1 / 38

Neil Palmer Chirik Group Seminar August 22, 2013

Radical C-C Bond-forming Reactions Catalyzed by First-row Transition Metals. Neil Palmer Chirik Group Seminar August 22, 2013. Why do we care about radical chemistry?. First-row transition metals often exhibit one-electron redox activity.

nia
Download Presentation

Neil Palmer Chirik Group Seminar August 22, 2013

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Radical C-C Bond-forming Reactions Catalyzed by First-row Transition Metals Neil Palmer Chirik Group Seminar August 22, 2013

  2. Why do we care about radical chemistry? • First-row transition metals often exhibit one-electron redox activity. • We spend a lot of time using redox-active ligands suppress radical chemistry in first-row metals and promote 2-electron reactivity usually seen in precious metals.

  3. Why do we care about radical chemistry? • Many processes take advantage of one-electron chemistry • First-row transition metals can be used to control and catalyze these types of one-electron processes Cyclization Polymerization Oxidation (and Reduction) Tarantino, K. T.; Lieu, P.; Knowles, R. R. J. Am. Chem. Soc.2013, 135, 10022-10025. Hoover, J. M.; Steves, J. E.; Stahl, S. S. NatureProtocols2012, 7 (6), 1162-1166.

  4. First: a brief refresher on organic radicals • Can have π or σ radicals • σ radicals invert rapidly, on the timescale of molecular vibrations, making stereoselective radical chemistry challenging • More substituted radicals are more stable (3° > 2° > 1°); benzyllic or allylic are also stabilized. • Persistent radicals are not short-lived π radicals σ radicals

  5. How are radical mechanisms detected? 1) Clocks • Design substrate such that radical is generated at desired center. • Look for rearrangements in products • Pro: • Provides relative rate information • Potential for interesting cyclization reactions • Con: • Making the substrates Newcomb, M. 2012. Radical Kinetics and Clocks. Encyclopedia of Radicals in Chemistry, Biology and Materials.

  6. How do we detect radical mechanisms? • 2) Radical traps • 3) Kinetic isotope effects (observed in H-atom transfer reactions) • Metal-deuteride usually reacts with olefin faster than metal hydride, causing inverse isotope effects Pro: pseudo-isolation or detection of radical intermediates Cons: trap selectivity or tolerance Pro: inverse isotope effects are solid evidence for atom transfer mechanism Con: pretty much only useful for HAT mechanisms Bullock, R. M.; Samsel, E. G. J. Am. Chem. Soc. 1990, 112, 6886-6898. Seany, R. L.; Halpern, J. J. Am. Chem. Soc.1977, 99, 8335-8337.

  7. How do we detect radical mechanisms? • 4) Spectroscopic methods • CIDNP – chemically induced dynamic nuclear polarization • NMR spectra of reactions with radical mechanisms exhibit changes in peak signal intensities due to spin-selective cage recombination of radicals intermediates. • Pro: Monitors the reaction as it’s being run, • interesting NMR spectra • Con: Must be able to run reaction in a tube • EPR • Pro: Monitors the reaction as it’s being run, • easy to tell if there’s an organic radical • Con: Must be able to run reaction in a • more narrow tube Ward, H. R. Acc. Chem. Res.1972, 5, 18-24.

  8. Old-school reagents for generating alkyl radicals “Flight from the Tyranny of Tin” Baguley, P. A.; Walton, J. C. Angew. Chem. Int. Ed. 1998, 37, 3072-3082

  9. Tin reagents • Abstraction of halides by organotin radical • Addition of organotin radical to C=S double bond of xanthates or thiohydroxamates: Hartung, J.; Pulling, M. E.; Smith, D. M.; Xang, D. X.; Norton, J. R. Tetrahedron 2008, 64, 11822-11830.

  10. “Better” tin reagents • Some Sn reagents facilitate easier disposal • Alternatives to tin hydrides • (Me3Si)3SiH • Bu3GeH • HGaCl2 • HInCl2 • All of these have stronger [M]-H bonds than Bu3SnH, so are less reactive towards H-atom transfer (quenching of radicals). • More recent works use first-row transition metals to catalyze radical generation, propagation, and termination. Baguley, P. A.; Walton, J. C. Angew. Chem. Int. Ed. 1998, 37, 3072-3082

  11. Strategies for initiating radical reactions using transition metals • Oxidative Processes • Atom abstraction (usually halide) • Single electron transfer from substrate to metal • Reductive Processes • Atom transfer to substrate (predominantly H-atom transfer) • Single electron transfer from metal to substrate • To make these processes catalytic, the resting state of the catalyst must be able to be restored by an oxidant/reductant.

  12. Transition metal catalyzed radical C-C bond formation

  13. Transition metal catalyzed radical C-C bond formation

  14. Basics of Intramolecular Radical cyclizations • Intramolecular radical cyclizations follow Baldwin’s rules • For cyclizations to alkenes, usually 5-exo-trig and 6-endo-trig are observed depending on olefin substitution • For substituted alkyl chains, the major cyclized product arises from the Beckwith-Houk rule. Spellmeyer, D. C.; Houk, K. N. J. Org. Chem.1987, 52, 959. Beckwith, A. L. J.; Schiesser, C. H.Tetrahedron1985, 41, 3925.

  15. Atom transfer radical cyclization • Claimed to be the first use of alkyl halides of this type for Cu(I)-mediated chlorine transfer radical cyclization. • However, Cu(I)Cl catalyzed intermolecular addition (and analogous intramolecular cyclization) of polychlorocarbons to acrylates was long-known. Udding, J. H.; Hiemstra, H.; van Zanden, M. N. A.; Speckamp, W. N. Tet. Lett. 1991, 26, 3123-3126. Murai, S.; Sonoda, N.; Tsutsumi, S. J. Org. Chem.1964, 29, 2104.

  16. ATRC Mechanism • Operates by abstraction, cyclization, back transfer • No net change in oxidation state for substrate or copper Udding, J. H.; Tuijp, K. J. M.; van Zanden, M. N. A.; Hiemstra, H.; Speckamp, W. N. J. Org. Chem. 1994, 59, 1993-2003

  17. As it turns out, copper(I) is quite popular • Has also been used to form larger macrocycles • Temperatures/loading/yields all depend on the ligand used • Variety of ligand frameworks have been used • Other scorpionates have also been used • Some of these have been tethered to solid supports • Ru complexes have also been used recently, presumably because they can be used in tandem with other reactivity. Clark, A. J. Chem. Soc. Rev. 2002, 31, 1-11. Pintauer, T. Eur. J. Inorg. Chem. 2010, 2449-2460

  18. Halide oxidation/cyclization without terminal back-transfer • Inclusion of external reductant allows regeneration of [Co(I)] catalyst without a halide back-transfer • Inclusion of reductantand proton source gives saturated heterocycle • hν required for conversion Giese, B.; Erdmann, P.; Göbel, T.; Springer, R. Tet. Lett.1992, 32, 4545-4548.

  19. A recent reminder that this motif still works • Also requires hν. • External base serves to reduce [Co(III)]-H • Strikingly similar substrates Weiss, M. E.; Kreis, L. M.; Lauber, A.; Carreira, E. M. Angew. Chem. Int. Ed. 2011, 50, 11125-11128.

  20. Hydrogen atom transfer: • Directly from metal hydride bonds • Rate of HAT is proportional to [M]-H BDE • To/From ligands • More closely resembles PCET Hartung, J.; Norton, J. R. Catalysis Involving H Transfer Reactions from First-Row Transition Metalsin Catalysis Without Precious Metals; Bullock, R. M.; WILEY-VCH Verlag GmbH & Co. KGaA: Weinheim; 2010 p 1-24. Mayer, J. M. Acc. Chem. Res.2011, 44 (1), 36-46.

  21. C-H bonds adjacent to radicals are weak • An adjacent radical center weakens a C-H bond by ~65 kcal/mol (ethane) Zhang, X. J. Org. Chem. 1998, 63, 1872-1877

  22. Radical cyclization using [M]-H complexes Jack Norton Columbia University Smith, D. M.; Pulling, M. E.; Norton, J. R. J. Am. Chem. Soc. 2007, 129, 770-771

  23. General Strategy • Use of first-row transition metals with weak [M]-H bonds promotes HAT • Ideally, [M]-H is regenerated under H2 • An unsaturated ester is used as an H-atom acceptor to increase the rate of HAT Choi, J.; Tang, L.; Norton, J. R. J. Am. Chem. Soc. 2007, 129, 234-240.

  24. Multiple competing rates to consider • Competing rates of back-transfer, subsequent HAT, and cyclization determine product distribution. • Adding substituents to the ring will increase kcyc(Thorpe-Ingold effect) • kH[M]-Handktr[M] depend on [M]-H BDE

  25. Major [M]-H complexes explored by Norton • Regenerated under H2; most commonly used. • Are not regenerated under H2, so must be used stoichiometrically • Generated in situ under H2from di-aqua complex; [Co]-H BDE not measured • Appears to be stronger than [Cr]-H bond Choi, J.; Pulling, M. E.; Smith, D. M.; Norton, J. R. J. Am. Chem. Soc.2008, 130, 4250-4252. Li, G.; Han, A.; Pulling, M. E.; Estes, D. P.; Norton, J. R. J. Am. Chem. Soc. 2012, 134, 14662-14665.

  26. A handful of diene substrates • Data is consistent with a stronger [M]-H bond in [Co]-H Hartung, J.; Norton, J. R. Catalysis Involving H Transfer Reactions from First-Row Transition Metalsin Catalysis Without Precious Metals; Bullock, R. M.; WILEY-VCH Verlag GmbH & Co. KGaA: Weinheim; 2010 p 1-24. Li, G.; Han, A.; Pulling, M. E.; Estes, D. P.; Norton, J. R. J. Am. Chem. Soc. 2012, 134, 14662-14665.

  27. A handful of diene substrates Hartung, J.; Norton, J. R. Catalysis Involving H Transfer Reactions from First-Row Transition Metalsin Catalysis Without Precious Metals; Bullock, R. M.; WILEY-VCH Verlag GmbH & Co. KGaA: Weinheim; 2010 p 1-24 Hartung, J.; Pulling, M. E.; Smith, D. M.; Xang, D. X.; Norton, J. R. Tetrahedron 2008, 64, 11822-11830.

  28. HAT to alkynes • HAT to alkynes is slower than to alkenes “because alkynes react with radicals more slowly than olefins do.” With this [Cr]-H, rate of HAT is ~6 times slower to phenylacetylene than to styrene. • More substituted alkynes accept H atoms even more slowly HAT to diphenylacetylene ~20 times slower than to phenylacetylene Estes, D. P.; Norton, J. R.; Jockusch, S.; Sattler, W. J. Am. Chem. Soc. 2012, 134, 15512-15518. Fischer, H.; Radom, L. Angew. Chem., Int. Ed. 2001, 40, 1340.

  29. HAT-catalyzed cyclization of enyne substrates • So far, just a single substrate reported as proof of concept. • Longer reaction times required than for diene substrates. Estes, D. P.; Norton, J. R.; Jockusch, S.; Sattler, W. J. Am. Chem. Soc. 2012, 134, 15512-15518.

  30. HAT-catalyzed cyclization of enyne substrates Proposed Mechanism: • Is the vinyl radical doing the cyclization? • Product 13 is never observed due to “fast isomerization to 10” Estes, D. P.; Norton, J. R.; Jockusch, S.; Sattler, W. J. Am. Chem. Soc. 2012, 134, 15512-15518.

  31. Other radical cyclization mechanisms Wilfred van der Donk University of Illinois Urbana-Champaign McGinley, C. M.; Relyea, H. A.; van der Donk, W. A. Synlett2006, 2, 211-214

  32. Interesting mechanistic considerations • With simple styrenes, this system produces tertiary dimers (no polymers) • Their proposed pathway: • Benzylcobalamin • Co-C bond: estimated ~23 kcal/mol • They suggest that • radical character is • generated through • homolysis of a secondary • or tertiary Co(III)-alkyl Shey, J.; McGinley, C. M.; McCauley, K. M.; Dearth, A. S.; Young, B. T.; van der Donk, W. A. J. Org. Chem. 2002, 67, 837-846

  33. Transition metal catalyzed radical C-C bond formation

  34. Radical Polymerization • As with radical cyclization reactions, polymerizations can be initiated and controlled by halide or H atom transfers • Atom transfer radical polymerization (ATRP) – control by atom transfers, usually halides • Catalytic chain transfer (CCT) – control by H-atom transfers

  35. Simplified kinetic considerations for radical polymerizations • CCT as an example • Rate of initiation (kH) and rate of back transfer (ktr) are dependent on [M]-H BDE • Chain transfer constant, Cs= ktr/kpindicates the “efficiency” of chain-transfer • Larger values for Cs result in shorterpolymer length • This means larger ktr (stronger [M]-H bonds) results in shorter polymers and vice-versa • ATRP is similar, where chain deactivation occurs by atom transfer from the metal catalyst back to the radical. kH kp ktr

  36. ATRP catalysts • A lot of things have been tried… • Iron • Nickel • Many of these catalysts are not very thermally stable • Copper(I), again, is the best • A multitude of bi- ,tri- ,and tetradentate N-chelating ligands Matyjaszewski, K.; Xia, J. Chem. Rev. 2001, 101, 2921-2990.

  37. CCT catalyst examples • Variations of the Norton HAT catalysts also act as CCT catalysts • Norton’s Vanadium hydride complexes have low Cs values due to the low [V]-H BDE • Not surprisingly, cobaloxime catalysts have the highest efficiency. • Choi, J.; Norton, J. R. Inorg. Chim. Acta. 2008, 361, 3089-3093. • Abramo, G. P.; Norton, J. R. Macromolecules2000, 33, 2790. • Gridnev, A. A.; Ittel, S. D. Chem. Rev. 2001, 101, 3611-3659.

  38. Summary • Atom transfer reactions are useful for carbon-based radical formation and subsequent C-C bond formation, mostly in cyclization and polymerization chemistry. • For halide atom transfers, Cu(I) salts work really, really well. • For HAT from metal hydrides, weaker BDEs ([V]-H) increase rates of desired reactions, but also increase undesired hydrogenation rate. Stronger BDEs ([Co]-H) slow reaction and increase undesired isomerization. • Macrocyclic cobalt compounds do a lot of radical chemistry

More Related