Silylation
Silylation is the introduction of one or more (usually) substituted silyl groups (R3Si) to a molecule. Silylations are core methods for production of organosilicon chemistry. Silanization, while similar to silylation, usually refers to attachment of silyl groups to solids.[1] Silyl groups are commonly used for: alcohol protection, enolate trapping, gas chromatography, electron-impact mass spectrometry (EI-MS), and coordinating with metal complexes.
Protection Chemistry
[edit]Protection
[edit]Silylation is often used to protect alcohols and amines. The products after silylation, namely silyl ethers and silyl amines, are resilient toward basic conditions.[2] Protection is typically done by reacting the functional group with a silyl halide by an SN2 reaction mechanism, typically in the presence of base.[3]
The protection mechanism begins with the base deprotonating the alcohol group. Next, the deprotonated alcohol group attacks the silyl atom of the silyl halide compound. The halide acts as a leaving group and ends up in solution. A workup step follows to remove any excess base within the solution.
1. ROH + NEt3 → RO− + H−NEt+3
2. RO− + Cl−SiMe3 → RO−SiMe3 + Cl−
A typical silyl halide used to protect alcohol groups is TMS (trimethylsilyl chloride). Bis(trimethylsilyl)acetamide ("BSA", Me3SiNC(OSiMe3)Me is an efficient silylation agent. The reaction of BSA with alcohols gives the corresponding trimethylsilyl ether, together with acetamide as a byproduct (Me = CH3):[4]
- 2 ROH + MeC(OSiMe3)NSiMe3 → MeC(O)NH2 + 2 ROSiMe3
Deprotection
[edit]Removal of the alkyl silyl/deprotection of the alcohol can be done using either brønsted/lewis acid conditions, or basic conditions.[5] Acidic deprotection occurs fastest for less sterically bulky alkyl silyl groups.[5] A commonly used deprotecting agent in basic conditions are fluoride ions/fluoride salts. Deprotection with a fluoride ion occurs via an SN2 mechanism. The fluoride ion has a strong affinity for silicon due to the strength of the Si-F bond.[6] The primary fluoride ion deprotecting agent is tetra-n-butylammonium fluoride (TBAF), as its aliphatic chains in help incorporate F- into organic solvent.[7][8][9]
Modifying Silyl Reactivity
[edit]
Sterically bulkier alkyl substituents tend to decrease the reactivity of the silyl group. Consequently, bulky substituents increase the silyl group's protective abilities. To add bulkier alkyl silyls, more strenuous conditions are required for alchohol protection. As bulkier groups require more stenuous conditions to add, they also require more strenuous conditions to remove. Additionally, bulkier silyl groups are more selective for the type of alcohols they react with, resulting is a preference for primary alcohols over secondary alcohols. Thus, silyl groups such as TBDMS and TIPS can be used to selectively protect primary alcohols over secondary alcohols.[10]
Enolate Trapping
[edit]Silylation can also be used to trap reactive compounds for isolation or identification. A common example of this is by trapping reactive enolates, such as silyl enol ethers, which represent reactive tautomers of many carbonyl compounds.[11] The original enolate can be reformed upon reaction with an organolithium, or other strong base.[11]
Applications in Analysis
[edit]The introduction of a silyl group(s) gives derivatives of enhanced volatility, making the derivatives suitable for analysis by gas chromatography and electron-impact mass spectrometry (EI-MS). For EI-MS, the silyl derivatives give more favorable diagnostic fragmentation patterns of use in structure investigations, or characteristic ions of use in trace analyses employing selected ion monitoring and related techniques.[12][13]
Of metals
[edit]
Coordination complexes with silyl ligands are well known. An early example is CpFe(CO)2Si(CH3)3, prepared by silylation of CpFe(CO)2Na with trimethylsilyl chloride. Typical routes include oxidative addition of Si-H bonds to low-valent metals. Metal silyl complexes are intermediates in hydrosilation, a process used to make organosilicon compounds on both laboratory and commercial scales.[14][15]
See also
[edit]References
[edit]- ^ Pape, Peter G. (2017). "Silylating Agents". Kirk-Othmer Encyclopedia of Chemical Technology. pp. 1–15. doi:10.1002/0471238961.1909122516011605.a01.pub3. ISBN 9780471238966.
- ^ Clayden, Jonathan; Greeves, Nick; Warren, Stuart (2012). Organic chemistry (2nd ed.). Oxford: Oxford university press. pp. 549–550. ISBN 978-0-19-927029-3.
- ^ Pagliano, Enea; Campanella, Beatrice; D'Ulivo, Alessandro; Mester, Zoltán (September 2018). "Derivatization chemistries for the determination of inorganic anions and structurally related compounds by gas chromatography - A review". Analytica Chimica Acta. 1025: 12–40. doi:10.1016/j.aca.2018.03.043.
- ^ Young, Steven D.; Buse, Charles T.; Heathcock, Clayton H. (1985). "2-Methyl-2-(Trimethylsiloxy)pentan-3-one". Organic Syntheses. 63: 79. doi:10.15227/orgsyn.063.0079.
- ^ a b Crouch, R. David (2013-09-02). "Recent Advances in Silyl Protection of Alcohols". Synthetic Communications. 43 (17): 2265–2279. doi:10.1080/00397911.2012.717241. ISSN 0039-7911.
- ^ Clayden, Jonathan; Greeves, Nick; Warren, Stuart (2012). Organic chemistry (2nd ed.). Oxford: Oxford university press. ISBN 978-0-19-927029-3.
- ^ Paquette, Leo A., ed. (1995). Encyclopedia of reagents for organic synthesis. Chichester ; New York: Wiley. ISBN 978-0-471-93623-7.
- ^ Mercedes Amat, Sabine Hadida, Swargam Sathyanarayana, and Joan Bosch "Regioselective Synthesis of 3-Substituted Indoles: 3-Ethylindole" Organic Syntheses 1997, volume 74, page 248. doi:10.15227/orgsyn.074.0248
- ^ Nina Gommermann and Paul Knochel "N,N-Dibenzyl-n-[1-cyclohexyl-3-(trimethylsilyl)-2-propynyl]-amine from Cyclohexanecarbaldehyde, Trimethylsilylacetylene and Dibenzylamine" Organic Syntheses 2007, vol. 84, page 1. doi:10.15227/orgsyn.084.0001
- ^ Clayden, Jonathan; Greeves, Nick; Warren, Stuart (2012). Organic chemistry (2nd ed.). Oxford: Oxford university press. ISBN 978-0-19-927029-3.
- ^ a b Clayden, Jonathan; Greeves, Nick; Warren, Stuart (2012). Organic chemistry (2nd ed.). Oxford: Oxford university press. pp. 466–467. ISBN 978-0-19-927029-3.
- ^ Luis-Alberto Martin; Ingrid Hayenga. "Silylation of Non-Steroidal Anti-Inflammatory Drugs". sigmaaldrich.com. Retrieved 24 September 2023.
- ^ Blau, Karl; J. M. Halket (1993). Handbook of Derivatives for Chromatography (2nd ed.). John Wiley & Sons. ISBN 0-471-92699-X.
- ^ Moris S. Eisen "Transition-metal silyl complexes" in The Chemistry of Organic Silicon Compounds. Volume 2 Edited by Zvi Rappoport and Yitzhak Apeloig, 1998, John Wiley & Sons
- ^ Corey, Joyce Y.; Braddock-Wilking, Janet (1999). "Reactions of Hydrosilanes with Transition-Metal Complexes: Formation of Stable Transition-Metal Silyl Compounds". Chemical Reviews. 99 (1): 175–292. doi:10.1021/CR9701086. PMID 11848982.