Reaction mechanisms hydride donors

Most SN reactions of hydride donors, organometallic compounds, and heteroatom-stabi-lized carbanions at the carboxyl carbon follow the mechanism shown in Figure 6.2. Thus, the substitution products, i.e., the aldehydes and ketones C, form in the presence of the nucleophiles. Thus, when the nucleophile and the acylating agent are used in a 2 1 ratio, alcohols F are always produced. 

Neither the mechanism for all addition reactions of hydride donors to the carbonyl carbon nor the mechanism for all addition reactions of organometallic compounds to the carbonyl carbon is known in detail. It is even doubtful whether only ionic intermediates occur. For instance, for some LiAlH4 additions an electron transfer mecha-... 

Because systematic variations in selectivity with reactivity are commonly quite mild for reactions of carbocations with n-nucleophiles, and practically absent for 71-nucleophiles or hydride donors, many nucleophiles can be characterized by constant N and s values. These are valuable in correlating and predicting reactivities toward benzhydryl cations, a wide structural variety of other electrophiles and, to a good approximation, substrates reacting by an Sn2 mechanism. There are certainly failures in extending these relationships to too wide a variation of carbocation and nucleophile structures, but there is a sufficient framework of regular behavior for the influence of additional factors such as steric effects to be rationally examined as deviations from the norm. Thus comparisons between benzhydryl and trityl cations reveal quite different steric effects for reactions with hydroxylic solvents and alkenes, or even with different halide ions... 

The hydride transfer reaction catalyzed by strong acids has also been successfully adapted in the natural product chemistry. Jacquesy et al.870 have found that protonated dienones and enones of steroid nucleus can be conveniently reduced in HF—SbF5 medium under hydrogen pressure. The reaction has also been carried out with added hydrocarbons (methylcyclopentane, cyclohexane) as hydride donors.871 The proposed mechanism is depicted in Scheme 5.89. 

Many substitution reactions on the carboxyl carbon undertaken by hydride donors or organometallic reagents take place according to the mechanism of Figure 6.4 (cf. Section 6.5). For the reaction between phenyllithium and lV,lV-dimethylbenzamide, the tetrahedral intermediate could even by crystallized and characterized by X-ray analysis. 

Alcohols (as well as amines, sulfides and many hydrocarbons) may act as overall hydride donors towards excited nonbonding-rr " states of carbonyl compounds and heterocycles. The synthetic as well as the photophysical aspects of these processes have been discussed extensively. These reactions will not be dealt with further here. Singlet oxygen also accepts hydride from alkoxides in the gas phase the mechanisms of such reactions have received considerable study. ... 

These kinetic data support a reaction mechanism in which the normally trimeric hydride (R2AIH)3, must dissociate into its monomer (40), which attacks the alkyne in a syn fashion in the rate-determining step (Scheme 11). The importance of tricoordinate (40) in initiating the electrophilic attack on the alkyne is seen in the effect of donor solvents the rate of reaction in hexane is 10 times faster than that in THF. The latter solvent is known to form a strong 1 1 complex with (40). 

For example, in the case of the reduction of acetaldehyde to ethanol (as catalyzed by alcohol dehydrogenases) the following sequence of events, where Donor-H represents a hydride donor, is composed of a hydride-transfer mechanism for the step in Eq. (4.2a), a proton-transfer mechanism for the step in Eq. (4.2b), and a hydride-transfer/proton-transfer mechanism for the overall reaction formed by Eqs. (4.2a) and (4.2b) ... 

The reactions of various analogs of NAD H with ketones and acridinium cations gave isotope effects on the rate constants for substrate reduction (ku/k ) that were different in magnitude from the isotope effects measured by isotope abundances in products compared to reactants (Yh/Td)- For example, Yh/Yd was found to be constant at around 6 in one series of reactions, while kn/k varied with the structure of the hydride donor from about 3.3 to about 5.7. A hydride-transfer mechanism therefore appeared to be excluded. 

Ionic hydrogenation reactions have been known for a long time in organic chemistry [59]. The basic mechanism is displayed in Scheme 6. In a first step, a carbenium ion is formed by i) protonation or ii) bond hydrolysis, which then reacts with hydride donors to the hydrogenation product. For an effective reaction it is required that the single components must not react with each other, that no side reactions take place with the substrate, and that the product evolution must not be hindered. 

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