Aluminum oxide aldol reactions

Aluminum oxide has been one of the most frequently used reagents for self-condensation of ketones and aldehydes. However applications of aluminum-mediated aldol reactions to cross-coupling have appeared only recently in the literature. Aluminum reagents, in common with other Lewis acids, form aldol product chelates so that unwanted side reactions such as dehydration or secondary condensation may be avoided. ... 

Homologation of ECHO to a-bromo-a, -enones.4 The initial steps of this homologation involve addition of dibromomethyllithium (1) to an aldehyde followed by oxidation of the adduct to a dibromomethyl ketone (2). The aluminum enolate of 2 undergoes an aldol reaction to provide an a-bromo-p-hydroxy ketone... 

When aldehydes, with or without a hydrogen, are treated with aluminum ethoxide, one molecule is oxidized and another reduced, as in 9-69, but here they are found as the ester. The process is called the Tishchenko reaction. Crossed Tishchenko reactions are also possible. With more strongly basic alkoxides, such as magnesium or sodium alkoxides, aldehydes with an a hydrogen give the aldol reaction. Like 9-69, this reaction has a mechanism that involves hydride transfer.751 The Tishchenko reaction can also be catalyzed752 by ruthenium complexes.753 by boric acid,754 and, for aromatic aldehydes, by disodium tetracarbonylferrate Na2Fe(CO)4,755 OS I, 104. 

Another common trapping method is an intramolecular aldol reaction of the initially formed anion, as shown in equation (91) and Schemes 53 and 54.% In the first case, an aldol-like trapping of the iminium salt produced (411 equation 91 ).96b The initial heteronucleophile in the other two cases is ultimately lost from the product by oxidation and elimination, so that the overall process is C—C bond formation at the a-center of an enone. Thus, treatment of the formyl enone (412 Scheme 53) with an aluminum thiolate afforded in 60% yield the trapped product (413) which could be oxidized and eliminated to give (414).96c Addition of the corresponding aluminate species to the ketoacrylate (415 Scheme 54) produced only one diastereomer of the aldol product (416) which was converted into the alkene (417) in excellent yield.96 1... 

The reduction of 569e with lithium aluminum hydride followed by monoprotection with er -butyldimethylsilyl chloride and Dess-Martin oxidation of the free hydroxyl group to an aldehyde affords 610. An aldol reaction of 610 with ( S)-(y-alkoxyallyl)stannane (611) in the presence of boron trifluoride etherate provides exculsively, in 80% yield, the alcohol 612. Ozonolysis of the olefin followed by sodium borohydride reduction affords diol 613, which is converted to acetonide 614 (Scheme 135). Interestingly, alcohol 612, the double bond of which is susceptible to stereocontrolled introduction of hydroxyl groups, could lead to o)-deoxy sugars [197]. 

More traditional carbon nucleophiles can also be used for an alkylative ring-opening strategy, as exemplified by the titanium tetrachloride promoted reaction of trimethylsilyl enol ethers (82) with ethylene oxide, a protocol which provides aldol products (84) in moderate to good yields <00TL763>. While typical lithium enolates of esters and ketones do not react directly with epoxides, aluminum ester enolates (e.g., 86) can be used quite effectively. This methodology is the subject of a recent review <00T1149>. 

Vicinal effects can also play a part in the course of the reaction utilizing Oppenauer conditions. 1,3-Diols or / -amino alcohols may not react, presumably on account of formation of an aluminum complex.5 5 46b> If oxidation were to take place it would probably be followed by dehydration to give an unsaturated ketone. Retro-aldol cleavage has been found to occur with a 17,21-dihydroxy steroid.32 The 11 -hydroxyl group which is generally inert to Oppenauer oxidation will react if a hydroxyl group is present on the... 

The reduction of aldols and ketols from the aldol condensation (method 102) is often a convenient route to branched 1,3-dio/s. Catalytic hydrogenation over platinum oxide, nickel-on-kieselguhr, and copper-chromium oxide has been used. Other procedures include electrolytic reduction and reduction by aluminum amalgam. 1,3-Diols may also be prepared by catalytic reduction of 1,3-diketones. Cleavage of the carbon-to-carbon and carbon-to-oxygen bonds accompanies this conversion. The effect of structure on the course of the reaction has been studied. ... 

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