“FORBIDDEN 1,2-CARBANION SHIFTS”

MECHANISM AND APPLICATION OF THE FRITSCH-

BUTTENBERG-WIECHELL REARRANGEMENT

Chun Ho Lam

17th November, 2010

1

Chun Ho Lam

17th November 2010

Contents

Section 1:

Discovery of the Fritsch-Buttenberg-Wiechell (FBW) Rearrangement

Section 2:

Mechanistic Probing with Ring Expansion Model

The Woodward-Hoffmann Rules

Effect of different conditions on the mechanism

Investigation of the mechanism

Section 3:

A recent application of the FBW Rearrangement

2

Section 1

3

Discovery of the

Fritsch-Buttenberg-Wiechell (FBW)

Rearrangement

In 1894, discovered by the 3 scientists:

• Paul Ernst Moritz Fritsch

• Wilhelm Paul Buttenberg

• Heinrich G. Wiechell

Fritsch, P. Justus Liebigs Annalen der Chemie 1894, 3, 319.Buttenberg, W. P. Justus Liebig's Annalen der Chemie 1894, 3, 324

Wiechell, H. Justus Liebig's Annalen der Chemie 1894, 3, 337

Introduction of the FBW Rearrangement

4

Possible Mechanisms for FBW

5

Fritsch, P. Justus Liebigs Annalen der Chemie 1894, 3, 319.Buttenberg, W. P. Justus Liebig's Annalen der Chemie 1894, 3, 324

Wiechell, H. Justus Liebig's Annalen der Chemie 1894, 3, 337

Route A

Route B

Route C

Section 2 – Part A

6

Mechanistic Probing

with Ring Expansion Model

The Woodward Hoffmann Forbidden Transformation

Introduction to the Ring Expansion Model

Mechanistic Probing Tool

Mechanism Probing:

Solvent

Halide group

Temperature

Substitute

7

Erickson, K.L.; Niu, T.; Samuel S.P. J. Am. Chem. Soc. 1989, 111, 1429.

Possible Routes

8

Erickson, K.L.; Niu, T.; Samuel S.P. J. Am. Chem. Soc. 1989, 111, 1429.

Elimination of Route A

9

“Diels-Alder Trap”

Erickson, K.L.; Niu, T.; Samuel S.P. J. Am. Chem. Soc. 1989, 111, 1429.

Elimination of Route C

Route C

Erickson, K.L.; Niu, T.; Samuel S.P. J. Am. Chem. Soc. 1989, 111, 1429.

10

The Only Way: Route B

However:

1. Anionic 1,2-sigmatropic rearrangement

11

Erickson, K.L.; Niu, T.; Samuel S.P. J. Am. Chem. Soc. 1989, 111, 1429.

2. Violates the Woodward-Hoffmann symmetry rule

3. This should be “impossible”

The Woodward-Hoffmann Rule

An anionic sigmatropic rearrangement is a 4e- process

12

Molecular Orbital Diagram

13

The Woodward-Hoffmann Rule

Definition: Conversation of orbital symmetry in a (concerted) pericyclic reaction

Thermodynamically Allowed

14

The “Forbidden” Examples

1,2-Wittig Rearrangement

Stevens rearrangement

15

Source: Strategic Application of Named Reaction in Organic Synthesis

The “Allowed” Examples

Wagner-Meerwein Rearrangement

Beckmann Rearrangement

16

Source: Strategic Application of Named Reaction in Organic Synthesis

Route B: The Forbidden Route

The only option left:

17

The important factors:

1. Vinyl Anion

2. Vinyl Group

3. Vinyl Anion Stabilizer (Bromine)

Erickson, K.L J. Org. Chem. 1973, 8, 1463.

Importance of these factors?

No Double Bond

No Vinyl Anion

No Bromine

18

Erickson, K.L J. Org. Chem. 1973, 8, 1463.

Polar vs. Non-Polar Solvent

In polar solvent:

In non-polar solvent:

19

Erickson, K.L J. Org. Chem. 1973, 8, 1463.

Isomerization in Polar Solvent

Where does come from?

Polar solvent can stabilize the charges on the

resonance form thereby promotes side reaction.

Erickson, K.L J. Org. Chem. 1973, 8, 1463.

20

Quick Summary

To trigger Route B, there must be:

Halogen

Vinyl Anion

Strong Base

Non-polar solvent

21

Route B: The Forbidden Route

Section 2: Part B

22

~ Investigation of the FBW rearrangement ~

Mechanistic Probing

with Ring Expansion Model

Possible Mechanism for Route B

Case 1

23

Erickson, K.L.; Niu, T.; Samuel S.P. J. Am. Chem. Soc. 1989, 111, 1429.

Possible Mechanism for Route B

Case 2:

Case 3

24

Erickson, K.L.; Niu, T.; Samuel S.P. J. Am. Chem. Soc. 1989, 111, 1429.

Elimination of Case 3

Case 3 is unlikely at low temperature because

The Diels-Alder trap shows Case 3 is not happening at

low temperature rearrangement.

25

Erickson, K.L.; Niu, T.; Samuel S.P. J. Am. Chem. Soc. 1989, 111, 1429.

The Remaining: Case 1 and Case 2

Case 1: Bromine attach to terminal carbon

Case 2: Bromine partially attach to vinyl group

26

Erickson, K.L.; Niu, T.; Samuel S.P. J. Am. Chem. Soc. 1989, 111, 1429.

Distinguish the 2 Cases with 13C

13C labeling reviews the reaction pathway depends

on the bromine position

Major Product

27

Erickson, K.L.; Niu, T.; Samuel S.P. J. Am. Chem. Soc. 1989, 111, 1429.

Cis

Trans

The Overall Results

28

Erickson, K.L.; Niu, T.; Samuel S.P. J. Am. Chem. Soc. 1989, 111, 1429.

Trans

Cis

The Overall Results Continued

29

Erickson, K.L.; Niu, T.; Samuel S.P. J. Am. Chem. Soc. 1989, 111, 1429.

Cis to Trans Isomerization

• ¾ reactions prefer Case 2, the migrating path.

• ¼ reaction prefers Case 1, the re-hybridization path.

30

Erickson, K.L.; Niu, T.; Samuel S.P. J. Am. Chem. Soc. 1989, 111, 1429.

Cis

Trans

Isomerization Analysis

31

Erickson, K.L.; Niu, T.; Samuel S.P. J. Am. Chem. Soc. 1989, 111, 1429.

The Cis-Isomer Reaction

32

Isomerization

Erickson, K.L.; Niu, T.; Samuel S.P. J. Am. Chem. Soc. 1989, 111, 1429.

Rehybridization

Rotation of 13C Labeled Carbon

Quick Summary

1. The trans migration pathway is strongly preferred.

2. Reaction happens in a stepwise rather than a

concerted mechanism.

W-H Rule Allow

W-H Rule Forbid

33

The Role of Halogen in Reaction

% Yield A: B

F 40 1.52 : 1

Cl 32 2.80 : 1

Br 20 2.84 : 1

I 21 3.88 : 1

34

Du Z.M.; Haglund M. J.; Pratt L. A.; Erickson K.L. J. Org. Chem. 1998, 63 , 8880

Trend Interpretation

35

Du Z.M.; Haglund M. J.; Pratt L. A.; Erickson K.L. J. Org. Chem. 1998, 63 , 8880

• Analysis with Newman Projection

Trend Interpretation at Orbital Level

36

Du Z.M.; Haglund M. J.; Pratt L. A.; Erickson K.L. J. Org. Chem. 1998, 63 , 8880

Trend Interpretation

% Yield A: B

F 40 1.52 : 1

Cl 32 2.80 : 1

Br 20 2.84 : 1

I 21 3.88 : 1

Single Mig.

Double Mig.

The Halogen dissociated

37

Du Z.M.; Haglund M. J.; Pratt L. A.; Erickson K.L. J. Org. Chem. 1998, 63 , 8880

BDE (kcal mol-1): F (117) > Cl (79) > Br (69) > I (51.7)

Quick Summary

The size of Halogen is important to the mechanism

The 13C method system was “misleading”

38

Stereo fate of the Migrating Group

1. Complete retention of stereogenic center

2. Double migration > Single migration

(Bromine is not on 13C)

3. High yield is due to tetra-substituted carbon

* ** *

39

Du Z.M.; Erickson K.L. J. Org. Chem. 2010, 75 , 7129

40

1. Mechanism agrees with 13C study and Halogen study.

2. Double migration is preferred

Du Z.M.; Erickson K.L. J. Org. Chem. 2010, 75 , 7129

The Mechanism

41

To Conclude the Findings

D.A. Trap

Ref. Study

Halogen Study

Du Z.M.; Erickson K.L. J. Org. Chem. 2010, 75 , 7129

The MP2 6-31+G(d) Calculation

-37

-32

-27

-22

-17

-12

-7

-2

3

8

13

React TS Int 1 TS 2 Int2 TS 3 Prod

Fre

e E

ne

rgy

(k

ca

l m

ol-1

)

Reaction Coordinate

F

Cl

Br

HHal Li C

42

Pratt, L.M.; Nguyen N. V.; O. Kwon, Chem. Lett. 2009, 38, 574.

Computational results vs. Ring Expansion model

Computational Results Ring Expansion Model

Carbene Carbene with Halogen

F, Cl, BrMakes no difference to

migration

F causes 50:50 Single : DoubleCl and Br causes mostly

Double.

Intermediate: the migrating group is in the vinyl system

Intermediate: the migrating Double Stepwise migration

43

Pratt, L.M.; Nguyen N. V.; O. Kwon, Chem. Lett. 2009, 38, 574.

Reliability of the results

44

Reliable

Gas phase cond. resemble the non-polar solvent.

MP2 gives good estimation of the T.S. and Int

Results suggest other mechanism is possible.

Pratt, L.M.; Nguyen N. V.; O. Kwon, Chem. Lett. 2009, 38, 574.

However

The ring strain issue is not addressed

The spectator ion is different: Li vs. K

Migrating group is H, not alkyl group

Summary

45

Mechanism bypasses WH Rule with a rehybridization

of the migrating group.

Mechanism is minor temp. dependent

Erickson, K.L.; Niu, T.; Samuel S.P. J. Am. Chem. Soc. 1989, 111, 1429.

Summary Continued

46

Du Z.M.; Haglund M. J.; Pratt L. A.; Erickson K.L. J. Org. Chem. 1998, 63 , 888046

Mechanism depends on:

Solvent polarity

Halide size

Temperature

Geometry of the reactant

Combining the REM with FBW

47

According to the Ring Expansion Model:

Route A

The Suggested FBW Rearrangement

48

The Modified FBW Rearrangement

49

Section 3

50

Recent Application of Modified FBW

Rearrangement

51

Introduction of Polyyne

What it is and what it does

Synthesis of Polyyne

with traditional Cu/Pd Coupling

with FBW rearrangement

Application of Modified FBW in Polyyne Synthesis

Introduction of Polyyne

52

PolyyneSp-Hybridized

Carbyne

Sp2-Hybridized CarbonGraphite

Sp3-Hybridized CarbonDiamonds

Properties

1. Extremely Rigid

1. Thermal Conductor

2. Electrical Conductor

1. Electrical Conductor?

2. Optical Applications?

Traditional Polyyne Synthesis

53

Homocoupling Reaction

Glaser Coupling

Eglinton Modification

Hay’s Modification

Source: Strategic Application of Named Reaction in Organic Synthesis

Traditional Polyyne Synthesis

54

Hetercoupling Reaction:

Chodkiewitz-Cadiot

Sonogashira Cross Coupling

Source: Strategic Application of Named Reaction in Organic Synthesis

Synthesis of Polyyne with Cu/Pd Coupling

55

Total Steps: 3

Overall Yield: 17%

Yamaguchi, M.; Park, H. J.; Hirama, M.; Torisu, K.; Nakamura, S.; Minami, T.; Nishihara, H.; Hiraoka, T. Bull. Chem. Soc. Jpn. 1994, 67, 1717.

56

Total Steps: 4

Overall Yield: 56%

1 pot

Synthesis of Polyyne with RBW Rearrangement

Luu, T.; Morisaki Y.; Cunningham N.; Tykwinski R. R. J. Org. Chem., 2007, 72, 9622.

Limitation of the FBW method

57

Can FBW take over Cu coupling in Polyyne Synthesis?

Jahnke E.; Tywinski R.R.; Chem. Commum. 2010, 46 , 3235

FBW vs. Copper Coupling

58

1. FBW can be a 1-pot convenient method

2. Copper Chemistry is still an important coupling reaction

Jahnke E.; Tywinski R.R.; Chem. Commum. 2010, 46 , 3235

Conclusion

59

Bypass W-H Rule with “Rehybridizations”, Radical

rearrangement

Mechanism of FBW is most likely a double migration

process.

Computational study disagrees with the experiment

Methods with more similar condition should be

employed

FBW offers 1-pot synthesis of Polyyne

At low module of alkyne

Copper chemistry still has its importance.

Acknowledgement

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60

o Dr. Jackson

o Dr. Maleczka

o Dr. Huang

o Dr. Redko, Dr. Saumitra, Abby, Crystal,

Laura, Megan, Melisa, Meisam, San, Xin,

Zhe, members from Baker and Wulff’s group