Aldehydes hydride donor additions

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... 

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... 

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... 

Finally, there are also some special NHC-mediated transformations that do not completely fit into the classification, such as triazolylidene-catalyzed hydroacylations (Chan and Scheldt 2006). Aldehydes can serve as hydride donors for activated ketones partly following a standard 1,2-addition of the NHC to the aldehyde, but instead of the usual carbonyl umpolung a hydride ( H-umpolung ) transfer is initiated. A related Cannizzaro-type transformation has been described for indazole-derived carbene catalysts (Schmidt et al. 2007). 

An additional complication in mechanistic interpretation is the fact that methoxide (reactions are often run in methanol) serves also as an effective hydride donor towards aldehydes and the derived formaldehyde may participate in a crossed Cannizzaro reaction. The conditions of the Cannizzaro reaction are fairly extreme (strong base, reasonably high temperatures) and complex mechanistic behavior is therefore not surprising. 

Chemists have found that if diisobutylaluminum hydride (DIBALH) is used as the hydride donor at a low temperature, the reaction can be stopped after the addition of one equivalent of hydride ion. This reagent, therefore, makes it possible to convert esters into aldehydes, which is initially surprising, since aldehydes are more reactive than esters toward hydride ion. 

This reaction of aromatic aldehydes, ArCHO, resembles the Cannizzaro reaction in that the initial attack [rapid and reversible—step (1)] is by an anion—this time eCN—on the carbonyl carbon atom of one molecule, the donor (125) but instead of hydride transfer (cf. Cannizzaro, p. 216) it is now carbanion addition by (127) to the carbonyl carbon atom of the second molecule of ArCHO, the acceptor (128), that occurs. This, in common with cyanohydrin formation (p. 212) was one of the earliest reactions to have its pathway established— correctly —in 1903. The rate law commonly observed is, as might be expected,... 

An additional result of our study focuses on the importance of the donor substituent on the chelating substrate. By comparison of the affinities of various iridiura(I) complexes for phosphi-no and arsino substituted aldehydes as outlined in Scheme 1, we were able to isolate the analytically pure acyl hydrides for three of the four permutations. 

Properly placed donor atoms in aldehyde ligands can stabilize the acyl metal hydrides that result from oxidative addition of aldehyde C—H bonds. In all reported examples, the donor atom (which can be nitrogen, oxygen or phosphorous) must be located so that a five-membered chelate is formed upon oxidative addition. Stabilization... 

Just as addition of a Grignard reagent to an aldehyde or ketone yields an alcohol, so does addition of hydride ion, H (Section 17.4). Although the details of carbonyl-group reductions arc complex, LiAll-14 and N aBH4 act as if they were donors of hydride ion in a nucleophilic addition reaction (Figure 19.7).. Addition of water or aqueous acid after the hydride addition step protonates the tetrahedral alkoxide intermediate and gives the alcohol product. 

The Cannizzaro reactionof non-enolizable aldehydes is another example of a hydride transfer reaction. It is carried out under alkaline conditions and involves not only the addition of a hydroxide ion to one aldehyde but the stabilization of the resultant acid as the anion (Scheme 3.41). Methanal (formaldehyde), which gives methanoic acid (formic acid), a relatively strong carboxylic acid, makes a good hydrogen donor in a cross-Cannizzaro reaction. 

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