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Base‐Dependent Stereodivergent Intramolecular Aza‐Michael Reaction: Asymmetric Synthesis of 1,3‐Disubstituted Isoindolines
Author(s) -
Fustero Santos,
Herrera Lidia,
Lázaro Ruben,
Rodríguez Elsa,
Maestro Miguel A.,
Mateu Natalia,
Barrio Pablo
Publication year - 2013
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.201301591
Subject(s) - intramolecular force , michael reaction , diastereomer , chemistry , nitrogen atom , base (topology) , stereochemistry , nucleophile , combinatorial chemistry , ring (chemistry) , organic chemistry , catalysis , mathematics , mathematical analysis
The nucleophilic addition (A N ) / intramolecular aza‐Michael reaction (IMAMR) process on Ellman’s tert ‐butylsulfinyl imines, bearing a Michael acceptor in the ortho position, is studied. This reaction affords 1,3‐disubstituted isoindolines with a wide range of substituents in good yields and diastereoselectivities. Interestingly, careful choice of the base for the aza‐Michael step allows either the cis or the trans diastereoisomers to be exclusively obtained. This stereodivergent cyclization has enabled the synthesis of C 2 ‐symmetric bisacetate‐substituted isoindolines. In addition, bisacetate isoindolines bearing two well‐differentiated ester moieties are also noteworthy because they may allow for the orthogonal synthesis of β,β′‐dipeptides using a single nitrogen atom as a linchpin.