Addition reactions without solvent molecules

A reverse peak in the cyclic voltammogram at -2.1 V shows the reoxidation of the latter species to the coordinatively unsaturated Cr(CO) which can be stabilized by the addition of a solvent molecule as a sixth ligand. Consequently, the ac electrolysis may proceed according to the following reaction scheme without invoking an electronically excited state in the back electron transfer (59) ... 

In the vapor phase, there are two additional considerations that are very important in understanding of carbene chemistry. The first point reflects the fact that carbene reactions are normally highly exothermic (about 90kcal mol for insertions or additions). Thus, a product molecule is frequently produced with a large amount of excess internal energy. In the vapor phase without solvent molecules to help dissipate the excess vibrational energy, the molecule may be subject to further reactions. Such reactions are often called hot molecule reactions. Cyclopropanes from cycloaddition reactions are particularly susceptible to hot molecule decomposition to the thermodynamically more stable olefin, since for cyclopropane isomerization is only 64kcal mol . ... 

Chemical reactivity is influenced by solvation in different ways. As noted before, the solvent modulates the intrinsic characteristics of the reactants, which are related to polarization of its charge distribution. In addition, the interaction between solute and solvent molecules gives rise to a differential stabilization of reactants, products and transition states. The interaction of solvent molecules can affect both the equilibrium and kinetics of a chemical reaction, especially when there are large differences in the polarities of the reactants, transition state, or products. Classical examples that illustrate this solvent effect are the SN2 reaction, in which water molecules induce large changes in the kinetic and thermodynamic characteristics of the reaction, and the nucleophilic attack of an R-CT group on a carbonyl centre, which is very exothermic and occurs without an activation barrier in the gas phase but is clearly endothermic with a notable activation barrier in aqueous solution [76-79]. 

The nature of proton sponges does not allow them to be used directly as kinetically active bases, e.g. in E2 elimination reactions, involving the ionization of C—H bonds213. However, due to the low nucleophilicity, the proton sponges are useful reagents when it is necessary to bind an acid liberated in the course of the reaction without any effect on other base-sensitive groups. As a rule, in such cases, a proton transfer from substrate to the proton sponge requires an additional carrier, which most frequently is the solvent molecule (such as alcohol, THF, DMSO, acetone)57,214,215. Let us consider some typical examples. 

When MeNOa [233a] and DMSO [81] are used as solvents, Michael addition of KSA proceeds smoothly at room temperature without additional catalyst. Coordination of the solvent molecule to the silicon atom would enhance the nucleophilicity of KSA to effect the uncatalyzed reaction. 

Let us now examine how substituent effects in reactants influence the rates of nucleophilic additions to carbonyl groups. The most common mechanism for substitution reactions at carbon centers is by an addition-elimination mechanism. The adduct formed by the nucleophilic addition step is tetrahedral and has sp hybridization. This adduct may be the product (as in hydride reduction) or an intermediate (as in nucleophilic substitution). For carboxylic acid derivatives, all of the steps can be reversible, but often one direction will be strongly favored by product stability. The addition step can be acid-catalyzed or base-catalyzed or can occur without specific catalysis. In protic solvents, proton transfer reactions can be an integral part of the mechanism. Solvent molecules, the nucleophile, and the carbonyl compound can interact in a concerted addition reaction that includes proton transfer. The overall rate of reaction depends on the reactivity of the nucleophile and the position of the equilibria involving intermediates. We therefore have to consider how the substituent might affect the energy of the tetrahedral intermediate. 

Solvent selection. One of the most important considerations when designing amicrowave-assisted reaction is whether or not a solvent is actually needed for the reaction. Some reactions will not be successful under solvent-free conditions however, since the solvents are typically disposed of at the end of reactions, the elimination of solvents from chemical reactions is a step forward when designing sustainable chemical reactions. The vast majority of molecules containing functional groups will have a dipole moment and absorb microwave irradiation without the addition of a solvent. If a solvent is required for the success of the reaction, a minimal amount of solvent should be used. These near-solvent-free reactions still significantly reduce the amount of solvent used by the synthesis. 

In the same year, Hayashi and coworkers [39] also reported the use of an amphiphihc L-proHne derivative bearing a long alkyl chain on the 4-position via an ether bond for the enantioselective aldehyde cross-aldol reaction without the need for an additional co-solvent or additives (Scheme 8.14). Probably, emulsions offer an ideal reaction environment in which organic molecules can be assembled through hydrophobic interactions, thus enabling the aldol reaction to proceed efficiently. As a result, the corresponding products, chiral 1,3-diols, could be obtained with high diastereo- and enantioselectivity. 

For this specific task, ionic liquids containing allcylaluminiums proved unsuitable, due to their strong isomerization activity [102]. Since, mechanistically, only the linkage of two 1-butene molecules can give rise to the formation of linear octenes, isomerization activity in the solvent inhibits the formation of the desired product. Therefore, slightly acidic chloroaluminate melts that would enable selective nickel catalysis without the addition of alkylaluminiums were developed [104]. It was found that an acidic chloroaluminate ionic liquid buffered with small amounts of weak organic bases provided a solvent that allowed a selective, biphasic reaction with [(H-COD)Ni(hfacac)]. 

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