Hiyama-Denmark Coupling

Hiyama-Denmark Coupling

The Hiyama-Denmark Coupling Is A Modification Of The Hiyama Coupling, In Which The Palladium-catalyzed Coupling Of Deprotonated Silanols With Vinyl And Aryl Halides Leads To Cross-coupled Products. In The Hiyama-Denmark Coupling, Fluoride Is Not Needed As Activator, So The Reaction Is Compatible With Substrates Bearing Silyl-protecting Groups And Can Be Performed In Large-scale Reactors.


Mechanism Of The Hiyama-Denmark Coupling

The Mechanistic Proposal For The Hiyama Coupling Includes Oxidative Addition To Give A Palladium(II) Species, Transmetalation And Reductive Elimination To Regenerate The Palladium Catalyst:

 

For The Hiyama-Denmark Coupling, Most Of These Steps Are Similar.

For The Transmetalation To Occur In The Hiyama Coupling, Fluoride Activation And The Formation Of A Pentavalent Silicon Is Essential. As The Hiyama-Denmark Coupling Occurs In The Presence Of A Base And Also Strongly Depends On The Steric And Electronic Properties Of The Silicon Center, It Was Convenient To Assume A Mechanism For The Transmetalation, In Which A Pentavalent Silicon Species Is Formed. Thus, It Was First Suggested That The in Situ-generated Silanolate Forms An Organopalladium Complex, Which Is Activated By A Second Equivalent Of The Silanolate Prior To Transmetalation.

Later, It Has Been Shown, That The Reaction Is First-order In Silanolate, So The Transmetalation Proceeds Directly From An Organopalladium(II) Silanolate Complex.

The New Reaction Is Especially Suitable For The Conversion Of Aryl- And Alkenyldimethylsilanolates, Although Aryldimethylsilanolates React Much More Slowly Than Alkenyl Derivatives. Thus A Second Proof Was Established By The Isolation And X-ray Characterization Of A Quite Stable Palladium Silanolate Complex Of An Aryldimethylsilanolate. Heating To 100°C Provided The Biaryl Product In Quantitative Yield In The Absence Of An Activator.

This Argued Against A Requirement For A Pentavalent Silicon Species. In Addition, The Importance Of Complexation (Si-O-Pd) For This New Transmetalation Pathway Was Shown.

Since Then, Many Protocols Have Been Developed That Allow The Conversion Of Ester, Ketone, And Silyl-protected Substrates. Mild Bases Such As KOSiMe3 allow The Reversible Deprotonation Of Alkenyl- Or Alkynyldimethylsilanols. Arylsilanolates Need More Forcing Conditions, For Example With Cs2CO3 in Toluene At 90 °C. Here, The Addition Of Water Suppresses Homocoupling Of The Halide. For Electron-rich Heterocycles, The Irreversible Deprotonation Using NaH For The Prior Generation Of Silanolates Proved To Be A Suitable Alternative.

Some Of The Protocols Can Be Found In The Recent Literature Section. A More Comprehensive Review Dealing With Mechanistic Details And Scope Of The Reaction Has Been Written By Denmark And Regens (Acc. Chem. Res.2008, DOI: 10.1021/ar800037p).

Recent Literature


Cross-Coupling Reactions Of Aromatic And Heteroaromatic Silanolates With Aromatic And Heteroaromatic Halides
S. E. Denmark, R. C. Smith, W.-T. T. Chang, J. M. Muhuhi, J. Am. Chem. Soc.2009131, 3104-3118.


Stereospecific Palladium-Catalyzed Cross-Coupling Of (E)- And (Z)-Alkenylsilanolates With Aryl Chlorides
S. E. Denmark, J. M. Kallemeyn, J. Am. Chem. Soc.2006128, 15958-19959.


Vinylation Of Aromatic Halides Using Inexpensive Organosilicon Reagents. Illustration Of Design Of Experiment Protocols
S. E. Denmark, C. R. Butler, J. Am. Chem. Soc.2008130, 3690-3704.


Sequential Cross-Coupling Of 1,4-Bissilylbutadienes: Synthesis Of Unsymmetrical 1,4-Disubstituted 1,3-Butadienes
S. E. Denmark, S. A. Tymonko, J. Am. Chem. Soc.2005127, 8004-8005.


Cross-Coupling Of Alkynylsilanols With Aryl Halides Promoted By Potassium Trimethylsilanolate
S. E. Denmark, S. A. Tymonko, J. Org. Chem.200368, 9151-9154.


Palladium-Catalyzed Cross-Coupling Reactions Of Substituted Aryl(dimethyl)silanols
S. E. Denmark, M. H. Ober, Adv. Synth. Catal.2004346, 1703-1715.


Cross-Coupling Of Aromatic Bromides With Allylic Silanolate Salts
S. E. Denmark, N. S. Werner, J. Am. Chem. Soc.2008130, 16382-16393.