TY - JOUR
T1 - Aminoalkylation of Alkenes Enabled by Triple Radical Sorting
AU - Lyon, William L.
AU - Wang, Johnny Z.
AU - Alcázar, Jesús
AU - MacMillan, David W.C.
N1 - Publisher Copyright:
© 2025 American Chemical Society.
PY - 2025/1/22
Y1 - 2025/1/22
N2 - The direct synthesis of C(sp3)-rich architectures is a driving force for innovation in synthetic organic chemistry. Such scaffolds impart beneficial properties onto drug molecules that correlate with greater clinical success. Consequently, there is a strong impetus to develop new methods by which to access sp3-rich molecules from commercial feedstocks, such as alkenes. Herein, we report a three-component aminoalkylation reaction that utilizes the principles of triple radical sorting to regioselectively add N-centered and C-centered radicals across alkenes. This process relies upon photoredox catalysis to transform alkyl bromides and reductively activated N-centered radical precursors into high-energy radical species in a redox-neutral fashion. A broad scope of coupling partners is demonstrated, with multiple synthetic applications, including facile syntheses of pharmacophoric substituted N-heterocycles.
AB - The direct synthesis of C(sp3)-rich architectures is a driving force for innovation in synthetic organic chemistry. Such scaffolds impart beneficial properties onto drug molecules that correlate with greater clinical success. Consequently, there is a strong impetus to develop new methods by which to access sp3-rich molecules from commercial feedstocks, such as alkenes. Herein, we report a three-component aminoalkylation reaction that utilizes the principles of triple radical sorting to regioselectively add N-centered and C-centered radicals across alkenes. This process relies upon photoredox catalysis to transform alkyl bromides and reductively activated N-centered radical precursors into high-energy radical species in a redox-neutral fashion. A broad scope of coupling partners is demonstrated, with multiple synthetic applications, including facile syntheses of pharmacophoric substituted N-heterocycles.
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U2 - 10.1021/jacs.4c14965
DO - 10.1021/jacs.4c14965
M3 - Article
C2 - 39786358
AN - SCOPUS:85214572128
SN - 0002-7863
VL - 147
SP - 2296
EP - 2302
JO - Journal of the American Chemical Society
JF - Journal of the American Chemical Society
IS - 3
ER -