most common mechanism of nucleophilic vinylic substitution163 is the two-step process of Equation (48) shown for the reaction of an anionic nucleophile with a vinylic substrate activated by one... 

The fact that the intrinsic rate constants for nucleophilic addition to Fischer carbene complexes are relatively low, for example, much lower than for most reactions with comparable vinylic substrates or carboxylic esters,188 constitutes strong evidence for the presence of substantial transition state imbalances. However, there have only been a few studies of substituent effects that demonstrate the imbalance directly by showing a uc > p uc or by providing an estimate of its magnitude from the difference a uc - p uc. One such study is the reactions of 76-Cr-Z and 76-W-Z with HC CCII20 and C.F3CH20, 183 It yielded a Llc 0.59 and p ]uc< 0.46 for 76-Cr-Z, and a[juc 0.56 and 0 42 for 76-W-Z, i.e., a ue > p uc as expected. 

The cyclocarbonylation of vinylic halides (usually the bromide or iodide) is another route to lactones and lactams. 1,2-Substituted vinyl compounds produce lactones where the double bond is incorporated into the ring (equation 27), while 1,1-substituted vinyl substrates give an exo double bond (equation 28). The 1,2-substituted vinyl reactions can be run under ambient conditions (24-72h), producing high yields of... 

Aryl and vinyl sulfonate esters are reactive toward oxidative addition, and the perfluoroaUcyl versions are useful substrates in the Heck reaction. Conditions can be mild, comparable to those for vinyl iodide reactions. The enol (vinyl) triflates are particularly attractive, since they are prepared directly from the corresponding ketone (equation 21). ... 

Unlike other cross-coupling reactions, for which the scope has rapidly expanded in recent years, the range of electrophilic substrates that can be used successfully in the Sonogashira protocol is still rather limited. Vinylic substrates (iodides, bromides, chlorides, triflates, and more recently tosylates) typically yield the best results. For aromatic substrates, iodides and triflates are preferred over bromides, which in turn give far better yields than aryl chlorides. This latter aspect of the reaction is particularly frustrating when one considers the recent advances in the activation of aryl chloride substrates for reactivity in other cross-coupling protocols. ... 

---