Chemoselectivity crossed aldol condensations

Chemoselective crossed aldol condensations between two different C,H-acidic aldehydes are impossible. There is only a single exception, and that is the intramolecular aldol condensation of an unsymmetrical dialdehyde. 

Crossed aldol condensations occur with chemoselectivity only if some of the foregoing options cannot be realized. The following possibilities exist. 

Crossed aldol condensations between benzaldehyde or cinnamic aldehyde or their derivatives ketones pose no chemoselectivity problems. The least sterically hindered ketone, acetone, may condense with benzaldehyde, cinnamic aldehyde, and their derivatives with both enolizable positions if an excess of the aldehyde is employed. 

Crossed aldol condensations between aliphatic aldehydes on the one hand and benzaldehyde or cinnamic aldehyde or their derivatives on the other also are possible. The reaction components can even be mixed together. The aldol adducts are formed without chemoselectivity, as a mixture of isomers, but their formations are reversible. The Elcb elimination to an a,/3-unsaturated carbonyl compound is fast only if the newly created C=C double bond is conjugated to an aromatic system or to another C=C double bond already present in the substrate. This effect is due to product-development control. All the starting materials thus react in this way via the most reactive aldol adduct. 

We find that we need a crossed aldol condensation between two ketones so tve chemoselectivity. We also need to make one enol(ate) from an unsymmetrical ketone so v. r regioselectivity too. The obvious solutions are a lithium enolate, a silyl enol ether, or a come with an extra ester group. 

The aldol condensation reaction has been extensively employed in organic chemistry toward the formation of carbon-carbon bonds. Early work by Leznoff and Wong demonstrated the ability to chemoselectively differentiate the carbonyl groups in dialdehydes through selective protection via immobilization on a solid support. In addition, given the presence of an immobilized aldehyde 136, it was feasible to conduct crossed aldol reactions toward 137 and 138 in high yields (96-100%) without the presence of undesired side products (Scheme 6.31). 

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