Aldehydes hydride donors

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... 

Krische et al. demonstrated intramolecular reaction with Co(dpm)2 (5mol%) and PhSiH3 (120 mol %) as a hydride donor (Scheme 8) [14-16]. Addition of aldehyde-enone 17 to a solution of the Co catalyst and phenylsi-lane resulted in the formation of the corresponding aldol cyclization product... 

Molybdenum and tungsten carbonyl hydride complexes were shown (Eqs. (16), (17), (22), (23), (24) see Schemes 7.5 and 7.7) to function as hydride donors in the presence of acids. Tungsten dihydrides are capable of carrying out stoichiometric ionic hydrogenation of aldehydes and ketones (Eq. (28)). These stoichiometric reactions provided evidence that the proton and hydride transfer steps necessary for a catalytic cycle were viable, but closing of the cycle requires that the metal hydride bonds be regenerated from reaction with H2. 

Stoichiometric Ionic Hydrogenation of Ketones and Aldehydes using Metal Hydrides as Hydride Donors and Added Acids... 

Dihydropyrrole triflate 55, which we have encountered earlier in this chapter, undergoes a Pd-catalyzed carbonylation reaction to give ester 158 [53, 81]. A similar carbonylation sequence in the presence of the hydride donor n-BusSnH gives the corresponding aldehyde in 56% yield [81]. 

Hydride donor Iminium ion Acyl halide Aldehyde Ketone Ester Amide Carboxy- late salt... 

Selective reduction to aldehydes can also be achieved using /V-methoxy-iV-methyla-mides.49 Lithium aluminum hydride and diisobutylaluminum hydride have both been used as the hydride donor. The partial reduction is believed to be the result of the stability of the initial reduction product. The /V-mcthoxy substituent permits a chelated structure which is... 

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. 

Acylation of Hydride Donors Reduction of Carboxylic Acid Derivatives to Aldehydes... 

In Section 6.5 you learned that the acylations of hydride donors or of organometallic compounds, which give aldehydes or ketones, often are followed by an unavoidable second reaction the addition of the hydride or organometallic compound to the aldehyde or the ketone. In this chapter, we will study the intentional execution of such addition reactions. 

The addition of a hydride donor to an aldehyde or to a ketone gives an alcohol. This addition is therefore also a redox reaction, namely, the reduction of a carbonyl compound to an alcohol. Nevertheless, this type of reaction is discussed here and not in the redox chapter (Chapter 17). 

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). 

When the plane of the double bond of a carbonyl compound is flanked by diastereotopic halfspaces, a stereogenic addition of a hydride can take place diastereoselectively (cf. Section 3.4.1). In Section 10.3.1, we will investigate which diastereomer is preferentially produced in such additions to the C=0 double bond of cyclic ketones. In Sections 10.3.2 and 10.3.3, we will discuss which diastereomer is preferentially formed in stereogenic additions of hydride donors and acyclic chiral ketones or acyclic chiral aldehydes. 

The addition of a hydride donor to an a-chiral aldehyde with an O or an N atom in the a position or to an analogous ketone takes place through the so-called Felkin-Anh transition state provided that the heteroatom at C-a is not incorporated in a five-membered chelate ring together with the O atom of the carbonyl group. This transition state is also shown in Figure 10.16 (center Nu = H ), both as a Newman projection and in the sawhorse... 

Transfer of a hydride from the dianion to the second aldehyde molecule leads to the carboxylate anion and the conjugate base of the alcohol, which then obtains a proton from the solvent. Although the dianion is less stable than the initial anion, it is a stronger hydride donor because of its two negative charges. 

The SN reaction under consideration is not terminated until water, a dilute acid, or a dilute base is added to the crude reaction mixture. The tetrahedral intermediate B is then protonated to give the compound E. Through an El elimination it liberates the carbonyl compound C (cf. discussion of Figure 6.4). Fortunately, at this point in time no overreaction of this aldehyde with the nucleophile can take place because the nucleophile has been destroyed during the aqueous workup by protonation or hydrolysis. In Figure 6.32 this process for chemoselective acylation of hydride donors, organometallic compounds, and heteroatom-stabilized carbanions has been included as strategy 1. ... 

The addition of a hydride donor to an a-chiral aldehyde with an OR or NR2 substituent at C-a or to an analogous ketone takes place via the so-called Cram chelate... 

Stereogenic additions of hydride donors to achiral deuterated aldehydes R—C(=0)D or to achiral ketones R1R2C(=0) take place without stereocontrol using the reagents which you learned about in Section 8.3. Thus, racemic deuterated alcohols R—C(OH) D or racemic secondary alcohols R1R2C(OH)H are produced. The reason for this is... 

Sodium borohydride is one of the weakest hydride donors available. The feet that it can be used in water is evidence of this as more powerful hydride donors such as lithium aluminium hydride, LiAlI-fe, react violently with water. Sodium borohydride reacts with both aldehydes and ketones, though the reaction with ketones is slower for example, benzaldehyde is reduced about 400 times faster than acetophenone in isopropanol. 

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