The origin of stereoselectivity in cycloaddition reactions promoted by stereoisomers of 8-phenylmenthyl glyoxylate oxime

A structural study of three synthesized stereoisomeric oximes, (−)-8-phenylmenthyl glyoxylate oxime (8-PMGO), (+)-8-phenylneomenthyl glyoxylate oxime (8-PnMGO), and (−)-8-phenylisoneomenthyl glyoxylate oxime (8-PinMGO), was performed by means of variable temperature 1H NMR spectroscopy, X-ray crystallography, and ab initio calculations. It was found that in 8-PMGO a conformation where the phenyl and oxime moieties are stacked is significantly favored, whereas in the other stereoisomers this preference was not so evident. The conformational differences found between the isomers were used to rationalize the outcome of the reaction (simultaneous 1,3-cycloaddition and aza-Diels–Alder reaction) between the referred oximes and cyclopentadiene, in which the stereoselectivity was evaluated and found to be nicely reproduced by a simple conformational analysis. The global results indicate that the stereoselectivity of the studied oximes, a bit higher for 8-PMGO, originates from their particular conformational distribution, in which the phenyl∙oxime aromatic interaction plays a decisive role.

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