TY - JOUR
T1 - Stream-lined synthesis of 3-hydroxy-β-lactams
T2 - Norrish-Yang type II photocyclizations of β-ketoformamides
AU - Markley, Jana L.
AU - Morse, Tyler L.
AU - Rath, Nigam P.
AU - Wencewicz, Timothy A.
N1 - Funding Information:
The authors thank Dr. Jeff Kao and Dr. Manmilan Singh (WUSTL, Dept. of Chemistry) for assistance with 2D-NMR experiments and Dr. Brad Evans (Danforth Plant Science Center, St. Louis, MO) for acquisition of high-resolution MS spectra (NSF Grant No. DBI-0922879). The X-ray structure determinations were made possible by NSF Instrument Grant No. CHE-042097 (Dr. Nigam Rath, UMSL). In addition, the authors thank Washington University in St. Louis for their financial support of this work and our program.
Funding Information:
The authors thank Dr. Jeff Kao and Dr. Manmilan Singh (WUSTL, Dept. of Chemistry) for assistance with 2D-NMR experiments and Dr. Brad Evans (Danforth Plant Science Center, St. Louis, MO) for acquisition of high-resolution MS spectra ( NSF Grant No. DBI-0922879 ). The X-ray structure determinations were made possible by NSF Instrument Grant No. CHE-042097 (Dr. Nigam Rath, UMSL). In addition, the authors thank Washington University in St. Louis for their financial support of this work and our program.
Publisher Copyright:
© 2018 Elsevier Ltd
PY - 2018/5/31
Y1 - 2018/5/31
N2 - A photochemical approach to 3-phenyl-3-hydroxy-β-lactams (3-HβLs) is reported. Irradiation of aryl-β-ketoformamides with a UV light band centered at 300 nm provides the corresponding 3-aryl-3-HβLs with good conversion. The scope of the photocyclization is explored with an electronically diverse panel of substrates that provides mechanistic insight supporting a Norrish-Yang type II cyclization. A flexible synthetic route to phenyl-β-ketoformamides, followed by photoirradiation, allows for efficient incorporation of the β-lactam pharmacophore into aromatic organic scaffolds. Taken collectively, the improved and optimized synthetic route to provide both β-ketoformamides and 3-HβLs—in combination with the expanded analysis of substrate scope and limitations—reported herein will serve as a necessary reference for the direct, atom-economical, radical-mediated installation of 3-HβL scaffolds en route to the generation of other biologically active small molecules.
AB - A photochemical approach to 3-phenyl-3-hydroxy-β-lactams (3-HβLs) is reported. Irradiation of aryl-β-ketoformamides with a UV light band centered at 300 nm provides the corresponding 3-aryl-3-HβLs with good conversion. The scope of the photocyclization is explored with an electronically diverse panel of substrates that provides mechanistic insight supporting a Norrish-Yang type II cyclization. A flexible synthetic route to phenyl-β-ketoformamides, followed by photoirradiation, allows for efficient incorporation of the β-lactam pharmacophore into aromatic organic scaffolds. Taken collectively, the improved and optimized synthetic route to provide both β-ketoformamides and 3-HβLs—in combination with the expanded analysis of substrate scope and limitations—reported herein will serve as a necessary reference for the direct, atom-economical, radical-mediated installation of 3-HβL scaffolds en route to the generation of other biologically active small molecules.
KW - 3-Hydroxy-β-lactams
KW - Norrish-Yang cyclization
KW - Photocyclization
KW - Radical chemistry
KW - β-Ketoformamide formation
KW - β-Lactam synthesis
UR - http://www.scopus.com/inward/record.url?scp=85045708779&partnerID=8YFLogxK
U2 - 10.1016/j.tet.2018.04.040
DO - 10.1016/j.tet.2018.04.040
M3 - Article
AN - SCOPUS:85045708779
SN - 0040-4020
VL - 74
SP - 2743
EP - 2753
JO - Tetrahedron
JF - Tetrahedron
IS - 22
ER -