Synergistic Peptide and Gold Catalysis: Enantioselective Addition of Branched Aldehydes to Allenamides |
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Authors: | Dr Leo D M Nicholls Prof Helma Wennemers |
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Institution: | Laboratory of Organic Chemistry ETH Zürich, Vladimir-Prelog-Weg 3, 8093 Zürich, Switzerland |
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Abstract: | The combination of a peptide catalyst and a gold catalyst is presented for enantioselective addition reactions between branched aldehydes and allenamides. The two catalysts act in concert to provide γ,δ-enamide aldehydes bearing a fully substituted, benzylic stereogenic center – a structural motif common in many natural products and therapeutically active compounds – with good yields and enantioselectivities. The reaction tolerates a variety of alkyl and alkoxy substituted aldehydes and the products can be elaborated into several chiral building blocks bearing either 1,4- or 1,5- functional group relationships. Mechanistic studies showed that the conformational features of the peptide are important for both the catalytic efficiency and stereochemistry, while a balance of acid/base additives is key for ensuring formation of the desired product over undesired side reactions. |
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Keywords: | asymmetric catalysis enamides fully substituted stereogenic centers gold peptides |
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