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Related Reactions
Hiyama-Denmark Coupling
Kumada Coupling
Negishi Coupling
Stille Coupling
Suzuki Coupling

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.

Nickel-Catalyzed Ligand-Free Hiyama Coupling of Aryl Bromides and Vinyltrimethoxysilane
S. Wei, Y. Mao, S.-L. Shi, Synlett, 2021, 32, 1670-1674.

Highly Stereospecific, Palladium-Catalyzed Cross-Coupling of Alkenylsilanols
S. E. Denmark, D. Wehrli, Org. Lett., 2000, 2, 565-568.

One-Pot Synthesis of Styrene Derivatives from Allyl Silanes via B(C6F5)3-Catalyzed Isomerization-Hiyama Coupling
B. A. Kustiana, R. L. Melen, L. C. Morrill, Org. Lett., 2022, 24, 8694-8697.

Palladium-Catalyzed Cross-Coupling Reaction of Alkenyldimethyl(2-pyridyl)silanes with Organic Halides:  Complete Switch from the Carbometalation Pathway to the Transmetalation Pathway
K. Itami, T. Nokami, J.-i. Yoshida, J. Am. Chem. Soc., 2001, 123, 5600-5601.

Highly Stereoselective Hydrocarbation of Terminal Alkynes via Pt-Catalyzed Hydrosilylation/Pd-Catalyzed Cross-Coupling Reactions
S. E. Denmark, Z. Wang, Org. Lett., 2001, 3, 933-935.

MIDA-Vinylsilanes: Selective Cross-Couplings and Applications to the Synthesis of Functionalized Stilbenes
M. G. McLaughlin, C. A. McAdam, M. J. Cook, Org. Lett., 2015, 17, 10-13.

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.

Regioselective Allene Hydroarylation via One-Pot Allene Hydrosilylation/Pd-Catalyzed Cross-Coupling
Z. D. Miller, J. Montgomery, Org. Lett., 2014, 16, 5486-5489.

Palladium-Catalyzed Hiyama Cross-Coupling of Aryltrifluorosilanes with Aryl and Heteroaryl Chlorides
G. A. Molander, L. Iannazzo, J. Org. Chem., 2011, 76, 9102-9108.

A Practical Protocol for the Hiyama Cross-Coupling Reaction Catalyzed by Palladium on Carbon
Y. Monguchi, T. Yanase, S. Mori, H. Sajiki, Synthesis, 2013, 45, 40-44.

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.

Advantageous Use of tBu2P-N=P(iBuNCH2CH2)3N in the Hiyama Coupling of Aryl Bromides and Chlorides
S. M. Raders, J. V. Kingston, J. G. Verkade, J. Org. Chem., 2010, 75, 1744-1747.

Magnetically Recoverable Pd/Fe3O4-Catalyzed Hiyama Cross-Coupling of Aryl Bromides with Aryl Siloxanes
B. Sreedhar, A. S. Kumar, D. Yada, Synlett, 2011, 1081-1084.

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.

Design, Synthesis, and Validation of an Effective, Reusable Silicon-Based Transfer Agent for Room-Temperature Pd-Catalyzed Cross-Coupling Reactions of Aryl and Heteroaryl Chlorides with Readily Available Aryl Lithium Reagents
D. Martinez-Solorio, B. Melillo, L. Sanchez, Y. Liang, E. Lam, K. N. Houk, A. B. Smith, III, J. Am. Chem. Soc., 2016, 138, 1836-1839.

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-Indolylphosphine-Catalyzed Hiyama Cross-Coupling of Aryl Mesylates
C. M. So, H. W. Lee, C. P. Lau, F. Y. Kwong, Org. Lett., 2009, 11, 317-320.

Palladium-Catalyzed Hiyama Cross-Couplings of Aryl Arenesulfonates with Arylsilanes
L. Zhang, J. Wu, J. Am. Chem. Soc., 2008, 130, 12250-12251.

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.

Palladium-Catalyzed Hiyama-Type Cross-Coupling Reactions of Arenesulfinates with Organosilanes
K. Cheng, S. Hu, B. Zhao, X.-M. Zhang, C. Qi, J. Org. Chem., 2013, 78, 5022-5025.

Palladium Nanoparticle Catalyzed Hiyama Coupling Reaction of Benzyl Halides
D. Srimani, A. Bej, A. Sarkar, J. Org. Chem., 2010, 75, 4296-4299.

An efficient Pd-catalyzed coupling of benzylic phosphates with arylsilanes provides straightforward access to diarylmethanes in very good yields. The reaction tolerates a wide range of functionalities such as halide, alkoxyl, and nitro groups.
P. Zhang, J. Xu, Y. Gao, X. Li, G. Tang, Y. Zhao, Synlett, 2014, 25, 2928-2932.

A cross-coupling reaction of allylic and benzylic carbonates with organo[2-(hydroxymethyl)phenyl]dimethylsilanes proceeds in the presence of a palladium catalyst and in the absence of any activator. Various functional groups are tolerated to give a diverse range of 1,4-diene and diarylmethane products.
Y. Nakao, S. Ebata, J. Chen, H. Imanaka, T. Hiyama, Chem. Lett., 2007, 606-607.

Palladium(0) Nanoparticle Catalyzed Cross-Coupling of Allyl Acetates and Aryl and Vinyl Siloxanes
R. Dey, K. Chattopadhyay, B. C. Ranu, J. Org. Chem., 2008, 73, 9461-9464.

Palladium-Catalyzed Acetylation of Arenes
S. D. Ramgren, N. K. Garg, Org. Lett., 2014, 16, 824-827.

Palladium-Catalyzed Amide N-C Hiyama Cross-Coupling: Synthesis of Ketones
M. A. Idris, S. Lee, Org. Lett., 2020, 22, 9184-9189.

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.

Palladium-Catalyzed Hiyama Cross-Couplings of Arylsilanes with 3-Iodoazetidine: Synthesis of 3-Arylazetidines
Z. Liu, N. Luan, L. Shen, J. Li, D. Zou, Y. Wu, Y. Wu, J. Org. Chem., 2019, 84, 12358-12365.