1,2 – Disubstituted Aromatics: Directed Ortho Metalation

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Presentation transcript:

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

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

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

Mechanism

Mechanism

Mechanism

Mechanism

Mechanism

Directed Metalation Groups (DMGs) Strong Moderate Weak

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

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

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

Successive DoM Reactions for Poly-Substituted Aromatics

Successive DoM Reactions

Synthetic Potential 1: Suzuki Reagents

Suzuki Coupling

Synthetic Potential 2: Stille Reagents

Stille Coupling

Further Functionalisation of Aromatics: Towards Liquid Crystals

Possible Synthetic Route to a Discotic Liquid Crystal

Possible Synthetic Route to a Discotic Liquid Crystal

Possible Synthetic Route to a Discotic Liquid Crystal

Possible Synthetic Route to a Calamitic Liquid Crystal

Possible Synthetic Route to a Calamitic Liquid Crystal

Possible Synthetic Route to a Calamitic Liquid Crystal

Possible Synthetic Route to a Calamitic Liquid Crystal

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.