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Abstract Palladium(II)‐catalyzed C(alkenyl)−H alkenylation enabled by a transient directing group (TDG) strategy is described. The dual catalytic process takes advantage of reversible condensation between an alkenyl aldehyde substrate and an amino acid TDG to facilitate coordination of the metal catalyst and subsequent C(alkenyl)−H activation by a tailored carboxylate base. The resulting palladacycle then engages an acceptor alkene, furnishing a 1,3‐diene with high regio‐ andE/Z‐selectivity. The reaction enables the synthesis of enantioenriched atropoisomeric 2‐aryl‐substituted 1,3‐dienes, which have seldom been examined in previous literature. Catalytically relevant alkenyl palladacycles were synthesized and characterized by X‐ray crystallography, and the energy profiles of the C(alkenyl)−H activation step and the stereoinduction model were elucidated by density functional theory (DFT) calculations.
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Rational Development of Remote C−H Functionalization of Biphenyl: Experimental and Computational Studies
Abstract A simple and efficient nitrile‐directedmeta‐C−H olefination, acetoxylation, and iodination of biaryl compounds is reported. Compared to the previous approach of installing a complex U‐shaped template to achieve a molecular U‐turn and assemble the large‐sized cyclophane transition state for the remote C−H activation, a synthetically useful phenyl nitrile functional group could also direct remotemeta‐C−H activation. This reaction provides a useful method for the modification of biaryl compounds because the nitrile group can be readily converted to amines, acids, amides, or other heterocycles. Notably, the remotemeta‐selectivity of biphenylnitriles could not be expected from previous results with a macrocyclophane nitrile template. DFT computational studies show that a ligand‐containing Pd–Ag heterodimeric transition state (TS) favors the desired remotemeta‐selectivity. Control experiments demonstrate the directing effect of the nitrile group and exclude the possibility of non‐directedmeta‐C−H activation. Substituted 2‐pyridone ligands were found to be key in assisting the cleavage of themeta‐C−H bond in the concerted metalation–deprotonation (CMD) process.
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- Award ID(s):
- 1700982
- PAR ID:
- 10134238
- Publisher / Repository:
- Wiley Blackwell (John Wiley & Sons)
- Date Published:
- Journal Name:
- Angewandte Chemie International Edition
- Volume:
- 59
- Issue:
- 12
- ISSN:
- 1433-7851
- Page Range / eLocation ID:
- p. 4770-4777
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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