E-Olefins through Intramolecular

Radical Relocation

Literature Report 2

Reporter: Han Wang

Checker: Bo Wu

Date: 2019.4.29

Schoenebeck, F.*; Kapat, A.; Sperger, T.; Guven, S.

Science 2019, 363, 391-396.

CV of Prof. Franziska Schoenebeck

Background:

2004-2008

2008-2010

2010-2013

2013-2016

2016-now

Research:

Studies of organometallic catalysis and state-of-the-art

computational methods.

2

Ph.D., University of Strathclyde (John A. Murphy)

Postdoctor, UCLA (K. N. Houk)

Assistant Professor, ETH Zürich

Associate Professor, RWTH Aachen University

Professor, RWTH Aachen University

Contents

1

2

Introduction

3

Metalloradical Induced Double-bond Transposition

Summary

3

Introduction

4

Introduction

5

Double Bond Transposition

Metal Hydrides Diradical Pairs Metalloradical

Alkyl Mechanism Allyl Mechanism

6

Double-Bond Transposition via Metal Hydrides

Alkyl Mechanism:

• Empty 2e- coordination

site

• Metal hydrides

M = transition metal; [L]n = bound

ligand(s); [L]0 = dissociating ligand

or vacant 2e- site

7

Alkyl Mechanism

Skrydstrup, T. et al. J. Am. Chem. Soc. 2010, 132, 7998.

8

Alkyl Mechanism

Holland, P. L. et al. J. Am. Chem. Soc. 2014, 136, 945.

9

Double-Bond Transposition via Metal Hydrides

Allyl Mechanism:

• Two vacant coordination

sites

• No metal hydride

M = transition metal; [L]n = bound

ligand(s); [L]0 = dissociating ligand

or vacant 2e- site

Allyl Mechanism

10

Grotjahn, D. B. et al. J. Am. Chem. Soc. 2007, 129, 9592.

Grotjahn, D. B. et al. J. Am. Chem. Soc. 2012, 134, 10357.

Entry Reactant Product mol% [Ru] Yield %

1 0.5 96

2 5 96

3 2 98

4 0.05 99

5 2 95

6 2 91

Allyl Mechanism

11

Grotjahn, D. B. et al. J. Am. Chem. Soc. 2007, 129, 9592.

12

Allyl Mechanism

Goldman, A. S. et al. Science 2006, 312, 257.

13

Allyl Mechanism

Goldman, A. S. et al. J. Am. Chem. Soc. 2012, 134, 13276.

14

Crossover Experiment

Casey, C. P. et al. J. Am. Chem. Soc. 1973, 95, 2248.

Chianese, A. R. et al. Organometallics 2014, 33, 473.

Allyl Mechanism:

• Intramolecular H transfer

• 1,3-Addition

Alkyl Mechanism:

• External hydride

• 1,2-Addition

15

Double-Bond Transposition via Biradical Pairs

Shenvi, R. A. et al. J. Am. Chem. Soc. 2014, 136, 16788.

16

Double-Bond Transposition via Biradical Pairs

Shenvi, R. A. et al. J. Am. Chem. Soc. 2014, 136, 16788.

Double-bond Transposition via Metalloradical

17

Proposed Machanism：

Schoenebeck, F. et al. Science 2019, 363, 391.

Mechanism Test

18

Mechanism Test

19

Conditions Time[h] cis-8/trans-8 ratioa

[Ni(μ-Cl)(IPr)]2 (5 mol%),

Cl-C6H5, rt

3 72:28

6 60:40

Ni(0)(IPr)2 (20 mol%),

Toluene-d8, rt 3 100:0

Ni(II)(H)(Cl)(IPr)2 (5 mol%),

Cl-C6H5, rt 3 100:0

Ni(II)(Cl)2(IPr)2 (5 mol%),

Cl-C6H5, rt 3 100:0

a Ratios (cis-8 versus trans-8) were determined by quantitative 1H NMR.

Optimization of reaction parameters

20

Entrya Solvent Time[h] 2a [%]b 3a [%]b

1 Cl-C6H5 3 - >98

2 DCM 16 - 84

3 benzene 28 50 30

4 DMF 28 28 57

5 EtOAc 28 42 36

6 THF 28 38 38

a Conditions:2 (0.1 mmol), 1 (5 mol%), solvent (100 μL). b Isolated yield.

Substrate Scope

21

Substrate Scope

22

Substrate Scope

23

24

Selectivity Test

Double isomerization：

Acyclic Trisubstituted Olefin：

Summary

25

The First Paragraph

The carbon–carbon double bond in olefins serves as a precursor to a

rich array of transformations and is a cornerstone in the materials,

pharmaceutical, agrochemical arenas, and food industry . Its construction

in a selective and stereochemically defined manner—i.e., E versus Z

olefin—is of utmost importance, as the geometry is ultimately coupled to

function. Although numerous strategies to construct olefins have become

established textbook knowledge, the E/Z selectivity is frequently

incomplete or comes at the expense of valuable functionality in these

classical approaches.

26

The First Paragraph

Mixtures of E and Z isomers are difficult to separate, however. More

modern catalytic strategies commonly achieve high selectivity through

semi-hydrogenations, requiring an atmosphere of H2 or stoichiometric

amounts of acid or other H sources. Olefin metathesis catalysts were

developed to selectively access Z-olefins, whereas the E-isomer is

accessible in high selectivity only with certain halogenated or low-

functionality compounds . Ring-opening strategies via C–C cleavage are

elegant alternatives to selectively install E-olefins.

27

The Last Paragraph

Overall, our protocol combines operational simplicity, ease of purification,

sustainability (no additional reagents, nonprecious metal, potential for

solvent-free reactivity), and scalability with functional group tolerance,

short reaction times, and mild conditions.

28

Acknowledgement

Synthesis of Radical Clock