Hydride donors mechanism

Sodium borohydride and lithium aluminum hydride react with carbonyl compounds in much the same way that Grignard reagents do except that they function as hydride donors rather than as carbanion sources Figure 15 2 outlines the general mechanism for the sodium borohydride reduction of an aldehyde or ketone (R2C=0) Two points are especially important about this process... 

This analogy is plausible on energetic grounds, since the decreased base strength of the proton acceptor should be approximately compensated by the increased acid strength of the proton donor. In view of the different species involved, however, it is reasonable to expect appreciable differences in the configurations of the transition states and hence in the activation barriers for the two paths. Therefore, the failure to observe an acid-catalyzed exchange reaction cannot be taken as conclusive evidence in favor of the alternative (hydride ion) mechanism. 

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. 

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-... 

In the transfer hydrogenation, the hydride donor such as 2-propanol or formic acid generates a metal hydride (ruthenium hydride in this case). The metal hydride selectively transfers the hydride to ketone via a bifunctional mechanism related to the one that operates for hydrogenation. The metal hydride is regenerated in situ from the hydrogen donor (Scheme 6.31). 

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. ... 

The first step of the mechanism is the coordination of BFI3 (Lewis acid) to the tertiary nitrogen atom (Lewis base) of the CBS catalyst from the -face. This coordination enhances the Lewis acidity of the endocyclic boron atom and activates the BH3 to become a strong hydride donor. The CBS catalyst-borane complex then binds to the ketone at the sterically more accessible lone pair (the lone pair closer to the smaller substituent) via the endocyclic boron atom. At this point the ketone and the coordinated borane in the vicinal position are cis to each other and the unfavorable steric interactions between the ketone and the CBS catalyst are minimal. The face-selective hydride transfer takes... 

The currently accepted concerted mechanism that goes through a chairlike six-membered transition state was first proposed by Woodward. The special activity of aluminum alkoxides for the MVP reduction can be explained as a result of the activation of both the hydride donor and the hydride acceptor. For aromatic ketones the involvement of radicals was suggested, but for aliphatic carbonyl compounds there is no evidence for a SET mechanism." " ... 

Lithium aluminium hydride (LiAlH4) or sodium borohydride (NaBR) can act as hydride donors. A simplified view of the mechanism involves the formation of an intermediate alkoxide, which on protonation yields a primary or secondary alcohol. 

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) ... 

A key line of evidence for a multistep mechanism, as opposed to the one-step hydride-transfer mechanism, had been derived from isotope effects measured in reduction of various substrates with monodeuterated analogs of NADH. One can compare the observed rate constants kHH and kno, which in the case of negligible secondary isotope effects should obey the relationship koH/kHM = (1 + kro/kyi])/2, allowing the calculation of the primary isotope effect kn/ku (if undeuterated, monodeuterated and dideuterated hydride donors are all used, both primary and secondary isotope effects can be obtained). In addition, for an oxidizing agent Acceptor one can determine the isotope ratio in the product Acceptor-H/Acceptor-D, called in these studies the product isotope effect Th/Td-... 

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