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α‐Branched Ketone Dienolates: Base‐Catalysed Generation and Regio‐ and Enantioselective Addition Reactions
Author(s) -
Urruzuno Iñaki,
Mugica Odei,
Zanella Giovanna,
Vera Silvia,
GómezBengoa Enrique,
Oiarbide Mikel,
Palomo Claudio
Publication year - 2019
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201901694
Subject(s) - ketone , electrophile , chemistry , bifunctional , reactivity (psychology) , enantioselective synthesis , addition reaction , organic chemistry , squaramide , adduct , amine gas treating , stereoselectivity , organocatalysis , catalysis , medicinal chemistry , medicine , alternative medicine , pathology
In this study, the unique capacity of bifunctional Brønsted bases to generate α‐branched ketone dienolates and control both site‐ and stereoselectivity of their addition reactions to representative classes of carbon electrophiles (i.e., vinyl sulfones, nitroolefins, formaldehyde) is documented. We demonstrate that by using selected chiral tertiary amine/squaramide catalysts, the reactions of β,γ‐unsaturated cycloalkanones proceed through the dienolate Cα almost exclusively and provide all‐carbon quaternary cyclic ketone adducts in good yields with very high enantioselectivities. A minor amount (<5 %) of γ‐addition is observed when nitroolefins are used as electrophiles. The parent acyclic ketone dienolates proved to be less reactive under these conditions, and thus still constitute a challenging class of substrates. Quantum chemical calculations correctly predict these differences in reactivity and explain the observed site‐specificity and enantioselectivity.