title: Base-dependent stereodivergent intramolecular aza-Michael reaction: asymmetric synthesis of 1,3-disubstituted isoindolines.
abstract: 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 C2-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.
authors.affiliation: Departamento de Química Orgánica, Universidad de Valencia, 46100 Burjassot, Valencia, Spain. santos.fustero@uv.es
authors.forename: Santos
authors.initials: S
authors.lastname: Fustero
authors.forename: Lidia
authors.initials: L
authors.lastname: Herrera
authors.forename: Ruben
authors.initials: R
authors.lastname: Lázaro
authors.forename: Elsa
authors.initials: E
authors.lastname: Rodríguez
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Maestro
authors.forename: Natalia
authors.initials: N
authors.lastname: Mateu
authors.forename: Pablo
authors.initials: P
authors.lastname: Barrio
keywords: asymmetric synthesis; aza-Michael addition; chiral auxiliaries; cyclization; heterocycles