Asymmetric Synthesis of Octahydroindoles via a Domino Robinson Annulation/5-Endo Intramolecular Aza-Michael Reaction.
A straightforward, two-step asymmetric synthesis of octahydroindoles has been developed on the basis of two complementary strategies: (i) an organocatalyzed Michael reaction followed by a tandem Robinson-aza-Michael double cyclization catalyzed by PS-BEMP, and (ii) a diastereoselective cyclization, which formally constitutes a remote 1,6 asymmetric induction mediated by PS-BEMP. This allowed the construction of complex octahydroindoles with up to four stereocenters, excellent enantioselectivities (up to 95% ee), and complete diastereoselective control in a single-pot operation. DFT calculations were performed to understand the origin of this effect.
Laboratori de Química Orgànica, Facultat de Farmàcia, IBUB, Universitat de Barcelona , Av Joan XXIII s/n, 08028 Barcelona, Spain.
Claudio
C
Parra
Laboratori de Química Orgànica, Facultat de Farmàcia, IBUB, Universitat de Barcelona , Av Joan XXIII s/n, 08028 Barcelona, Spain.
Caroline
C
Bosch
Departamento de Química Orgánica I, Universidad del País Vasco , Manuel Lardizábal 3, 20018 San Sebastián, Spain.
Enrique
E
Gómez-Bengoa
Laboratori de Química Orgànica, Facultat de Farmàcia, IBUB, Universitat de Barcelona , Av Joan XXIII s/n, 08028 Barcelona, Spain.
Josep
J
Bonjoch
Laboratori de Química Orgànica, Facultat de Farmàcia, IBUB, Universitat de Barcelona , Av Joan XXIII s/n, 08028 Barcelona, Spain.
Ben
B
Bradshaw