Switchable Catalysis

Switchable Catalysis hν 1 hν 2 Tiffany Chen MacMillan Lab June 5, 2018

Switchable Catalysis: Inspiration from ature the synthetic machinery of natural systems makes complex polymers with fine temporal and spatial control example: actin filament polymerization provides structure and allows cells to move initiation, chain-growth, and cross-linking regulated by >100 accessory proteins Pollard, T.D.; Cooper, J.. Science 2009, 326, 1208.

Switchable Catalysis: Inspiration from ature the synthetic machinery of natural systems makes complex polymers with fine temporal and spatial control enzymatic activity modulated through feedback loops and trigger-induced effects to prevent parallel reactions in ature from interfering with one another: operations must be controlled function must be switchable switching must be reversible switchable catalysis toggling chemical reactivity of a catalyst between multiple distinct states through application of external stimuli basic requirements for switches: bistability: occurrence of 2 forms of molecule that can be interconverted by an external stimulus fast response times thermal stability fatigue resistance

Switchable Catalysis: Inspiration from ature switchable catalysis toggling chemical reactivity of a catalyst between multiple distinct states through application of external stimuli basic requirements for switches: bistability: occurrence of 2 forms of molecule that can be interconverted by an external stimulus fast response times thermal stability fatigue resistance Stoll, R.S.; echt, S. ngew. Chem. Int. Ed. 2010, 49, 5054.

Switchable Catalysis switchable catalysis: biological inspiration types of switchable external stimuli light p ion coordination redox switching mechanical forces

Switchable Catalysis switchable catalysis: biological inspiration types of switchable external stimuli light p ion coordination redox switching mechanical forces

Light-Gated Catalysis light is an attractive external regulator: low-cost, ubiquitous, noninvasive, precise control initiates and regulates complex processses with precision in ature e.g., photosynthesis, vision) types of photocontrol of catalytic activity photoswitchable catalysis photocaged catalysis photocatalysis cat* cat* reactive cat* hv 1 hv 2 k 1 cat cat k 2 k 1 k 2 hv cat inactive cat reactive inactive hv cat reversible toggling between active and inactive catalytic states irreversible formation of active catalytic state transient excited state is reactive Stoll, R.S.; echt, S. ngew. Chem. Int. Ed. 2010, 49, 5054. elson,.m.; iewlawski, C.W. CS Catal. 2013, 3, 1874.

Light-Gated Catalysis light is an attractive external regulator: low-cost, ubiquitous, noninvasive, precise control initiates and regulates complex processses with precision in ature e.g., photosynthesis, vision) types of photocontrol of catalytic activity photoswitchable catalysis photocaged catalysis photocatalysis cat* cat* reactive cat* hv 1 hv 2 k 1 cat cat k 2 k 1 k 2 hv cat inactive cat reactive inactive hv cat reversible toggling between active and inactive catalytic states irreversible formation of active catalytic state transient excited state is reactive catalytic activity from ground-state species Stoll, R.S.; echt, S. ngew. Chem. Int. Ed. 2010, 49, 5054. elson,.m.; iewlawski, C.W. CS Catal. 2013, 3, 1874.

Light-Gated Catalysis a photoswitchable catalyst involves a catalytically active species that undergoes a reversible photochemical transformation altering its catalytic properties azobenzene/stilbene hv X X 1 X X hv 2 X =, C diarylethene hv 1 R R X R X R hv 2 R X R R X R X = S,, R spiropyran hv 1 hv 2 elson,.m.; iewlawski, C.W. CS Catal. 2013, 3, 1874.

Light-Gated Catalysis photoswitchable base catalysis 365 nm > 400 nm accessible basic site basicity of deshielded Z isomer increases by almost an order of magnitude accessible basic site Peters, M.V.; Stoll, R.S.; Kuhn,.; echt, S. ngew. Chem. Int. Ed. 2008, 47, 5968.

Light-Gated Catalysis photoswitchable base catalysis 365 nm > 400 nm accessible basic site 2 2 E- or Z-cat (10 mol%) T, rt 2 2 k Z /k E = 35.5 photoreversible steric shielding in a small molecule catalyst Peters, M.V.; Stoll, R.S.; Kuhn,.; echt, S. ngew. Chem. Int. Ed. 2008, 47, 5968.

Light-Gated Catalysis i-pr chiral Cu chelation high enantioselectivity S S 313 nm > 434 nm S S no Cu chelation low enantioselectivity i-pr i-pr i-pr large geometrical change induces change in orientation 2 C 2 Et Cu(L) (10 mol%) enantiomer C 2 Et of key sites on catalyst (cooperative effect) C 2 Et enantiomer ligand trans cis d.r. 30 50 55:45 5 5 63:37 in situ photoinduced ring-opening first in situ photoswitching of stereoselective catalysis Sud, D.; orsten, T..; randa,.r. ngew. Chem. Int. Ed. 2005, 44, 2019.

Light-Gated Catalysis i-pr chiral Cu chelation high enantioselectivity S S 313 nm > 434 nm S S no Cu chelation low enantioselectivity i-pr i-pr i-pr 2 C 2 Et Cu(L) (10 mol%) C 2 Et enantiomer C 2 Et enantiomer ligand trans cis d.r. 30 50 55:45 5 5 63:37 in situ photoinduced ring-opening first in situ photoswitching of stereoselective catalysis Sud, D.; orsten, T..; randa,.r. ngew. Chem. Int. Ed. 2005, 44, 2019.

Light-Gated Catalysis i-pr chiral Cu chelation high enantioselectivity S S 313 nm > 434 nm S S no Cu chelation low enantioselectivity i-pr i-pr i-pr 2 C 2 Et Cu(L) (10 mol%) C 2 Et enantiomer C 2 Et enantiomer ligand trans cis d.r. 30 50 55:45 5 5 63:37 limitation: photoinduced ring-closing inefficient with Cu(I) only 23% of closed form at stationary state at 313 nm Sud, D.; orsten, T..; randa,.r. ngew. Chem. Int. Ed. 2005, 44, 2019.

Light-Gated Catalysis photoinduced changes in electronic properties to alter catalytic activity UV S S visible light S S electronically insulated (inactive) electronically connected (active) mimic of bioactive form of vitamin 6 (pyridoxal 5 -phosphate, PLP) proof-of-concept: photoinduced regulation of biomimetic, small molecule cofactors R C 2 2 R C 2 R R 2 C 2 R R PLP aldimine quinonoid Wilson, D.; randa,.r. ngew. Chem. Int. Ed. 2012, 51, 5431.

Light-Gated Catalysis photoinduced changes in electronic properties to alter catalytic activity UV S S visible light S S electronically insulated (inactive) electronically connected (active) mimic of bioactive form of vitamin 6 (pyridoxal 5 -phosphate, PLP) proof-of-concept: photoinduced regulation of biomimetic, small molecule cofactors R C 2 2 R C 2 R R 2 C 2 R R PLP enzyme cofactor responsible for amino acid metabolism Wilson, D.; randa,.r. ngew. Chem. Int. Ed. 2012, 51, 5431. aldimine quinonoid

Light-Gated Catalysis photoinduced changes in electronic properties to alter catalytic activity UV S S visible light S S electronically insulated (inactive) electronically connected (active) D 3 D C 2 D catalytic activity for racemization of L-alanine catalyst (20 mol%) L-d 5 -alanine dependent on electronic connectivity between functional groups D 3 C 2 D L-d 4 -alanine CD 3 C 2 D/D 2 D D 3 C 2 D D-d 5 -alanine /D-exchange to monitor catalytic racemization Wilson, D.; randa,.r. ngew. Chem. Int. Ed. 2012, 51, 5431.

Light-Gated Catalysis photoinduced changes in electronic properties to alter catalytic activity UV S S visible light S S electronically insulated (inactive) electronically connected (active) D 3 D C 2 D catalyst (20 mol%) L-d 5 -alanine D 3 C 2 D CD 3 C 2 D/D 2 D L-d 4 -alanine D 3 C 2 D D-d 5 -alanine after 140 h at 40 o C: 30% conversion with ring-closed catalyst < 3% conversion with ring-opened Wilson, D.; randa,.r. ngew. Chem. Int. Ed. 2012, 51, 5431.

Light-Gated Catalysis light is an attractive external regulator: low-cost, ubiquitous, noninvasive, precise control initiates and regulates complex processses with precision in ature e.g., photosynthesis, vision) types of photocontrol of catalytic activity photoswitchable catalysis photocaged catalysis photocatalysis cat* cat* reactive cat* hv 1 hv 2 k 1 cat cat k 2 k 1 k 2 hv cat inactive cat reactive inactive hv cat reversible toggling between active and inactive catalytic states irreversible formation of active catalytic state transient excited state is reactive catalytic activity from ground-state species Stoll, R.S.; echt, S. ngew. Chem. Int. Ed. 2010, 49, 5054. elson,.m.; iewlawski, C.W. CS Catal. 2013, 3, 1874.

Light-Gated Catalysis light is an attractive external regulator: low-cost, ubiquitous, noninvasive, precise control initiates and regulates complex processses with precision in ature e.g., photosynthesis, vision) types of photocontrol of catalytic activity photoswitchable catalysis photocaged catalysis photocatalysis cat* cat* reactive cat* hv 1 hv 2 k 1 cat cat k 2 k 1 k 2 hv cat inactive cat reactive inactive hv cat reversible toggling between active and inactive catalytic states irreversible formation of active catalytic state transient excited state is reactive Stoll, R.S.; echt, S. ngew. Chem. Int. Ed. 2010, 49, 5054. elson,.m.; iewlawski, C.W. CS Catal. 2013, 3, 1874.

Photocontrolled Living Radical Polymerization light used to reversibly activate/deactivate living radical polymerization why light? high degree of temporal control over chain growth highly responsive external control *Ir III P n r Ir IV P n R Ir III in absence of light, no excited state Ir polymerization rests in bromo-capped dormant state reactivation upon reexposure to light Ir III = fac-[ir(ppy) 3 ] Et Ph r Ir III (0.005 mol%) 50 W lamp, DM, rt Et Ph r n C 2 initiator MM monomer bromo-terminated chain end ors,.p.; awker, C.J. ngew. Chem. Int. Ed. 2012, 51, 8850.

Photocontrolled Living Radical Polymerization light used to reversibly activate/deactivate living radical polymerization ln([m 0 ]/[M t ]) vs. time of light exposure linear relationship between M n and conversion polymerization stops immediately without light existing chain ends reactivated no new chain ends initiated during polymerization ors,.p.; awker, C.J. ngew. Chem. Int. Ed. 2012, 51, 8850.

Photocontrolled Living Radical Polymerization light used to reversibly activate/deactivate living radical polymerization ln([m 0 ]/[M t ]) vs. time of light exposure linear relationship between M n and conversion polymerization stops immediately without light existing chain ends reactivated no new chain ends initiated during polymerization ors,.p.; awker, C.J. ngew. Chem. Int. Ed. 2012, 51, 8850.

Photocontrolled Living Radical Polymerization light used to reversibly activate/deactivate living radical polymerization a living polymerization should give efficient block copolymer formation Et Ph r Ir III (0.005 mol%) 50 W lamp, DM, rt Et Ph r n C 2 M W /M n = 1.28 macroinitiator Et Ph r n m C 2 C 2 n Ir III (0.01 mol%) 50 W lamp, DM, rt n efficient block copolymer formation - LRP little to no starting macroinitiator minimal termination occurring during polymerization ors,.p.; awker, C.J. ngew. Chem. Int. Ed. 2012, 51, 8850.

Switchable Catalysis switchable catalysis: biological inspiration types of switchable external stimuli light p ion coordination redox switching mechanical forces

Switchable Catalysis switchable catalysis: biological inspiration types of switchable external stimuli light p ion coordination redox switching mechanical forces

p-driven Switching chemically driven processes based on changes in p common in both ature and molecular machines in catalysis, p-switching can modify catalyst solubility 2 2 Cl Ru Cl + benzene 2 Cl Cl Ru 2 RMP RMP 80% yield in 28 min n n catalyst removal after metathesis can be challenging after protonation, efficient removal of Ru catalyst by filtration alof, S.L.; P Pool, S.J.; erger,.j.; Valente, E.J.; Shiller,.M.; Schanz,.-J. Dalton Trans. 2008, 5791.

Redox Switching control of oxidation state of redox-active ligands to mediate catalytic activity i-pr Ti e i-pr e gtf Cp* 2 e + gtf Cp* 2 e + g g Cp* Cp* 2 e 2 e i-pr Ti e i-pr e Gregson, K..G.; Gibson, V.C.; Long,.J.; Marshall, E.L.; xford, P.J.; White,.J.P. J. m. Chem. Soc. 2006, 128, 7410.

Redox Switching control of oxidation state of redox-active ligands to mediate catalytic activity i-pr Ti e i-pr e rapid 2e - + 2e - slow n k red /k ox = ~ 30 i-pr Ti e i-pr e lactide polymerization known to be slow for e-deficient Ti IV -salen catalysts Gregson, K..G.; Gibson, V.C.; Long,.J.; Marshall, E.L.; xford, P.J.; White,.J.P. J. m. Chem. Soc. 2006, 128, 7410.

Redox Switching control of oxidation state of redox-active ligands to mediate catalytic activity i-pr Ti reversible nature of redox event demonstrates switching effect e i-pr e rapid 2e - + 2e - slow n i-pr Ti e i-pr e before oxidation: k app = 4.73 x 10-6 s -1 after (Cp*) 2 e added: k app = 4.98 x 10-6 s -1 k app = rate of propagation Gregson, K..G.; Gibson, V.C.; Long,.J.; Marshall, E.L.; xford, P.J.; White,.J.P. J. m. Chem. Soc. 2006, 128, 7410.

Redox Switching control of oxidation state of redox-active ligands to mediate catalytic activity i-pr Ti reversible nature of redox event demonstrates switching effect e i-pr e rapid can redox-switching 2e - + 2e - be used to make micro-block copolymers? slow n i-pr Ti e i-pr e before oxidation: k app = 4.73 x 10-6 s -1 after (Cp*) 2 e added: k app = 4.98 x 10-6 s -1 k app = rate of propagation Gregson, K..G.; Gibson, V.C.; Long,.J.; Marshall, E.L.; xford, P.J.; White,.J.P. J. m. Chem. Soc. 2006, 128, 7410.

Redox Switching block copolymer synthesis via redox switching of ligands e II Ti () 2 e II Zr () 2 c cr Co(Cp) 2 c cr Co(Cp) 2 e III Ti () 2 e III Zr () 2 Wang, X.; Thevenon,.; rosmer, J.L.; Yu, I.; Khan, S.I.; hrkhodavandi, P.; Diaconescu, P.L. J. m. Chem. Soc. 2014, 136, 11264.

Redox Switching change in oxidation state changes binding profile of catalyst e II Zr () 2 and or e - + e - n 93% conversion 92% conversion n e III Zr () 2 Wang, X.; Thevenon,.; rosmer, J.L.; Yu, I.; Khan, S.I.; hrkhodavandi, P.; Diaconescu, P.L. J. m. Chem. Soc. 2014, 136, 11264.

Redox Switching change in oxidation state changes binding profile of catalyst e II Zr () 2 L and or e - + e - n 93% conversion CL 92% conversion n e III Zr () 2 minimal change in rate of reaction before/after changing oxidation state of e Wang, X.; Thevenon,.; rosmer, J.L.; Yu, I.; Khan, S.I.; hrkhodavandi, P.; Diaconescu, P.L. J. m. Chem. Soc. 2014, 136, 11264.

Redox Switching in situ redox-switching to achieve a block copolymer e II Ti () 2 n L + m CL e - + e - (L) n (CL) m e III Ti () 2 ox. Zr complex did not polymerize caprolactone in mixed monomer pool more Lewis acidic Zr = increases bond strengths of all intermediates for ox. compound Wang, X.; Thevenon,.; rosmer, J.L.; Yu, I.; Khan, S.I.; hrkhodavandi, P.; Diaconescu, P.L. J. m. Chem. Soc. 2014, 136, 11264.

Electrochemically diated tom Transfer Radical Polymerization redox control of activity of metal catalyst E 1/2 = 0.40 V vs g/g + anodic current e - in absence of potential, equilibrium favors starting materials k a P n r Cu I r/ 6 TRE Cu II r 2 / 6 TRE P n k da k t t termination cathodic current E 1/2 = 0.69 V vs g/g + e - Et r initiator monomer extent of reduction dictated by applied potential (E app ) shifting E app to more positive values deactivates polymerization Magenau,.J.D.; Strandwitz,.C.; Gennaro,.; Matyjaszewski, K. Science 2011, 332, 81.

Electrochemically diated tom Transfer Radical Polymerization redox control of activity of metal catalyst P n r Cu I X(L) R Cu II X(L) initiation M k a P n X Cu I X(L) P Cu II X(L) equilibrium with dormant species k d M propagation TRP depends on active/dormant equilibrium between (lower oxidation state) activators and alkyl halides (P n r) and between (higher oxidation state) deactivators and radicals (P n ) K TRP = k a /k da concerted atom transfer mechanism via inner-sphere electron transfer favoring dormant state mediates polymerization, allowing for simultaneous growth of each polymer chain excess reducing agent used to regenerate Cu I X activators from Cu II X 2 deactivators (RGET) Matyjaszewski, K.; Xia, J. Chem. Rev. 2001, 101, 2921.

Electrochemically diated tom Transfer Radical Polymerization redox control of activity of metal catalyst P n r Cu I X(L) R Cu II X(L) initiation M k a P n X Cu I X(L) P Cu II X(L) equilibrium with dormant species k d M propagation TRP depends on active/dormant equilibrium between (lower oxidation state) activators and alkyl halides (P n r) and between (higher oxidation state) deactivators and radicals (P n ) K TRP = k a /k da concerted atom transfer mechanism via inner-sphere electron transfer favoring dormant state mediates polymerization, allowing for simultaneous growth of each polymer chain excess reducing agent used to regenerate Cu I X activators from Cu II X 2 deactivators (RGET) Matyjaszewski, K.; Xia, J. Chem. Rev. 2001, 101, 2921.

Electrochemically diated tom Transfer Radical Polymerization E 1/2 = 0.40 V vs g/g + e - anodic current k a P n r Cu I r/ 6 TRE Cu II r 2 / 6 TRE P n k da k t t termination cathodic current E 1/2 = 0.69 V vs g/g + e - applying potential of 0.69 V: 80% conversion in 2 h low dispersity at high conversion (M w /M n = 1.06) Magenau,.J.D.; Strandwitz,.C.; Gennaro,.; Matyjaszewski, K. Science 2011, 332, 81.

Electrochemically diated tom Transfer Radical Polymerization toggling between E 1/2 = 0.69 V and E 1/2 = 0.40 V exhibits responsive on/off switching of polymerization E 1/2 = 0.40 V vs g/g + e - anodic current k a P n r Cu I r/ 6 TRE Cu II r 2 / 6 TRE P n k da k t t termination cathodic current E 1/2 = 0.69 V vs g/g + e - e - repetitive stepping of E app acts as electrochemical switch to modulate Cu oxidation state Magenau,.J.D.; Strandwitz,.C.; Gennaro,.; Matyjaszewski, K. Science 2011, 332, 81.

Switchable Catalysis switchable catalysis: biological inspiration types of switchable external stimuli light p ion coordination redox switching mechanical forces