Nucleophilic, and carbocations

We have assumed that the values of as for formation weak encounter complexes between nucleophile and substrate, and between nucleophile and carbocation are similar. This is supported by the observation of similar values of [see above] for formation of encounter complexes between neutral substrate and anionic nucleophile (0.7 between cationic substrate and anionic nucleophile (0.2 and... 

The second factor is the dependence of bonding interactions between the nucleophile and carbocation at the transition state upon the distance between the charge centers. The importance of this is suggested by a comparison of rate and equilibrium constants for the reactions of chloride ion and Me2S with the quinone methide 57 and / -methoxybenzyl cation. 

We have assumed that the values of Kas for formation weak encounter complexes between nucleophile and substrate, and between nucleophile and carbocation are similar. This is supported by the observation of similar values of Kas [see above] for formation of encounter complexes between neutral substrate and anionic nucleophile (0.7 M-1),2 between cationic substrate and anionic nucleophile (0.2 M 1),27 and between neutral substrate and neutral nucleophile (0.3 M-1).20 We use the value of k-d= 1.6 X 10los-1 that can be calculated from Xas = 0.3 M-1 formation of encounter complexes with 1-phenylethyl derivatives and kA = 5 X 109 M-1 s-1 (equation (2)).20 The uncertainty in this value for fc d is approximately equal to the range of experimental values for Xas (0.2-0.7 m 1) 2-20-27... 

A similar Nicolas-Pauson-Khand combination was used in a synthesis of the ketone analogue of biotin 7.98, required for biochemical studies (Scheme 7.25). In this case, the Nicholas reaction was intermolecular, between allyl thiol as the nucleophile and carbocation 7.94 generated from alcohol 7.93. The Pauson-Khand reaction was then between the dicobalt complexed alkyne 7.95 and the double bond from the thiol moiety. The Pauson-Khand reaction proceeded with no stereoselectivity, and the diastereoisomers had to be chromatographically separated at a later stage. The synthesis was completed by reduction of the alkene of cyclopentenone 7.96, without using palladium-catalysed hydrogenation due to the sulfide moiety, and ester hydrolysis. 

Scheme 10. Mechanislic possibililies for PF condensalion. Mechanism a involves an SN2-like attack of a phenolic ring on a methylol. This attack would be face-on. Such a mechanism is necessarily second-order. Mechanism b involves formation of a quinone methide intermediate and should be Hrst-order. The quinone methide should react with any nucleophile and should show ethers through both the phenolic and hydroxymethyl oxygens. Reaction c would not be likely in an alkaline solution and is probably illustrative of the mechanism for novolac condensation. The slow step should be formation of the benzyl carbocation. Therefore, this should be a first-order reaction also. Though carbocation formation responds to proton concentration, the effects of acidity will not usually be seen in the reaction kinetics in a given experiment because proton concentration will not vary.

Certain nucleophilic substitution reactions that normally involve carbocations can take place at norbomyl bridgeheads (though it is not certain that carbocations are actually involved in all cases) if the leaving group used is of the type that cannot function as a nucleophile (and thus come back) once it has gone, for example. 

How Does Structure Determine Organic Reactivity Partitioning of Carbocations between Addition of Nucleophiles and Deprotonation... 

Carbocations, partitioning between addition of nucleophiles and deprotonation, 35, 67... 

Partitioning of carbocations between addition of nucleophiles and deprotonation, 35, 67 Perchloro-organic chemistry structure, spectroscopy and reaction pathways, 25, 267 Permutational isomerization of pentavalent phosphorus compounds, 9, 25 Phase-transfer catalysis by quaternary ammonium salts, 15, 267 Phosphate esters, mechanism and catalysis of nucleophilic substitution in, 25, 99 Phosphorus compounds, pentavalent, turnstile rearrangement and pseudoration in permutational isomerization, 9, 25... 

Compound 10 has a new C4-C11 bond. Either C4 is the nucleophile and Cll is the electrophile, or vice versa. Either way, compounds 5 and 9 are excluded as the immediate precursors to 10, since they both have a saturated Cll that cannot be rendered nucleophilic or electrophilic (except by isomerization to 6,7, or 8). If C11 is the nucleophile, this would put a carbocation at C9, which is where we want it so that we can deprotonate C8 to form the C8=C9 n bond in 10. So we might protonate 6, 7, or 8 at C3, C5, or C6, respectively, to make an electrophile at C4. However, note the stereochemistry of the H atom at C3 in 10. Both 7 and 8 have the opposite stereochemistry at C3. This means that 6 must be the immediate precursor to 10. Protonation of C3 of 6 from the top face gives a carbocation at C4. Attack of the Cl 1=C9 n bond on C4 gives a new a bond and a carbocation at C9. Loss of H+ from C8 gives 10. 

Nucleophilic addition of anthocyanins and flavanols on electrophiles such as quinones, flavylium cations, protonated aldehydes, and carbocations resulting from acid-catalyzed cleavage of proanthocyanidins. 

SnI reaction means substitution nucleophilic unimolecular. The SnI reaction occurs in two steps, with the first being a slow ionization reaction generating a carbocation. Thus, the rate of an S l reaction depends only on the concentration of the alkyl halide. First, the C—X bond breaks without any help from the nucleophile, and then there is quick nucleophilic attack by the nucleophile on the carbocation. When water or alcohol is the nucleophile, a quick loss of a proton by the solvent gives the hnal product. For example, the reaction of t-butylbromide and methanol gives t-butyl methyl ether. 

There is clear differentiation of the alkylation of alkenes (jt-donor nucleophiles) and alkanes (a donors). The former follows Markovnikov addition, giving a trivalent carbocation and derived branched products. The latter proceeds through a five-coordinate carbocation without involvement of trivalent carbenium ions and thus without necessary branching. 

Cationic polymerization of alkenes involves the formation of a reactive carbo-cationic species capable of inducing chain growth (propagation). The idea of the involvement of carbocations as intermediates in cationic polymerization was developed by Whitmore.5 Mechanistically, acid-catalyzed polymerization of alkenes can be considered in the context of electrophilic addition to the carbon-carbon double bond. Sufficient nucleophilicity and polarity of the alkene is necessary in its interaction with the initiating cationic species. The reactivity of alkenes in acid-catalyzed polymerization corresponds to the relative stability of the intermediate carbocations (tertiary > secondary > primary). Ethylene and propylene, consequently, are difficult to polymerize under acidic conditions. 

The two basic prerequisites to obtain high-molecular-weight polymers via cationic polymerization are the high nucleophilicity of the monomer and the relative stability of the carbocation to sustain propagation. The difficulty of ethylene and propylene to yield high-molecular-weight polymers in acid-catalyzed polymerization exemplifies this statement both have relatively low nucleophilicity and the derived ethyl and isopropyl cations have relatively low stability. 

We may seem to have contradicted ourselves because Equation 10-1 shows a carbocation to be formed in bromine addition, but Equation 10-5 suggests a bromonium ion. Actually, the formulation of intermediates in alkene addition reactions as open ions or as cyclic ions is a controversial matter, even after many years of study. Unfortunately, it is not possible to determine the structure of the intermediate ions by any direct physical method because, under the conditions of the reaction, the ions are so reactive that they form products more rapidly than they can be observed. However, it is possible to generate stable bromonium ions, as well as the corresponding chloronium and iodonium ions. The technique is to use low temperatures in the absence of any strong nucleophiles and to start with a 1,2-dihaloalkane and antimony penta-fluoride in liquid sulfur dioxide ... 

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