title: Palladium-catalyzed C(sp(3))-H Arylation of N-Boc benzylalkylamines via a deprotonative cross-coupling process.
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.
authors.affiliation: Department of Chemistry, University of Pennsylvania, 231 S, 34th St. Philadelphia, PA 19104 (USA) http://titanium.chem.upenn.edu/walsh/index.html.
authors.forename: Nusrah
authors.initials: N
authors.lastname: Hussain
authors.affiliation: Department of Chemistry, University of Pennsylvania, 231 S, 34th St. Philadelphia, PA 19104 (USA) http://titanium.chem.upenn.edu/walsh/index.html.
authors.forename: Byeong-Seon
authors.initials: BS
authors.lastname: Kim
authors.affiliation: 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.
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Walsh
mesh_terms: D000478:Alkylation; D001555:Benzene Derivatives / Q000737:chemistry*; D002384:Catalysis; D006841:Hydrocarbons, Aromatic / Q000737:chemistry; D008744:Methylamines / Q000737:chemistry*; D010165:Palladium / Q000737:chemistry*; D011522:Protons; D013237:Stereoisomerism
chemical_list: D001555:Benzene Derivatives; D006841:Hydrocarbons, Aromatic; D008744:Methylamines; D011522:Protons; D010165:Palladium; C027451:methylamine
keywords: CH functionalization; NiXantPhos ligand; cross-coupling; diarylmethylamines; pallladium