Palladium-catalyzed C(sp(3))-H Arylation of N-Boc benzylalkylamines via a deprotonative cross-coupling process

Nusrah Hussain; Byeong-Seon Kim; Patrick J Walsh

doi:10.1002/chem.201502017

Palladium-catalyzed C(sp(3))-H Arylation of N-Boc benzylalkylamines via a deprotonative cross-coupling process

Chemistry. 2015 Jul 27;21(31):11010-3. doi: 10.1002/chem.201502017. Epub 2015 Jun 30.

Authors

Nusrah Hussain¹, Byeong-Seon Kim¹, Patrick J Walsh²

Affiliations

¹ Department of Chemistry, University of Pennsylvania, 231 S, 34th St. Philadelphia, PA 19104 (USA) http://titanium.chem.upenn.edu/walsh/index.html.
² Department of Chemistry, University of Pennsylvania, 231 S, 34th St. Philadelphia, PA 19104 (USA) http://titanium.chem.upenn.edu/walsh/index.html. pwalsh@sas.upenn.edu.

Abstract

Diarylmethylamines are key intermediates and products in the pharmaceutical industry. Herein we disclose a novel method toward the synthesis of these important compounds via CH functionalization. Presented is a reversible deprotonation of N-Boc benzylalkylamines at the benzylic CH with in situ arylation by a NiXantPhos-based palladium catalyst (50-93 % yield, 29 examples). The method is also successful with N-Boc-tetrahydroisoquinolines. The advantages of this method are it avoids strong bases, low temperatures, and the need to transmetallate to main group metals for the coupling.

Keywords: CH functionalization; NiXantPhos ligand; cross-coupling; diarylmethylamines; pallladium.

Publication types

Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Alkylation
Benzene Derivatives / chemistry*
Catalysis
Hydrocarbons, Aromatic / chemistry
Methylamines / chemistry*
Palladium / chemistry*
Protons
Stereoisomerism

Substances

Benzene Derivatives
Hydrocarbons, Aromatic
Methylamines
Protons
Palladium
methylamine

Abstract

Publication types

MeSH terms

Substances

Grants and funding