Substitution reactions SrnI mechanism

Vinylic halides can react by a SrnI mechanism (p. 855) in some cases. An example is the FeCl2 catalyzed reaction of l-bromo-2-phenylethene and the enolate anion of pinacolone (t-BuCOCH2 ), which gave a low yield of substitution products along with alkynes. ... 

This is called the SrnI mechanism," and many other examples are known (see 13-3, 13-4,13-6,13-12). The lUPAC designation is T+Dn+An." Note that the last step of the mechanism produces ArT radical ions, so the process is a chain mechanism (see p. 895)." An electron donor is required to initiate the reaction. In the case above it was solvated electrons from KNH2 in NH3. Evidence was that the addition of potassium metal (a good producer of solvated electrons in ammonia) completely suppressed the cine substitution. Further evidence for the SrnI mechanism was that addition of radical scavengers (which would suppress a free-radical mechanism) led to 8 9 ratios much closer to 1.46 1. Numerous other observations of SrnI mechanisms that were stimulated by solvated electrons and inhibited by radical scavengers have also been recorded." Further evidence for the SrnI mechanism in the case above was that some 1,2,4-trimethylbenzene was found among the products. This could easily be formed by abstraction by Ar- of Ft from the solvent NH3. Besides initiation by solvated electrons," " SrnI reactions have been initiated photochemically," electrochemically," and even thermally." ... 

Furthermore, Saveant et al. have shown elegant examples of electrochemi-cally induced nucleophilic substitution of perfluoroalkyl halides. The reaction mechanism is a slightly modified version of the classical SRNI mechanism in... 

More complicated reactions that combine competition between first- and second-order reactions with ECE-DISP processes are treated in detail in Section 6.2.8. The results of these theoretical treatments are used to analyze the mechanism of carbon dioxide reduction (Section 2.5.4) and the question of Fl-atom transfer vs. electron + proton transfer (Section 2.5.5). A treatment very similar to the latter case has also been used to treat the preparative-scale results in electrochemically triggered SrnI substitution reactions (Section 2.5.6). From this large range of treated reaction schemes and experimental illustrations, one may address with little adaptation any type of reaction scheme that associates electrode electron transfers and homogeneous reactions. 

The first clue to the existence of the SrnI mechanism came from product studies both in aliphatic and aromatic cases. It was noticed that in the reaction of benzyl and substituted benzyl chlorides with the 2-nitropropane anion, oxygen alkylation, yielding the oxime and then the aldehyde, occurs exclusively in the case of benzyl chloride and 3-nitrobenzyl chloride, whereas, with 4-nitrobenzyl chloride, the yield of aldehyde is only 6% and the carbon-alkylated (104) product is obtained in 92% yield (Kornblum, 1975). This was interpreted as the result of a competition between 8, 2 (O-alkylation) and S l (C-alkylation) reactions. In the aromatic case, it was observed that the reaction of 5- and 6-halopseudocumenes with KNHj in liquid ammonia (Kim and Bunnett, 1970) forms the 5- and 6-pseudocumi-dines in a ratio which is the same whether the starting compound is the 5- or 6-isomer in the case of the chloro- and bromo-derivatives, as expected from an aryne mechanism (Scheme 9), whereas much more non-rearranged... 

Halothiophenes undergo photostimulated reaction with acetone enolate ion to form substitution products (76H(5j377). This is believed to occur by the radical-chain SrnI mechanism. The propagation steps are as follows ... 

A more intriguing type of competition is due to radical processes, which usually involve the substrate radical anion. These can fragment, if they carry a suitable substituent, via anion expulsion.56 The resulting aryl radical, Ar, can form the reduced product, ArH, by hydrogen abstraction57 or the product of substitution via reaction with the nucleophile according to the SrnI mechanism, discussed in Chapter 2.2 of this volume. Examples of competition between SnAt and radical processes of this type have been reported.57-59... 

However, the competition between Srn 1 and polar abstraction mechanisms is complicated in certain reactions by the formation of disulfides which is inhibited by radical and radical anion traps, and requires photolysis [23, 24]. These results implicate a third possibility, the chain SET redox mechanism (Srt2, i.e. substitution, electron transfer, bimolecular), Scheme 10.34. This alternative mechanism occurs when the intermediate radical anion can be intercepted by the thiolate (Equation 10.23) prior to the dissociation required in the SrnI mechanism (Equation 10.17 in Scheme 10.29). It becomes possible when either... 

Solvation of thiolates is similarly low in both protic and dipolar aprotic solvents because of the size and polarisability of the large weakly basic sulfur atom, so is unlikely to contribute appreciably to the observed solvent effect. The intermediate nitro radical anion is stabilised by H-bonding in a manner which retards its dissociation in the SrnI mechanism (upper equation in Scheme 10.35). In contrast, the electron flow in the direct substitution at X (lower equation in Scheme 10.35) is such that solvation by methanol promotes the departure of the nucleofuge. In summary, protic solvation lowers the rate of the radical/radical anion reactions, but increases the rate of the polar abstraction yielding disulfide. 

Another example of SET substitution at carbon and metal by metal-14 anions was evident in the reaction of Me3SnNa with 2-chloropyridine, p-ch loro ben zoni tri Ic, o- and m-dichlorobenzene, 1,3,5-trichlorobenzene, 2,5-,2,6- and 3,5-dichloropyridine, which gave good yields of substitution products through a suggested SrnI mechanism (equation 183)193. 

A practical access to 2-biphenyl alcohols 95 has been discovered by Petrillo (Scheme 36) [152]. Azo sulfides 96, which are employed as masked diazonium salts, do not undergo azo coupling reactions. In combination with 4-substituted phenolates 97, photochemically initiated arylations can even be conducted as chain processes according to the SrnI mechanism. Given their high reductive potential, the cyclohexadienyl intermediates 98 are able to rearomatize by a single electron... 

Unactivated aryl halides will undergo nucleophilic displacement via electron transfer in the initial step the so-called SrnI mechanism. It is now clear that in the case of heteroaromatic compounds, nucleophilic substitution by the SRN process often competes with the additionelimination pathway. SRN reactions are radical chain processes and are usually photochemically promoted. For example, ketone 913 is formed by the SRN1 pathway from 2-chloroquinoxaline 912. 

The reaction between triorganostannyl ions and haloarenes in liquid ammonia can lead to substitution and reduction products. It was found that in some cases the reaction can follow an SrnI mechanism exclusively. With triphenylstannyl ions, good yields of products of the SrnI mechanism were obtained when reactions were conducted with chloroarenes... 

Reaction of o-iodoaniline 84 with carbanions under irradiation produced several 2-substituted indoles 85, or various fused indolic systems in moderate yields. The events leading to this outcome featured a C-C bond formation via the SrnI mechanism <03JOC2807>. 

Alternatively, the SrnI mechanism can be coupled to nucleophilic additions as was the case during the formation of substituted indole 212 [182], an interesting variation on a reaction first reported by Beugelmans and Roussi [183]. 

Pyridazine and its derivatives were substituted with nucleophilic radicals. They react either with 1-formylpyrrolidine or with A/-acetylproline in the presence of radical generators to give 5-substituted pyridazines (78TL619 86MI6). Also, reactions of 3-chloro-6-methoxypyridazine with ketone enolates in liquid ammonia show typical characteristics of a radical chain (SrnI) mechanism, and ketones 105 are obtained (81JOC294). 

Simple aryl halides undergo substitution reactions with very strong bases such as -NH2. Neither the addition-elimination mechanism nor the SrnI mechanism seems very likely for this pair of substrates. 

A third mechanism for substitution at C(sp3)-X bonds under basic conditions, elimination-addition, is occasionally seen. The stereochemical outcome of the substitution reaction shown in the figure tells us that a direct Sn2 substitution is not occurring. Two sequential Sn2 reactions would explain the retention of stereochemistry, but the problem with this explanation is that backside attack of MeO- on the extremely hindered top face of the bromide is simply not reasonable. The SrnI mechanism can also be ruled out, as the first-row, localized nucleophile MeO- and the 2° alkyl halide are unlikely substrates for such a mechanism. 

It is not possible to distinguish the electron transfer mechanism from the Sn2 or SRNI mechanism by cursory examination of the reaction conditions and substrates, so it is rarely appropriate to propose this mechanism. However, you should be aware that some chemists believe that all substitution reactions are initiated by electron transfer. 

The aryldiazonium ion is usually prepared in situ and then immediately combined with a nucleophile to give a substitution product. The mechanisms of the substitution reactions vary greatly with the nucleophile, ranging all across the mechanistic spectrum of organic chemistry. For example, both hypophosphorous acid (H3P02) and I react with diazonium ions by an SrnI mechanism (Chapter 2) to give the reduced arenes or aryl iodides, respectively. 

Electron transfer is also the first step of the SrnI substitution mechanism (Chapter 2). In reactions that proceed by the SrnI mechanism, the electron donor is usually the nucleophile. The nucleophile may be photoexcited to give its electron more energy and make it more prone to transfer. 

Copper(I) salts such as CuCN and ROCu undergo aromatic substitution reactions very readily with ordinary aryl halides. The mechanism has not been established with certainty. One reasonable possibility is an SrnI mechanism. Another reasonable possibility involves oxidative addition of Ar X to N=C Cu(I) to give a Cu(III) complex, followed by reductive elimination of Ar-CN to give CuX. 

The enolate anions of 2-acetylthiophene and 2-acetylfuran have been arylated under photochemical conditions in the presence of t-BuOK and good electron donors such as acetone enolate (entrainment reaction) to give the corresponding benzyl 2-thienyl and 2-furanyl ketones respectively. Use of FeBr2 as initiator in a dark reaction gives good yields of the substitution products without the need for added nucleophiles, and it is suggested that these arylation processes occur by an SrnI mechanism. 

There is good evidence that some nucleophilic substitution reactions do involve a single electron transfer, but the best established use a slightly different mechanism. These are the SrnI reactions, with the subscript RN standing for radical nucleophilic. Examples are the reaction of the nitronate anion 4.14 with p-nitrobenzyl chloride 4.15, 251 and the reaction of the pinacolone enolate 4.16 with bromobenzene.252 The former might have been a straightforward SN2 reaction, but actually takes the S l pathway because the nitro groups make the electron transfer exceptionally easy. The latter cannot take place by a conventional Sn2 reaction, because aryl (and vinyl) halides are not susceptible to direct displacement, and the S l pathway overcomes this difficulty. 

Note that the overall reaction for this scheme is simply A B, with no net transfer of electrons. Thus, at a suitable potential, the electrode accelerates a reaction that presumably would proceed slowly without the electrode. An interesting extension of this mechanism is the electron-transfer-catalyzed substitution reaction (equivalent to the organic chemist s SrnI mechanism) (7, 14) ... 

The mechanism classification and the overall transformation classification are orthogonal to each other. For example, substitution reactions can occur by a polar acidic, polar basic, free-radical, pericyclic, or metal-catalyzed mechanism, and a reaction under polar basic conditions can produce an addition, a substitution, an elimination, or a rearrangement. Both classification schemes are important for determining the mechanism of a reaction, because knowing the class of mechanism and the overall transformation rules out certtdn mechanisms and suggests others. For example, under acidic conditions, aromatic substitution reactions take place by either one of two mechanisms electrophilic addition-elimination or SnI substitution of aryldiazonium ions. Under basic conditions, they take place by one of three mechanisms nucleophilic addition-elimination, elimination-addition, or SrnI. If you know the class of the overall transformation and the class of mechanism, your choices are narrowed considerably. 

Nucleophilic substitution can also occur at aryl rings not substituted with electron-withdrawing groups, although it is not seen as often. Two mechanisms are possible SrnI and elimination-addition. The SrnI mechanism is a radical chain mechanism. (The R in SrnI stands for radical.) As such, it has three parts initiation, propagation, and termination. Consider the following reaction ... 

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