Redox Non-Innocent Ligands as Electron Reservoirs in Catalysis

edox on-innocent Ligands as Electron eservoirs in Catalysis Carina Jette toltz/eisman Literature etings 3/9/2018

edox-active Ligands: ome Definitions Jørgenson, 1966: Chirik, 2010: "Ligands are innocent when they allow the oxidation state of the central atoms to be defined" therefore: non-innocent ligands: formal and spectroscopically determined oxidation state of the metalligand system is ambiguous "edox-active, or 'noninnocent,' ligands have more energetically accessible levels that allow redox reactions to change their charge state." edox on-innocent Ligands: arry Gray, 1960's: i i III, 4 - i i II, 1L, 3 - which resonance structure is the main contributor? Is the M primarily ligand or metal-based? Coord. Chem. ev. 1966, 1, 164. Inorg. Chem. 2011, 50, 9752-9765. Inorg. Chem. 2011, 50, 9741-9751.

Jørgenson, 1966: edox-active Ligands: ome Definitions Chirik, 2010: "Ligands are innocent when they allow the oxidation state of the central atoms to be defined" therefore: non-innocent ligands: formal and spectroscopically determined oxidation state of the metalligand system is ambiguous "edox-active, or 'noninnocent,' ligands have more energetically accessible levels that allow redox reactions to change their charge state." edox -active ligands can be: on-innocent ligands: not all non-innocent ligands are redox-active today! This term is also used to indicate the perturbation of metal coordination due to unexpected reactivity at the ligand in response to external stimuli (i.e. Protonation/deprotonation) Cooperating ligands: a ligand in a metal complex tht actively participates in substrate activation Bifunctional catalysts: a catalyst comprised of two different functionalities that activate both substrates within the same scaffold BUT: not all non-innocent ligands, cooperating ligands, and bifunctional catalysts are redox active ligands! Coord. Chem. ev. 1966, 1, 164. Inorg. Chem. 2011, 50, 9752-9765.

Types of edox-active Ligands i.modulation of reactivity of metal (LA): L M +n -e - M +n L iii. involved in substrate bond breaking/making - M L M L pectator L M reactant L M M L Actor: reactant ii. electron reservoir: iv. reactive ligand radical L n M - L n+2 M L M +n L M (n+1) AC Catal. 2012, 2, 270-279.

edox-active Ligands as Electron eservoirs xidative Addition with Innocent Ligands - L M L M n+2 xidative Addition with edox-active Ligands L M - L n+2 M eductive Elimination from Zr(IV): 2- TF Zr TF TF Zr Zr IV, 2L, 2 Zr IV, 4 - xidation state of metal remains unchanged - Ligands are not directly involved in the bond-forming process - tore reducing equivalents in the ligand, rather than the metal - ature's enzymes operate close to the thermodynamic potential - Impart novel reactivity patterns to certain transition metals -Chirik: give noble character to first row transition metals Chem. Eur. J. 2015, 21, 4308-4314.

Aminophenols: a well-established class of redox-active ligands - inspired by galactose oxidase: (catalyzes the oxidation of alcohols to aldehydes) is is Tyr Cu II Tyr hydrogen abstraction (rds) Tyr is is Cu II Tyr Proton transfer Tyr is is Cu II Tyr - aminophenols shuttle between 3 distinct states: - -2 + - - e - e aminophenol amidophenolate iminosemiquinonate iminoquinone - related to quinones ( adds another functional handle, more coordinating) - iminoquinones have lower reduction potential - fine tune M-L complex (electrophilicity, bond lengths) - complex synthesis varies - Cu, i, Fe, Pt, Pd, u, s Coord. Chem. ev. 2009, 253, 291-324.

Copper and Zinc-catalyzed Aerobic oxidation of alcohols catalysts: 0.01-2.5 mol % catalyst =, Et Et 3, TF, rt, 2 40 h M II confirmed by EP, Magnetic and electrochemical data stoichiometric (anaerobic conditions), catalytic (aerobic) M = Cu II, TF = 0.03 s -1 (5000 turnovers in 50 h) M = Zn II, TF = 0.002 s -1 can access 5 different ligand-centered oxidation states (both Zn and Cu) Active Cu catalyst generated from: Cu 2 2 2 M II J. Am. Chem. oc. 1999, 121, 9599-9610.

chanism for the aerobic oxidation of alcohols 2 2 2 M II C 2 coordination M II M II electron transfer M = Cu II, Zn II M II intramolecular -atom abstraction (r.d.s) J. Am. Chem. oc. 1999, 121,9599-9610.

A to Zr(IV): disproportionation of hydrazine eyduk and coworkers, 2008 2 10 mol % catalyst 24 h, rt 2 2 L Zr L L educed Ligand Zr IV - d 0 metal catalyzing a multielectron reaction through the use of ligand-based valence changes - disproportionation is thermodynamically favorable - electrophilic metal coupled with redox properties of the ligand - control reactions with Zr( 4 (TF) 2, Zr() 4, Zr() resulted in J. Am. Chem. oc. 2008, 130, 2728-2729. Inorg. Chem. 2011, 50, 9849-9863.

A to Zr(IV): disproportionation of hydrazine elimination 2 L Zr L L educed Ligand Zr IV L coordination L Zr L 2 educed Ligand Zr IV L Zr L educed Ligand Zr IV oxidation of hydrazine L Zr L xidized Ligand Zr IV (detected by UV-vis absorption) 2 elimination "A" J. Am. Chem. oc. 2008, 130, 2728-2729. Inorg. Chem. 2011, 50, 9849-9863.

egishi couplings with Co III oper and coworkers, 2010: ZnBr Co III catalyst 15% yield chanism: Ligand centered radical pseudo oxidative addition - - Co III nucleophilic, triplet ground state Co III e - for A stem from ligand EI-M, deuterium labeling, -ray structure mech studies- similar trends to 2 displacement no follow up reports -' 'Zn J. Am. Chem. oc. 2010, 132, 14358-14360.

Fe(III)-catalyzed synthesis of -eterocycles 3 Boc 2 LFe III (5 mol %) C 6 6, 100 C, 24 h Boc Fe III LFe III Catalyst synthesis: 1. Fe 3, air, -80 C 2. Et 3, air, -80 C-rt Fe III Characterized by: - UV-vis spectroscopy (semiquinone) - Magnetic susceptibility ( = 2 ground state) - confirmed spin by QUID and Mössbauer - -ray structure determination (geometry, BL's) - DFT calculations (5.3 kcals to = 3) - Löwdin population analysis (4 unpaired electrons) - CV for 1e - reduction and oxidation potentials LFe III air stable, recyclable catalyst - linear, Boc protected amine was the main byproduct - for Pd version see: J. Am. Chem. oc. 2014, 136, 11574-11577. J. Am. Chem. oc. 2017, 139, 5117-5124

Fe(III)-catalyzed synthesis of -eterocycles Van der Vlugt et. al, 2017 3 Boc 2 LFe III (5 mol %) C 6 6, 100 C, 24 h Boc Fe III LFe III Boc Boc Bn Boc Et Boc 96% yield 51% yield 39% yield 90% yield Boc Boc Boc Boc 48% yield 46% yield 44% yield 95% yield air stable, recyclable catalyst - linear, Boc protected amine was the main byproduct - for Pd version see: J. Am. Chem. oc. 2014, 136, 11574-11577. J. Am. Chem. oc. 2017, 139, 5117-5124

Fe(III)-catalyzed synthesis of -eterocycles Boc 2 Fe III Boc 2 catalyst activation zero-order in substrate: activation of azide is not rds no Boc 2, no azide-fe complex [L Fe III ]* [LFe III ]* activated catalyst 3 nitrene insertion azide coordination [L Fe IV ]* [L 0 Fe III ]* nitrene stabilization [L Fe III ]* 2 [L Fe III ]* 2 loss 2 J. Am. Chem. oc. 2017, 139, 5117-5124

Fe(III)-catalyzed synthesis of -eterocycles: Possible modes of catalyst activation Chloride Dissociation Boc 2 Fe III, C 2, - Fe III LFe III eaction with the Ligand Fe III Boc 2 C 2, - Fe III LFe III J. Am. Chem. oc. 2017, 139, 5117-5124

Copper-Catalyzed Aziridination Ts complex 1 (1 mol%) I C 2 2, rt, 20 min 5 equiv 1 equiv 99% yield Ts Cu II complex 1 F Ts 97% 65%, 2h Ts Ts Ts 86%, 2h 29%, overnight Ts Ts Ts Ts 44%, overnight 86%, 3h 73%, overnight 23%, overnight Ts Ts Ts Ts 36%, overnight 12%, overnight 81%, 5 h 47%, overnight * reaction is not air sensitive, all run under air Chem. Eur. J. 2018, 24, 1-6.

Copper-Catalyzed Aziridination: edox Active ligand for spin fluxionality Cu II I Ts = 1/2 rt = 3/2 I ITs I Ts Ts Cu II Ts = 3/2 Cu II Ts I Ts Cu II Ts = 1/2 - Cu (II) is maintained throughout - UV-Vis, YCE, time dpt DFT, variable temp EP, broken symmetry calculations redox active ligand allows for access to different spin states at rt (energy diff is low) Chem. Eur. J. 2018, 24, 1-6.

2,6-Diiminepyridine Ligand as an Electron eservoir Chirik and coworkers, 2006: 10 mol% catalyst 23 C, 2-5 h = C 2, Alk, C(C 2 Et) 2 up to 95% yield 2 Fe 2 Fe II reduced ligand Catalyst ynthesis: Fe Fe II oxidized ligand 0.5% a(g) 2 atmosphere toluene Fe 2 2 or: Fe 2 2 Fe II reduced ligand The ligand stores two reducing equivalents in an iron(ii) complex! -ay crystal structure, Mössbauer, QUID, DFT J. Am. Chem. oc. 2006, 128, 13340-13341.

2,6-Diiminepyridine Ligand as an Electron eservoir - energetically favorable Fe II 10 mol% catalyst 23 C, 2-5 h = C 2, Alk, C(C 2 Et) 2 up to 95% yield -electrons for A/ E stem from ligand L Fe L Fe II reduced ligand - DFT, experimental, spectroscopic, crystal structure Ar Fe II oxidized ligand Fe Ar Ar Fe Ar Fe II reduced ligand J. Am. Chem. oc. 2012, 134, 17125-17137. J. Am. Chem. oc. 2006, 128, 13340-13341.

2,6-Diiminepyridine Ligand as an Electron eservoir 1,6- enyne cycloaddition E 5 mol% 1-( 2 ) 2 4 atm 2, 23 C 1-3h =, TM E = Ts, Bn, (EtC 2 ) 2 C E 70-95% yield 2 Fe 2 ydrogenation of olefins: 1-( 2 ) 2 =, C(), C 2 Et, 2 0.3-5 mol% 1-( 2 ) 2 4 atm 2, 23 C 15 min-24 h up to 95% yield ydrosilylation: TM TM i 200 ppm 1-( 2 ) 2 < 15 min, 23 C TM i TM ydroboration: B 1 mol% 1-( 2 ) 2 rt, 15 min-24 h B > 98 % yield in most examples J. Am. Chem. oc. 2009, 131, 8772-8774. rganometallics, 2008, 27, 1470-1478. cience, 2012, 335, 567 570. AC Catal. 2012, 2, 2169-2172. rg. Lett. 2013, 15, 2680-2683.

2,6-Diiminepyridine Ligand as an Electron eservoir: The eal tory 10 mol% catalyst -Ligand helps adopt Fe III - - C-C E over β- elim. - Ligand prevents Fe(0) 23 C, 2-5 h = C 2, Alk, C(C 2 Et) 2 up to 95% yield Fe L Fe I Ar Fe Ar Ar Fe Ar Fe III -Isolated metallocyclic intermediates -magnetochemistry, Mössbauer, DFT Fe I J. Am. Chem. oc. 2012, 134, 17125-17137. J. Am. Chem. oc. 2006, 128, 13340-13341. J. Am. Chem. oc. 2013, 135, 4862-4877.

2,6-Diiminepyridine Ligand as an Electron eservoir: The eal tory -1 e - at oxidation of both L and Fe 5 mol % 1-( 2 ) 2 4 atm 2, 23 C 1-3 h Fe L Fe II Ar Fe Ar Ar Fe Ar Fe III -Isolated metallocyclic intermediates -magnetochemistry, Mössbauer, DFT 2 Fe III J. Am. Chem. oc. 2012, 134, 17125-17137. J. Am. Chem. oc. 2006, 128, 13340-13341. J. Am. Chem. oc. 2013, 135, 4862-4877.

2,6-Diiminepyridine Ligand as an Electron eservoir: Intermolecular 2+2 omo-dimerization: 2 = alkyl, benzyl 1 mol% Fe cat. 1 neat, 23 C, 48 h 14-85% yield ' ' Fe 2 ' ' ' = C 5 9 Fe cat. 1 ' ' etero-coupling: 5 mol% Fe cat. 2 neat, 23 C, 48 h ipr Fe 2 ipr 5 equiv = alkyl 80-98% yield 95:5 dr in most cases ipr ipr Fe cat. 2 no homo-dimerization no 4+2 cycloaddition products With Cobalt: J. Am. Chem. oc. 2015, 137, 7903-7914. AC Catal., 2016, 6, 2632-2636. cience, 2015, 349, 960-963.

Fe-catalyzed C- activation/arylation Fensterbank et al, 2014 Br L-FeBr 2 (15 mol%) KMD, 80 C, 18 h L Et TB 53% yield 20% yield 35% yield 35% yield Bn TM 7% yield 16 % yield 50% yield 26% yield 2 F CF 3 55% yield 20% yield 41% yield Chem. Eur. J. 2014, 20, 4754-4761.

Fe-catalyzed C- activation/arylation Fensterbank et al, 2014 Br L-FeBr 2 (15 mol%) KMD, 80 C, 18 h L May proceed through a metal-based inner-spere C- activation TM ET from KMD Fe Br TM chanistic studies show: - structure of the base is more important than basicity - not a homolytic aromatic substitution - spectroscopy- ligand centered radical - DFT calculations- - electron transfer from base to starting complex (ligand-centered radical) - -abstraction to form Fe-C bond Putative transition state for C- activation Chem. Eur. J. 2014, 20, 4754-4761. Chem. Cat. Chem. 2016, 8, 3310-3316.

Vicic and coworkers, 2006: i-catalyzed C(sp 3 )-C(sp 3 ) cross couplings I C 5 11 ZnBr i(cd) 2 (5 mol%) ligand (5 mol%) TF, 23 h, rt 98% yield C 5 11 chanism: i II -alkyl cation w/reduced ligand Zn i II ' I DFT/EP - evidence for organic π system-based radical ligand-based alkyl halide reduction I i I i II ' I otes: - o ligand, - no E from a 2 i II species - imine-type ligand is critical to reactivity - thermodynamically favorable - reduction ' i III I J. Am. Chem. oc. 2006, 128, 13175-13183 Chem. Commun. 2005, 4211-4213. Chem. Cat. Chem. 2016, 8, 3310-3316. J. Am. Chem. oc. 2004, 126, 8100-8101.

Catalytic ydrogenation with Bis(arylimidazol-2-ylidene)pyridine Co complexes Chirik and coworkers: catalyst: ' = alkyl, aryl ' = C 2 Et, alkyl, aryl 5 mol% cat. 4 atm 2 benzene, 1-120 h ' > 95% yield Co 2 Evidence for Pyridyl-based adical intermediate: Ar Co Ar 1 atm 2 minutes, 22 C Co 2 Ar Ar confirmed by -ray diffraction Co 2 - M analysis of intermediates, - EP: ligand-centered radical Chiral cobalt hydrogenation catalysts: - -ray crystal structure J. Am. Chem. oc. 2012, 134, 4561-4564. - spin density calculations - DFT J. Am. Chem. oc. 2013, 135, 13168-13184.

What about more common ligands such as B/ PyBox?

What about more common ligands such as B/ PyBox? eduction Potentials of free ligands: Et Et Et Et -2.62 V -2.72 V -2.55 V -2.83 V -2.64 V -2.53 V Cyclic voltammograms were recorded in TF solution (~ 1 mm in compound) with [nbu4]pf6 electrolyte (~ 0.1 M), using a 3 mm glassy carbon working electrode, Pt wire counter electrode, and Ag/Ag+ reference electrode. Values are reported versus ferrocene/ferrocinium emember: ΔG = -nfε, the more positive the P, the greater the affinity for electrons or tendency to be reduced - more electron rich ligands, lower P - PyBox ligands fall within the range of the bis(imino)pyridine ligands rganomet. 2009, 28, 3928-3940.

What about more common ligands such as B/ PyBox? ynthesis of the reduced Fe(PyB) complexes: Fe 0.5% a(g) 2 atmosphere toluene Fe L L Chirik and coworkers: synthesis of active Fe catalyst for 2+2, alkene hydrogenation, etc. Fe 0.5% a(g) 2 atmosphere toluene Fe only bis(chelate) was isolated under a wide variety of reduction conditions Fe 0.5% a(g) C atmosphere toluene Fe C C compared I-stretching frequency - ligands are more electron donating than bis(imino)pyridine, less likely to be reduced - PyBox and B exhibited decent reactivity but low enantioselectivity in hydrosilylation of ketones - not as efficient as bis(imino)pyridines, more info is needed to confirm similar reaction pathway - bis(chelate) formation is principal catalyst deactivation pathway rganomet. 2009, 28, 3928-3940.

What About more common ligands such as PyBox/ Box? Greg Fu (2014): Br n-bu TM racemic 2 Zn 1.6 equiv 3.0 mol % ibr 2 DME 3.9 mol % (-)--pybox DME, -20 C, 17h TM 77% yield 82% ee n-bu EP spectrum of proposed intermediate: i I ipr revised mechanism doesnt involve this intermediate EP spectrum of (--pybox)i I (2; black) and corresponding fit (red). Fit parameters: g1 = 2.0067, g2 = 2.0075, g3 = 1.9889, 14 coupling (Mz) = 0.0205, 0.0124, 47.2047, line width = 0.9929. -band EP spectra were collected at 77 K in a toluene glass at œö = 9.411 Gz at 2 mw power and a modulation amplitude of 2 G. (reproduced from JAC, 2014, 136, 16588-16593) axial signal at g = 2.00, indicative of coupling to a single 14 in one g component, which is consistent with a largely ligand-centered radical J. Am. Chem. oc. 2014, 136, 16588-16593.

utlook Ligand Characteristics: Ar Ar Ar - high degree of delocalization - itrogen is key! verall conclusions: - Limited scope- - ow should they be studied? - sterics: Tolman angle, % buried volume, etc - electronics: Crabtree: CV of free ligand, ligand bound to redox-inactive metal - establish, ID radical ligands, physical/chemical consequences - ole of tal in the reaction- structural stability or crucial role? - Versatile new tools Chem. oc. ev. 2013, 42, 1440-1459.

ome eviews: Fensterbank, Chem. Cat. Chem. 2016, 8, 3310-3316. Crabtree, Chem. oc. ev. 2013, 42, 1440-1459. Caulton, Eur. J. Inorg. Chem. 2012, 435-443. Kaim. Inorg. Chem. 2011, 50, 9752-9765. Ward, Angew. Chem. Int. Ed. 2012, 51, 10228-10234. van der Vlugt, Chem. oc. ev., 2015, 44, 6886-6915. de Bruin, AC Catal. 2012, 2, 270-279.