Metal Catalyzed Redox Reactions



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tal Catalyzed edox eactions athan Jui MacMillan Group eting January 27, 2010

tal Catalyzed edox eactions! Many metal-catalyzed reactions involve redox processes Cross-Coupling Chemistry eduction Chemistry M catalyst catalyst H 2 Heck-Type Chemistry xidation Chemstry Ar catalyst Ar DG catalyst [] DG! These reactions and their mechanisms will not be addressed

tal Catalyzed edox eactions! Many metal-catalyzed reactions involve redox processes Constraints Applied 1. Catalytic in metal S M n S 2. Single electron transfer processes 3. et redox neutral (no terminal oxidant) 4. o light (purely chemical activation) S M n+1 ATA Cycle M n+1 S 5. Selective generation of organic radicals If electron transfer is accompanied occurs via inner-sphere mechanism Atom Transfer adical Chemistry

adical Addition chanism as First Defined! The The 'Peroxide 'Peroxide Effect' Effect' as as observed observed by by Kharasch Kharasch and and co-workers co-workers (1933) (1933) HBr HBr H 3 C 3 room temp room temp Br Br sole product sole product HBr, HBr, room temp room temp H 3 C 3 Br Br minor minor Br Br major major "The "The presence presence of of benzoyl benzoyl peroxide peroxide or or ascaridole ascaridole modified modified profoundly profoundly the the course course of of the the addition addition and and the the product product of of the the reaction reaction was was largely, largely, if if not not all, all, normal normal propyl propyl bromide" bromide" -Morris Kharasch -Morris Kharasch Kharasch, M. S. J. Am. Chem. Soc. 1933, 55, 2531. Kharasch, M. S. J. Am. Chem. Soc. 1933, 55, 2531.

adical Addition chanism as First Defined adical Addition chanism as First Defined! The 'Peroxide Effect' independantly defined by Kharash et al. as well as Hey and Waters (1937)! The 'Peroxide Effect' independantly defined by Kharash et al. as well as Hey and Waters (1937) HBr, HBr, HBr, room temp room room temp temp H 3 C H 3 C Br Br Br minor minor minor Br Br Br major major major "...it may be suggested that the addition process is one Kharasch, requiring M. S. the J. rg. transient Chem. 1937, 2, 288. "...it may be suggested that the addition process is one requiring the transient production of neutal atoms of hydrogen and broming from hydrogen bromide"! Kharasch production later reported of neutal the radical atoms addition of hydrogen of halomethanes and broming from to olefins hydrogen (1945) bromide" -Hey and Waters -Hey and Waters (Bz) 2, heat Bz H Br C 4 Br Bz H Br Br > 60% yield 3 CBr H Br Br H Br Kharasch, M. S. J. rg. Chem. 1937, 2, 288. Hey, Kharasch, D.; Waters, M. M. S. W. S. et Chem. J. al. rg. Science, ev. Chem. 1937, 1945 1937, 21, 122, 2, 1969. 288. 108. Hey, D.; Waters, W. Chem. ev. 1937, 21, 1969.

adical Addition chanism as First Defined! The 'Peroxide Effect' independantly defined by Kharash et al. as well as Hey and Waters (1937) HBr, room temp H 3 C Br minor Br major Kharasch, M. S. J. rg. Chem. 1937, 2, 288.! Kharasch later reported the radical addition of halomethanes to olefins (1945) C 4 (Bz) 2, heat > 60% yield 3 C Kharasch, M. S. et al. Science, 1945 122, 108.

The Kharasch Addition eaction of Halomethanes to lefins! Kharasch reported the radical addition of carbon-based radicals to olefins (1945) C 4 Ac! Ac 3 C Ac Ac 2 H 3 C 2 C 2 Initiation H 3 C C 4 CH 3 3 C 3 C 3 C 3 C C 3 C 4 3 C Propagation 3 C 3 C Polymerization = Ar Kharasch, M. S. Science 1945, 122, 108.

The Kharasch Addition eaction of Halomethanes to lefins! Kharasch reported the use of several radical electrophiles in his new radical reaction hex hex Br CBr 3 hex Br C 3 hex Br Et (Ac) 2, 40% yield h!, 88% yield (Ac) 2, 78% yield (Ac) 2, 54% yield JACS, 1945, 1626 JACS, 1946, 154 JACS, 1947, 1105 JACS, 1948, 1055 Halogen was used in excess (3- or 4-fold) for optimum yields Higher order products made up mass balances Highly activated bromomethanes were the best substrates Br CBr 3 CBr 4, light C 4, (Ac) 2 C 3 96% quant n

The Failed Polymerizations of Minisci! Surprisingly, substantial monoadduct formation was observed with carbon tetrachloride C C 4, autoclave, 160 C C C 3 n C C 3 'significant amount' C CH 3, autoclave, 160 C H C C 3 n C CH 2 new regioisomer! Standard peroxide initiated radical mechanisms occur via hydrogen abstraction C H C 3 3 C C C 3 C C 3 H H C 3 3 C Complete selectivity for opposite regioisomer suggested a new mechanism Minisci, F. Chem. Ind. (Milan), 1956, 122, 371.

adical Chain Termination by tal Halide Salts (Jay Kochi)! Also in 1956, Kochi was studying the oxidation of alkyl radicals by metal salts 2 Cu or Fe 2 acetone good yields 0% polymer Cu erwein Arylation!Cu Cu 2 Cu 1. The rate of benzylic radical oxidation by Cu 2 (or Fe 3 ) is much faster than styrene addition 2. xidation occurs through a 'ligand transfer' mechanism (inner-sphere electron transfer) Minisci's reaction could have contained metal halides Kochi, J. J. Am. Chem. Soc. 1956, 78, 4815.

Accidental Discovery of Catalytic Atom Transfer adical Chemstry! Minisci's steel autoclave was corroded and had likely leached iron into the reaction and could have been oxidized to Fe 3 by chlorine radicals 2 C 4 Fe (s) 2 3 C Fe 2 C 4 Fe 2 3 C Fe 3! Minisci's group and Vofsi and Asscher first describe catalytic atom transfer radical addition 1 equiv 2 equiv 1 mol% Cu (or Fe 2 ) 2 equiv solvent, 80!120 C 3 C 46-89% yield C C 2 Et C 6 H 13 Minisci, F. et al. Gazzeta 1961, 91, 1030. Asscher, M. et al. J. Chem. Soc. 1963, 1887.

Proposed chanism of Atom Transfer adical Addition (ATA)! tal catalyst participates in both initiation and termination steps, relative rates dictate selectivity Catalytic edox chanism:! ed. halogen abstraction Cu I ' monoadduct generates radical! xid. halogen abstraction terminates radical k a1 k d1 k a2 k d2 ' ' ' Selective ATA equires: Cu II 2 k add ' k t ' telomer 1. Low radical concentration k t ' k t k p k d1 and k d2 >> k a1 and k a2 n ' 2. Slow product activation (vs sm) k a1 >> k a2 ' ' polymer 3. xidation must be fast vs prop. k d2 >> k p Figure adapted from: Matyjaszewski, K. et al. Chem. Soc. ev. 2008, 1087.

So Many Different Catalysts... Y Y Y ML n n (cat.) Y Y Y! The many metals that catalyze CH 3, CHBr 3, C 4, and/or CBr 4 radical addition! The most commonly used catalysts for ATA reactions are Cu I and u II 2 derivatives! Exact nature of free radical intermediates is not known

Evaluation of the Proposed adical chanism! Kharasch systems likely proceed via radical intermediates (u, Cu, Fe, Mo, Cr) C 4 hex u 2 (P 3 ) 3 galvinoxyl 3 C hex 0% yield (76%, no spintrap) 80 C, 4 h Matsumoto, H. et al. Tetrahedron Lett. 1973, 14, 5147.! tal catalyst impacts diastereoselectivity of C 4 addition to cyclohexene u 2 (P 3 ) 3 C 4 80 C, 4 h C 3 77% yield 96:4 (trans:cis) C 4 (Bz) 2 80 C, 4 h C 3 low yield 53:47 (trans:cis) Matsumoto, H. et al. Tetrahedron Lett. 1975, 15, 899. Effect not seen with Cu: Asscher, M. et al. J. Chem. Soc. Perkin Trans. 2 1973, 1000. Intermediate radical species likely exist as coordinated radical pairs (u system)

Attempts at Enantioselective Kharasch Addition! Chiral ligands could potentially induce enantioselectivity 73% yield C 3 u 2 4 (diop) 3 C 4 13% ee 100 C, 6 h! Coordinated metal-radical pair should participate in enantiodetermining chlorination 3 C ul* n 2 C 4 L* = (!)-diop 3 CCH 2 CH u III 3 ATA Cycle 3 C u III 3 H H CH 2 P 2 CH 2 P 2 Kamigata,. et al. Bull. Chem. Soc. Jpn. 1987, 60, 3687. Similar result with h-diop system: Murai, S. et al. Angew. Chem. Int. Ed. Eng. 1981, 20, 475.

Selected Examples of Atom Transfer adical Addition Chemistry! Area 1. Intramolecular Atom Transfer eactions (ATC) ML 2 n FG FG (cat.)! Area 2. Intermolecular Kharasch Type Haloalkylation eactions FG ML 2 n (cat.) FG

Selected Intramolecular ATA: 5-Exo Trig Cyclizations! A variety of cyclization substrates and catalytic systems have been developed over 35+ years u 2 (P 3 ) 3 catalysts: 1973 (agai) Cu catalysts: 1963 (Asscher & Vofsi) 1-10% typical loadings, > 80 C temperatures ~30% typical loading, > 100 C temperatures u 2 (P 3 ) 3 H, 155 C 79% yield Cu C, 110 C 95% yield 2 C u 2 (P 3 ) 3 H, 165 C 77%, 1:1 dr 2 C H H Cu C, 140 C 57% yield H 2 C u 2 (P 3 ) 3 H, 165 C 71%, 2:1 dr 2 C H F F Br H CuBr C, 80 C F F 84% yield H Br Weinreb, S. et al. J. rg. Chem. 1990, 55, 1281. ark, A. Chem. Soc. ev. 2002, 31, 1.

Intramolecular Atom Transfer adical Cyclization Ligand Effects! 5-Exo trig cyclization of unsaturated!-haloamide substrates yields lactam scaffolds 30 mol% catalyst solvent, temp Ts Ts Catalyst Solvent Temp. Time Yield Cu C 80 C 24 h 97% Cu-bipy (5%) CH 2 2 23 C 0.2 h 91% Cu-bipy H CH 2 2 23 C 24 h 0% Cu-PMI H CH 2 2 23 C 72 h 15% Cu-tren- 6 H CH 2 2 23 C 2 h 90% 2 bipy PMI 2 2 tren- 6 ark, A. Tetrahdron Lett. 1999, 40, 4885.

adical-polar Crossover chanism: Addition to Enamides! Electrophilic radicals add to acyl enamines, terminate via radical-polar crossover mechanism Br Bn 30 mol% CuBr L CH 2 2, rt, 20 min 82%, 1:1 ratio Bn 2 = L 2 2 CuLBr CuLBr 2!H +!CuLBr 2!CuLBr Bn Bn Bn! While this triethylenetetramine ligand is highly active, the perfect Cu system remains unknown 30 mol% CuBr L 0% yield CH 2 2, rt complex mixture Bn Bn ark, A. Tetrahdron Lett. 1999, 40, 4885.

Cascade Cyclization Using Copper edox Catalyst! adical mono- and bicyclization utilizing copper-bipy as catalyst (Dan Yang) Et Cu bipy DCE, 80 C 21 h C 2 Et 79% yield 3:1 dr! Bicyclization under the conditions outlined above give modest yields and diastereocontrol Et 61% C 2 Et Et 33% C 2 Et 2:1 dr 3:2 dr Yang, D. et al. rg. Lett. 2006, 8, 5757.

Intramolecular Atom Transfer adical Cyclization! dium ring heterocycle formation via redox reaction affords 8 and 9 membered lactones n 3 30 mol% Cu-bipy 0.1 M DCE 80 C, 18 h n n = 1: 60% yield n = 2: 59% yield Pirrung, F. et al. Synlett. 1993, 50, 739.! Macrocyclization reactions were also accomplished using a tridentate ligand 10 mol% Cu-ligand C 3 0.2 M DCE, 80 C 70% yield ark, A. et al. J. Chem. Soc. Perkin Trans. 1, 2000, 671.

Selected Examples of Atom Transfer adical Addition Chemistry! Area 1. Intramolecular Atom Transfer adical Addition eactions (ATC) ML 2 n FG FG (cat.) n n= 0-13 n! Successful radical precursors in ATC reactions so far are highly activated 2 2 F I F 2 2 H 2 2

Selected Examples of Atom Transfer adical Addition Chemistry! Area 1. Intramolecular Atom Transfer adical Addition eactions (ATC) ML 2 n FG FG (cat.) n n= 0-13 n! Successful Area 2. Intermolecular radical precursors Kharasch in ATC Addition reactions eactions so far of are Polyhaloalkanes highly activated Y 2 Y ' 2 ML 2 n F (cat.) I F ' Y 2 Y 2 H 2 2

Perfluoroalkylation of lefins Using ATA! Kamigata's group describe a ruthenium catalyzed radical trifluromethylation protocol F 3 C S 1 equiv 2 equiv 1 mol% u 2 (P 3 ) 2 benzene, 120 C! The reaction works well with highly activated olefins but is sensitive to sterics (1,2-substitution) F 3 C ul* n 2 F 3 CS 2 2 79% yield ATA 87% yield Cycle S 2 46% yield Et u III 3 u III 3 41% yield 66% yield 23% yield Kamigata. J. Chem. Soc. Perkin Trans. 1. 1991, 627.

Perfluoroalkylation of lefins Using ATA! Kamigata's group describe a ruthenium catalyzed radical trifluromethylation protocol F 3 C S 1 equiv 2 equiv 1 mol% u 2 (P 3 ) 2 benzene, 120 C! The reaction works well with highly activated olefins but is sensitive to sterics (1,2-substitution) 2 79% yield 87% yield 46% yield Et 41% yield 66% yield 23% yield Kamigata. J. Chem. Soc. Perkin Trans. 1. 1991, 627.

Arene Perfluoroalkylation Using Sulfonyl Chloride eagents! Kamigata's group describe a ruthenium catalyzed radical trifluromethylation protocol F 3 C S 1 equiv 2-5 equiv 1 mol% u 2 (P 3 ) 2 benzene, 120 C! Benzene substrates react but are completely regio-permiscuous 53% yield 2:1:1 (o:m:p) 36% yield 1:1:1 (o:m:p) 41% yield Br 39% yield 1:1:1 (o:m:p) trace C 63% yield Kamigata.. J. Chem. Soc. Perkin Trans. 1. 1994, 1339.

Arene Perfluoroalkylation Using Sulfonyl Chloride eagents! Kamigata's group describe a ruthenium catalyzed radical trifluromethylation protocol F 3 C S F 3 C S 1 1 equiv 2-5 2-5 equiv 1 1 mol% mol% u u 2 (P 3 ) 2 2 (P 3 ) 2 benzene, benzene, 120 120 C C CF 3! Five-membered Benzene substrates heterocyclic react but compounds are completely work regio-permiscuous with increased regiocontrol 53% yield 36% yield S S HC S CF 2:1:1 (o:m:p) 1:1:1 (o:m:p) 3 30% 77% 73% 26% 41% yield CF 3 39% yield H Bn Br 1:1:1 (o:m:p) CF 3 C trace 0% 53% 61% 92% Ac C 63% yield Kamigata.. J. Chem. Soc. Perkin Trans. 1. 1994, 1339.

Trifluoromethylation of Electron-Poor Enolsilane Substrates! uthenium catalyzed sulfonyl chloride decomposition also works on silyl enol ethers TMS F 3 C S ' 1 equiv 2 equiv 1 mol% u 2 (P 3 ) 2 benzene, 120 C ' CF3 CF3 2 55% yield 51% yield 58% yield 0% yield H Bn CF3 t Bu CF3 28% yield 35% yield 43% yield 0% yield Kamigata.. osporus, Sulphur, and Silicon 1997, 155.

Atom Transfer adical Addition eactions With Titanium Enolates! Zakarian group published the first highly diastereoselective intermolecular Kharasch addition Ti 4, i-pr 2 Et, CH 2 2 ' BrC 3 (3 equiv) ' 7 mol% u 2 (P 3 ) 3 45 C, 12 h C 3 4 Ti 4 Ti ' ' C 3 BrC 3 u III + Br u II 4 Ti ' 4 Ti ' 4 Ti ' C 3 C 3 C 3 Zakarian, A. et al. J. Am. Chem. Soc. 2010, ASAP.

Atom Transfer adical Addition eactions With Titanium Enolates! Zakarian group published the first highly diastereoselective intermolecular Kharasch addition Ti 4, i-pr 2 Et, CH 2 2 ' BrC 3 (3 equiv) ' 7 mol% u 2 (P 3 ) 3 45 C, 12 h C 3 4 Ti Bn 89%, >98:2 dr 4 Ti ' ' C 3 Bn 4 Ti 4 Ti C 4 H 9 ' C 3 C 3 Bn Bn 99%, >98:2 dr 63%, >98:2 dr 87%, >98:2 dr C 3 6 BrC 3 C 3 u III + Br u II ' Bn 4 C C 3 C 3 3 Bn 61%, >98:2 dr Zakarian, A. et al. J. Am. Chem. Soc. 2010, ASAP. Bn 4 Ti C 3 91%, >98:2 dr Ts ' C 3

Atom Transfer adical Addition eactions With Titanium Enolates! Zakarian group published the first highly diastereoselective intermolecular Kharasch addition Ti 4, i-pr 2 Et, CH 2 2 ' BrC 3 (3 equiv) ' 7 mol% u 2 (P 3 ) 3 45 C, 12 h C 3 4 Ti Bn Bn ' 64%, >98:2 dr 4 Ti 71%, 1.6:1 dr ' C 3 4 Ti ' Bn 4 Ti Bn C 3 83%, >98:2 dr ' 76%, >98:2 dr Et u III + Br C 3 C 2 Bn u II BrC 3 75%, 1.3:1 dr Zakarian, A. et al. J. Am. Chem. Soc. 2010, ASAP. Bn 4 Ti Bn 71%, >98:2 dr C 3 '

Atom Transfer adical Polymerization (ATP) Atom Transfer adical Polymerization (ATP)! In In 1995, Krzysztof Matyjaszewski and Mitsuo Sawamoto picked up up where Minisci left off off (1956)! In They 1995, independantly Krzysztof Matyjaszewski reported a a new and method Mitsuo (ATP Sawamoto or or living picked radical up where polymerization) Minisci left off (1956)! They independantly reported a new method (ATP or living radical polymerization) Sawamoto Kyoto University Sawamoto Kyoto University Matyjaszewski Carnegie Matyjaszewski llon Carnegie llon 'Living adical Polymerization' 'Atom Transfer adical Polymerization' submitted September 6, 6, 1994 'Living adical Polymerization' submitted February 16, 1995 'Atom Transfer adical Polymerization' Macromolecules, 1995, 28, 1721. submitted September 6, 1994 J. J. Am. Chem. Soc., 1995, 117, 5614. submitted February 16, 1995 cited 1,571 times Macromolecules, 1995, 28, 1721. cited 2,374 times J. Am. Chem. Soc., 1995, 117, 5614. cited 1,571 times cited 2,374 times

Atom Transfer adical Polymerization (ATP)! In 1995, Krzysztof Matyjaszewski and Mitsuo Sawamoto picked up where Minisci left off (1956) Selective ATA equires: Cu I ' monoadduct 1. Low radical concentration ' k d1 and k d2 >> k a1 and k a2 k d1 k a2 2. Slow product activation (vs sm) k a1 k d2 ' ' k a1 >> k a2 3. xidation must be fast vs prop. Cu II 2 ' k t ' teleomer k d2 >> k p k add k t ' k t k p Polymerization Can ccur If: 1. Above requirements are met ' ' n polymer ' 2. Starting Halogen is consumed Figure adapted from: Matyjaszewski, K. et al. Chem. Soc. ev. 2008, 1087.

Atom Transfer adical Polymerization (ATP)! In 1995, Krzysztof Matyjaszewski and Mitsuo Sawamoto picked up where Minisci left off (1956) Selective ATA equires: Cu I ' monoadduct 1. Low radical concentration ' k d1 and k d2 >> k a1 and k a2 k d1 k a2 2. Slow product activation (vs sm) k a1 k d2 ' ' k a1 >> k a2 3. xidation must be fast vs prop. Cu II 2 ' k t ' teleomer k d2 >> k p k add k t ' k t k p Polymerization Can ccur If: 1. Above requirements are met ' ' n polymer ' 2. Starting Halogen is consumed Figure adapted from: Matyjaszewski, K. et al. Chem. Soc. ev. 2008, 1087.

Atom Transfer adical Polymerization (ATP)! In 1995, Krzysztof Matyjaszewski and Mitsuo Sawamoto picked up where Minisci left off (1956) Selective ATA equires: Cu I ' monoadduct 1. Low radical concentration k d1 and k d2 >> k a1 and k a2 k d1 k a2 2. Slow product activation (vs sm) k a1 k d2 k a1 >> k a2 3. xidation must be fast vs prop. Cu II 2 ' ' k d2 >> k p k add ' kp Polymerization Can ccur If: ' n ' 1. Above requirements are met P M n n P M n n polymer +m 2. Starting Halogen is consumed Figure adapted from: Matyjaszewski, K. et al. Chem. Soc. ev. 2008, 1087.

Atom Transfer adical Polymerization (ATP)! Matyjaszewski polymerized styrene using a copper chloride bipy system Atom Transfer adical Polymerization (ATP)! Matyjaszewski polymerized styrene using a copper chloride bipy system 1 mol% Cu 95% consumption! Matyjaszewski polymerized styrene using a copper chloride bipy system 3 mol% bipy n PDI = 1.3!1.45 1 equiv 0.01 equiv 1130 mol% C, Cu 3 h 95% consumption 1 mol% Cu 95% consumption 3 mol% bipy n PDI = 1.3!1.45 Atom Transfer adical 3 mol% bipy Polymerization (ATP) PDI = 1.3!1.45 n 1 equiv 0.01 equiv 130 C, 3 h 1 equiv 0.01 equiv! PDI = polydispersity index, 130 a measure C, 3 h of how consistent chain growth is! Matyjaszewski! PDI equal polymerized to one: all of styrene the chains using in a a copper given chloride sample are bipy of system the same length! Sawamoto PDI = polydispersity system utilized index, some a well-developed measure of how ruthenium consistent phosphine chain growth conditions is! Good PDI values are typically > 1.5! PDI equal to one: all of the 1 mol% chains Cu in a given sample are of the same length M n = number average molecular 95% weight consumption 0.5! Good PDI values are typically 3 mol% u > bipy 1.5 2 (P 3 ) 3 n C 2 PDI 90% = consumption 1.3!1.45 C 2 C 4 total weight / number of molecules C 1 equiv 0.01 equiv PDI = M 2.0 130 3 n / mol% M C, w 3 Al(Ar) h 2 PDI = 1.3!1.4 n M n = number average molecular weight 1 equiv 0.01 equiv toluene, 60 C, 4 M h w = weight average molecular weight total weight / number of molecules PDI = M n / M w average weight of average molecule! Upon! PDI complete = polydispersity conversion, index, more a measure monomer of was how added consistent and completely chain growth incorporated is M w = weight average molecular weight! adical! PDI scavengers equal to one: completely all of the chains inhibited a / stopped given average sample reactions weight are of of average the same molecule length Matyjaszewski, K. et al. J. Am. Chem. Soc. 1995, 117, 5614.! Addition! Good of PDI different values monomers are typically allowed > 1.5 for 'Block polymers' (""""####) PDI = M n / M w Matyjaszewski, M n = number K. average et al. J. Am. molecular Chem. weight Soc. 1995, 117, 5614. Sawamoto, M. et al. Macromolecules 1995, 28, 1721. total weight / number of molecules Matyjaszewski, K. et al. J. Am. Chem. Soc. 1995, 117, 5614. M w = weight average molecular weight

Atom Transfer adical Polymerization (ATP)! Matyjaszewski polymerized styrene using a copper chloride bipy system 1 mol% Cu 95% consumption 1 equiv 0.01 equiv 3 mol% bipy 130 C, 3 h n PDI = 1.3!1.45! Sawamoto system utilized some well-developed ruthenium phosphine conditions C 2 C 4 1 equiv 0.01 equiv 0.5 mol% u 2 (P 3 ) 3 2.0 mol% Al(Ar) 2 toluene, 60 C, 4 h C 2 C 3 n 90% consumption PDI = 1.3!1.4! Upon complete conversion, more monomer was added and completely incorporated! adical scavengers completely inhibited / stopped reactions! Addition of different monomers allowed for 'Block polymers' (""""####) Sawamoto, M. et al. Macromolecules 1995, 28, 1721. Matyjaszewski, K. et al. J. Am. Chem. Soc. 1995, 117, 5614.

Atom Transfer adical Polymerization (ATP) I M n / Ligand I M n+1 2 / Ligand k act P M n / Ligand P M n+1 2 / Ligand k deact +m m k t k p termination! Different ATP systems possess discrete rate properties based on the following I Initiator (Alkyl Halide) redox potential M n / Ligand Catalyst solubilities, redox potentials m monomer unique ATP k eq Matyjaszewski, K. et al. Chem. ev. 2001, 101, 2921.

Atom Transfer adical Polymerization (ATP) I M n / Ligand I M n+1 2 / Ligand k act P M n / Ligand P M n+1 2 / Ligand k deact +m m k t k p termination! Different ATP systems possess discrete rate properties based on the following! Each monomer has a specific k eq (k act /k deact ) and requires specific conditions for ATP! nly copper catalysts have been successful in polymerizing all of the above classes Matyjaszewski, K. et al. Chem. ev. 2001, 101, 2921.

Atom Transfer adical Polymerization (ATP) I M n / Ligand I M n+1 2 / Ligand k act P M n / Ligand P M n+1 2 / Ligand k deact +m m k t k p termination! Different ATP systems possess discrete rate properties based on the following! Each monomer has a specific k eq (k act /k deact ) and requires specific conditions for ATP P! nly copper catalysts have been successful in polymerizing all of the above classes Matyjaszewski, K. et al. Chem. ev. 2001, 101, 2921.

Atom Transfer adical Polymerization (ATP) I M n / Ligand I M n+1 2 / Ligand k act P M n / Ligand P M n+1 2 / Ligand k deact +m m k t k p termination! Different ATP systems possess discrete rate properties based on the following! Each monomer has a specific k eq (k act /k deact ) and requires specific conditions for ATP P M! nly copper catalysts have been successful in polymerizing all of the above classes Matyjaszewski, K. et al. Chem. ev. 2001, 101, 2921.

Atom Transfer adical Polymerization (ATP) I M n / Ligand I M n+1 2 / Ligand k act P M n / Ligand P M n+1 2 / Ligand k deact +m m k t k p termination! Different ATP systems possess discrete rate properties based on the following! Each monomer has a specific k eq (k act /k deact ) and requires specific conditions for ATP P! nly copper catalysts have been successful in polymerizing all of the above classes Matyjaszewski, K. et al. Chem. ev. 2001, 101, 2921.

Atom Transfer adical Polymerization (ATP) I M n / Ligand I M n+1 2 / Ligand k act P M n / Ligand P M n+1 2 / Ligand k deact +m m k t k p termination! Different ATP systems possess discrete rate properties based on the following! Each monomer has a specific k eq (k act /k deact ) and requires specific conditions for ATP P! Initiators tend to look like the desired monomer units (similar redox, kinetic properties) Matyjaszewski, K. et al. Chem. ev. 2001, 101, 2921.

Atom Transfer adical Polymerization (ATP) I M n / Ligand I M n+1 2 / Ligand k act P M n / Ligand P M n+1 2 / Ligand k deact +m m k t k p termination! Different ATP systems possess discrete rate properties based on the following! Each monomer has a specific k eq (k act /k deact ) and requires specific conditions for ATP P Cu Cu, u 2, i 2 i 2, u 2 Fe 2, Cu Cu! tals typically used to initiate each indicated monomer class (ligands play huge role)

Atom Transfer adical Polymerization (ATP) I M n / Ligand I M n+1 2 / Ligand m k act P M n / Ligand P M n+1 2 / Ligand k deact +m k t k p termination! Different ATP systems possess discrete rate properties based on the following! Each monomer has a specific k eq (k act /k deact ) and requires specific conditions for ATP more stable cations P ubrcp*p 3 2 faster ATP catalysts ucp*p 3 Cu(TPA) Fe III (phen) 3 u 2 (P 3 ) 3 Cu(bipy) 2 Cu( 6 -tren) Cu Cu, u 2, i 2 i 2, u 2 Fe 2, Cu Cu +1 V 0.5 0-0.5! Initiators tend to look like the desired monomer units (similar redox, kinetic properties) -1 V (vs SCE)! tals typically used to initiate each indicated Matyjaszewski, monomer class K. et (ligands al. Chem. play ev. huge 2001, role) 101, 2921. 2 2

Atom Transfer adical Polymerization (ATP) I M n / Ligand I M n+1 2 / Ligand m k act P M n / Ligand P M n+1 2 / Ligand k deact +m k t k p termination! Different ATP systems possess discrete rate properties based on the following! Each monomer has a specific k eq (k act /k deact ) and requires specific conditions for ATP more stable cations P ubrcp*p 3 2 faster ATP catalysts ucp*p 3 Cu(TPA) Fe III (phen) 3 u 2 (P 3 ) 3 Cu(bipy) 2 Cu( 6 -tren) Cu Cu, u 2, i 2 i 2, u 2 Fe 2, Cu Cu +1 V 0.5 0-0.5! Initiators tend to look like the desired monomer units (similar redox, kinetic properties) -1 V (vs SCE)! tals typically used to initiate each indicated Matyjaszewski, monomer class K. et (ligands al. Chem. play ev. huge 2001, role) 101, 2921. 2 2

Atom Transfer adical Polymerization (ATP) I M n / Ligand I M n+1 2 / Ligand m k act P M n / Ligand P M n+1 2 / Ligand k deact +m k t k p termination! Different ATP systems possess discrete rate properties based on the following! Each monomer has a specific k eq (k act /k deact ) and requires specific conditions for ATP more stable cations P ubrcp*p 3 2 faster ATP catalysts ucp*p 3 Cu(TPA) Fe III (phen) 3 u 2 (P 3 ) 3 Cu(bipy) 2 Cu( 6 -tren) Cu Cu, u 2, i 2 i 2, u 2 Fe 2, Cu Cu +1 V 0.5 0-0.5! Initiators tend to look like the desired monomer units (similar redox, kinetic properties) -1 V (vs SCE)! tals typically used to initiate each indicated Matyjaszewski, monomer class K. et (ligands al. Chem. play ev. huge 2001, role) 101, 2921. 2 2

Atom Transfer adical Polymerization (ATP) I M n / Ligand I M n+1 2 / Ligand m k act P M n / Ligand P M n+1 2 / Ligand k deact +m k t k p termination! Different ATP systems possess discrete rate properties based on the following! Each monomer has a specific k eq (k act /k deact ) and requires specific conditions for ATP more stable cations P ubrcp*p 3 2 faster ATP catalysts ucp*p 3 Cu(TPA) Fe III (phen) 3 u 2 (P 3 ) 3 Cu(bipy) 2 Cu( 6 -tren) Cu Cu, u 2, i 2 i 2, u 2 Fe 2, Cu Cu +1 V 0.5 0-0.5! Initiators tend to look like the desired monomer units (similar redox, kinetic properties) -1 V (vs SCE)! tals typically used to initiate each indicated Matyjaszewski, monomer class K. et (ligands al. Chem. play ev. huge 2001, role) 101, 2921. 2 2

ew Catalyst Systems Allow for ATA eactions Under Mild Conditions! ewer highly active ruthenium catalysts initiate rapidly at room temperature Et u 3 P 0.1 mol% catalyst Mg powder Et H 2 equiv 1 equiv toluene, rt 24 h, 97% yield 5% u 2 (P 3 ) 3 : 155 C, 16 h: 71% yield Severin, K. Chem. Eur. J. 2007, 6899.

ML 2 n FG n (cat.) n= 0-13 Potential Future Atom Transfer adical Chemistry n Potential Future Atom Transfer adical Chemistry! Successful radical precursors in ATC reactions so far are highly activated 2 2 F I F 2 2 H 2 2 Br Br ' Br ' Br ' Br ' Br Br ' Br ' Br ' Br '