TY - JOUR T1 - Palladium-Catalyzed C(sp[3])-H Arylation of Primary Amines Using a Catalytic Alkyl Acetal to Form a Transient Directing Group. AU - St John-Campbell,Sahra, AU - Ou,Alex K, AU - Bull,James A, Y1 - 2018/11/08/ PY - 2018/09/04/received PY - 2018/9/27/pubmed PY - 2018/9/27/medline PY - 2018/9/27/entrez KW - C−H functionalization KW - amines KW - homogeneous catalysis KW - palladium KW - reaction kinetics SP - 17838 EP - 17843 JF - Chemistry (Weinheim an der Bergstrasse, Germany) JO - Chemistry VL - 24 IS - 67 N2 - C-H Functionalization of amines is a prominent challenge due to the strong complexation of amines to transition metal catalysts, and therefore typically requires derivatization at nitrogen with a directing group. Transient directing groups (TDGs) permit C-H functionalization in a single operation, without needing these additional steps for directing group installation and removal. Here we report a palladium catalyzed γ-C-H arylation of amines using catalytic amounts of alkyl acetals as transient activators (e.g. commercially available (2,2-dimethoxyethoxy)benzene). This simple additive enables arylation of amines with a wide range of aryl iodides. Key structural features of the novel TDG are examined, demonstrating an important role for the masked carbonyl and ether functionalities. Detailed kinetic (RPKA) and mechanistic investigations determine the order in all reagents, and identify cyclopalladation as the turnover limiting step. Finally, the discovery of an unprecedented off-cycle free-amine directed ϵ-cyclopalladation of the arylation product is reported. SN - 1521-3765 UR - https://www.unboundmedicine.com/medline/citation/30255961/Palladium_Catalyzed_C_sp3__H_Arylation_of_Primary_Amines_Using_a_Catalytic_Alkyl_Acetal_to_Form_a_Transient_Directing_Group_ DB - PRIME DP - Unbound Medicine ER -