Cocatalytic Activity of the Furfuryl and Oxanorbornane-Substituted Guanidines in the Aldol Reaction Catalyzed by (S)-Proline

TL;DR

This study explores how certain guanidinium salts affect the efficiency and selectivity of a chemical reaction catalyzed by (S)-proline.

Contribution

The paper introduces new guanidinium salts as cocatalysts with high enantioselectivity in aldol reactions.

Findings

Oxanorbornane units as flexible substituents negatively impact reaction selectivity.

Furfurylguanidinium and rigid polycyclic salts showed enantioselectivities above 90% and up to >99.5%.

Computed reaction barriers align qualitatively with experimental results for anti-enantiomers.

Abstract

This work investigated the cocatalytic activity of recently prepared guanidinium salts containing an oxanorbornane subunit in an (S)-proline-catalyzed aldol reaction. The activity was interpreted by the diastereoselectivity of the reaction (anti/syn ratio) and for the most interesting polycyclic guanidinium salt, the enantioselectivity of the reaction was determined. The results indicated a negative impact on the oxanorbornane unit if present as the flexible substituent. For most of the tested aldehydes, the best cocatalysts provided enantioselectivities above 90% and above 95% at room temperature and 0 °C, respectively, culminating in >99.5% for 4–chloro– and 2–nitrobenzaldehyde as the substrate. The barriers for forming four possible enantiomers were calculated and the results for two anti–enantiomers are qualitatively consistent with the experiment. Obtained results suggest that the representatives of furfurylguanidinium and rigid polycyclic oxanorbornane-substituted guanidinium salts are good lead structures for developing new cocatalysts by tuning the chemical space around the guanidine moiety.

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