Relative rates of nucleophilic attack

We can restate the HSAB principle. Hard nucleophiles favor binding with hard electrophiles soft nucleophiles favor binding with soft electrophiles. Most nucleophilicity charts show relative rates of nucleophilic attack with methyl iodide as the electrophile. A carbon-iodine bond is very soft because the electronegativity difference is nearly zero (Section 1.2). Therefore softer (less electronegative, more polarizable) atoms have lone pairs that are better electron sources toward soft electrophiles. 

Catalytic symmetric synthesis of P-stereogenic phosphines by cross-coupling of secondary phosphines with benzyl or other alkyl halides was promoted by chiral ft and Ru complexes [112-114]. The key step is believed to be the nucleophilic attack of a metal-phosphido complex on a free electrophile the background reaction of the unactivated nucleophilic substrate is much slower. The origin of enantioselec-tivity, as in the Pd-catalyzed asymmetric cross-couplings described above, is the interconversion of diastereomeric phosphido complexes, whose speciation and relative rates of nucleophilic attack determine the product ratio. In the case of ft ((R./ )-Me-DuPhos)(Ph)(PMels), as with the Pd analog in Scheme 43 above, the major product phosphine was formed from the major diastereomeric phosphido complex (Scheme 63) [112-113]. 

Protonated 2-methylthiiran exists as cis- and trans-isomers in FSOaH-ShF at — 78 °C according to n.m.r. data. Data pertinent to the relative rates of nucleophilic attack at carbon and sulphur in thiiranium ions were provided by an investigation concerned primarily with the exchange of 4-chloro-benzenesulphenyl chloride between cyclic chloroalkyl 4-chlorophenyl... 

Table 3 Relative rates of nucleophilic attack on ketones...

By examining the rates of intramolecular nucleophilic cyclization of 13 at different pH values, Kirby has determined the relative reactivity of RCH=CH2, RCH=CHCOO and RCH=CHCOOH towards nucleophilic substitution14. The ratios 1 4000 8 x 107 are in broad agreement with the relative rates, 3 x 104 1, for nucleophilic attack of ammonia on fumaric acid in the neutral and dianionic forms at 135 °C. The relative rates for nucleophilic attack of hydroxide on fumaric acid in the neutral and dianionic forms at 135 °C changed to 3 x 107 1 because of the adverse electrostatic interaction between the hydroxide ion and the dianion15. 

Many simple models in use today are based on notions of electron density distributions and/or MOs derived from more sophisticated theoretical treatments. These quantities are fundamental to many (but not all) theoretical schemes. Certainly, a variety of reactivity indices are based on MO and/or charge distributions [12]. At a simple qualitative level, such distributions can be used, for example, to rationalise the sites and relative rates of nucleophilic and electrophilic attack. 

The success of the double carbonylation shown in Scheme 8.6 relies on the relative rate of the attack of amine at the Pd-bound CO vs. the insertion of CO into the Pd-Ar bond [9c]. If an amine of strong nucleophilicity and small steric... 

Several experimental variables impact the relative rates of isomerization and nucleophilic attack in the allylic substitution reaction in Figure 14.15. For example, an increase in the rate of interconversion of the ir-allyl intermediates, such that the rate of this process is faster than nucleophilic attack, will change the enantioselectivity-determining step, because the diastereomeric complexes now equilibrate rapidly. Because isomerization of the diastereomeric ir-allyl complexes is a unimolecular process, but nucleophilic attack on the ir-allyl intermediates is a bimolecular process, reactions under dilute conditions will decrease the rate of nucleophilic attack, relative to the unimolecular ir-u-ir isomerization, and will help to achieve Curtin-Hammett conditions. 

Tertiary haloalkanes react by an S l mechanism because 3° carbocation intermediates are relatively stable and tertiary haloalkanes are protected against backside attack. In fact, 3° haloalkanes are never observed to react by an mechanism. In contrast, halomethanes and primary haloalkanes are never observed to react by an mechanism. They have little crowding around the reaction site and react ty an Sj 2 mechanism because methyl and primary carbocations are unstable. Secondary haloalkanes may react by either 8, 1 or 8, 2 mechanisms, depending on the nucleophile and solvent. The competition between electronic and steric factors and their effects on relative rates of nucleophilic substitution reactions of haloalkanes are summarized in Figure 9.3. 

Use as a Nucleophile. The rate of nucleophilic substitution of 1,3-dichloropropane with potassium acetate in a range of polar solvents has been studied and correlates with the solubility of the salt. Quaternary ammonium salts (e.g., triethyl ammonium chloride, TEAC) catalyze these nucleophilic reactions by solubilizing the acetate anion. The relative rates of nucleophilic substitution of variously substituted 2-chloroethyl compounds with KOAc in DME and TEAC/MeCN solutions have a Unear free-energy relationships with the Taft substituent constant, a, showing that these reactions proceed through nucleophilic attack of acetate on RCH2CH2CI (eq 1). ... 

Finally, does the structure of the alkyl portion of the substrate, particularly in the vicinity of the atom bearing the leaving group, affect the rate of nucleophilic attack Once again, we can get a sense of comparative reactivities by looking at relative rates of reaction. Let us examine the kinetic data that have been obtained. 

During addition of HOBr and AcOBr, irreversible formation of bromonium ion intermediates (192) and (193) is proposed the overall process is controlled in the first instance by the relative rates of attack of positive bromine cis and trans to the t-butyl group and then within each bromonium ion by the rate of nucleophilic attack on C-1 and C-2. Accordingly, cis electrophilic attack on (185) to give (192) is hindered, as is nucleophilic attack on C-2 of (193X and the major product is expected to be the bromohydrin (191), or its acetoxy-derivative these are formed in upwards of 58 % yield. 

Halopyridines undergo self-quaternization on standing while the less reactive 2-halo isomers do not. However, more is involved here than the relative reactivity at the ring-positions. The reaction rate will depend on the relative riucleophilicity of the attack-ing pyridine-nitrogens (4-chloropyridine is more basic) and on the much lower steric hindrance at the 4-position. Related to this self-quatemization are the reactions of pyridine and picolines as nucleophiles with 4-chloro- and 2-chloro-3-nitropyridines. The 4-isomer (289) is. again the more reactive by 10-30-fold (Table VII, p. 276). 

So far as the overall substitution reaction (— 107) is concerned, marked differences from electrophilic and nucleophilic attack become apparent as soon as the behaviour of substituted benzene derivatives (C6HjY) is considered. Thus homolytic attack on C6H5Y is found to be faster than on C6H6, no matter whether Y is electron-attracting or -withdrawing, as shown by the relative rate data for attack by Ph ... 

A comprehensive kinetic, spectroscopic, and analysis study into the Rh-catalyzed carbonylation of ROH (R = Me, Et, Pr) has been reported.4,5 In all cases, the reaction rate is first order in both [Rh] and added [HI] and independent of CO pressure. The only Rh species observed under catalytic conditions was (1). The rates of carbonylation decreased in the stated order of R, with relative rates of 21 1 0.47, respectively at 170 °C. All the data are consistent with rate-determining nucleophilic attack by the Rh complex anion on the corresponding alkyl iodide. 

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