Palladium‐Catalyzed PIDA‐Mediated δ‐C(sp3)−H Acetoxylation of Amino Acid Derivatives: Overriding Competitive Intramolecular Amination

• Published in: Angewandte Chemie International Edition Vol. 61; no. 47; pp. e202209865 - n/a
• Main Authors: Martínez‐Mingo, Mario, García‐Viada, Andrés, Prendes, Daniel Sowa, Alonso, Inés, Rodríguez, Nuria, Arrayás, Ramón Gómez, Carretero, Juan C.
• Format: Journal Article
• Language: English
• Published: WEINHEIM Wiley 21.11.2022; Wiley Subscription Services, Inc; John Wiley and Sons Inc
• Edition: International ed. in English
• Subjects: Acetoxylation; Amination; Amino Acids; Carbonyl compounds; Carbonyls; Catalysis; Chemistry; Chemistry, Multidisciplinary; Communication; Communications; Directing Groups; Oxidants; Oxidizing agents; Palladium; Palladium - chemistry; Palladium Catalysis; Physical Sciences; Regioselectivity; Remote C−H Activation; Science & Technology; Selectivity; GAMMA; C(SP)-H BONDS; DESIGN; GAMMA-C(SP)-H BONDS; Remote C-H Activation; OXYGENATION; DELTA; Directing Groups; Palladium Catalysis; C-H ACTIVATION; Amino Acids; FUNCTIONALIZATION; Acetoxylation; C(SP)-H; Remote C−H Activation
• ISSN: 1433-7851; 1521-3773; 1521-3773
• DOI: 10.1002/anie.202209865

The selective δ‐C(sp3)−H acetoxylation of N‐(SO2Py)‐protected amino acid derivatives has been accomplished by using palladium‐catalysis and PhI(OAc)2 (PIDA) as both terminal oxidant and acetoxy source. The distinct structural and electronic features of the SO2Py compared to more traditional carbonyl‐based directing groups is essential to override the otherwise more favourable competitive intramolecular C−H amination. The δ‐site selectivity predominates over traditionally more favorable 5‐membered cyclopalladation at competitive γ‐CH2. Experimental and DFT mechanistic studies provide important insights about the mechanism and the underlying factors controlling the chemo‐ and regioselectivity. Selective δ‐C(sp3)−H acetoxylation of amino acid derivatives has been achieved by using palladium‐catalysis and PhI(OAc)2 (PIDA) as terminal oxidant and acetoxy source. The N‐SO2Py protecting/directing group plays a key role in enabling control of chemoselectivity (intermolecular C−O over intramolecular C−N bond formation) and regioselectivity (favoring δ‐CH3 over γ‐CH2 activation).