Y-Hydroxycarbonyl compounds

The reductive coupling of a,p-unsaturated carbonyl compounds can lead to three types of dimerization products pinacols (1,2-coupling), 1,6-diones (1,4-coupling), and y-hydroxycarbonyl compounds (mixed coupling). These couplings are further complicated by the ability of the initially formed dimerization products to undergo further reactions and complex product mixtures can sometimes result. ... 

When as the nucleophilic component a-carbanion stabilized by a carbonyl group or masked as enamine reacts, the reaction products are 1,4- or Y-hydroxycarbonyl compounds. The next example illustrates the utility of such retrosynthetic considerations. 

Although initially developed as a rather exotic reaction, the intramolecular transace-talization reaction can also be a very useful tool in asymmetric synthesis of important chiral compounds and natural products. Both, starting materials and products of the intramolecular transacetalization reaction are protected y-hydroxycarbonyl compounds, orhomoaldols (Scheme 13). Homoaldols are versatile motifs in organic synthesis that can be easily transformed into a vast array of important chiral compounds. However, due to the problematic homoaldol disconnection, these compounds are not readily available in a catalytic asymmetric fashion. 

There is one type of carbonyl compound that cannot be converted into 0,0-acetals of the type so far presented by treatment with alcohols and acid y- or 5-hydroxycarbonyl compounds. As you know from Figure 9.4, these compounds usually exist as lactols. In an acidic solution their OH group is exchanged very rapidly by an OR group via the SN1 mechanism of Figure 9.12. This produces an 0,0-acetal, which is derived from two different alcohols, a so-called mixed acetal. However, there is no further reaction delivering an open-chain nonmixed O, O-acetal of the y- or 5-hydroxycarbonyl compound. This is because such a reaction would be accompanied by an unfavourable entropy loss A single molecule would have been produced from two. 

Many of the chiral molecules containing amide groups were bonded to a solid support for the preparation of CSPs [16-19]. The racemic compounds resolved on these CSPs include a-hydroxycarbonyls, /i-hydroxycarbonyls, amino acids, amino alcohols, amine, and derivatized and underivatized diols. The preliminary chiral diamide phase [(/V-foriuyl-L-valyl)aminopropyl)silica gel] has sufficient separability for racemic /Y-acylatcd a-amino acid esters but not in other types of enantiomer [16]. Most of the eluents used with these CSPs are of normal phase mode, including w-hcxanc, 2-propanol, chlorinated organic solvents, and acetonitrile. 

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