Salt, concentration, and temperature effects on an asparagine-based, aqueous Diels-Alder cycloaddition

Results are reported on the salt, concentration, and temperature effects in an aqueous, auxiliary-mediated asymmetric Diels-Alder cycloaddition. The auxiliaries were prepared under basic aqueous conditions from asparagine and trimethylacetaldehyde, and coupled to acryloyl chloride to generate dienophiles in one pot. Temperature and concentration modestly impacted cycloaddition stereochemistry. Experiments with a range of salts examined the speculation that complexation between the counterion of the auxiliary carboxylate and the dienophile carbonyl promotes the formation of the minor endo product, reducing cycloaddition diastereoselectivity for the endo products. The transformation was poorly selective for the carboxylic acid but gave moderate selectivities for several metallated carboxylates. The magnitude of the diastereoselectivity of the endo products was weakly dependent on carboxylate counterion and more strongly influenced by the basicity of the salt anion. Data presented suggest that Lewis acid catalysis reduces cycloaddition diastereoselectivity for the endo products.

Graphical Abstract