KETONES, ALDOLIZATION

The intramolecular reductive aldol reaction of keto-enones was successfully conducted under conditions similar to those described above, employing a cationic Rh complex and PI13P (Scheme 20) [34]. The keto-enone 63 was cyclized in the presence of added K2CO3 to give the ketone-aldol 64 in 72% yield with exclusive ds-selectivity. Dione-enone derivatives, for example 68 and 70, were efficiently cyclized to furnish bicyclic aldol products 69 and 71, respectively, wherein three stereogenic centers of the bicyclic product form stereoselectivity through the intermediacy of a Rh-enolate. 

In spite of the attractiveness of the aldol manifold, there are several problems that need to be addressed in order to render the process catalytic and effective. The first problem is a thermodynamic one. Most aldol reactions are reversible. Furthermore, the equilibrium is also just barely on the side of the prodncts in the case of simple aldehyde-ketone aldol reactions [79, 80]. In the case of ketone-ketone aldol reactions, the equilibrinm generally lies on the side of starting materials (Scheme 14). Overall, this means that relatively high concentrations of starting materials should be used, and very often one of the components mnst be used in excess. 

Ketone-Aldehyde and Ketone-Ketone Aldol Processes... 

This chapter deals mainly with the 1,3-dipolar cycloaddition reactions of three 1,3-dipoles azomethine ylides, nitrile oxides, and nitrones. These three have been relatively well investigated, and examples of external reagent-mediated stereocontrolled cycloadditions of other 1,3-dipoles are quite limited. Both nitrile oxides and nitrones are 1,3-dipoles whose cycloaddition reactions with alkene dipolarophiles produce 2-isoxazolines and isoxazolidines, their dihydro derivatives. These two heterocycles have long been used as intermediates in a variety of synthetic applications because their rich functionality. When subjected to reductive cleavage of the N—O bonds of these heterocycles, for example, important building blocks such as p-hydroxy ketones (aldols), a,p-unsaturated ketones, y-amino alcohols, and so on are produced (7-12). Stereocontrolled and/or enantiocontrolled cycloadditions of nitrones are the most widely developed (6,13). Examples of enantioselective Lewis acid catalyzed 1,3-dipolar cycloadditions are summarized by J0rgensen in Chapter 12 of this book, and will not be discussed further here. 

Dipolar cycloaddition reactions between nitrile oxides and aUcenes produce 2-isoxazolines. Through reductive cleavage of the N—O bond of the 2-isoxazohnes, the resulting heterocycles can be readily transformed into a variety of important synthetic intermediates such as p-hydroxy ketones (aldols), p-hydroxy esters, a,p-unsaturated carbonyl compounds, y-amino alcohols, imino ketones and so forth (7-12). 

Dihydroisoxazoles 1 are key intermediates24 in the preparation of a,/ -enones18,1,3-amino-alcohols17,25 and /8-hydroxy ketones (aldol adducts)12-27,... 

Reaction between alkyl or acyl hal- ketones (aldol)... 

An important variation on the Claisen condensation is to use a ketone as the anionic reagent. This often works well because ketones usually are more acidic than simple esters and the base-induced self-condensation of ketones (aldol addition) is thermodynamically unfavorable (Section 17-3C). A typical example is the condensation of cyclohexanone with diethyl ethanedioate (diethyl oxalate) ... 

Keywords aldehyde, ketone, Aldol condensation, chalcone... 

A systematic study of methyl ketone aldol additions with a-alkoxy and o ,/5-bisalkoxy aldehydes has been undertaken, under non-chelating conditions.130 With a single a-alkoxy stereocentre, diastereoselectivity generally follows Cornforth/polar Felkin-Anh models. With an additional /5-alkoxy stereocentre, 7r-facial selectivity is dramatically dependent on the relative configuration at a- and /3-centres if they are anti, high de results, but not if they are syn. A model for such acyclic stereocontrol is proposed in which the /5-alkoxy substituent determines the position in space of the a-alkoxy relative to the carbonyl, thus determining the n-facial selectivity. 

Boron-mediated ketone-ketone aldol reactions have been described, using boron enolates formed with dicyclohexylboron chloride and triethylamine.124 Following addition of the acceptor ketone to form a boron aldolate, oxidation with peroxide yields the aldol product. 

Aldol condensations produce /3-hydroxy aldehydes and ketones (aldols) and a,/3-unsaturated aldehydes and ketones. If a target molecule has one of these functionalities, an aldol should be considered. To determine the starting materials, divide the structure at the a, (3 bond. In the case of the dehydrated product, the a,(3 bond is the double bond. The following analyses show the division of some aldol products into their starting materials. 

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