1. 1,2 – Disubstituted Aromatics: Directed Ortho Metalation
Dennis Hoffart
Nov. 17, 2003
59-636

2. Outline Mechanism of DoM Reaction Evidence for Proposed Mechanism
Properties and Hierarchy of DMGs
Relative Competition of DMGs
Cooperative Metalation of meta-Substituted Aromatics
Electrophilic substitution of Lithiated Aromatics

3. Outline Successive DoM as a Route to Poly-Substituted Aromatics
Synthetic Consequences of ortho-Lithiation
Synthesis of Boronic Acids: Reagents for Suzuki Coupling
Synthesis of Stannyl Compounds: Reagents for Stille Coupling
Further Functionalisation of DoM Products: Towards Liquid Crystals
Potential Synthesis of Liquid Crystals

4. Mechanism

5. Mechanism

6. Mechanism

7. Mechanism

8. Mechanism

9. Directed Metalation Groups (DMGs)
Strong
Moderate
Weak

10. Relative Competition of DMGs
DMG1 > DMG2
a >>> b

11. Cooperative Metalation Effects
Deprotonation at ‘a’ will be favoured over deprotonation at ‘b’.
This can be used to our advantage in designing synthetic pathways.

12. Electrophilic Substitution of Ortho-Lithiated Aromatics
MeI
CO2
EtI
DMF S8
TsN3 / NaBH4
Br2
R3SiCl I2
R3SnCl
O2 / H+
B(OMe)3 Me
CO2H Et
CHO SH
NH2 Br
SiR3 I
SnR3 OH
B(OH)2

13. Successive DoM Reactions for Poly-Substituted Aromatics

14. Successive DoM Reactions

15. Synthetic Potential 1: Suzuki Reagents

16. Suzuki Coupling

17. Synthetic Potential 2: Stille Reagents

18. Stille Coupling

19. Further Functionalisation of Aromatics: Towards Liquid Crystals

20. Possible Synthetic Route to a Discotic Liquid Crystal

21. Possible Synthetic Route to a Discotic Liquid Crystal

22. Possible Synthetic Route to a Discotic Liquid Crystal

23. Possible Synthetic Route to a Calamitic Liquid Crystal

24. Possible Synthetic Route to a Calamitic Liquid Crystal

25. Possible Synthetic Route to a Calamitic Liquid Crystal

26. Possible Synthetic Route to a Calamitic Liquid Crystal

27. Conclusions and References
DoM reaction is an excellent strategy for the (poly-)substitution of aromatic systems.
Straight forward mechanism with a wide scope.
Excellent method for the generation of coupling precursors, such as boronic acids and stannyl reagents.
Snieckus, V. Chem. Rev. 1990, 90, 879.
Queguiner, G.; Marsais, F.; Snieckus, V.; Epsztajn, J. Adv. Heterocycl. Chem. 1991, 52, 187.