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Mechanistically informed selection rules for competing β-hydride and β-heteroatom eliminations

Nature Synthesis volume 1, pages 787–793 (2022)Cite this article

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Abstract

Alkylpalladium complexes are important intermediates in several industrially relevant catalytic reactions, such as the Mizoroki–Heck reaction, alkyl C–H activation and ethylene polymerization. β-elimination—of either a hydride (β-Η) or a heteroatom (β-Χ)—is the most common decomposition pathway for these intermediates; this can either lead to the desired reaction, as in the Mizoroki–Heck reaction, or it can hinder the reaction progress, as in ethylene and/or vinyl halide co-polymerizations. Despite the importance of these elimination processes, little mechanistic understanding exists with respect to the factors that control them. Here we present a systematic investigation of the factors that govern the competition between β-Η and β-Χ in catalytically relevant alkylpalladium complexes. These results enabled us to derive selection rules that dictate ligand choice to control the selectivity for either elimination. This knowledge may allow chemists to manipulate β-eliminations in the design of chemoselective catalytic reactions for a wide range of applications.

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Fig. 1: Background and description of current work.
Fig. 2: Investigation of the influence of heteroatom (X) group.
Fig. 3: Effect of phosphine ligand choice on reaction outcome.

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Data availability

The experimental data as well as the characterization data for all the compounds prepared during these studies are provided in the Supplementary Information. Crystallographic data are available from the Cambridge Crystallographic Data Centre (CCDC) with the following codes: CCDC 2150620 (31) and CCDC 2150621 (34). Copies of the data can be obtained free of charge via https://www.ccdc.cam.ac.uk/structures/.

Code availability

All code and raw data files are available on Zenodo at 10.5281/zenodo.6617212 (https://zenodo.org/record/6617212).

References

  1. Crabtree, R. H. The Organometallic Chemistry of the Transition Metals 4th edn (Wiley, 2005).

  2. Prashad, M. Palladium-catalyzed Heck arylations in the synthesis of active Pharmaceutical Ingredients. Top. Organomet. Chem. 6, 181–203 (2004).

    CAS  Google Scholar 

  3. Hartwig, J. F. Organotransition Metal Chemistry: From Bonding to Catalysis (Wiley, 2010).

  4. Rudolph, A. & Lautens, M. Secondary alkyl halides in transition-metal-catalyzed cross-coupling reactions. Angew. Chem. Int. Ed. 48, 2656–2670 (2009).

    Article  CAS  Google Scholar 

  5. de Meijere, A. & Meyer, F. E. Fine feathers make fine birds: the Heck reaction in modern garb. Angew. Chem. Int. Ed. 33, 2379–2411 (1995).

    Article  Google Scholar 

  6. Lu, X. Control of the β-hydride elimination making palladium-catalyzed coupling reactions more diversified. Top. Catal. 35, 73–86 (2005).

    Article  Google Scholar 

  7. Ramnauth, J., Poulin, O., Rakhit, S. & Maddaford, S. P. Palladium(II) acetate catalyzed stereoselective C-glycosidation of peracetylated glycals with arylboronic acids. Org. Lett. 3, 2013–2014 (2001).

    Article  CAS  PubMed  Google Scholar 

  8. Or, Y. S. et al. Design, synthesis, and antimicrobial activity of 6-O-substituted ketolides active against resistant respiratory tract pathogens. J. Med. Chem. 43, 1045–1049 (2000).

    Article  CAS  PubMed  Google Scholar 

  9. Chirik, P. J. & Bercaw, J. E. Cyclopentadienyl and olefin substituent effects on insertion and β-hydrogen elimination with group 4 metallocenes. Kinetics, mechanism, and thermodynamics for zirconocene and hafnocene alkyl hydride derivatives. Organometallics 24, 5407–5423 (2005).

    Article  CAS  Google Scholar 

  10. Wada, S. & Jordan, R. F. Olefin insertion into a Pd–F bond: catalyst reactivation following β-F elimination in ethylene/vinyl fluoride copolymerization. Angew. Chem. 129, 1846–1850 (2017).

    Article  Google Scholar 

  11. Stockland, R. A. & Jordan, R. F. Reaction of vinyl chloride with a prototypical metallocene catalyst: stoichiometric insertion and β-Cl elimination reactions with rac-(EBI)ZrMe+ and catalytic dechlorination/oligomerization to oligopropylene by rac-(EBI)ZrMe2/MAO. J. Am. Chem. Soc. 122, 6315–6316 (2000).

    Article  CAS  Google Scholar 

  12. Luckham, S. L. J. & Nozaki, K. Toward the copolymerization of propylene with polar comonomers. Acc. Chem. Res. 54, 344–355 (2021).

    Article  CAS  PubMed  Google Scholar 

  13. Carpenter, A. E. et al. Direct observation of β-chloride elimination from an isolable β-chloroalkyl complex of square-planar nickel. J. Am. Chem. Soc. 136, 15481–15484 (2014).

    Article  CAS  PubMed  Google Scholar 

  14. Munro-Leighton, C., Adduci, L. L., Becker, J. J. & Gagné, M. R. Oxidative addition of secondary C–X bonds to palladium(0): a beneficial anomeric acceleration. Organometallics 30, 2646–2649 (2011).

    Article  CAS  Google Scholar 

  15. Yeung, S. K. & Chan, K. S. 1,2-Rearrangements of β-nitrogen-substituted (porphyrinato) rhodium(III) ethyls. Organometallics 24, 2561–2563 (2005).

    Article  CAS  Google Scholar 

  16. Galinkina, J. et al. Synthesis, characterization, and reactivity of (fluoroalkyl)- and (fluorocycloalkyl)cobaloximes: molecular structure of a (2-fluorocyclohexyl)cobaloxime complex and hindered rotation of 2-fluorocycloalkyl ligands. Organometallics 22, 4873–4884 (2003).

    Article  CAS  Google Scholar 

  17. Huang, D., Renkema, K. B. & Caulton, K. G. Cleavage of F–C(sp2) bonds by MHR(CO)(PtBu2Me)2 (M = Os and Ru; R = H, CH3 or aryl): product dependence on M and R. Polyhedron 25, 459–468 (2006).

    Article  CAS  Google Scholar 

  18. Braun, T. & Hughes, R. P. Organometallic Fluorine Chemistry (Springer, 2015).

  19. Strazisar, S. A. & Wolczanski, P. T. Insertion of H2C=CHX (X = F, Cl, Br, OiPr) into (tBu3SiO)3TaH2 and β-X-elimination from (tBu3SiO)3HTaCH2CH2X (X = OR): relevance to Ziegler–Natta copolymerizations. J. Am. Chem. Soc. 123, 4728–4740 (2001).

    Article  CAS  PubMed  Google Scholar 

  20. Tran, V. T., Gurak, J. A., Yang, K. S. & Engle, K. M. Activation of diverse carbon–heteroatom and carbon–carbon bonds via palladium(II)-catalysed β-X elimination. Nat. Chem. 10, 1126–1133 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Paioti, P. H. S. et al. Catalytic enantioselective boryl and silyl substitution with trifluoromethyl alkenes: scope, utility, and mechanistic nuances of Cu–F β-elimination. J. Am. Chem. Soc. 141, 19917–19934 (2019).

    Article  CAS  PubMed  Google Scholar 

  22. Vela, J. et al. Synthesis and reactivity of low-coordinate iron(II) fluoride complexes and their use in the catalytic hydrodefluorination of fluorocarbons. J. Am. Chem. Soc. 127, 7857–7870 (2005).

    Article  CAS  PubMed  Google Scholar 

  23. Butcher, T. W., Yang, J. L. & Hartwig, J. F. Copper-catalyzed defluorinative borylation and silylation of gem-difluoroallyl groups. Org. Lett. 22, 6805–6809 (2020).

    Article  CAS  PubMed  Google Scholar 

  24. le Bras, J. & Muzart, J. β-Elimination competitions leading to C=C bonds from alkylpalladium intermediates. Tetrahedron 68, 10065–10113 (2012).

    Article  Google Scholar 

  25. Zhang, Z., Lu, X., Xu, Z., Zhang, Q. & Han, X. Role of halide ions in divalent palladium-mediated reactions: competition between β-heteroatom elimination and β-hydride elimination of a carbon–palladium bond. Organometallics 20, 3724–3728 (2001).

    Article  CAS  Google Scholar 

  26. Zhu, G. & Lu, X. Reactivity and stereochemistry of β-heteroatom elimination. A detailed study through a palladium-catalyzed cyclization reaction model. Organometallics 14, 4899–4904 (1995).

    Article  CAS  Google Scholar 

  27. Lovering, F. Escape from Flatland 2: complexity and promiscuity. MedChemComm 4, 515–519 (2013).

    Article  CAS  Google Scholar 

  28. Lovering, F., Bikker, J. & Humblet, C. Escape from Flatland: increasing saturation as an approach to improving clinical success. J. Med. Chem. 52, 6752–6756 (2009).

    Article  CAS  PubMed  Google Scholar 

  29. McGuiness, D. Alkene oligomerisation and polymerisation with metal–NHC based catalysts. Dalton Trans. 2009, 6915–6923 (2009).

    Article  Google Scholar 

  30. Pignolet, L. H. & Fackler, J. P. Jr Modern Inorganic Chemistry—Homogeneous Catalysis with Metal Phosphine Complexes (Plenum, 1983).

  31. He, L. Y. Bis(tri-tert-butylphosphine)palladium(0) [Pd(t-Bu3P)2. Synlett 26, 851–852 (2015).

    Article  CAS  Google Scholar 

  32. Johnson, C. D. Linear free energy relationships and the reactivity–selectivity principle. Chem. Rev. 75, 755–765 (1963).

    Article  Google Scholar 

  33. Purser, S., Moore, P. R., Swallow, S. & Gouverneur, V. Fluorine in medicinal chemistry. Chem. Soc. Rev. 37, 320–330 (2008).

    Article  CAS  PubMed  Google Scholar 

  34. Gillis, E. P., Eastman, K. J., Hill, M. D., Donnelly, D. J. & Meanwell, N. A. Applications of fluorine in medicinal chemistry. J. Med. Chem. 58, 8315–8359 (2015).

    Article  CAS  PubMed  Google Scholar 

  35. Hagmann, W. K. The many roles for fluorine in medicinal chemistry. J. Med. Chem. 51, 4359–4369 (2008).

    Article  CAS  PubMed  Google Scholar 

  36. Fujita, T., Fuchibe, K. & Ichikawa, J. Transition-metal-mediated and -catalyzed C−F bond activation by fluorine elimination. Angew. Chem. Int. Ed. 58, 390–402 (2019).

    Article  CAS  Google Scholar 

  37. Corberán, R., Mszar, N. W. & Hoveyda, A. H. NHC-Cu-catalyzed enantioselective hydroboration of acyclic and exocyclic 1,1-disubstituted aryl alkenes. Angew. Chem. Int. Ed. 50, 7079–7082 (2011).

    Article  Google Scholar 

  38. Yuan, K., Feoktistova, T., Cheong, P. H. Y. & Altman, R. A. Arylation of gem-difluoroalkenes using a Pd/Cu Co-catalytic system that avoids β-fluoride elimination. Chem. Sci. 12, 1363–1367 (2021).

    Article  CAS  Google Scholar 

  39. Zhao, H., Ariafard, A. & Lin, Z. β-Heteroatom versus β-hydrogen elimination: a theoretical study. Organometallics 25, 812–819 (2006).

    Article  CAS  Google Scholar 

  40. Liu, J., Yang, J., Ferretti, F., Jackstell, R. & Beller, M. Pd-catalyzed selective carbonylation of gem-difluoroalkenes: a practical synthesis of difluoromethylated esters. Angew. Chem. Int. Ed. 58, 4690–4694 (2019).

    Article  CAS  Google Scholar 

  41. Schoenebeck, F. & Houk, K. N. Ligand-controlled regioselectivity in palladium-catalyzed cross coupling reactions. J. Am. Chem. Soc. 132, 2496–2497 (2010).

    Article  CAS  PubMed  Google Scholar 

  42. Yang, Y. & Buchwald, S. L. Ligand-controlled palladium-catalyzed regiodivergent Suzuki–Miyaura cross-coupling of allylboronates and aryl halides. J. Am. Chem. Soc. 135, 10642–10645 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Fey, N. et al. Development of a ligand knowledge base, part 1: computational descriptors for phosphorus donor ligands. Chem. Eur. J. 12, 291–302 (2005).

    Article  PubMed  Google Scholar 

  44. Tolman, C. A. Steric effects of phosphorus ligands in organometallic chemistry and homogeneous catalysis. Chem. Rev. 77, 313–348 (1977).

    Article  CAS  Google Scholar 

  45. McMullin, C. L., Jover, J., Harvey, J. N. & Fey, N. Accurate modelling of Pd(0) + PhX oxidative addition kinetics. Dalton Trans. 39, 10833–10836 (2010).

    Article  CAS  PubMed  Google Scholar 

  46. Kim, D. et al. The site-selectivity and mechanism of Pd-catalyzed C(sp2)-H arylation of simple arenes. Chem. Sci. 12, 363–373 (2021).

    Article  CAS  Google Scholar 

  47. Stambuli, J. P., Incarvito, C. D., Bühl, M. & Hartwig, J. F. Synthesis, structure, theoretical studies, and ligand exchange reactions of monomeric, T-shaped arylpalladium(II) halide complexes with an additional, weak agostic interaction. J. Am. Chem. Soc. 126, 1184–1194 (2004).

    Article  CAS  PubMed  Google Scholar 

  48. Tan, Y. & Hartwig, J. F. Assessment of the intermediacy of arylpalladium carboxylate complexes in the direct arylation of benzene: evidence for C–H bond cleavage by ‘ligandless’ species. J. Am. Chem. Soc. 133, 3308–3311 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Narahashi, H., Shimizu, I. & Yamamoto, A. Synthesis of benzylpalladium complexes through C–O bond cleavage of benzylic carboxylates: development of a novel palladium-catalyzed benzylation of olefins. J. Organomet. Chem. 693, 283–296 (2008).

    Article  CAS  Google Scholar 

  50. Larini, P. et al. On the mechanism of the palladium-catalyzed β-arylation of ester enolates. Chem. Eur. J. 18, 1932–1944 (2012).

    Article  CAS  PubMed  Google Scholar 

  51. de Gombert, A., McKay, A. I., Davis, C. J., Wheelhouse, K. M. & Willis, M. C. Mechanistic studies of the palladium-catalyzed desulfinative cross-coupling of aryl bromides and (hetero)aryl sulfinate salts. J. Am. Chem. Soc. 142, 3564–3576 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  52. Lee, W., Shin, C., Park, S. E. & Joo, J. M. Regio- and stereoselective synthesis of thiazole-containing triarylethylenes by hydroarylation of alkynes. J. Org. Chem. 84, 12913–12924 (2019).

    Article  CAS  PubMed  Google Scholar 

  53. Newman-Stonebraker, S. H. et al. Univariate classification of phosphine ligation state and reactivity in cross-coupling catalysis. Science 308, 301–308 (2021).

    Article  Google Scholar 

  54. Sugita, T., Shiraiwa, Y., Hasegawa, M. & Ichikawa, K. Elimination reactions of halohydrin derivatives with a palladium(0) complex. Bull. Chem. Soc. Jpn. 52, 3692–3631 (1979).

    Google Scholar 

  55. Cárdenas, D. J. Advances in functional-group-tolerant metal-catalyzed alkyl–alkyl cross-coupling reactions. Angew. Chem. Int. Ed. 42, 384–387 (2003).

    Article  Google Scholar 

  56. Michael, F. E. & Cochran, B. M. Room temperature palladium-catalyzed intramolecular hydroamination of unactivated alkenes. J. Am. Chem. Soc. 128, 4246–4247 (2006).

    Article  CAS  PubMed  Google Scholar 

  57. Alexanian, E. J. & Hartwig, J. F. Mechanistic study of β-hydrogen elimination from organoplatinum(II) enolate complexes. J. Am. Chem. Soc. 130, 15627–15635 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Wang, T., Ji, W. H., Xu, Y. Z. & Zeng, B. B. An efficient and convenient protocol for highly regioselective cleavage of terminal epoxides to β-halohydrins. Synlett https://doi.org/10.1055/s-0029-1217182 (2009).

  59. Gopinath, P. & Chandrasekaran, S. A sequential one-pot synthesis of functionalized esters and thioesters through a ring-opening acylation of cyclic ethers and thioethers. Eur. J. Org. Chem. 2018, 6541–6547 (2018).

    Article  CAS  Google Scholar 

  60. Tenza, K., Northen, J. S., O’Hagan, D. & Slawin, A. M. Z. The role of organic fluorine in directing alkylation reactions via lithium chelation. J. Fluorine Chem. 125, 1779–1790 (2004).

    Article  CAS  Google Scholar 

  61. Camps, F., Chamorro, E., Gasol, V. & Guerrerro, A. Efficient utilization of tetrabutylammonium bifluoride in halofluorination reactions. J. Org. Chem. 54, 4294–4298 (1989).

    Article  CAS  Google Scholar 

  62. Mayr, H. & Ofial, A. R. Philicities, fugalities, and equilibrium constants. Acc. Chem. Res. 49, 952–965 (2016).

    Article  CAS  PubMed  Google Scholar 

  63. Guthrie, P. J. Hydrolysis of esters of oxy acids: pKa values for strong acids; Brønsted relationship for attack of water at methyl; free energies of hydrolysis of esters of oxy acids; and a linear relationship between free energy of hydrolysis and pKa holding over a range of 20 pK units. Can. J. Chem. 56, 2342–2354 (1979).

    Article  Google Scholar 

  64. Zhang, S. A reliable and efficient first principles-based method for predicting pKa values. III. Adding explicit water molecules: can the theoretical slope be reproduced and pKa values predicted more accurately? J. Comput. Chem. 33, 517–526 (2012).

    Article  PubMed  Google Scholar 

  65. Nagai, Y., Matsumoto, H., Taichi, N. & Watanabe, H. Polar substituent constants for substituted phenyl groups. The extended Taft equation. Bull. Chem. Soc. Jpn 45, 2560–2565 (1972).

    Article  CAS  Google Scholar 

  66. Hansch, C., Leo, A. & Taft, R. W. A survey of Hammett substituent constants and resonance and field parameters. Chem. Rev. 91, 165–195 (1991).

    Article  CAS  Google Scholar 

  67. Song, B., Knauber, T. & Gooßen, L. J. Decarboxylative cross-coupling of mesylates catalyzed by copper/palladium systems with customized imidazolyl phosphine ligands. Angew. Chem. Int. Ed. 52, 2954–2958 (2013).

    Article  CAS  Google Scholar 

  68. Reeves, D. C. et al. Palladium catalyzed alkoxy- and aminocarbonylation of vinyl tosylates. Org. Lett. 13, 2495–2497 (2011).

    Article  CAS  PubMed  Google Scholar 

  69. Doucet, H., Martin-Vaca, B., Bruneau, C. & Dixneuf, P. H. General synthesis of (Z)-Alk-1-en-1-yl esters via ruthenium-catalyzed anti-Markovnikov trans-addition of carboxylic acids to terminal alkynes. J. Org. Chem. 60, 7247–7255 (1995).

    Article  CAS  Google Scholar 

  70. Araki, S. & Butsugan, Y. Indium reactions. Bull. Chem. Soc. Jpn. 64, 727–729 (1991).

    Article  CAS  Google Scholar 

  71. Nishiumi, M., Miura, H., Wada, K., Hosokawa, S. & Inoue, M. Active ruthenium catalysts based on phosphine-modified Ru/CeO2 for the selective addition of carboxylic acids to terminal alkynes. ACS Catal. 2, 1753–1759 (2012).

    Article  CAS  Google Scholar 

  72. Liu, M. T. H. & Sunramanian, R. Reaction of benzylchlorocarbene with hydrogen chloride. J. Am. Chem. Soc. 50, 3218–3220 (1985).

    CAS  Google Scholar 

  73. Petasis, N., Yudin, A. K., Zavialov, I. A., Prakash, S. G. K. & Olah, G. A. Facile preparation of fluorine-containing alkenes, amides and alcohols via the electrophilic fluorination of alkenyl boronic acids and trifluoroborates. Synlett 5, 606–608 (1997).

    Article  Google Scholar 

  74. Yi, C. S. & Gao, R. Scope and mechanistic investigations on the solvent-controlled regio- and stereoselective formation of enol esters from the ruthenium-catalyzed coupling reaction of terminal alkynes and carboxylic acids. Organometallics 28, 6585–6592 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Tan, S. T. & Fan, W. Y. Ligand-controlled regio- and stereoselective addition of carboxylic acids onto terminal alkynes catalyzed by carbonylruthenium(0) complexes. Eur. J. Inorg. Chem. https://doi.org/10.1002/ejic.201000579 (2010).

  76. Heck, R. F. The palladium-catalyzed arylation of enol esters, ethers, and halides. A new synthesis of 2-aryl aldehydes and ketones. J. Am. Chem. Soc. 90, 5535–5538 (1968).

    Article  CAS  Google Scholar 

  77. Maitlis, P. M. The Organic Chemistry of Palladium Volume II: Catalytic Reactions (Academic, 1971).

  78. Saito, R., Izumi, T. & Kasahara, A. Pd catalysed arylation of 4-chromanone esters. Bull. Chem. Soc. Jpn 46, 1776–1779 (1973).

    Article  CAS  Google Scholar 

  79. Johansson Seechurn, C. C. C., Sperger, T., Scrase, T. G., Schoenebeck, F. & Colacot, T. J. Understanding the unusual reduction mechanism of Pd(II) to Pd(I): uncovering hidden species and implications in catalytic cross-coupling reactions. J. Am. Chem. Soc. 139, 5194–5200 (2017).

    Article  CAS  PubMed  Google Scholar 

  80. Durá-Vilá, V., Mingos, D. M., Vilar, R., White, A. J. P. & Williams, D. J. Reactivity studies of [Pd2(μ-X)2(PBut3)2] (X = Br, I) with CNR (R = 2,6-dimethylphenyl), H2 and alkynes. J. Organomet. Chem. 600, 198–205 (2000).

    Article  Google Scholar 

  81. Sheldrick, G. M. Crystal structure refinement with SHELXL. Acta Crystallogr. C 71, 3–8 (2015).

    Article  Google Scholar 

  82. Sheldrick, G. M. SHELXT—integrated space-group and crystal-structure determination. Acta Crystallogr A 71, 3–8 (2015).

    Article  Google Scholar 

  83. Sheldrick, G. M. A short history of SHELX. Acta Crystallogr A 64, 112–122 (2008).

    Article  CAS  PubMed  Google Scholar 

  84. Dolomanov, O. V., Bourhis, L. J., Gildea, R. J., Howard, J. A. K. & Puschmann, H. OLEX2: a complete structure solution, refinement and analysis program. J. Appl. Crystallogr. 42, 339–341 (2009).

    Article  CAS  Google Scholar 

  85. Mohite, A. R. et al. Thiourea-mediated halogenation of alcohols. J. Org. Chem. 85, 12901–12911 (2020).

    Article  CAS  PubMed  Google Scholar 

  86. Zhu, Q. & Nocera, D. G. Catalytic C(sp3)–O bond cleavage of lignin in a one-step reaction enabled by a spin-center shift. ACS Catal. 11, 14181–14187 (2021).

    Article  CAS  Google Scholar 

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Acknowledgements

We acknowledge O. Green for helpful discussions during the development of the work. We also acknowledge S. Roediger and L. Schlemper for providing chemicals. The NMR service and SMoCC service of ETHZ are acknowledged for their help in variable-temperature-NMR and XRD experiments, respectively. The Morandi group is acknowledged for discussions regarding the project during group meetings and for critically proofreading and providing feedback on the manuscript. ETHZ is thanked for generous funding to all authors.

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  1. Laboratory of Organic Chemistry, Department of Chemistry and Applied Biosciences, ETH Zürich, Zürich, Switzerland

    Michael K. Bogdos, Olivera Stepanović, Alessandro Bismuto, Mauro G. Luraschi & Bill Morandi

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Contributions

M.K.B. conceived the project. All the authors contributed to the design of experiments. M.K.B., O.S., A.B. and M.G.L. performed all the experiments. B.M. supervised the research. All the authors contributed to the writing and editing of the manuscript and Supplementary information. M.K.B. wrote the code used for data analysis and data visualization.

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Correspondence to Bill Morandi.

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Supplementary Information

Supplementary Information main file, Figs. 1–99, synthesis and characterization of compounds, selectivity versus pKaH graphs, intramolecular competition reactions, other observations, X-ray data, NMR spectra.

Supplementary Data 1

Crystallographic data for 31; CCDC reference 2150620.

Supplementary Data 2

Crystallographic data for 34; CCDC reference 2150621.

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Bogdos, M.K., Stepanović, O., Bismuto, A. et al. Mechanistically informed selection rules for competing β-hydride and β-heteroatom eliminations. Nat. Synth 1, 787–793 (2022). https://doi.org/10.1038/s44160-022-00145-x

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