By Reduction of Carbonyl Compounds

Support-bound aldehydes or ketones can be reduced to alcohols under mild reaction conditions that are compatible with most supports and linkers. Typical reducing agents are sodium borohydride or diisobutylaluminum hydride, which can penetrate cross-linked polystyrene provided that a solvent with sufficient swelling ability is 

Polystyrene-bound carboxylic esters have been reduced with diisobutylaluminum hydride or lithium aluminum hydride. Use of the latter reagent can, however, lead to the formation of insoluble precipitates, which could readily cause problems if reactions are performed in fritted reactors. An alternative procedure for reducing carboxylic esters to alcohols involves saponification, followed by activation (e.g. as the mixed anhydride) and reduction with sodium borohydride (Entries 10 and 11, Table 

Care must be taken in the activation of carboxylic acids with alkyl chlorofor-mates, because the resulting anhydrides decompose at room temperature to yield carboxylic esters. 

Support-bound carbonyl compounds can be converted into alcohols by treatment with suitable carbon nucleophiles. Aldehydes react readily with ketones or other C,H-acidic compounds under acid- or base-catalysis to yield the products of aldol addition (Table 7.2). Some types of C,H-acidic compound, such as 1,3-dicarbonyl compounds, can give the products of aldol condensation directly (Section 5.2.2.2). 

Catalyzed aldol additions do not generally proceed with high diastereoselectivity at ambient temperature. Improved stereoselectivity can be achieved by using preformed, diastereomerically pure enolates at low temperatures (Entry 5, Table 7.2). This strategy enables the solid-phase preparation of stereochemically defined polyketides. On cross-linked polystyrene, the observed diastereoselectivity in the addition of boron enolates to aldehydes is the same as that in the homogeneous phase reaction [14,18]. 

---

Alcohols are generally prepared on insoluble supports by reduction of carbonyl compounds or by addition of carbon nucleophiles to carbonyl compounds, although other strategies have also been used (Figure 7.1). 

Table 7.1. Preparation of alcohols by reduction of carbonyl compounds.

Alcohols are easily accessible by reduction of carbonyl compounds, such as aldehydes, ketones or carboxylic acid derivatives. While aldehydes, ketones and esters have been frequently used in microwave-assisted reductions, there have been no reports about the use of microwave technology in the reduction of nitriles or amides. 

By Reduction of Carbonyl Compounds. Use of high (10 kbar) pressures has been shown to effect trialkylstannane reductions of ketones in the absence of radical initiators or Lewis acids.10 Zinc borohydride has been demonstrated to be a mild reducing agent for the conversion of benzenethiol esters into alcohols in good yield. Use of mixed solvents containing methanol has been found to confer some chemoselectivity upon reductions with lithium borohydride and permits enhanced rates of reduction of esters, lactones, and... 

If we are going to use enolate chemistry, we have to make the diols by reduction of carbonyl compounds. As both diols have a 1,3-relationship between the OH groups, the carbonyl precursors will be the very enolizable 1,3-dicarbonyl compounds, which can be alkylated and reduced. We have chosen arbitrarily to use ethyl esters here, so we should use ethoxide as the base in the alkylation step. 

Preparation by Reduction of Carbonyl Compounds.- Reductions of carbonyl compounds have been reported using diphenylstibine, anionic Group 6 transition-metal carbonyl hydrides (chromium and... 

Electrogenerated Reactive Species, Fig. 9 Intermediates produced by reduction of carbonyl compounds in aprotic media... 

---