Journal Club Topic of the Week Highlighting Recent Examples of Iodonio-Sigmatropic Rearrangements Grenning Research Lab May 28, 2020 Journal Club Iodonio-Sigmatropic Introduction Rearrangements Original discovery of ortho C-H allylation of aryliodane by Oh Examples from the literature of iodonio-sigmatropic and coworkers. Oh et al. Tetrahedron Lett. 1988, 29, 667-668. rearrangements featuring different nucleophiles. Benefits of this process: Shafir, A. Tetrahedron Lett. 2016, 57, 2673-2682. • Direct ortho C-H functionalization without the requirement of a transition metal catalyst • No additional oxidant is necessary as the directing group is comprised of an oxidant Keywords: aryliodane, ortho C-H functionalization, C-H coupling, iodonio-sigmatropic rearrangement, reductive iodonio-Claisen rearrangement (RICR) Figure from Peng et al. J. Am. Chem. Soc. 2020, 142, 6884-6890. May 28, 2020 Journal Club “Sigmatropic Rearrangements of Hypervalent‐Iodine‐Tethered Iodonio-Sigmatropic Intermediates for the Synthesis of Biaryls” Rearrangements Hideki Yorimitsu Group (Kyoto University) Summary Reaction development • Dehydrogenative C-H/C-H biaryl coupling via aryl iodonio-sigmatropic rearrangement proceeding through a dual-dearomatized intermediate. • Transition metal-catalyzed cross couplings are the norm for synthesizing biaryl systems. Precedent Further screenings Lewis acid did not promote reaction • Tandem interrupted Pummerer/[3,3] rearrangements yield C-H/C-H cross coupling of aryl sulfoxides with phenols. • Limitations: Csp2-S bond functionalizations lesser explored than Csp2-X bonds Yorimitsu et al. J. Am. Chem. Soc. 2016, 138, 14582–14585. Suggests a radical mechanism isn't operative Hori, M.; Guo, J.-D.; Yanagi, T.; Nogi, K.; Sasamori, T.; Michael D. Mannchen May 28, 2020 Yorimitsu, H. Angew. Chem. Int. Ed. 2018, 57, 4663-4667. Journal Club “Sigmatropic Rearrangements of Hypervalent‐Iodine‐Tethered Iodonio-Sigmatropic Intermediates for the Synthesis of Biaryls” Rearrangements Hideki Yorimitsu Group (Kyoto University) Noteworthy Scope Synthesis of extended aromatic systems Proposed Mechanism Key Takeaways • Iodonio-sigmatropic rearrangement yielding racemic 2-iodo-2’-hydroxy- biaryl systems. • Scope limited to substituted benzene-, naphthalene-, and phenanthrene- derivatives. • Products can be readily elaborated to p-extended furans and benzo- fused helicenes. DFT calculations show that excess AcOH (solvent) lowers transition state by • (Diacetoxyiodo)arene can be generated in situ from aryl iodide with ~9 kcal/mol by hydrogen bonding with acetate leaving group. mCPBA and acetic acid. Hori, M.; Guo, J.-D.; Yanagi, T.; Nogi, K.; Sasamori, T.; Michael D. Mannchen May 28, 2020 Yorimitsu, H. Angew. Chem. Int. Ed. 2018, 57, 4663-4667. Journal Club “Selective ortho C-H Cyanoalkylation of (Diacetoxyiodo)arenes Iodonio-Sigmatropic through [3,3]-Sigmatropic Rearrangement” Rearrangements Bo Peng Group (Zhejiang Normal University) Summary: Precedent: Reaction development: • Precedent • Previous ortho C-H functionalizations • Rearrangement accelerated via released congestion • Reaction development • Based on previous work done in lab • Looked at various nucleophiles and bases • Catalyst-free but activator essential • Scope • Nitrile scope tested with electron- deficient and rich functional groups • Arene scope tested through different aryliodane substrates. • Recent study by lab assembled ketenimine(aryl)sulfonium intermediate • Computational Studies a) Zhu et al.; Ochiai et al.; Shafir and Vallribera; using alkylnitriles and bases. Yorimitsu et al. • Tested different nitrile nucleophiles and b) Walters et al.; Bruckner and Huisgen; Molina various bases et al.; Peng Tian, J.; Luo, F.; Zhang, C.; Huang, X.; Zhang, Y.; Zhang, L.; Kong, L.; Hu, Mariana M. Alves May, 28, 2020 X.; Wang, Z.-X.; Peng, B. Angew. Chem. Int. Ed. 2018, 57, 9078-9082. Journal Club “Selective ortho C-H Cyanoalkylation of (Diacetoxyiodo)arenes Iodonio-Sigmatropic through [3,3]-Sigmatropic Rearrangement” Rearrangements Bo Peng Group (Zhejiang Normal University) Noteworthy scope and further transformations: Key takeaways: • Achieved a catalyst-free cross-coupling between (diacetoxyiodo)arenes with α-stannyl nitriles while retaining iodine on the ring. • Reaction takes place in 5 min. at -78 °C with good selectivity, functional-group compatibility, and broad substrate scope. • Reaction can efficiently be scaled up and can undergo further synthetic transformations. • DFT computations demonstrate potential reaction mechanism. Tian, J.; Luo, F.; Zhang, C.; Huang, X.; Zhang, Y.; Zhang, L.; Kong, L.; Hu, Mariana M. Alves May, 28, 2020 X.; Wang, Z.-X.; Peng, B. Angew. Chem. Int. Ed. 2018, 57, 9078-9082. Journal Club “The Coming of Age in Iodane-Guided ortho-C-H Iodonio-Sigmatropic Propargylation: From Insight to Synthetic Potential” Rearrangements Alexandr Shafir Group (Barcelona Institute of Science and Technology) -PhI(OAc)2 undergoes acid-catalyzed reactions with propargyl-silanes, germanes, and stannanes yielding ortho-propargyl iodobenzenes. -The proposed mechanism of this formal C-H functionalization is an iodonio-based [3,3] sigmatropic rearrangement via an allenylsilane intermediate -A newly optimized reaction protocol has been developed and employed in the synthesis of ortho-iodo propargyl/allenyl arenes. Izquierdo, S.; Bouvet, S.; Wu, Y.; Molina, S.; Shafir, A. Chem. Sara E. Kearney May 28, 2020 Eur. J. 2018, 24, 15517-15521. Journal Club “The Coming of Age in Iodane-Guided ortho-C-H Iodonio-Sigmatropic Propargylation: From Insight to Synthetic Potential” Rearrangements Alexandr Shafir Group (Barcelona Institute of Science and Technology) -Reproducible on 20 mmol scale Key Takeaways: -Lower yields obtained for o-OMe and p-OMe iodoarenes -Iodane-guided C-H propargylation demonstrates a broad substrate tolerance about the due to competing deiodinative ipso substitution iodoarene core -Aryl allenes can also be accessed via -Electron-deficient iodoarenes, previously outside the scope of this reaction, are now amenable under this newly optimized protocol. -From a mechanistic standpoint, though bearing some resemblance to a classic Claisen rearrangement, interesting differences between this reaction and the aromatic Claisen rearrangement have been identified by DFT calculations. -Access to a broad class of ortho-propargyl iodoarenes facilitates building block synthesis by a variety of cross coupling or cyclization reactions. Izquierdo, S.; Bouvet, S.; Wu, Y.; Molina, S.; Shafir, A. Chem. Sara E. Kearney May 28, 2020 Eur. J. 2018, 24, 15517-15521. Journal Club “Dearomative Dual Functionalization of Aryl Iodanes” Iodonio-Sigmatropic Rearrangements Bo Peng Group (Zhejiang Normal University) Main points of abstract: • Two-stage dearomatization of aryl iodanes: [3,3] sigmatropic rearrangement of the aryl iodane, then nucleophilic addition. • In one reaction, two different FGs installed (Nu1 and Nu2) • Nu1 is α‐stannyl nitrile, Nu2 can be H or a variety of different nucleophiles Precedent Reaction development • First step conditions from previous publication (B. Peng, 2018) • Second step – other reducing agents tried: Me2PhSiH, Ph3SiH, Me2ClSiH • Other temperatures: -100 oC, -60 oC – lower yields • 1.5 equiv. stannane, 2.5 equiv. silane – optimal stoichiometry Zhao, W.; Huang, X.; Zhan, Y.; Zhang, Q.; Li, D.; Zhang, Y.; Kong, Jenya Semenova May 28, 2020 L.; Peng, B. Angew. Chem. Int. Ed. 2019, 58, 17210-17214. Journal Club “Dearomative Dual Functionalization of Aryl Iodanes” Iodonio-Sigmatropic Rearrangements Bo Peng Group (Zhejiang Normal University) Notable members of the scope Mechanism Functional Group Interconversion In-situ NMR study Key takeaways • Dual functionalization of aryl iodanes • [3,3] with α‐stannyl nitrile gives a highly electrophilic dearomatized intermediate, trapped by nucleophile • Broad scope and functional group compatibility due to low temperature of rxn • Rxn products have wide potential for FGI • IM characterized by low‐temperature NMR • IM forms due to high electrophilicity of II Zhao, W.; Huang, X.; Zhan, Y.; Zhang, Q.; Li, D.; Zhang, Y.; Kong, Jenya Semenova May 28, 2020 L.; Peng, B. Angew. Chem. Int. Ed. 2019, 58, 17210-17214. Journal Club “Asymmetric Iodonio-[3,3]-Sigmatropic Rearrangement to Iodonio-Sigmatropic Access Chiral α-Aryl Carbonyl Compounds” Rearrangements Bo Peng Group (Zhejiang Normal University) Table of Contents Graphic Notable Reaction Development Literature Precedent Peng et al. J. Am. Chem. Soc. 2017, 139, 4211-4217. Mechanism Maulide et al. Angew. Chem. Int. Ed. 2017, 56, 2212-2215. Tian, J.; Luo, F.; Zhang, Q.; Liang, Y.; Li, D.; Zhan, Y.; Kong, L.; Breanna Tomiczek May 28, 2020 Wang, Z.-X.; Peng, B. J. Am. Chem. Soc. 2020, 142, 6884-6890. Journal Club “Asymmetric Iodonio-[3,3]-Sigmatropic Rearrangement to Iodonio-Sigmatropic Access Chiral α-Aryl Carbonyl Compounds” Rearrangements Bo Peng Group (Zhejiang Normal University) Noteworthy Scope Notable Further Functionalizations Key Takeaways • First example of an asymmetric iodonio-sigmatropic rearrangement employing an “assembly/deprotonation” method for synthesizing chiral α-aryl carbonyl compounds Asymmetric Catalysis Preliminary Result • Utilizes commercially available or readily accessible known compounds as starting materials • Reaction tolerates a wide variety of functional groups • The iodine atom in the product can undergo further functional group interconversion reactions Tian, J.; Luo, F.; Zhang, Q.; Liang, Y.; Li, D.; Zhan, Y.; Kong, L.; Breanna Tomiczek May 28,