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syn ‐Selective Michael Reaction of α‐Branched Aryl Acetaldehydes with Nitroolefins Promoted by Squaric Amino Acid Derived Bifunctional Brønsted Bases
Author(s) -
GarcíaUrricelqui Ane,
Cózar Abel,
Campano Teresa E.,
Mielgo Antonia,
Palomo Claudio
Publication year - 2021
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.202100355
Subject(s) - chemistry , michael reaction , aryl , bifunctional , organic chemistry , squaric acid , catalysis , squaramide , medicinal chemistry , intramolecular force , transition state , organocatalysis , cinchona alkaloids , alkyl , enantioselective synthesis
Here we describe a direct access to 2,2,3‐trisubstituted syn γ‐nitroaldehydes by addition of α‐branched aryl acetaldehydes to nitroolefins promoted by a cinchona based squaric acid‐derived amino acid peptide. Different α‐methyl arylacetaldehydes react with β‐aromatic and β‐alkyl nitroolefins to afford the Michael adducts in high enantioselectivity and syn ‐selectivity. NMR experiments and DFT calculations predict the reaction to occur through the intermediacy of E ‐enolate. The interaction between the substrates and the catalyst follows Pápai's model, wherein an intramolecular H‐bond interaction in the catalyst between the NH group of one of the tert ‐leucines and the squaramide oxygen seems to be key for discrimination of the corresponding reaction transition states.