Enolates, aluminum condensation with aldehydes

Aldol reaction. The reagent (I) adds in a 1,4-fashion to an a,/J-unsaturated ketone lo give an aluminum enolate, which undergoes aldol condensation with an aldehyde. The adduct is converted into an a-substituted-a./l-unsaturated ketone on sulfoxide elimination.1... 

Aldol-Type Condensation. The aldol-type condensation of the enolate anion of sulfinylpropionate, which was prepared as usual with the base t-butylmagnesium bromide, with aldehydes afforded after desulfurization with Aluminum Amalgam the corresponding 3-hydroxy esters in high yield (90%) and, with aliphatic aldehydes, high diastereoselectivity (eq 3). The amount of asymmetric induction was determined by transformation of the 3-hydroxy esters to the corresponding isopropyl-substituted alcohols. 

An interesting metal effect was observed in the aldol condensations of the enolate derived from the iron acetyl complex (r)"-C HdFe(CO)(PPhd(COMe) with aldehydes [56,57]. Although the lithium enolate did not show any selectivity, the corresponding aluminum enolate by transmetalation with Et.AlCl exhibited exceptionally high diastereoselectivity (>99% de). The resultant P-hydroxy acyl complexes are transformed to P-hydroxy acids on decomplexation with Br.. 

Another variation of this classic reaction is called the aldol-transfer reaction, reported by Nevalainen. In the presence of a suitable catalyst, usually an aluminum compound, an aldol product reacts with an aldehyde, gen-erating a ketone and a new aldol. An example is the reaction of benzaldehyde with aldol 143 in the pres-ence of 5% of aluminum catalyst (144). In dichloromethane at ambient temperatures, a 62% yield of aldol 145 was obtained after a reaction time of 43 h. The other product of this reaction was acetone, which was readily removed. This transformation involves a retro-aldol reaction of 143 (see sec. 9.5.A.vi.) and the resul-tant enolate anion reacts with benzaldehyde. This reaction has been done with several aldehydes and 143 is particularly attractive (the aldol condensation product of acetone), because acetone is the second product. 

A key step in the synthesis of the spiroketal subunit is the convergent union of intermediates 8 and 9 through an Evans asymmetric aldol reaction (see Scheme 2). Coupling of aldehyde 9 with the boron enolate derived from imide 8 through an asymmetric aldol condensation is followed by transamination with an excess of aluminum amide reagent to afford intermediate 38 in an overall yield of 85 % (see Scheme 7). During the course of the asymmetric aldol condensation... 

Examples of aldol condensations involving chiral aldehydes have also been reported. Condensation of the aluminum enolate derived from (2) with Boc-L-prolinal has been shown to proceed in a highly stereoselective manner and the iron chirality overpowered the latent stereoselectivity inherent in Boc-L-prolinal. ... 

General Discussion. Aldol-type condensation of the magnesium enolate of (R)-(+)-phenyl (p-toluenesulfinyl)acetate, prepared with f-butylmagnesium bromide, with the aldehyde precursor of maytansine afforded, after desulfurization with Aluminum Amalgam, the desired 4,5-unsaturated 3-(5)-hydroxy ester in high yield and high diastereoselectivity (eq 3). ... 

Stevens and co-workers have also attempted to develop a fundamentally different approach to the tricyclic amino ketone 463 which is used in the Fischer cyclization approach to the Aspidosperma skeleton (240). Condensation of the aldehyde-ester 553 with protected keto amine 554 gave an imine (555) which, upon heating with ammonium chloride at 160°, afforded the 2-pyrroline ester 556 in 70% yield. Treatment with dry hydrochloric acid gas in ether was followed by acid hydrolysis of the ketal, and base-catalyzed cyclization produced a mixture of two enol ethers (557 and 558) the latter predominating. The major isomer was reduced with lithium aluminum hydride and the hydroxy enol ether dehydrated in hot... 

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