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1. On-resin Cα-functionalization of N -arylglycinyl peptides with boronic acids

   https://doi.org/10.1039/d2ob00524g  

   Young, Hailey A.; Proulx, Caroline (August 2022, Organic & Biomolecular Chemistry)

   A late-stage α-C–H functionalization reaction of resin-bound, electron-rich N -aryl peptides with boronic acid nucleophiles under mild conditions is reported. We explore the impact of the N -arylglycinyl peptide structure on reactivity, and present a scope of the optimized reaction where both the peptide sequence and nature of boronic acid derivatives are varied. 

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2. Oxidative Mizoroki–Heck reaction of unprotected cinnamylamines at ambient temperature under air

   https://doi.org/10.1039/D3QO00778B  

   Farinde, Olutayo N.; Satheesh, Vanaparthi; Shrestha, Kendra K.; Rhinehalt, Carmen R.; Landge, Vinod G.; Young, Michael C. (July 2023, Organic Chemistry Frontiers)

   Cinnamylamines make-up many important drugs that target G protein-coupled receptors. While 3,3-diarylallylamines can be prepared via existing synthetic methods, these often require poorly-selective Wittig addition to unsymmetrical ketones, and multistep sequences thereafter to reach the allylamine product. Methods that make use of direct aryl addition to N -protected cinnamylamines via a Mizoroki–Heck pathway are known, however, unprotected cinnamylamines are sensitive to a mixture of C–H activation and Mizoroki–Heck arylation under Pd-catalysed arylation conditions using aryl iodides. This leads to a decrease in the trans / cis selectivity that can be achieved under these reaction conditions. By reimagining the reaction and using aryl boronic acids, we have herein demonstrated how in many cases the yield and E / Z selectivity can be improved. The in situ -formed active catalyst is more sensitive under these conditions, and was observed to shut down at elevated temperatures. 

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3. Boronic Acid Reagents for Transition‐Metal‐Mediated Cross‐Coupling with Proteins and Peptides

   https://doi.org/10.1002/ijch.202100012  

   Miller, Mary K.; Ball, Zachary T. (April 2021, Israel Journal of Chemistry)

   Abstract Transition‐metal catalysis provides new approaches to selectivity and the activation of otherwise inert functional groups. Bioconjugation with protein and peptide substrates presents numerous challenges of functional group activation and selectivity, and transitional‐metal approaches provide important alternative solutions to these challenges. This article describes the development of boronic acid reagents for new selective approaches to modification of peptides and proteins, focusing primarily on catalytic C−X bond formation. 

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4. Quantitative Functionalization of the Tyrosine Residues in Silk Fibroin through an Amino‐Tyrosine Intermediate

   https://doi.org/10.1002/macp.202200119  

   Hausken, Kian G.; Frevol, Romane L.; Dowdle, Kimberly P.; Young, Aleena N.; Talusig, Jeremy M.; Holbrook, Carolynne C.; Rubin, Benjamin K.; Murphy, Amanda R. (June 2022, Macromolecular Chemistry and Physics)

   Abstract Here, a reaction sequence that can be used to quantitatively modify the tyrosine residues in silk protein fromB. morisilkworms is demonstrated. A primary amine is installed ortho to the hydroxyl group on the tyrosine ring using a diazonium coupling reaction followed by reduction of the azo bond. The resulting amine is then acylated using carboxylic acid or NHS‐ester derivatives at room temperature and neutral pH conditions. The silk derivatives are characterized using¹H NMR, UV–vis spectroscopy, ATR‐FTIR, and a unique method to follow this reaction sequence using isotopically labeled reagents and 2D NMR spectroscopy is also used. This study further demonstrates that this sequence can be used to install alkyne or azide functional groups which can undergo further bio‐orthogonal cycloaddition reactions under mild conditions. Finally, methods to carry out these modifications on solid silk microparticles and electrospun mats are also described. 

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5. Synergistic N‐Heterocyclic Carbene/Palladium‐Catalyzed Umpolung 1,4‐Addition of Aryl Iodides to Enals

   https://doi.org/10.1002/anie.201912584  

   Yang, Wenjun; Ling, Bo; Hu, Bowen; Yin, Haolin; Mao, Jianyou; Walsh, Patrick J. (November 2019, Angewandte Chemie International Edition)

   Abstract An umpolung 1,4‐addition of aryl iodides to enals promoted by cooperative (terpy)Pd/NHC catalysis was developed that generates various bioactive β,β‐diaryl propanoate derivatives. This system is not only the first reported palladium‐catalyzed arylation of NHC‐bound homoenolates but also expands the scope of NHC‐induced umpolung transformations. A diverse array of functional groups such as esters, nitriles, alcohols, and heterocycles are tolerated under the mild conditions. This method also circumvents the use of moisture‐sensitive organometallic reagents. 

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