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1. Asymmetric intermolecular allylic C–H amination of alkenes with aliphatic amines

   https://doi.org/10.1126/science.abq1274  

   Pak Shing Cheung, Kelvin ; Fang, Jian ; Mukherjee, Kallol ; Mihranyan, Andranik ; Gevorgyan, Vladimir ( December 2022 , Science)

   Aliphatic allylic amines are found in a great variety of complex and biorelevant molecules. The direct allylic C–H amination of alkenes serves as the most straightforward method toward these motifs. However, use of widely available internal alkenes with aliphatic amines in this transformation remains a synthetic challenge. In particular, palladium catalysis faces the twin challenges of inefficient coordination of Pd(II) to internal alkenes but excessively tight and therefore inhibitory coordination of Pd(II) by basic aliphatic amines. We report a general solution to these problems. The developed protocol, in contrast to a classical Pd(II/0) scenario, operates through a blue light–induced Pd(0/I/II) manifold with mild aryl bromide oxidant. This open-shell approach also enables enantio- and diastereoselective allylic C–H amination.

    

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2. Unconventional mechanism and selectivity of the Pd-catalyzed C–H bond lactonization in aromatic carboxylic acid

   https://doi.org/10.1038/s41467-022-27986-6  

   Xu, Li-Ping ; Qian, Shaoqun ; Zhuang, Zhe ; Yu, Jin-Quan ; Musaev, Djamaladdin G. ( January 2022 , Nature Communications)

   The search for more effective and highly selective C–H bond oxidation of accessible hydrocarbons and biomolecules is a greatly attractive research mission. The elucidating of mechanism and controlling factors will, undoubtedly, help to broaden scope of these synthetic protocols, and enable discovery of more efficient, environmentally benign, and highly practical new C–H oxidation reactions. Here, we reveal the stepwise intramolecular S_N2 nucleophilic substitution mechanism with the rate-limiting C–O bond formation step for the Pd(II)-catalyzed C(sp³)–H lactonization in aromatic 2,6-dimethylbenzoic acid. We show that for this reaction, the direct C–O reductive elimination from both Pd(II) and Pd(IV) (oxidized by O₂oxidant) intermediates is unfavorable. Critical factors controlling the outcome of this reaction are the presence of the η³-(π-benzylic)–Pd and K⁺–O(carboxylic) interactions. The controlling factors of the benzylic vs ortho site-selectivity of this reaction are the: (a) difference in the strains of the generated lactone rings; (b) difference in the strengths of the η³-(π-benzylic)–Pd and η²-(π-phenyl)–Pd interactions, and (c) more pronounced electrostatic interaction between the nucleophilic oxygen and K⁺cation in the ortho-C–H activation transition state. The presented data indicate the utmost importance of base, substrate, and ligand in the selective C(sp³)–H bond lactonization in the presence of C(sp²)–H.

    

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3. Recent advances in oxidative allylic C–H functionalization via group IX-metal catalysis

   https://doi.org/10.1039/D0CC05554A  

   Kazerouni, Amaan M. ; McKoy, Quincy A. ; Blakey, Simon B. ( November 2020 , Chemical Communications)

   null (Ed.)

   Allylic substitution, pioneered by the work of Tsuji and Trost, has been an invaluable tool in the synthesis of complex molecules for decades. An attractive alternative to allylic substitution is the direct functionalization of allylic C–H bonds of unactivated alkenes, thereby avoiding the need for prefunctionalization. Significant early advances in allylic C–H functionalization were made using palladium catalysis. However, Pd-catalyzed reactions are generally limited to the functionalization of terminal olefins with stabilized nucleophiles. Insights from Li, Cossy, and Tanaka demonstrated the utility of RhCp x catalysts for allylic functionalization. Since these initial reports, a number of key intermolecular Co-, Rh-, and Ir-catalyzed allylic C–H functionalization reactions have been reported, offering significant complementarity to the Pd-catalyzed reactions. Herein, we report a summary of recent advances in intermolecular allylic C–H functionalization via group IX-metal π-allyl complexes. Mechanism-driven development of new catalysts is highlighted, and the potential for future developments is discussed. 

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4. Tailored quinones support high-turnover Pd catalysts for oxidative C–H arylation with O 2

   https://doi.org/10.1126/science.abd1085  

   Salazar, Chase A. ; Flesch, Kaylin N. ; Haines, Brandon E. ; Zhou, Philip S. ; Musaev, Djamaladdin G. ; Stahl, Shannon S. ( December 2020 , Science)

   null (Ed.)

   Palladium(II)-catalyzed C–H oxidation reactions could streamline the synthesis of pharmaceuticals, agrochemicals, and other complex organic molecules. Existing methods, however, commonly exhibit poor catalyst performance with high Pd loading (e.g., 10 mol %) and a need for (super)stoichiometric quantities of undesirable oxidants, such as benzoquinone and silver(I) salts. The present study probes the mechanism of a representative Pd-catalyzed oxidative C–H arylation reaction and elucidates mechanistic features that undermine catalyst performance, including substrate-consuming side reactions and sequestration of the catalyst as inactive species. Systematic tuning of the quinone co-catalyst overcomes these deleterious features. Use of 2,5-di- tert -butyl- p -benzoquinone enables efficient use of molecular oxygen as the oxidant, high reaction yields, and >1900 turnovers by the palladium catalyst. 

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5. Catalytic β C–H amination via an imidate radical relay

   https://doi.org/10.1039/c8sc05685d  

   Stateman, Leah M. ; Wappes, Ethan A. ; Nakafuku, Kohki M. ; Edwards, Kara M. ; Nagib, David A. ( February 2019 , Chemical Science)

   null (Ed.)

   The first catalytic strategy to harness imidate radicals for C–H functionalization has been developed. This iodine-catalyzed approach enables β C–H amination of alcohols by an imidate-mediated radical relay. In contrast to our first-generation, (super)stoichiometric protocol, this catalytic method enables faster and more efficient reactivity. Furthermore, lower oxidant concentration affords broader functional group tolerance, including alkenes, alkynes, alcohols, carbonyls, and heteroarenes. Mechanistic experiments interrogating the electronic nature of the key 1,5 H-atom transfer event are included, as well as probes for chemo-, regio-, and stereo-selectivity. 

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