Solvation nucleophilic addition

Example Solvation can have a profound effect on the potential energy profile for a reaction. Jorgensen s research group provided important insights into the role of solvation. Consider the nucleophilic addition of the hydroxide anion to formaldehyde ... 

The tetraimidosulfate anion [S(NtBu)4] , isoelectronic with 804 , is prepared by a methodology similar to that employed for the synthesis of triimidosulfites. The reaction of the sulfur triimide S(N Bu)3 with two equivalents of LiNH Bu produces the solvated monomeric complex [(thf)4Li2S(N Bu)4] (10.21) (Eq. 10.8). The nucleophilic addition of... 

The observed value of kjkp for partitioning of the simple tertiary carbocation [1+] is smaller than that expected if the nucleophilic addition of solvent were to occur by rate-determining chemical bond formation. This is probably because solvent addition is limited by the rate constant for reorganization of the solvation shell that surrounds the carbocation. 

Nucleophilic addition of phenolic nucleophiles to l,l-dicyano-2-arylethenes in the gas phase and in water has been studied theoretically" using the semiempirical AMI method and the Cramer-Truhlar solvation model SM2.1. The difference between the Brpnsted coefficients (a" = 0.81 and P" =0.65) determined for the gas-phase reaction is indicative of a small positive transition state imbalance of / = 0.16. For reaction in water the estimates (a" = 0.61 and P" = 0.36, giving I = 0.25) are close to the experimental values (a" = 0.55 and P" = 0.35) obtained with amine bases, and the small imbalance is as expected for a reaction involving no hybridization change at the incipient carbanion site. 

He have found that, In hydrocarbon solvents, the activating effect of the pyridine ring upon the reactivity of the doublebond, allows nucleophilic addition from non-solvated R Mg R derivatives. 

The second-order rate constant for the reaction between methoxycarbonyl-acetylene and piperidine increases with increasing solvent polarity. This can be attributed to the increased solvation of the strongly dipolar activated complex, which is formed from neutral molecules [88], Analogous solvent effects have been observed for the nucleophilic addition of aziridine to 3-dimethylaminopropynal [89] and the addition of diethylamine to / -alkoxyvinyl methyl ketones [793],... 

Further detailed investigations of the solvation of carbonyl compounds as the predominant factor influencing the diastereoselectivity of nucleophilic additions of various organometallics (n-BuLi, t-BuLi, n-BuMgBr) to a-RsSiO-substituted aldehydes can be found in reference [853]. 

The mechanism of the reaction is well-known. The first step is formation of a carbanion, followed by nucleophile addition to the carbonyl carbon atom halo-hydrin alcoholates are produced finally, ring-closure takes place by intramolecular substitution. The stereochemistry of the reaction is much disputed the reason why a unified viewpoint has not emerged is that the configuration of the end-product is influenced by the structure of the starting compound (including steric hindrance), the base employed, and solvation by the solvent, sometimes in an unclear manner. The stereochemical course of the reaction is controlled by the kinetic and thermodynamic factors in the second step the structure of the oxirane formed is decided by the reversibility of the aldolization and the reaction rate of the ring-closure. 

Upon direct irradiation in inert solvents, aliphatic alkenes undergo E Z or other isomerization reactions (Sections 6.1.1 and 6.1.2). The same excited states responsible for such transformations, particularly the Rydberg n,R(.is) singlet state, are involved in nucleophilic addition or photoprotonation reactions in protic media.662 663 671 For example, the jt,R(3s) state of tetramethylethene (93), having cation-radical character of the central bond, is readily attacked by a nucleophile (such as methanol) to form a solvated electron and a radical intermediate 94 that disproportionates to a mixture of the ethers 95 (30%) and 96 (37%) (Scheme 6.37).671 The solvated electrons produced are trapped by the solvent molecules. 

The addition of a nucleophile to a carbonyl compound with a chiral a carbon generates a mixture of two diastereoisomers. The ratio of these diastereoisomers depends on the relative bulks of the (non-coordinating) substituents on the chiral center, the effective bulkiness of the nucleophile as well and the reaction conditions. By effective bulkiness, we mean the bulk of the solvated nucleophile, if the same is imminent. The reaction is schematically represented in Eq. 1. 

The relative energies of the intermediates and transition structures along the reaction coordinates are subject to the influence of solvation, which may alter relative stabilities and rates. This may explain the solvent effects discussed earlier (c/. Table 4.3, entries 1, 3 and 4). The energetic features outlined above may also explain the lack of selectivity in the nucleophilic additions to P-alkoxy carbonyl compounds. It is possible that even though 6-membered chelates are formed, their rates of formation are slower than addition via the nonchelated path, or that they are less reactive than a 5-membered chelate. Either of these circumstances (or a combination of both) would raise the transition state energy for the chelate path and the primary addition mode could be shifted to the less selective nonchelated mechanism. ... 

Nucleophiles, 142-143, 162, 302-305 relative reactivity, 312—315 solvation and reactivity, 322—323 Nucleophilic acyl substitution, 774—830 of acyl chlorides, 780-783, 820 of amides, 804—807, 808, 821 of carboxyhc acid anhydrides, 783—787, 820 of esters, 790—800, 820 of thioesters, 800 Nucleophilic addition... 

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