Organocatalytic Domino Oxa-Michael/1,6-Addition Reactions: Asymmetric Synthesis of Chromans Bearing Oxindole Scaffolds

Kun Zhao; Ying Zhi; Tao Shu; Arto Valkonen; Kari Rissanen; Dieter Enders

doi:10.1002/anie.201606947

Organocatalytic Domino Oxa-Michael/1,6-Addition Reactions: Asymmetric Synthesis of Chromans Bearing Oxindole Scaffolds

Angew Chem Int Ed Engl. 2016 Sep 19;55(39):12104-8. doi: 10.1002/anie.201606947. Epub 2016 Sep 7.

Authors

Kun Zhao¹, Ying Zhi¹, Tao Shu¹, Arto Valkonen², Kari Rissanen², Dieter Enders³

Affiliations

¹ Institute of Organic Chemistry, RWTH Aachen University, Landoltweg 1, 52074, Aachen, Germany.
² Department of Chemistry, Nanoscience Center, University of Jyvaskyla, 40014, JYU, Finland.
³ Institute of Organic Chemistry, RWTH Aachen University, Landoltweg 1, 52074, Aachen, Germany. enders@rwth-aachen.de.

PMID: 27600477
DOI: 10.1002/anie.201606947

Abstract

An asymmetric organocatalytic domino oxa-Michael/1,6-addition reaction of ortho-hydroxyphenyl-substituted para-quinone methides and isatin-derived enoates has been developed. In the presence of 5 mol % of a bifunctional thiourea organocatalyst, this scalable domino reaction affords 4-phenyl-substituted chromans bearing spiro-connected oxindole scaffolds and three adjacent stereogenic centers in good to excellent yields (up to 98 %) and with very high stereoselectivities (up to >20:1 d.r., >99 % ee).

Keywords: chromans; domino reactions; organocatalysis; oxa-Michael addition; para-quinone methides.

Publication types

Research Support, Non-U.S. Gov't

Grants and funding

320493/ERC_/European Research Council/International