Directed Metalation-Suzuki-Miyaura Cross-Coupling Strategies: Regioselective Synthesis of Hydroxylated 1-Methyl-phenanthrenes

Kåre B Jørgensen; Toni Rantanen; Thilo Dörfler; Victor Snieckus

doi:10.1021/acs.joc.5b01300

Directed Metalation-Suzuki-Miyaura Cross-Coupling Strategies: Regioselective Synthesis of Hydroxylated 1-Methyl-phenanthrenes

J Org Chem. 2015 Oct 2;80(19):9410-24. doi: 10.1021/acs.joc.5b01300. Epub 2015 Sep 30.

Authors

Kåre B Jørgensen¹, Toni Rantanen², Thilo Dörfler², Victor Snieckus²

Affiliations

¹ Faculty of Science and Technology, University of Stavanger , N-4036 Stavanger, Norway.
² Snieckus Innovations and Department of Chemistry, Queen's University , Kingston, ON, Canada K7L 3N6.

PMID: 26301487
DOI: 10.1021/acs.joc.5b01300

Abstract

A general, efficient, and regioselective synthesis of a series of hydroxylated 1-methylphenanthrenes 9 by a combined directed ortho metalation (DoM)-Suzuki-Miyaura cross-coupling-directed remote metalation (DreM) sequence is reported. Diversity to this methodology was achieved by a regioselective DoM rather than DreM reaction, affording more highly substituted phenanthrols ( Table 2 ). Application of the turbo-Grignard reagent (i-PrMgCl·LiCl) in the Ni-catalyzed Corriu-Kumada reaction gave efficient decarbamoylation ( Tables 3 and 4 ). Additional features are the TMS protecting group and halo-induced ipso-desilylation tactics applied to the regioselective synthesis of phenanthrenes ( Scheme 2 ).