Open AccessTransient Directing Group Enabled Pd-Catalyzed γ-C(sp3)–H Oxygenation of Alkyl Amines
Author(s) -
YanQiao Chen,
Yongwei Wu,
Zhen Wang,
Jennifer X. Qiao,
JinQuan Yu
Publication year - 2020
Publication title -
acs catalysis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.898
H-Index - 198
ISSN - 2155-5435
DOI - 10.1021/acscatal.0c01310
Subject(s) - chemistry , amine gas treating , catalysis , electrophile , aryl , nucleophile , acetic acid , alkyl , organic chemistry , substituent , functional group , medicinal chemistry , combinatorial chemistry , polymer
We report a general protocol for γ-C(sp 3 )-H acyloxylation and alkoxylation of free amines using 2-hydroxynicotinaldehyde as the transient directing group. In the presence of an electrophilic fluorinating bystanding oxidant and acetic acid, a wide range of aliphatic amines could be oxygenated selectively at the γ-methyl positions. A vast variety of aryl, heteroaryl, and aliphatic acids could also be successfully coupled under this C-O bond formation reaction to afford amine containing esters. Switching the nucleophile from acids to alcohols enables alkoxylation of free amines. Importantly, natural products and drug molecules such as ibuprofen, isozepac, fenbufen, and lithocholic acid are all compatible coupling partners. Notably, synthesis of these mono-protected amino alcohols from free amino alcohols using conventional selective protection are not always feasible.