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1. 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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2. Distal Allylic/Benzylic C−H Functionalization of Silyl Ethers Using Donor/Acceptor Rhodium(II) Carbenes

   https://doi.org/10.1002/anie.201916530  

   Vaitla, Janakiram; Boni, Yannick_T; Davies, Huw_M_L (March 2020, Angewandte Chemie International Edition)

   Abstract Regio‐ and stereoselective distal allylic/benzylic C−H functionalization of allyl and benzyl silyl ethers was achieved using rhodium(II) carbenes derived from N‐sulfonyltriazoles and aryldiazoacetates as carbene precursors. The bulky rhodium carbenes led to highly site‐selective functionalization of less activated allylic and benzylic C−H bonds even in the presence of electronically preferred C−H bonds located α to oxygen. The dirhodium catalyst Rh₂(S‐NTTL)₄is the most effective chiral catalyst for triazole‐derived carbene transformations, whereas Rh₂(S‐TPPTTL)₄works best for carbenes derived from aryldiazoacetates. The reactions afford a variety of δ‐functionalized allyl silyl ethers with high diastereo‐ and enantioselectivity. The utility of the present method was demonstrated by its application to the synthesis of a 3,4‐disubstitutedl‐proline scaffold. 

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3. Intermolecular Allylic C−H Etherification of Internal Olefins

   https://doi.org/10.1002/anie.201809863  

   Nelson, Taylor A. F.; Blakey, Simon B. (October 2018, Angewandte Chemie International Edition)

   Abstract Herein we report on the development of an oxidative allylic C−H etherification reaction, utilizing internal olefins and alcohols as simple precursors. Key advances include the use of RhCp* complexes to promote the allylic C−H functionalization of internal olefins and the compatibility of the oxidative conditions with oxidatively sensitive alcohols, enabling the direct etherification reaction. Preliminary mechanistic studies, consistent with C−H functionalization as the rate determining step, are presented. 

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4. Catalytic Behavior of Mono‐ N ‐Protected Amino‐Acid Ligands in Ligand‐Accelerated C−H Activation by Palladium(II)

   https://doi.org/10.1002/anie.202002484  

   Salazar, Chase A.; Gair, Joseph J.; Flesch, Kaylin N.; Guzei, Ilia A.; Lewis, Jared C.; Stahl, Shannon S. (April 2020, Angewandte Chemie International Edition)

   Abstract Mono‐N‐protected amino acids (MPAAs) are increasingly common ligands in Pd‐catalyzed C−H functionalization reactions. Previous studies have shown how these ligands accelerate catalytic turnover by facilitating the C−H activation step. Here, it is shown that MPAA ligands exhibit a second property commonly associated with ligand‐accelerated catalysis: the ability to support catalytic turnover at substoichiometric ligand‐to‐metal ratios. This catalytic role of the MPAA ligand is characterized in stoichiometric C−H activation and catalytic C−H functionalization reactions. Palladacycle formation with substrates bearing carboxylate and pyridine directing groups exhibit a 50–100‐fold increase in rate when only 0.05 equivalents of MPAA are present relative to Pd^II. These and other mechanistic data indicate that facile exchange between MPAAs and anionic ligands coordinated to Pd^IIenables a single MPAA to support C−H activation at multiple Pd^IIcenters. 

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5. The Enantioselective Synthesis of Eburnamonine, Eucophylline, and 16′‐ epi ‐Leucophyllidine

   https://doi.org/10.1002/anie.202106184  

   Reimann, Christopher E.; Ngamnithiporn, Aurapat; Hayashida, Kohei; Saito, Daisuke; Korch, Katerina M.; Stoltz, Brian M. (July 2021, Angewandte Chemie International Edition)

   Abstract A synthetic approach to the heterodimeric bisindole alkaloid leucophyllidine is disclosed herein. An enantioenriched lactam building block, synthesized through palladium‐catalyzed asymmetric allylic alkylation, served as the precursor to both hemispheres. The eburnamonine‐derived fragment was synthesized through a Bischler–Napieralski/hydrogenation approach, while the eucophylline‐derived fragment was synthesized by Friedländer quinoline synthesis and two sequential C−H functionalization steps. A convergent Stille coupling and phenol‐directed hydrogenation united the two monomeric fragments to afford 16′‐epi‐leucophyllidine in 21 steps from commercial material. 

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