Enantioselective trihalohydroxyalkylation of activated phenols
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| Year of publication | 2023 |
| Type | Appeared in Conference without Proceedings |
| MU Faculty or unit | |
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| Description | At the onset of our work, the asymmetric trihalohydroxyalkylation of activated phenols has only been described on a few substrates using a stoichiometric amount of the chiral Lewis acid. To identify a competent organocatalyst for this Friedel–Crafts reaction, an extensive screening comprising 41 organocatalysts was performed, and the 3,5-dinitrobenzoyl derivative of 9-amino-epi-cinchonidine was identified as a lead catalyst candidate. By employing just 10–20 mol% of the chiral organocatalyst, our process offered a reasonably general scope regarding both the nucleophilic and electrophilic reaction partners. About 30 enantioenriched products were isolated in fair yields and good to excellent enantioselectivities. Moreover, several stereoselective downstream transformations of the chiral adducts were discovered, which opened up a chemical space for their possible applications in organic synthesis. Retro-aldol cleavage and dehydration, together with the gaseous or low-boiling nature of trihaloacetaldehydes, represented just a fraction of the challenges we faced to achieve high enantioselectivity. |
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