Hydride donors reactivity

Comparative Reactivity of Common Hydride Donor Reagents... 

Table 5.3. Reactivity of Hydride-Donor Reducing Agents 397... 

There are also reactions in which hydride is transferred from carbon. The carbon-hydrogen bond has little intrinsic tendency to act as a hydride donor, so especially favorable circumstances are required to promote this reactivity. Frequently these reactions proceed through a cyclic TS in which a new C—H bond is formed simultaneously with the C-H cleavage. Hydride transfer is facilitated by high electron density at the carbon atom. Aluminum alkoxides catalyze transfer of hydride from an alcohol to a ketone. This is generally an equilibrium process and the reaction can be driven to completion if the ketone is removed from the system, by, e.g., distillation, in a process known as the Meerwein-Pondorff-Verley reduction,189 The reverse reaction in which the ketone is used in excess is called the Oppenauer oxidation. 

In transfer hydrogenation with 2-propanol, the chloride ion in a Wilkinson-type catalyst (18) is rapidly replaced by an alkoxide (Scheme 20.9). / -Elimination then yields the reactive 16-electron metal monohydride species (20). The ketone substrate (10) substitutes one of the ligands and coordinates to the catalytic center to give complex 21 upon which an insertion into the metal hydride bond takes place. The formed metal alkoxide (22) can undergo a ligand exchange with the hydride donor present in the reaction mixture, liberating the product (15). 

Two current alternative views are available as to how remotely boimd NADPH may work. One sees its action as involving two successive one-electron oxidations (52, 53). The effectiveness of NADPH in preventing compound II formation is then due to the high reactivity of the NADP intermediate as reductant of the compound II generated in the first one-electron step. The other model (47) prefers to see NADPH as a hydride donor responsible for the almost simultaneous reduction of the ferryl iron and the protein radical species. 

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... 

Catalytic reduction of alkynes to ds-alkenes. This reduction is not possible with 10% Pd/C alone because this metal is too reactive and the alkane is formed readily. The selective reaction is possible if the Pd/C is deactivated by either Hg(0) or Pb(0), obtained by reduction of metal acetate with NaBH4. Sodium phosphinate, H2P02Na, is the preferred hydride donor. Since this donor is not soluble in the Organic solvents used, a phase-transfer catalyst, benzyltriethylammonium chloride, is added.3... 

It is important to recognise that it is only through alkoxy/acetoxy interchange around the parent triacetoxyborohydride that a sufficiently reactive hydride donor can be generated that can perform the ketone reduction at an acceptable rate. Ordinarily, Me4NBH(OAc)3 will reduce ketones exceedingly slowly. 

A requirement for an a/m-orientation of the hydridic p-C—H and C—metal bonds as in [10] is indicated by the reaction of threo-3-deuterio-2-(trimethylstannyl)butane with triphenylcarbenium tetrafluoroborate in methylene chloride at 24° which yields a mixture of 3-deuterio-l -butene, /ra v-2-deuterio-2-butene, and undeuteriated c/.v-2-butene as the major product (Hannon and Traylor, 1981). Comparison of the product distributions for the protio- and deuterio-stannanes yields primary and secondary isotope effects of 3.7 and 1.1 respectively. These reactions appear to avoid the complications of adduct formation between the triarylcarbenium salt and the hydride donor, but the preferential formation of the cw-2-butenes is not fully explained. The requirement for the anti-orientation is also shown by the relatively low hydride-donating properties of tris[(triphenylstannyl)methyl-methane (Ducharme et ai, 1984a) which adopts a C3-conformation with the P-C—H gauche to all three C—Sn bonds. In contrast, 1,3,5-triphenyl-2,4,6-trithia-1,3,5-tristannyladamantane, in which anti-orientations with respect to the bridgehead C—H bond are locked, shows high reactivity (Ducharme et al., 1984b). 

For the reaction of hydride donors, organometallic compounds and heteroatom-stabilized carbanions with acylating agents or carbonyl compounds one encounters a universal reactivity order RC(=0)C1 > RC(=0)H > R2C=0 > RC(=0)0R > RC C NR It applies to both good and poor nucleophiles, but—in agreement with the reactivity/selectivity principle (Section 1.7.4)—the reactivity differences are far larger for poor nucleophiles. 

In the addition of hydride donors to aldehydes (other than formaldehyde) the tetrahedral intermediate is a primary alkoxide. In the addition to ketones it is a secondary alkoxide. When a primary alkoxide is formed, the steric hindrance is smaller. Also, when the C=0 double bond of an aldehyde is broken due to the formation of the CH(0 M ) group of an alkoxide, less stabilization of the C=0 double bond by the flanking alkyl group is lost than when the analogous transformation occurs in a ketone (cf. Table 9.1). For these two reasons aldehydes react faster with hydride donors than ketones. With a moderately reactive hydride donor such as NaBH4 at low temperature one can even chemoselectively reduce an aldehyde in the presence of a ketone (Figure 10.6, left). 

Other cyclic or bicyclic ketones do not have a convex side but only a less concave and a more concave side. Thus, a hydride donor can add to such a carbonyl group only from a concave side. Because of the steric hindrance, this normally results in a decrease in the reactivity. However, the addition of this hydride donor is still less disfavored when it takes place from the less concave (i.e., the less hindered) side. As shown in Figure 10.10 (top) by means of the comparison of two reductions of norbomanone, this effect is more noticeable for a bulky hydride donor such as L-Selectride than for a small hydride donor such as NaBH4. As can be seen from Figure 10.10 (bottom), the additions of all hydride donors to the norbomanone derivative B (camphor) take place with the opposite diastereoselectivity. As indicated for each substrate, the common selectivity-determining factor remains the principle that the reaction with hydride takes place preferentially from the less hindered side of the molecule. 

The first group of H nucleophiles includes NaBH4 (which can be used in MeOH, EtOH, or HOAc), the considerably more reactive LiAlH4 (with which one works in THF or ether), and alcoholysis products of these reagents such as Red-Al [NaAlH2 (O—CH2—CH2—OMe)2] or the sterically very hindered LiAlH(0-fert-Bu)3. The last important hydride donor in this group is LiBH(.vec-Bu)3 (L-Selectride), a sterically very hindered derivative of the rarely used LiBH4. 

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