Hiyama coupling
Hiyama coupling | |
---|---|
Named after | Tamejiro Hiyama |
Reaction type | Coupling reaction |
Identifiers | |
Organic Chemistry Portal | hiyama-coupling |
RSC ontology ID | RXNO:0000193 |
Examples and Related Reactions | |
Similar reactions | Hiyama-Denmark coupling |
The Hiyama coupling is a
-
- : aryl, alkenyl or alkynyl
- : aryl, alkenyl, alkynyl or alkyl
- : Cl, F or alkyl
- : Cl, Br, I or OTf
Reaction history
The Hiyama coupling was developed to combat the issues associated with other
Mechanism
The organosilane is activated with
The mechanism for the Hiyama coupling follows a catalytic cycle, including an A) oxidative addition step, in which the organic halide adds to the palladium oxidizing the metal from palladium(0) to palladium(II); a B) transmetalation step, in which the C-Si bond is broken and the second carbon fragment is bound to the palladium center; and finally C) a reductive elimination step, in which the C-C bond is formed and the palladium returns to its zero-valent state to start the cycle over again.[7] The catalytic cycle is shown below.
Scope and limitations
Scope
The Hiyama coupling can be applied to the formation of Csp2-Csp2 (e.g.
The scope of this reaction was expanded to include closure of medium-sized rings by Scott E. Denmark.[8]
The coupling of alkyl halides with organohalosilanes as alternative organosilanes has also been performed. Organochlorosilanes allow couplings with aryl chlorides, which are abundant and generally more economical than aryl iodides.[9] A nickel catalyst allows for access to new reactivity of organotrifluorosilanes as reported by GC Fu et al.[10] Secondary alkyl halides are coupled with aryl silanes[11] with good yields using this reaction.
Limitations
The Hiyama coupling is limited by the need for fluoride in order to activate the organosilicon reagent. Addition of fluoride cleaves any silicon protecting groups (e.g. silyl ethers[12]), which are frequently employed in organic synthesis. The fluoride ion is also basic, so base sensitive protecting groups, acidic protons, and functional groups may be affected by the addition of this activator. Most of the active research concerning this reaction involves circumventing this problem. To overcome this issue, many groups have looked to the use of other basic additives for activation, or use of a different organosilane reagent all together, leading to the multiple variations of the original Hiyama coupling.
Variations
One modification of the Hiyama coupling utilizes a silacyclobutane ring and a fluoride source that is hydrated as shown below.[13] This mimics the use of an alkoxysilane/organosilanol rather than the use of alkylsilane. The mechanism of this reaction, using a fluoride source, allowed for the design of future reactions that can avoid the use of the fluoride source.
Fluoride-free Hiyama couplings
Many modifications to the Hiyama coupling have been developed that avoid the use of a fluoride activator/base. Using organochlorosilanes, Hiyama found a coupling scheme utilizing NaOH as the basic activator.[14] Modifications using alkoxysilanes have been reported with the use of milder bases like NaOH [15] and even water.[16] Study of these mechanisms have led to the development of the Hiyama–Denmark coupling which utilize organosilanols as coupling partners.
Another class of fluoride-free Hiyama couplings include the use of a Lewis acid additive, which allows for bases such as K3PO4[17] to be utilized, or for the reaction to proceed without a basic additive.[18][19] The addition of a copper co-catalyst has also been reported to allow for the use of a milder activating agent[17] and has even been shown to get turnover in which both the palladium(II) and copper(I) turnover in the catalytic cycle rather than addition of stoichiometric Lewis acid (e.g. silver(I),[18] copper(I)[19]).
Hiyama–Denmark coupling
The Hiyama–Denmark coupling is the modification of the Hiyama coupling that does not require a fluoride additive to utilize organosilanols and organic halides as coupling partners. The general reaction scheme is shown below, showcasing the utilization of a
A specific example of this reaction is shown with reagents. If fluoride had been used, as in the original Hiyama protocol, the
Hiyama–Denmark coupling mechanism
Examination of this reaction's mechanism suggests that the formation of the silonate is all that is needed to activate addition of the organosilane to the palladium center. The presence of a pentavalent silicon is not needed and kinetic analysis has shown that this reaction has first order dependence on silonate concentration.[2] This is due to the key bond being formed, the Pd-O bond during the transmetalation step, that then allows for transfer of the carbon fragment onto the palladium center. Based on this observation, it seems that the rate limiting step in this catalytic cycle is the Pd-O bond formation, in which increased silonate concentrations increase the rate of this reaction (indicative of faster reactions).
See also
- Heck reaction
- Kumada coupling
- Negishi coupling
- Sonogashira coupling
- Stille reaction
- Suzuki reaction
- Palladium-catalyzed coupling reactions
External links
References
- ^ .
- ^ PMID 18681465.
- ^
- ^ PMID 11878949
- PMID 11667637
- PMID 15212521
- PMID 17444579
- ^ Greene, T. W.; Wuts, P. G. M. Protective Groups In Organic Synthesis, 3rd ed.;
John Wiley & Sons: New York, 1991. ISBN 0471160199
- ^ PMID 10956529
- ^
- PMID 17585827
- PMID 15040744
- ^
- ^ PMID 10993364
- ^ PMID 10814151
- ^ PMID 19199785