Organic Electrosynthesis
M1 Toyama
2019/07/25

Contents

1. Introduction
2. Electrochemical Allylic C-H Oxidation
3. Electrochemical Birch Reduction

4. Summary2

Introduction: Organic Electrosynthesis
Faraday showed first example of organic electrosynthesis(1834) :Michael Faraday
1791-1867

Kolbe generalized Faraday’s discovery (1849) :Hermann Kolbe
1818-1884
3

Overview of Organic Electrosynthesis

4

Examples of Organic Electrosynthesis

5

Shono Oxidation

Functionalization of a position of amine

Shono, T.; Hamaguichi, H.; Matsumura, Y. J. Am. Chem. Soc. 1975, 97, 4264. 6

MediatorAvoid over-potential
Mild conditions
Different selectivity
Avoid passivation of electrodeR. Francke and R. D. Little. Chem. Soc. Rev., 2014, 43, 2492. 7

Examples of Mediator (1)L. Zhu, P. Xiong, Z.-Y. Mao, Y.-H. Wang, X. Yan, X. Lu and H.-C. Xu, Angew. Chem. Int. Ed., 2016, 55, 2226.
8

Examples of Mediator (2)二電子的な酸化還元反応と一電子的な酸化還元反応はどうやって制御しているの？

ヒドロキシラジカル出せる▶この方法機構解析に使えるか？

ヒドロキシラジカルだけを出す方法があるか？

Z. Zhang, J. Su, Z. Zha and Z. Wang, Chem. Eur. J., 2013, 19, 17711. 9

Examples of Mediator (3)片方のエナンチオマーだけが酸化させれる理由??

M. Kuroboshi, et al., Tetrahedron Lett., 2000, 41, 8131.

10Cation Pool Method

Cation intermediate accumulation
Various nucleophile can be introduced

J. –I. Yoshida, Chem. Eur. J., 2002, 12, 2650.11

Examples of Cation Pool Method (1)S. Suga, M. Okajima, K. Fujiwara and J.-I. Yoshida, J. Am. Chem. Soc., 2001, 123, 7941.12

Examples of Cation Pool Method (2)

ここの抜け方?

T. Morofuji, A. Shimizu and J.-I. Yoshida, J. Am. Chem. Soc., 2013, 135, 5000. 13Phil S. Baran
Phil S. Baran (born 1977) is aProfessor in the Department ofChemistry at the Scripps ResearchInstitute and Member of the Skaggs
Institute for Chemical Biology. He
received his B.S. in chemistry fromNew York University in 1997 and hisPh.D. from The Scripps ResearchInstitute in 2001, under thesupervision of K.C. Nicolaou. He did
his postdoctoral fellowship in thelaboratory of Nobel Laureate E. J.
Corey at Harvard University.
His work is focused on synthesizing
complex organic compounds, thedevelopment of new reactions,andthe development of new reagents. 14

Contents

1. Introduction
2. Electrochemical Allylic C-H Oxidation
3. Electrochemical Birch Reduction

4. Summary
15

Allylic C-H Oxidation

P. S. Baran et al. Nature, 2016, 533, 77.

16

Initial Trial

Masui, M., Hosomi, K., Tsuchida, K. & Ozaki, S. Chem. Pharm. Bull. 1985 33, 4798.
P. S. Baran et al. Nature, 2016, 533, 77.

17

Screening of Mediator

メディエーター分子
どんな指針で決められているのか？

P. S. Baran et al. Nature, 2016, 533, 77.

18

Electrochemical Allylic C-H Oxidation

PGS
環境負荷への指標% 表記
高いほど環境への負荷が小さい
Crなど ca 37 %本反応 ca 58 %P. S. Baran et al. Nature, 2016, 533, 77.

19

Substrate Scope (1)P. S. Baran et al. Nature, 2016, 533, 77.

20

Substrate Scope (2)P. S. Baran et al. Nature, 2016, 533, 77.

21

Reaction Mechanism
ここは容易に脱プロトン化進むの??

P. S. Baran et al. Nature, 2016, 533, 77.

22

Contents

1. Introduction
2. Electrochemical Allylic C-H Oxidation
3. Electrochemical Birch Reduction

4. Summary23

Birch Reduction

Low chemoselectivity

Not Scalable

P. S. Baran et al. Science, 2019, 363, 838. 24

Screening
電極の選び方・化合物の吸着能・酸化還元電位
・陰極は水素を発生しやすさ

過充電によりLi が析出してしまう。
これはリチウムイオン電池の開発でも見られる現象
Li イオンのトラップ剤 TPPA

P. S. Baran et al. Science, 2019, 363, 838. 25

Electrochemical Birch Reaction

Safe

電極の決め方は?
電圧などによる？？
なん電子か？

Ammonia / amine free

Improved substrate scope
Scalable (batch and flow)

P. S. Baran et al. Science, 2019, 363, 838. 26

Substrate Scope (1)P. S. Baran et al. Science, 2019, 363, 838. 27

Substrate Scope (2)P. S. Baran et al. Science, 2019, 363, 838. 28

Li0 pathway vs On-electrode pathway◀ 一度目のプロトン化が律速段階

Li0 は実験からも計算からも否定的

二度目のプロトン化が律速段階↓P. S. Baran et al. Science, 2019, 363, 838. 29

Role of DMU and LiBrATR IR of DMU with / without LiBr

P. S. Baran et al. Science, 2019, 363, 838. 30

Role of TPPA

With TPPA, Zn electrodewas still accessible.

P. S. Baran et al. Science, 2019, 363, 838. 31

Reaction Mechanism

P. S. Baran et al. Science, 2019, 363, 838. 32

Contents

1. Introduction
2. Electrochemical Allylic C-H Oxidation
3. Electrochemical Birch Reduction

4. Summary33

Summary- Organic electrosynthesis can avoid toxic oxidant / reductant.
- Redox potential can be easily tunable.

- Chemoselectivity can be tunable by mediator and cation
pool method.
- Mild allylic C-H bond oxidation was developed using Cl4-NHPImediator.
- Mild electrochemical Birch reduction was developed withLiBr, DMU, TPPA
34

Appendix: square wave voltammetry

35

Appendix: Cyclic voltammetry

36Appendix: Cyclic voltammetry

37