Cross-Coupling Reactions Functionnalized Organometallic ... · Cross-Coupling Reactions...

R-M

R-X-R’

R-X-M

R-B(R’)2

R-Si(R’)3

Cross-Coupling Reactions

Functionnalized Organometallic Reagents

C-N, C-O and C-S Bond Formation

Introduction to Organoboron Chemistry

Introduction to Organosilicon Chemistry

Carbometallation Reactions

R-M

R’-XR-R’

Introduction to Organoboron Chemistry

Synthesis of Boron Derivatives

Generalities and Nomenclature

Hydroboration of Unsaturated Systems

R-M

R-X-R’

R-X-M

R-B(R’)2

R-Si(R’)3

Carbonylation Reactions

Allylation Reactions

Matteson Homologation

R-M

R’-XR-R’

Assembly-Line Synthesis

R-M

R-X-R’

R-X-M

R-B(R’)2

R-Si(R’)3

Introduction to Organoboron Chemistry

Generalities and Nomenclature

R-M

R’-XR-R’

Mild Lewis Acid

Electrophile

Trigonal, Planar

Nucleophile

Tetrahedral

R-M

R-X-R’

R-X-M

R-B(R’)2

R-Si(R’)3

Introduction to Organoboron Chemistry

Generalities and Nomenclature

R-M

R’-XR-R’

Borane Borinic Acid Boronic Acid Boric Acid

Borinic Ester Boronic Ester Boric Ester

« Borate »« Boronate »

Ate BoronComplex

R-M

R-X-R’

R-X-M

R-B(R’)2

R-Si(R’)3

Introduction to Organoboron Chemistry

Generalities and Nomenclature

R-M

R’-XR-R’

Inductive Effects

Mesomeric Effects

R-M

R-X-R’

R-X-M

R-B(R’)2

R-Si(R’)3

Introduction to Organoboron Chemistry

Synthesis of Boron Derivatives

R-M

R’-XR-R’

From Boronic Acids

From Boronic Esters – Equilibrium Displacement

R-M

R-X-R’

R-X-M

R-B(R’)2

R-Si(R’)3

Introduction to Organoboron Chemistry

Synthesis of Boron Derivatives

R-M

R’-XR-R’

Examples

R-M

R-X-R’

R-X-M

R-B(R’)2

R-Si(R’)3

Introduction to Organoboron Chemistry

Synthesis of Boron Derivatives

R-M

R’-XR-R’

Arylboronic Acids

1) Halogen-Metal Exchange / Electrophilic Trapping

2) Orthometallation / Electrophilic Trapping

R-M

R-X-R’

R-X-M

R-B(R’)2

R-Si(R’)3

Introduction to Organoboron Chemistry

Synthesis of Boron Derivatives

R-M

R’-XR-R’

Arylboronic Acids

3) Transmetallation from Silanes and Stannanes

4) Cross-Coupling with Diboron

R-M

R-X-R’

R-X-M

R-B(R’)2

R-Si(R’)3

Introduction to Organoboron Chemistry

Synthesis of Boron Derivatives

R-M

R’-XR-R’

Arylboronic Acids

R-M

R-X-R’

R-X-M

R-B(R’)2

R-Si(R’)3

Introduction to Organoboron Chemistry

Synthesis of Boron Derivatives

R-M

R’-XR-R’

Arylboronic Acids

R-M

R-X-R’

R-X-M

R-B(R’)2

R-Si(R’)3

Introduction to Organoboron Chemistry

Synthesis of Boron Derivatives

R-M

R’-XR-R’

Arylboronic Acids

R-M

R-X-R’

R-X-M

R-B(R’)2

R-Si(R’)3

Introduction to Organoboron Chemistry

Synthesis of Boron Derivatives

R-M

R’-XR-R’

Arylboronic Acids

R-M

R-X-R’

R-X-M

R-B(R’)2

R-Si(R’)3

Introduction to Organoboron Chemistry

Synthesis of Boron Derivatives

R-M

R’-XR-R’

Alkenylboronic Acids

1) Halogen-Metal Exchange / Electrophilic Trapping

2) Transmetallation from Si / Zr

R-M

R-X-R’

R-X-M

R-B(R’)2

R-Si(R’)3

Introduction to Organoboron Chemistry

Synthesis of Boron Derivatives

R-M

R’-XR-R’

Alkenylboronic Acids

3) Cross-Coupling with Diboron

4) Reduction

R-M

R-X-R’

R-X-M

R-B(R’)2

R-Si(R’)3

Introduction to Organoboron Chemistry

Synthesis of Boron Derivatives

R-M

R’-XR-R’

Alkenylboronic Acids

5) Cis-Hydroboration of Alkynes

6) Rhodium and Iridium-Catalyzed Trans-Hydroboration

R-M

R-X-R’

R-X-M

R-B(R’)2

R-Si(R’)3

Introduction to Organoboron Chemistry

Synthesis of Boron Derivatives

R-M

R’-XR-R’

Alkenylboronic Acids

7) Cross-Metathesis

R-M

R-X-R’

R-X-M

R-B(R’)2

R-Si(R’)3

Introduction to Organoboron Chemistry

Synthesis of Boron Derivatives

R-M

R’-XR-R’

Alkenylboronic Acids

R-M

R-X-R’

R-X-M

R-B(R’)2

R-Si(R’)3

Introduction to Organoboron Chemistry

Synthesis of Boron Derivatives

R-M

R’-XR-R’

Alkenylboronic Acids

R-M

R-X-R’

R-X-M

R-B(R’)2

R-Si(R’)3

Introduction to Organoboron Chemistry

Synthesis of Boron Derivatives

R-M

R’-XR-R’

Alkenylboronic Acids

R-M

R-X-R’

R-X-M

R-B(R’)2

R-Si(R’)3

Introduction to Organoboron Chemistry

Synthesis of Boron Derivatives

R-M

R’-XR-R’

Alkenylboronic Acids

R-M

R-X-R’

R-X-M

R-B(R’)2

R-Si(R’)3

Introduction to Organoboron Chemistry

Synthesis of Boron Derivatives

R-M

R’-XR-R’

Alkenylboronic Acids

R-M

R-X-R’

R-X-M

R-B(R’)2

R-Si(R’)3

Introduction to Organoboron Chemistry

Synthesis of Boron Derivatives

R-M

R’-XR-R’

Alkenylboronic Acids

R-M

R-X-R’

R-X-M

R-B(R’)2

R-Si(R’)3

Introduction to Organoboron Chemistry

Hydroboration of Unsaturated Systems

R-M

R’-XR-R’

Syn-addition

Depends on Both Electronic and Steric Effects

Boron Adds Generally at the less Hindered Position

R-M

R-X-R’

R-X-M

R-B(R’)2

R-Si(R’)3

Introduction to Organoboron Chemistry

Hydroboration of Unsaturated Systems

R-M

R’-XR-R’

Proposed Mechanism

R-M

R-X-R’

R-X-M

R-B(R’)2

R-Si(R’)3

Introduction to Organoboron Chemistry

Hydroboration of Unsaturated Systems

R-M

R’-XR-R’

R-M

R-X-R’

R-X-M

R-B(R’)2

R-Si(R’)3

Introduction to Organoboron Chemistry

Hydroboration of Unsaturated Systems

R-M

R’-XR-R’

9-Borabicyclo[3.3.1]nonane

9-BBN

R-M

R-X-R’

R-X-M

R-B(R’)2

R-Si(R’)3

Introduction to Organoboron Chemistry

Hydroboration of Unsaturated Systems

R-M

R’-XR-R’

R-M

R-X-R’

R-X-M

R-B(R’)2

R-Si(R’)3

Introduction to Organoboron Chemistry

Hydroboration of Unsaturated Systems

R-M

R’-XR-R’

Enantioelective Hydroboration

a-pinene

R-M

R-X-R’

R-X-M

R-B(R’)2

R-Si(R’)3

Introduction to Organoboron Chemistry

Hydroboration of Unsaturated Systems

R-M

R’-XR-R’

Enantioelective Hydroboration

Steric Effects

R-M

R-X-R’

R-X-M

R-B(R’)2

R-Si(R’)3

Introduction to Organoboron Chemistry

Hydroboration of Unsaturated Systems

R-M

R’-XR-R’

Enantioelective Hydroboration

Steric Effects

R-M

R-X-R’

R-X-M

R-B(R’)2

R-Si(R’)3

Introduction to Organoboron Chemistry

Hydroboration of Unsaturated Systems

R-M

R’-XR-R’

Enantioelective Hydroboration

Steric Effects

R-M

R-X-R’

R-X-M

R-B(R’)2

R-Si(R’)3

Introduction to Organoboron Chemistry

Hydroboration of Unsaturated Systems

R-M

R’-XR-R’

Enantioelective Hydroboration

R-M

R-X-R’

R-X-M

R-B(R’)2

R-Si(R’)3

Introduction to Organoboron Chemistry

Hydroboration of Unsaturated Systems

R-M

R’-XR-R’

Enantioelective Hydroboration

Electronic Effects

R-M

R-X-R’

R-X-M

R-B(R’)2

R-Si(R’)3

Introduction to Organoboron Chemistry

Hydroboration of Unsaturated Systems

R-M

R’-XR-R’

Treatment of Boranes with Aldehydes

R-M

R-X-R’

R-X-M

R-B(R’)2

R-Si(R’)3

Introduction to Organoboron Chemistry

Carbonylation Reactions

R-M

R’-XR-R’

3 Different Conditions = 3 Different Products

R-M

R-X-R’

R-X-M

R-B(R’)2

R-Si(R’)3

Introduction to Organoboron Chemistry

Carbonylation Reactions

R-M

R’-XR-R’

Aldehyde Synthesis

R-M

R-X-R’

R-X-M

R-B(R’)2

R-Si(R’)3

Introduction to Organoboron Chemistry

Carbonylation Reactions

R-M

R’-XR-R’

Ketone Synthesis

R-M

R-X-R’

R-X-M

R-B(R’)2

R-Si(R’)3

Introduction to Organoboron Chemistry

Carbonylation Reactions

R-M

R’-XR-R’

Alcohols Synthesis

R-M

R-X-R’

R-X-M

R-B(R’)2

R-Si(R’)3

Introduction to Organoboron Chemistry

Carbonylation Reactions

R-M

R’-XR-R’

Examples

R-M

R-X-R’

R-X-M

R-B(R’)2

R-Si(R’)3

Introduction to Organoboron Chemistry

Carbonylation Reactions

R-M

R’-XR-R’

Examples

R-M

R-X-R’

R-X-M

R-B(R’)2

R-Si(R’)3

Introduction to Organoboron Chemistry

Carbonylation Reactions

R-M

R’-XR-R’

Examples

R-M

R-X-R’

R-X-M

R-B(R’)2

R-Si(R’)3

Introduction to Organoboron Chemistry

Carbonylation Reactions

R-M

R’-XR-R’

Examples

R-M

R-X-R’

R-X-M

R-B(R’)2

R-Si(R’)3

Introduction to Organoboron Chemistry

Allylation Reactions

R-M

R’-XR-R’

R-M

R-X-R’

R-X-M

R-B(R’)2

R-Si(R’)3

Introduction to Organoboron Chemistry

Crotylboration Reactions

R-M

R’-XR-R’

R-M

R-X-R’

R-X-M

R-B(R’)2

R-Si(R’)3

Introduction to Organoboron Chemistry

Crotylboration Reactions

R-M

R’-XR-R’

R-M

R-X-R’

R-X-M

R-B(R’)2

R-Si(R’)3

Introduction to Organoboron Chemistry

Allylboration Reactions

R-M

R’-XR-R’

R-M

R-X-R’

R-X-M

R-B(R’)2

R-Si(R’)3

Introduction to Organoboron Chemistry

Allylboration Reactions

R-M

R’-XR-R’

R-M

R-X-R’

R-X-M

R-B(R’)2

R-Si(R’)3

Introduction to Organoboron Chemistry

Allylboration Reactions

R-M

R’-XR-R’

R-M

R-X-R’

R-X-M

R-B(R’)2

R-Si(R’)3

Introduction to Organoboron Chemistry

Allylboration Reactions

R-M

R’-XR-R’

For Small R2

For Large R2

R-M

R-X-R’

R-X-M

R-B(R’)2

R-Si(R’)3

Introduction to Organoboron Chemistry

Allylboration Reactions

R-M

R’-XR-R’

Enhanced Reactivity

Increasing of Electron Density Around the Boron

Gives Increased Nucleophilicity to the Ligands

Allyl-substituant More Nucleophilic

R-M

R-X-R’

R-X-M

R-B(R’)2

R-Si(R’)3

Introduction to Organoboron Chemistry

Allylboration Reactions

R-M

R’-XR-R’

Enhanced Reactivity

R-M

R-X-R’

R-X-M

R-B(R’)2

R-Si(R’)3

Introduction to Organoboron Chemistry

Allylboration Reactions

R-M

R’-XR-R’

Enhanced Reactivity

R-M

R-X-R’

R-X-M

R-B(R’)2

R-Si(R’)3

Introduction to Organoboron Chemistry

Allylboration Reactions

R-M

R’-XR-R’

Enhanced Reactivity

R-M

R-X-R’

R-X-M

R-B(R’)2

R-Si(R’)3

Introduction to Organoboron Chemistry

Matteson Homologation

R-M

R’-XR-R’

R-M

R-X-R’

R-X-M

R-B(R’)2

R-Si(R’)3

Introduction to Organoboron Chemistry

Matteson Homologation

R-M

R’-XR-R’

R-M

R-X-R’

R-X-M

R-B(R’)2

R-Si(R’)3

Introduction to Organoboron Chemistry

Matteson Homologation

R-M

R’-XR-R’

Stereospecific

R-M

R-X-R’

R-X-M

R-B(R’)2

R-Si(R’)3

Introduction to Organoboron Chemistry

Matteson Homologation

R-M

R’-XR-R’

R-M

R-X-R’

R-X-M

R-B(R’)2

R-Si(R’)3

Introduction to Organoboron Chemistry

Matteson Homologation

R-M

R’-XR-R’

FAVOURED

UNFAVOURED

Steric and Electronic Factors

R-M

R-X-R’

R-X-M

R-B(R’)2

R-Si(R’)3

Introduction to Organoboron Chemistry

Matteson Homologation

R-M

R’-XR-R’

R-M

R-X-R’

R-X-M

R-B(R’)2

R-Si(R’)3

Introduction to Organoboron Chemistry

Matteson Homologation

R-M

R’-XR-R’

R-M

R-X-R’

R-X-M

R-B(R’)2

R-Si(R’)3

Introduction to Organoboron Chemistry

Matteson Homologation

R-M

R’-XR-R’

R-M

R-X-R’

R-X-M

R-B(R’)2

R-Si(R’)3

Introduction to Organoboron Chemistry

Matteson Homologation

R-M

R’-XR-R’

japonilure

R-M

R-X-R’

R-X-M

R-B(R’)2

R-Si(R’)3

Introduction to Organoboron Chemistry

Matteson Homologation

R-M

R’-XR-R’

R-M

R-X-R’

R-X-M

R-B(R’)2

R-Si(R’)3

Introduction to Organoboron Chemistry

Matteson Homologation

R-M

R’-XR-R’

R-M

R-X-R’

R-X-M

R-B(R’)2

R-Si(R’)3

Introduction to Organoboron Chemistry

Matteson Homologation

R-M

R’-XR-R’

R-M

R-X-R’

R-X-M

R-B(R’)2

R-Si(R’)3

Introduction to Organoboron Chemistry

Matteson Homologation

R-M

R’-XR-R’

R-M

R-X-R’

R-X-M

R-B(R’)2

R-Si(R’)3

Introduction to Organoboron Chemistry

Matteson Homologation – Reagent Control ?

R-M

R’-XR-R’

Substrate Control

Reagent Control

Diastereoselective

Stereospecific

R-M

R-X-R’

R-X-M

R-B(R’)2

R-Si(R’)3

Introduction to Organoboron Chemistry

Matteson Homologation – Hoppe’s Carbamates

R-M

R’-XR-R’

R-M

R-X-R’

R-X-M

R-B(R’)2

R-Si(R’)3

Introduction to Organoboron Chemistry

Matteson Homologation – Hoppe’s Carbamates

R-M

R’-XR-R’

Stereospecific

R-M

R-X-R’

R-X-M

R-B(R’)2

R-Si(R’)3

Introduction to Organoboron Chemistry

Matteson Homologation

R-M

R’-XR-R’

R-M

R-X-R’

R-X-M

R-B(R’)2

R-Si(R’)3

Introduction to Organoboron Chemistry

Matteson Homologation

R-M

R’-XR-R’

R-M

R-X-R’

R-X-M

R-B(R’)2

Introduction to Organoboron Chemistry

Matteson Homologation

R-M

R’-XR-R’

Stereospecific Synthesis of all 4 Stereoisomers

R-M

R-X-R’

R-X-M

R-B(R’)2

R-Si(R’)3

Introduction to Organoboron Chemistry

Assembly-Line Synthesis

R-M

R’-XR-R’

R-M

R-X-R’

R-X-M

Introduction to Organoboron Chemistry

Assembly-Line Synthesis

R-M

R’-XR-R’

R-M

R-X-R’

R-X-M

Introduction to Organoboron Chemistry

Assembly-Line Synthesis

R-M

R’-XR-R’

R-M

R-X-R’

R-X-M

Introduction to Organoboron Chemistry

Assembly-Line Synthesis

R-M

R’-XR-R’

R-M

R-X-R’

R-X-M

Introduction to Organoboron Chemistry

Assembly-Line Synthesis

R-M

R’-XR-R’

R-M

R-X-R’

R-X-M

Introduction to Organoboron Chemistry

Assembly-Line Synthesis

R-M

R’-XR-R’

R-M

R-X-R’

R-X-M

Introduction to Organoboron Chemistry

Assembly-Line Synthesis

R-M

R’-XR-R’

R-M

R-X-R’

R-X-M

R-B(R’)2

R-Si(R’)3

Introduction to Organoboron Chemistry

Our research group (AK Didier)

R-M

R’-XR-R’

D. Didier et al. Angew. Chem. Int. Ed. 2015, 52, 15884.

R-M

R-X-R’

R-X-M

R-B(R’)2

R-Si(R’)3

Introduction to Organoboron Chemistry

Our research group (AK Didier)

R-M

R’-XR-R’

D. Didier et al. Chem. Commun. 2016, 52, 2529.

R-M

R-X-R’

R-X-M

R-B(R’)2

R-Si(R’)3

Introduction to Organoboron Chemistry

Our research group (AK Didier)

R-M

R’-XR-R’

D. Didier et al. Chem. Eur. J. 2016, 23, 1634.

R-M

R-X-R’

R-X-M

R-B(R’)2

R-Si(R’)3

Introduction to Organoboron Chemistry

Our research group (AK Didier)

R-M

R’-XR-R’

D. Didier et al. Org. Lett., 2016, 18, 3022.

R-M

R-X-R’

R-X-M

R-B(R’)2

R-Si(R’)3

Introduction to Organoboron ChemistryR-M

R’-XR-R’

First experiment

G. Zweifel et al. J. Am. Chem. Soc. 1967, 89, 3652.

Zweifel olefination

R-M

R-X-R’

R-X-M

R-B(R’)2

R-Si(R’)3

Introduction to Organoboron ChemistryR-M

R’-XR-R’

Aggarwal’s extensions for olefination

V. K. Aggarwal et al. Org. Lett. 2017, 19, 2762.

Zweifel olefination

R-M

R-X-R’

R-X-M

R-B(R’)2

R-Si(R’)3

Introduction to Organoboron ChemistryR-M

R’-XR-R’

Aggarwal’s diastereoselective method

V. K. Aggarwal et al. Angew. Chem. Int. Ed. 2016, 56, 786.

Zweifel olefination

R-M

R-X-R’

R-X-M

R-B(R’)2

R-Si(R’)3

Introduction to Organoboron ChemistryR-M

R’-XR-R’

Aggarwal’s diastereoselective method

V. K. Aggarwal et al. Angew. Chem. Int. Ed. 2016, 56, 786.

Zweifel olefination