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Abstract Ketone functionalization is a cornerstone of organic synthesis. Herein, we describe the development of an intermolecular C−H alkenylation of enamides with the feedstock chemical vinyl acetate to access diverse functionalized ketones. Enamides derived from various cyclic and acyclic ketones reacted efficiently, and a number of sensitive functional groups were tolerated. In this iridium‐catalyzed transformation, two structurally and electronically similar alkenes—enamide and vinyl acetate—underwent selective cross‐coupling through C−H activation. No reaction partner was used in large excess. The reaction is also pH‐ and redox‐neutral with HOAc as the only stoichiometric by‐product. Detailed experimental and computational studies revealed a reaction mechanism involving 1,2‐Ir‐C migratory insertion followed bysyn‐β‐acetoxy elimination, which is different from that of previous vinyl acetate mediated C−H activation reactions. Finally, the alkenylation product can serve as a versatile intermediate to deliver a variety of structurally modified ketones.
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Photochemical Decarbonylation of Oxetanone and Azetidinone: Spectroscopy, Computational Models, and Synthetic Applications**
Abstract Photoexcitation of cyclic ketones leads to the expulsion of carbon monoxide and a mixture of products derived from diradical intermediates. Here we show that synthetic utility of this process is improved if strained heterocyclic ketones are used. Photochemistry of 3‐oxetanone and N ‐Boc‐3‐azetidinone has not been previously described. Decarbonylation of these 4‐membered rings proceeds through a step‐wise Norrish type I cleavage of the C−C bond from the singlet excited state. Ylides derived from both compounds are high‐energy species that are kinetically stable long enough to undergo [3+2] cycloaddition with a variety of alkenes and produce substituted tetrahydrofurans and pyrrolidines. The reaction has a sufficiently wide scope to produce scaffolds that were either previously inaccessible or difficult to synthesize, thereby providing experimental access to new chemical space.
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- Award ID(s):
- 1956387
- PAR ID:
- 10443780
- Date Published:
- Journal Name:
- Angewandte Chemie International Edition
- Volume:
- 62
- Issue:
- 3
- ISSN:
- 1433-7851
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
-
Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1002/anie.202215856
