Catalysis

Enantioselective synthesis

Reactivity (psychology)

Methylene

Crystal structure

Stereochemistry

Physical chemistry

Medicinal chemistry

Alternative medicine

Combinatorial chemistry

Organic chemistry

Amine gas treating

Denticity

Surface modification

Regioselectivity

Medicine

Stereoselectivity

Chemistry

Selectivity

Isopropyl

Pyridine

Pathology

Chinese Journal of Chemistry

Improving the reactivity and selectivity is a long pursuing goal in C—H functionalization reactions. In line with this goal, a well‐designed bidentate 2‐(pyridine‐yl)isopropyl amine (PIP amine) directing group was developed by our group to achieve the activation of unbiased methylene C(sp 3 )–H activation, which also found its broad applications in C—H activation reactions catalyzed by base metals, such as Cu, Ni, Co and Fe, to form various C—C and C—X bonds. Moreover, PIP amine has also been applied in the strategic step toward the total synthesis of aeruginosin marine natural products. Its highly tunable structure has triggered the design of a series of chiral auxiliaries for diastereoselective C—H activation. More recently, Pd(II)‐catalyzed enantioselective functionalization of unbiased methylene C(sp 3 )–H bonds enabled by the cooperative effects between PIP amine and chiral ligands with axially chiral binaphthyl scaffold has also been realized. In this account, we briefly summaries the journey of developing PIP amine for C—H activation, from controlling the reactivity and regioselectivity to stereoselectivity.

From Reactivity and Regioselectivity to Stereoselectivity: An Odyssey of Designing PIP Amine and Related Directing Groups for C—H Activation