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, 2020 Wang, Z.-X.; Peng, B. J. Am. Chem. Soc. 2020, 142, 6884-6890. Journal Club Iodonio-Sigmatropic References Rearrangements

Featured in this presentation: Additional iodonio-sigmatropic rearrangement references: Lee, K.; Kim, D. Y.; Oh, D. Y. Tetrahedron Lett. 1988, 29, 667-668. Ochiai, M.; Ito, T.; Takaoka, Y.; Masaki, Y. J. Am. Chem. Soc. 1991, 113, 1319-1323. Hori, M.; Guo, J.-D.; Yanagi, T.; Nogi, K.; Sasamori, T.; Yorimitsu, H. Angew. Chem. Int. Ed. 2018, 57, 4663-4667. Gately, D. A.; Luther, T. A.; Norton, J. R.; Miller, M. M.; Anderson, O. P. J. Org. Chem. 1992, Tian, J.; Luo, F.; Zhang, C.; Huang, X.; Zhang, Y.; Zhang, L.; Kong, L.; Hu, X.; Wang, Z.-X.; Peng, B. Angew. Chem. Int. Ed. 2018, 57, 9078- 9082. 57, 6496-6502.

Izquierdo, S.; Bouvet, S.; Wu, Y.; Molina, S.; Shafir, A. Chem. Eur. J. 2018, 24, 15517-15521. Ochiai, M.; Ito, T. J. Org. Chem. 1995, 60, 2274-2275.

Zhao, W.; Huang, X.; Zhan, Y.; Zhang, Q.; Li, D.; Zhang, Y.; Kong, L.; Peng, B. Angew. Chem. Int. Ed. 2019, 58, 17210-17214. Khatri, H. R.; Zhu, J. Chem. Eur. J. 2012, 18, 12232-12236. Tian, J.; Luo, F.; Zhang, Q.; Liang, Y.; Li, D.; Zhan, Y.; Kong, L.; Wang, Z.-X.; Peng, B. J. Am. Chem. Soc. 2020, 142, 6884-6890. Jia, Z.; Gálvez, E.; Sebastián, R. M.; Pleixats, R.; Álvarez-Larena, Á.; Martin, E.; Vallribera, See also references for related aryl sulfoxide sigmatropic rearrangements: A.; Shafir, A. Angew. Chem. Int. Ed. 2014, 53, 11298-11301. Khatri, H. R.; Nguyen, H.; Dunaway, J. K.; Zhu, J. Front. Chem. Sci. Eng. 2015, 9, 359-368. Wu, Y.; Arenas, I.; Broomfield, L. M.; Martin, E.; Shafir, A. Chem. Eur. J. 2015, 21, 18779- 18784. Wu, Y.; Bouvet, S.; Izquierdo, S.; Shafir, A. Angew. Chem. Int. Ed. 2019, 58, 2617-2621. Bycroft, B. W.; Landon, W. J. Chem. Soc. D. 1970, 913, 967-968. Huang, X.; Zhang, Y.; Zhang, C.; Zhang, L.; Xu, Y.; Kong, L.; Wang, Z.-X.; Peng, B. Angew. Yoshida, S.; Yorimitsu, H.; Oshima, K. Org. Lett. 2009, 11, 2185-2188. Chem. Int. Ed. 2019, 58, 5956-5961.

Eberhart, A. J.; Procter, D. J. Angew. Chem. Int. Ed. 2013, 52, 4008-4011. Fernández-Salas, J. A.; Eberhart, A. J.; Procter, D. J. J. Am. Chem. Soc. 2016, 138, 790-793. Reviews: Yanagi, T.; Otsuka, S.; Kasuga, Y.; Fujimoto, K.; Murakami, K.; Nogi, K.; Yorimitsu, H.; Osuka, A. J. Am. Chem. Soc. 2016, 138, 14582- 14585. Shafir, A. Tetrahedron Lett. 2016, 57, 2673-2682. Kaldre, D.; Maryasin, B.; Kaiser, D.; Gajsek, O.; González, L.; Maulide, N. Angew. Chem. Int. Ed. 2017, 56, 2212-2215. Chen, W. W.; Cuenca, A. B.; Shafir, A. Angew. Chem. Int. Ed. 2019, DOI: Shang, L.; Chang, Y.; Luo, F.; He, J.-N.; Huang, X.; Zhang, L.; Kong, L.; Li, K.; Peng, B. J. Am. Chem. Soc. 2017, 139, 4211-4217. 10.1002/anie.201908418.

May 28, 2020