Pd(II)-Catalyzed Enantioselective
γ‑C(sp3)–H Functionalizations of Free
Cyclopropylmethylamines
Posted on 2020-07-07 - 14:37
Prized
for their ability to reliably forge stereocenters with precise
regiocontrol from simple and abundant starting materials, substrate-directable
enantioselective reactions are widely used in modern organic synthesis.
As such, enantioselective C(sp3)–H functionalization
reactions directed by innate functional groups could provide new routes
to introduce molecular complexity within the inert hydrocarbon moiety,
but to date this approach has been met with little success. While
free primary aliphatic amines are common, versatile intermediates
in synthesis, they are traditionally unreactive in C(sp3)–H activation reactions. Herein we report the Pd-catalyzed
enantioselective C(sp3)–H functionalization of free
aliphatic amines (cyclopropylmethylamines) enabled by a chiral bidentate
thioether ligand. This ligand’s privileged bidentate coordination
mode and thioether motif favor the generation of the requisite mono(amine)-Pd(II)
intermediate, thus enabling the enantioselective C–H activation
of free amines. The resulting C–Pd(II) species could engage
in either Pd(II)/Pd(IV) or Pd(II)/Pd(0) catalytic cycles, enabling
access to a diverse range of products through (hetero)arylation, carbonylation,
and olefination reactions. Consequently, this versatile reactivity
offers medicinal chemists a general strategy to rapidly prepare and
functionalize biologically relevant amines.
CITE THIS COLLECTION
DataCite
3 Biotech
3D Printing in Medicine
3D Research
3D-Printed Materials and Systems
4OR
AAPG Bulletin
AAPS Open
AAPS PharmSciTech
Abhandlungen aus dem Mathematischen Seminar der Universität Hamburg
ABI Technik (German)
Academic Medicine
Academic Pediatrics
Academic Psychiatry
Academic Questions
Academy of Management Discoveries
Academy of Management Journal
Academy of Management Learning and Education
Academy of Management Perspectives
Academy of Management Proceedings
Academy of Management Review
Zhuang, Zhe; Yu, Jin-Quan (2020). Pd(II)-Catalyzed Enantioselective
γ‑C(sp3)–H Functionalizations of Free
Cyclopropylmethylamines. ACS Publications. Collection. https://doi.org/10.1021/jacs.0c04801
or
Select your citation style and then place your mouse over the citation text to select it.