Yu Kawamata Electroorganic Chemistry: Choice of Electrodes Baran Group Meeting 12/10/2016 1

Also see: Electrochemistry in Synthesis (Ambhaikar, 2005) Electroorganic Chemistry (Rosen, 2014)

Unique parameters in electrochemistry: Electrochemical cell ••••• devided or undivided Current and potential ••••• constant current (c.c.) or constant potential (c.p.) Electrolyte ••••• various ammonium or alkali metal salts

Electrodes ••••• anode (oxidation), cathode (reduction) Divided cell Undivided cell • Anode compartment is always • Net reduction proceeds if a sacrificial Topics not discussed: oxidation. anode is employed. • Chemically modified electrodes • Cathode compartment is always • In other cases, reaction type (net oxidation • Electrodes for inorganic and analytical electrochemistry reduction. or reduction) depends on the balance of redox potentials of compounds in the cell.

1. Electrode material Review: Pletcher, Chem. Rev. 1990, 90, 837. 1-3. Overpotential Overpotential is the potential 1-1. General Consideration difference between a half- i) Physical stability v) cost and lifetime reaction's thermodynamically determined potential and the ii) chemical stability vi) suitable physical form potential at which the redox event iii) overpotential vii) electrical conductivity is experimentally observed. iv) rate and product selecticity Thermodinamically defined potential: 1-2. Modes of action of electrodes Oxygen O + 4H+ + 4e- 2H O º = 1.23 (V) Electrodes can: transfer electrons 2 2 E red (vs SHE) absorb organic compounds Hydrogen + - º 2H + 2e H2 E = 0.00 (V) Reactivity and product selectivity might be red https://en.wikipedia.org/wiki/overpotential affected by electrode materials. act as reagents Generally, material with large O2 overpotential is used for anode and material with large H2 ovarpotential is used for cathode. e.g. • Sacrificial anode (source of electron for cathodic reduction) 1-4. Anode material • NiOOH, PbO anode 2 Sacrificial anode ••••• Al, Zn, Mg, steel etc. • Ni and Pt cathode for hydrogenation anode Non-sacrificial ••••• Pt, carbon based material (graphite, glassy carbon, RVC, BDD) Yu Kawamata Electroorganic Chemistry: Choice of Electrodes Baran Group Meeting 2 12/10/2016

Sacrificial anode Source of electron for cathodic reduction Boron-Doped Diamond (BDD) Panizza, Electrochimica Acta, 2005, 51, 191. Macpherson, Phys. Chem. Chem. Phys. 2015, 17, 2935. Top. Curr. Chem. 2012, 320, 1. Mg Al Zn Fe Ni Sn Pb Cu Hg Ag Au Pt • Highly durable under oxidative conditions Dissolve when used as anode material • Large O2 overpotential (1.1 V) and H2 overpotential (-1.1 V)

Platinum • Due to its large O2 overpotential, OH radical and ozone can be generated under aqueous conditions. • Highly durable under oxidative conditions • Used for waste-water treatment (complete mineralization of organic • Wide potential range due to the large O2 overpotential molecule using OH radical) and ozone generation. • Most common anode material • Recently introduced to electroorganic synthesis

Graphite • Highly stable, but can be eroded under highly oxidative conditions.

• Wide potential range due to the large O2 overpotential • Absorption or intercalation of organic material may occur. • Most common anode material BDD disk SEM image of BDD Glassy carbon (Vitreous carbon) Other anode material • Amorphous form of carbon • Very hard (as hard as quartz) Lead dioxide (PbO2) Review: Hampson, Chem. Rev. 1972, 72, 680. • Good chemical stability and wide potential range • Large O2 overpotential, wide potential range. • Prepared by electrochemical deposition of PbO2 onto conductive materials • Used for production of inorganic oxidant such as perchlorate, periodate and ozone • Electroorganic application is oxidation of alkenes, arenes and alcohols Proposed structure of glassy carbon. Glassy carbon rods All carbon atoms are sp2 carbon. Ni(O)OH anode Review: Petrosyan, Russ. J. Electrochem. 2010, 46, 1199. Prepared by forming Ni(OH) on Ni plate Reticulated Vitreous Carbon (RVC) • 2 • Anodically stable only under basic conditions Review: Ponce-de-León, J. Electroanal. Chem. 2004. 561. 203. . • Oxidation of alcohol and amine proceeds by anodically generated Ni(III) • Glassy carbon produced as a form on the electrode. • Same chemical property as glassy carbon Carbon sulfide electrode Review: Guillanton, Sulfur Reports. 1992, 12, 405. • Large surface area • Sacrificial anode . SEM image of RVC • Used for thiolation of organic compounds Yu Kawamata Electroorganic Chemistry: Choice of Electrodes Baran Group Meeting 12/10/2016 3

1-5. Cathode material 3. Electrode Degradation

Platinum anode Littauer, Corrosion Science, 1970, 10, 29. High H2 overpotential ••••• Carbon-based material, Pb, Sn, Hg, Cd, Zn Useful for cathodic reduction of various Pt is known to be corroded slowly in the presence of halide ion. organic molecules (corrosion rate: 5mgA-1h-1 in the electrolysis of 8 M HCl for 80 h)

Low H2 overpotential ••••• Pt, Ni, Cu, Ag, Fe(steinless steel) Graphite anode Hudson, J. Mater. Chem. 1997, 7, 301. These electrodes are used when H2 evolution Srivastava, J. Nanosci. Nanotechnol. 2015, 15, 1984. at cathode is desireble. Generally, graphite is not tolerated under strongly oxidizing conditions or high voltage due to the formation of graphene oxide.

Glassy carbon anode Isse, Mussini, Electrochem. Comm. 2010, 12, 1531. OH radical can cause erosion of glassy carbon

Conditions: H2O2, Fe(NH4)2(SO4)2 and EDTA in 0.01 M acetate buffer Example of reaction set-up with platinum anode and mercury pool cathode Wright, Chem. Soc. Rev. 2006, 35, 605

2. Price of Electrodes Micrographs of GC surface: before treatment (left), after 60 min (right) Material Supplier Quantity Price BDD anode Comninellis, J. Appl. Electrochem. 2004, 34, 935. Aldrich 1.5 g $ 480 Pt foil BDD is also known to be eroded under harsh electrchemical conditions. Alfa Aesar 0.025 mm × 25 mm × 25 mm $ 107 Pt coated Ti ebay 30 mm × 40 mm $ 12.8

Graphite many 1 lb < $ 10 Glassy carbon rod Alfa Aesar 3 mm × 25 mm × 25 mm $ 98

RVC KRRaynolds 40 mm × 40 mm $15 BDD windsor scientific 3 mm diameter $ 305

Hg Aldrich 1 kg $ 422 Al, Mg, Ni, Cu, many 1 lb < $ 10 Before electrolysis After severe anodic polarization at Pb, Sn, Fe, Zn -2 1Acm in 1 M HClO4 for 576 h at 40 °C Yu Kawamata Electroorganic Chemistry: Choice of Electrodes Baran Group Meeting 12/10/2016 4

4. Selected Electroorganic Reactions and Suitable Electrodes Oxidation of amides and carbamates (Shono oxidation) 4-1. Anodic oxidation O O Oxidation of carboxylic acids (Kolbe reaction) Review: Schäfer, Chemistry and O Physics of Lipids, 1979, 24, 321. anodic oxidation R MeOH R R N N anodic oxidation N RCOO R R R OMe -CO2 Anode: Pt (most common), Glassy carbon Cathode (not critical): Pt, carbon, Fe, Hg etc. Anode: Pt, graphite Cathode (not critical): Graphite, stainless steel, Pt, Hetero coupling Boland, Steckhan, Tetrahedron Lett. 1996, 37, 8715.

Pt anode O O steel cathode Application to toal synthesis Braekman, Daloze, Eur. J. Org. Chem. 2000, 2057. MeONa + HOOC COOEt CO Me 5 MeOH, c.c. 2 graphite anode CO2Me O COOH COOEt O 4.2 eq undivided cell 5 R N graphite cathode R N OMe 43% R N Steel cathode was chosen to avoid catalytic hydrogenetion of the double bond. Et4NOTs, MeOH R = nC H c.c., undivided cell 5 11 78% Cascade cyclization Schäfer, Synthesis, 1995, 1432. (+)-calvine Regioselectivity of methoxylation is usually kinetic control, i.e., less substituted O Me O O α-position is functionalized preferentially. Pt anode H Me steel cathode + MeCO2H + Late-stage functionalization of polycyclyc lactams 5 eq MeOH, KOH, c.c. undivided cell Aubé, Angew. Chem. 2015, 127, 10701. CO2H 42% 15% O graphite anode O OMe graphite cathode Effects of anode material Bretle, J. Chem. Soc. Perkin Trans. I, 1973, 257. N N anode anode LiClO4, MeOH CO2Et c.c. undivided cell CO Et Pt cathode Pt 62% 2 COOH Graphite 5-9% 91% (dr = 4:1) Et N, EtOH, c.c. 4 4 4 3 10 other examples undivided cell RVC 45-53% Major products with graphite anode A mobile phone charger was used as a power supply. O O O

O O O 4 4 4 4 Platinum anode gives radical intermediates, whereas graphite anode gives cationic intermediates. Yu Kawamata Electroorganic Chemistry: Choice of Electrodes Baran Group Meeting 12/10/2016 5

Oxidation of peptides Papadopoulos, Steckhan, Tetrahedron, 1991, 47, 563. Oxidation of electron-rich π-system Pt anode Me O Anode: Pt, graphite, RVC, BDD O Me O H Pt cathode Cathode: Pt, graphite N Ph N OMe Bz N NH H Et NCl, MeCN/MeOH Application to a natural product synthesis Moeller, J. Am. Chem. Soc. 2004, 126, 9106. O Me 4 Me CO Me c.c, undivided cell 2 84% (1.5:1 dr) TBSO Me RVC anode O anodically graphite cathode + generated Cl 2,6-lutidine, LiClO4 O Me Cl O O Me O TBSO TBSO O MeOH/CH2Cl2 O N N c.c. undivided cell Ph N OMe Ph N OMe H MeO H O Me O Me most electron-rich O O Unusual oxidation Shono, J. Am. Chem. Soc. 1990, 112 , 2369. TsOH O OH Pt anode HO Pt cathode OMe O halide additive O NHTs + OMe 88% (+)-Alliacol A N MeONa, MeOH C-H arylation Yoshida, Angew. Chem. Int. Ed. 2012, 51, 7259. c.c., undivided cell NHTs Ts 1 2 OMe carbon felt anode additive: KBr 30% 22% OMe Pt cathode naphthalene KI 82% - Bu4NB(C6F5)4 (1 eq.) radical cation Br OMe CH Cl , -90 ºC, Proposed mechanism: Br OMe 2 2 OMe c.c., divided cell OMe 6 eq. + R Br R X R R N NHTs NHTs 73% MeOH NTs Ts Br 9 other examples MeOH N-Br bond C-H amination Yoshida, J. Am. Chem. Soc. 2013, 135, 5000. homolysis 1 carbon felt anode R Hofmann-Loffler-Freytag Pt cathode N 2 NH2 pyridine N piperidine Ts

Bu4NBF4, MeCN MeCN, 80 ºC c.c., divided cell 99% 12 other examples Yu Kawamata Electroorganic Chemistry: Choice of Electrodes Baran Group Meeting 12/10/2016 6

Organocatalyzed oxidation Boydston, J. Am. Chem. Soc. 2012, 134, 12734. Oxidation of other compounds graphite anode BF4 Though choice of electrodes varies, Pt is often the first choice for anode. O Pt cathode O + R' OH S N Ar R H 10 mol% cat., DBU, TBAB R OR' c.p., undivided cell > 20 examples Me Electrochemical aziridination Yudin, J. Am. Chem. Soc. 2002, 124, 530. Proposed mechanism catalyst O Pt anode Pt cathode N NH2 + Phth N Graphite cathode gave inferior HNEt3OAc, MeCN c.p., divided cell 85% effect due to the sluggish H2 O evolution. 13 other examples This reaction didn't work with graphite anode due to competing alkene oxidation on graphite.

Effects of anode material Coupling of phenols on BDD Waldvogel, Euro. J. Org. Chem. 2006, 4569.

Nyberg, Acta Chem. Scand. B. 1978, 32, 157. BDD anode OH Me OH Me OAc Ni cathode Me anode Me Me [Et3NMe]O3SOMe Pt cathode OAc + AcOH, AcONa H2O, 70 ºC c.c., undivided cell Me HO Me Me Me c.c., undivided cell Me Me Me Me Me 3 4 49% Me Me anode: Pt 3/4 = 4.4 (19% yield) O O Glassy carbon 3/4 = 21 (35% yield) was obtained with Pt anode. H Nishiyama, Angew. Chem. Int. Ed. 2012, 51, 5443. Me Me

OMe OTBDPS OMe anode MeO OMe Oxidation of phosphorus Ohmori, J. Chem. Soc. Chem. Commun. 1995, 871. CHO Pt cathode OTBDPS + graphite anode KOH, MeOH graphite cathode O c.c., undivided cell O 3 eq. nBu P OH OMe MeO OMe OMe 3 2 eq. MeSO3H anode: Pt 100% 0% COOH BnNEt Cl, CH Cl BDD 100% 0% 5 3 2 2 6 undivided cell, c.c. glassy carbon 0% 100% 63% (trans:cis=81:19) Generation of MeO was confirmed in the case of Pt and BDD as anode. 6 other examples Yu Kawamata Electroorganic Chemistry: Choice of Electrodes Baran Group Meeting 7 12/10/2016

Mechanism: Shono, J. Am. Chem. Soc, 1986, 108, 4676, Shono, J. Org. Chem. 1994, 59, 1407. nBu P 3 graphite anode Me OH O O Sn cathode H 5 nBu3P OPnBu3 PnBu3 nBu3PCl2 Et4NOTs, iPrOH -nBu3PO O O O c.c., divided cell anode 70% single diastereomer O >20 examples OH O OH OH Cu, Ag, Pb, Zn and Pb cathode gave lower yields, whereas Pt, Ni and Ti PnBu3 PnBu 3 gave no desired product. - nBu3P OH cathode 6 Reduction of esters Shono, J. Org. Chem. 1992, 57, 1061. Mg anode Oxidation of sulfur Matsumoto, Yoshida, Asian J. Org. Chem. 2013, 2, 325. Mg cathode O carbon felt anode LiClO4 R OH Pt cathode Ph SAr Me R OMe tBuOH, THF Bu4NB(C6F5)4 ArSSAr Ph 70-90% ArSSAr Me R=alkyl c.c., undivided cell CH Cl , -78 ºC SAr SAr Ar=4-FC H 2 2 Me 6 4 c.c., divided cell 78% tBuOH same conditions OH 11 other examples as above 60% CO Me 2 OMe 4-2. Cathodic reduction O TMSCl OTMS 67% Reduction of carbonyl group Grimshaw, Electrochemical reactions and mechanism in organic chemistry, Elsevier, 2000. Esters are not reduced with Zn, Pb, Ni, Cu, Pt and C cathode Anode: Pt, graphite, sacrificial anodes Cathode: Hg, Sn, Mg, Pb, Pt, graphite Reduction of amides Waldvogel, Euro. J. Org. Chem. 2014, 5144. Reductive cyclization of ketones Shono, J. Am. Chem. Soc. 1971, 93, 5284. Pt anode Shono, J. Am. Chem. Soc. 1978, 100, 545. Pb cathode O HO electrolyte, H SO graphite anode Me 2 4 graphite cathode Ph NH Ph NH 2 MeOH, c.c 2 Me 62% divided cell Et4NOTs, dioxane/MeOH O c.p., divided cell 66% (single diastereomer) 10 other examples including 2º and 3º amine product 6-membered & piperidine ring formation and transannular cyclization were also demonstrated. Yu Kawamata Electroorganic Chemistry: Choice of Electrodes Baran Group Meeting 12/10/2016 8

Nédélec, J. Org. Chem. 1990, 55, 2503. Reduction of alkenes and conjugated alkenes Grimshaw, Electrochemical reactions An example of notable anode effect and mechanism in organic chemistry, Anode: Pt, graphite, sacrificial anodes Elsevier, 2000. Al anode MeO Cathode: Hg, Sn, Mg, Pb, Zn, Pt, graphite MeO2C CO2Me steel cathode CO2Me Br O + Al NBu BF , NBu I, Reduction of dienes Shono, J. Org. Chem. 1992, 57, 5561. Br Br 4 4 4 CO2Me NMP, c.c. O undivided cell 50% Mg anode iPr MeO Mg cathode Mg Mg, Zn anode • • • yield < 10% + OH CO2Me LiClO4, THF c.c., undivided cell Reduction of other compounds 62% intermediate Anode: Pt, graphite, sacrificial anodes Pt, Al, Zn, Ni, Cu, Pb as cathode • • • 0% Cathode: Materials with large H2 overpotential

same conditions OH Me as above Reductive carbon-halogen bond cleavage Waldvogel, Chem. Euro. J. 2015, 21, 13878. + MeCO2Me Me Ph Me Ph Br Pt anode H Leaded bronze cathode 94% (single diastereomer) Br H [Et3NMe]O3SOMe Reduction of unsaturated esters N • Dimerization NIshiguchi, Angew. Chem. Int. Ed. 1983, 22, 52. H3PO3, MeCN, c.c. N Boc COOH divided cell Boc COOH Pt anode CO2Me Cu cathode Ph Ph Leaded bronze was found to be more tolerant against corrosion than pure lead. 2 CO Me O 2 TBAOTs, DMF Ph c.p. divided cell 76% Birch reduction Kariv-Millar, J. Org. Chem. 1983, 48, 4210. OH OH • Natural product synthesis Little,Tetrahedron Lett. 1990, 31, 485. Me steel anode Me Hg cathode H O CO Me 2 OH O O H CO2Me Bu4NOH, THF Hg cathode c.c. undivided cell O MeO MeO H TBABr, MeCN 92% quadrone 89% (combined yield Electrochemical transition-metal catalysis Durandetti, J. Org. Chem. 1997, 62, 7914. with minor diastereomer) Al anode e- O O O O NC Ni cathode NC OTBDPS Me TBABF , NiBr bpy * Me 5 steps OTBDPS MeN N + PhI 4 2 MeN N Ph HO Cl DMF, c.c. Ph CHO H Ph undivided cell (slow addition) 57%, 90% ee Yu Kawamata Electroorganic Chemistry: Choice of Electrodes Baran Group Meeting 12/10/2016 9

Mechanism: Useful material for electroorganic synthesis

NiBr2(bpy) Redox potential of organic coumpounds Nicewicz, Synlett, 2016, 27, 714. cathodic reduction

Ni(0) II R-Cl PhI Ni Ph R Ph I cathodic reduction

This step might be similar to Weix's system. Weix, J. Org. Chem. 2014, 79, 4793. Weix, J. Am. Chem. Soc. 2013, 135, 16192.

Summary

Anode material

Do you use sacrificial anode?

Reviews for further study yes no I don't know • Indirect (mediated) electrolysis (a) Steckhan, Angw. Chem. Int. Ed.1986, 28, 683. Al, Zn, Mg, Fe etc. Pt, carbon based material (b) Little, Chem. Soc. Rev. 2014, 43, 2492.

Cathode material • Application to complex molecule syntheses (a) Wright, Chem. Soc. Rev. 2006, 35, 605. Is your target reaction reduction? (b) Moeller, Tetrahedron, 2000, 56, 9527.

yes no • Electrochemical halogenation Petrosyan, Russ. J. Electrochem. 2013, 49, 497.

I don't care Electrochemistry with transition-metal catalysis Hg, Pb, Sn, Mg, and Whatever • Is H2 evolution OK? conductive other material with large Duñach, Euro. J. Org. Chem. 2003, 1605. H2 overpotential yes no

Pt, Ni, Fe and other carbon based material material with small H2 and other material with overpotential large H2 overpotential