Epoxidein

Organic Synthesis

M1 Yuki Hirao

2

Introduction

Epoxides are important intermediates in total synthesis.

3

Asymmetric Epoxidation

The Nobel Prize

in Chemistry 2001

4

Contents

1. Introduction

2. Ring-Opening of Epoxide・Nucleophilic addition

・Reductive-opening by SET

3. Titanocene-catalyzed Epoxide Opening

4. Recent Achievements・Isomerization of epoxides to Allylic Alcohols

・Anti-Markovnikov alcohols via epoxide

hydrogenation

5

Ring-Opening of Epoxide

6

Nucleophilic addition

Jacobsen, E, N. et al. J. Org. Chem. 1997, 62, 4197.

Jacobsen, E, N. et al. Tetrahedron Lett. 1997, 38, 773.

Jacobsen, E, N. et al. Science. 1997, 277, 936.

7

Reductive-opening by SET

Opening of epoxides with low-valent metal complexes

General Ideas

8

Reductive-opening by SET

9

Reductive-opening by SET

10

Contents

1. Introduction

2. Ring-Opening of Epoxide・Nucleophilic addition

・Reductive-opening by SET

3. Titanocene-catalyzed Epoxide Opening

4. Recent Achievements・Isomerization of epoxides to Allylic Alcohols

・Anti-Markovnikov alcohols via epoxide

hydrogenation

11

Titanocene-catalyzed Epoxide Opening

12

Titanocene-catalyzed Epoxide Opening

Fürstner, A. et al. J. Am. Chem. Soc. 1995, 117, 4468.

Fürstner, A. et al. J. Am. Chem. Soc. 1996, 118, 2533.

Ikeda, I. et al. J. Org. Chem. 1996, 61, 366.

13

Titanocene-catalyzed Epoxide Opening

A. Gansäuer. et al. J. Org. Chem. 1998, 66, 2070.

A. Gansäuer. et al. Eur. J. Org. Chem. 1998, 2673.

14

Titanocene-catalyzed Epoxide Opening

15

Computational Studies

A. Gansäuer. et al. J. Am. Chem. Soc. 2007, 129, 1359.

DFT calculations (BP86/TZVP)

Favored Disfavored

In disfavored transition state, the larger CH3 group gets into closer contact with Cp ligand.

16

Computational Studies

A. Gansäuer. et al. J. Am. Chem. Soc. 2007, 129, 1359.

DFT calculations (BP86/TZVP)

Epoxide opening is exothermic. The formation of the higher substituted radicals is thermodynamically

favored.

17A. Gansäuer. et al. J. Am. Chem. Soc. 1998, 120, 12849.

A. Gansäuer. et al. J. Am. Chem. Soc. 2007, 129, 1359.

Computational Studies

18

Titanocene-catalyzed Epoxide Opening

19

Short Summary

Reductive Opening of Epoxides by SETRadical Stability

Steric Interactions between R1, R2 and Cp ligand

more highly substituted radical

opposed to SN2 Reaction (from less substituted carbon)

20

Contents

4. Recent Achievements

21

Purpose

J. Andersson. et al. J. Am. Chem. Soc. 2000, 122, 6610.

K. Y. Ye, T. M. Callum, S. Lin. J. Am. Chem. Soc. 2019, 141, 9548.

22

Optimization

K. Y. Ye, T. M. Callum, S. Lin. J. Am. Chem. Soc. 2019, 141, 9548.

23

Proposed Catalytic Cycle

K. Y. Ye, T. M. Callum, S. Lin. J. Am. Chem. Soc. 2019, 141, 9548.

24

Substrate Scope

K. Y. Ye, T. M. Callum, S. Lin. J. Am. Chem. Soc. 2019, 141, 9548.

25

Kinetic Resolution

K. Y. Ye, T. M. Callum, S. Lin. J. Am. Chem. Soc. 2019, 141, 9548.

26

Radical Rearrangement

K. Y. Ye, T. M. Callum, S. Lin. J. Am. Chem. Soc. 2019, 141, 9548.

27

Asymmetric Reaction

K. Y. Ye, T. M. Callum, S. Lin. J. Am. Chem. Soc. 2019, 141, 9548.

28

Contents

4. Recent Achievements

29

Anti-Markovnikov alcohols

C. Yao, T, Dahmen, A. Gansäuer, J. Norton. Science. 2019, 364, 764.

30

Previous Work

31

This Work

C. Yao, T, Dahmen, A. Gansäuer, J. Norton. Science. 2019, 364, 764.

32

Proposed Catalytic Cycle

C. Yao, T, Dahmen, A. Gansäuer, J. Norton. Science. 2019, 364, 764.

33

Side Reaction

C. Yao, T, Dahmen, A. Gansäuer, J. Norton. Science. 2019, 364, 764.

34

Substrate Scope

C. Yao, T, Dahmen, A. Gansäuer, J. Norton. Science. 2019, 364, 764.

35

Substrate Scope

C. Yao, T, Dahmen, A. Gansäuer, J. Norton. Science. 2019, 364, 764.

36

Summary

Appendix

38

Titanocene-catalyzed Epoxide Opening

39

Unsuccessful Substrates Isomerization of epoxides to Allylic Alcohols

40

Radical Rearrangement

K. Y. Ye, T. M. Callum, S. Lin. J. Am. Chem. Soc. 2019, 141, 9548.

41

Cyclic Voltammetry Studies

42

Optimization of anti-Markovnikov hydrogenation

43

NMR Studies

C. Yao, T, Dahmen, A. Gansäuer, J. Norton. Science. 2019, 364, 764.

44

NMR Studies

45

NMR Studies

46

Cyclic Voltammetry Studies