Hiyama Coupling

The Hiyama Coupling is the palladium-catalyzed C-C bond formation between aryl, alkenyl, or alkyl halides or pseudohalides and organosilanes. This reaction is comparable to the Suzuki Coupling and also requires an activating agent such as fluoride ion or a base.

---

Mechanism of the Hiyama Coupling

Crucial for the success of the Hiyama Coupling is the polarization of the Si-C bond. Activation of the silane with base or fluoride ions (TASF, TBAF) leading to a pentavalent silicon compound is a first necessary step.

However, the reaction rate is also increased by using silanes with R” groups such as fluoro or alkoxy instead of alkyl. In fact, there are only a few successful examples of coupling reactions using trimethylsilane derivatives.

Another approach uses silacyclobutanes. These small-ring silanes offer enhanced Lewis acidity because angle strain is released when the silicon transitions from tetrahedral to pentavalent, which favors the activation.

Lewis acidity enhanced by strain release

A careful investigation of the reaction mechanism by Denmark (Org. Lett., 2000, 2, 2491. DOI) revealed that silacyclobutanes undergo rapid ring opening with TBAF • 3 H₂O to afford a mixture of silanols and disiloxanes. Transmetallation occurs from a fluoride-activated disiloxane.

Both silanols and siloxanes have been synthesized independently and both underwent cross-coupling. These findings paved the way for the use of silanols as cross-coupling partners. In a specific approach - the Hiyama-Denmark Coupling - a fluoride activator is no longer needed.

Organosilanes are stable and easily prepared compounds with low toxicity. With the many improvements in the reaction conditions that have been reported, the Hiyama Coupling has become an interesting alternative to the Suzuki Coupling that offers a comparable scope of conversions. On the other hand, the broad commercial availability of boronic acids and boronates currently makes the Suzuki Coupling the more convenient choice.

---

Recent Literature

Room-Temperature Hiyama Cross-Couplings of Arylsilanes with Alkyl Bromides and Iodides
J.-Y. Lee, G. C. Fu, J. Am. Chem. Soc., 2003, 125, 5616-5617.

Nickel-Catalyzed Cross-Couplings of Organosilicon Reagents with Unactivated Secondary Alkyl Bromides
D. A. Powell, G. C. Fu, J. Am. Chem. Soc., 2004, 126, 7788-7789.

Aqueous Sodium Hydroxide Promoted Cross-Coupling Reactions of Alkenyltrialkoxysilanes under Ligand-Free Conditions
E. Alacid, C. Nájera, J. Org. Chem., 2008, 73, 2315-2322.

Highly Stereospecific, Cross-Coupling Reactions of Alkenylsilacyclobutanes
S. E. Denmark, J. Am. Chem. Soc., 1999, 121, 5821-5822.

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., 2005, 127, 8004-8005.

C-C Coupling Reactions of Aryl Bromides and Arylsiloxanes in Water Catalyzed by Palladium Complexes of Phosphanes Modified with Crown Ethers
I. Gordillo, E. de Jesús, C. López-Mardomingo, Org. Lett., 2006, 8, 3517-3520.

Convenient Synthesis of Palladium Nanoparticles and Catalysis of Hiyama Coupling Reaction in Water
D. Srimani, S. Sawoo, A. Sarkar, Org. Lett., 2007, 9, 3639-3642.

A Pd(OAc)₂-catalyzed, mild, fluoride-free cross-coupling between aryl bromides and arylsiloxanes in good to high yields has been achieved in aqueous medium in the presence of poly(ethylene glycol) (PEG) and sodium hydroxide. The product was easily separated with ethyl ether extraction, and the catalytic system can be reused eight times with high efficiency.
S. Shi, Y. Zhang, J. Org. Chem., 2007, 72, 5927-5930.

Pd(OAc)₂/DABCO as an Inexpensive and Efficient Catalytic System for Hiyama­ Cross-Coupling Reactions of Aryl Halides with Aryltrimethoxysilanes
J.-H. Li, C.-L. Deng, W.-J. Liu, Y.-X. Xie, Synthesis, 2005, 3039-3044.

Palladium-Catalyzed Cross-Coupling Reaction of Aryltriethoxysilanes with Aryl Bromides under Basic Aqueous Conditions
M. Murata, R. Shimazaki, S. Watanabe, Y. Masuda, Synthesis, 2001, 2231-2233.

Catalytic Asymmetric Hiyama Cross-Couplings of Racemic α-Bromo Esters
X. Dai, N. A. Strotman, G. C. Fu, J. Am. Chem. Soc., 2008, 130, 3302-3303.