Superbase

Summary

A superbase is a compound that has a particularly high affinity for protons. Superbases are of theoretical interest and potentially valuable in organic synthesis.[1][2] Superbases have been described and used since the 1850s.[3][4]

DefinitionsEdit

Generically IUPAC defines a superbase as a "compound having a very high basicity, such as lithium diisopropylamide."[5] Superbases are often defined in two broad categories, organic and organometallic.

Organic superbases are charge-neutral compounds with basicities greater than that of proton sponge (pKBH+ = 18.6 in MeCN)."[1] In a related definition: any species with a higher absolute proton affinity (APA = 245.3 kcal/mol) and intrinsic gas phase basicity (GB = 239 kcal/mol) than proton sponge.[6] Common superbases of this variety feature amidine, guanidine, and phosphazene functional groups. Strong superbases can be designed by utilizing multiple intramolecular hydrogen bonds that stabilize the conjugate acid.[7][8][9][10]

Organometallic superbases, sometimes called Lochmann–Schlosser superbases, result from the combination of alkali metal alkoxides and organolithium reagents.[11] Caubère defines superbases as "bases resulting from a mixing of two (or more) bases leading to new basic species possessing inherent new properties. The term superbase does not mean a base is thermodynamically and/or kinetically stronger than another, instead it means that a basic reagent is created by combining the characteristics of several different bases."[12]

Organic superbasesEdit

 
Protonation of Verkade base. Its conjugate acid has a pKa of 32.9 in acetonitrile.[13]

Organic superbases are mostly charge-neutral, nitrogen containing species, where nitrogen act as a proton acceptor. These include the phosphazenes, phosphanes, amidines, and guanidines. Other organic compounds that meet the physicochemical or structural definitions of 'superbase' include proton chelators like the aromatic proton sponges and the bispidines. Multicyclic polyamines, like DABCO might also be loosely included in this category.[4] Phosphanes and carbodiphosphoranes are also strong organosuperbases.[14][15][16][17]

Despite enormous proton affinity, the organosuperbases can exhibit low nucleophilicity.

OrganometallicEdit

 
Deprotonation using LDA [18].

Organometallic compounds of electropositive metals are superbases, but they are generally strong nucleophiles. Examples include organolithium and organomagnesium (Grignard reagent) compounds. Another type of organometallic superbase has a reactive metal exchanged for a hydrogen on a heteroatom, such as oxygen (unstabilized alkoxides) or nitrogen (metal amides such as lithium diisopropylamide).

The Schlosser base (or Lochmann-Schlosser base), the combination of n-butyllithium and potassium tert-butoxide, is commonly cited as a superbase. n-Butyllithium and potassium tert-butoxide form a mixed aggregate of greater reactivity than either component reagent.[19]

InorganicEdit

Inorganic superbases are typically salt-like compounds with small, highly charged anions, e.g. lithium hydride, potassium hydride, and sodium hydride. Such species are insoluble, but the surfaces of these materials are highly reactive and slurries are useful in synthesis.

Superbases in organic chemistryEdit

Superbases are used in organocatalysis.[20]

See alsoEdit

ReferencesEdit

  1. ^ a b Puleo, Thomas R.; Sujansky, Stephen J.; Wright, Shawn E.; Bandar, Jeffrey S. (2021). "Organic Superbases in Recent Synthetic Methodology Research". Chemistry – A European Journal. 27 (13): 4216–4229. doi:10.1002/chem.202003580. PMID 32841442.
  2. ^ Pozharskii, Alexander F.; Ozeryanskii, Valery A. (2012). "Proton Sponges and Hydrogen Transfer Phenomena". Mendeleev Communications. 22 (3): 117–124. doi:10.1016/j.mencom.2012.05.001.
  3. ^ "BBC - h2g2 - History of Chemistry - Acids and Bases". Retrieved 2009-08-30.
  4. ^ a b Superbases for Organic Synthesis Ed. Ishikawa, T., John Wiley and Sons, Ltd.: West Sussex, UK. 2009.
  5. ^ IUPAC, Compendium of Chemical Terminology, 2nd ed. (the "Gold Book") (1997). Online corrected version: (2006–) "superacid". doi:10.1351/goldbook.S06135
  6. ^ Raczynska, Ewa D.; Decouzon, Michele; Gal, Jean-Francois; Maria, Pierre-Charles; Wozniak, Krzysztof; Kurg, Rhio; Carins, Stuart N. (3 June 2010). "ChemInform Abstract: Superbases and Superacids in the Gas Phase". ChemInform. 31 (33): no. doi:10.1002/chin.200033267.
  7. ^ Maksić, Zvonimir B.; Kovačević, Borislav; Vianello, Robert (2012-10-10). "Advances in Determining the Absolute Proton Affinities of Neutral Organic Molecules in the Gas Phase and Their Interpretation: A Theoretical Account". Chemical Reviews. 112 (10): 5240–5270. doi:10.1021/cr100458v. ISSN 0009-2665.
  8. ^ Formica, Michele; Rozsar, Daniel; Su, Guanglong; Farley, Alistair J. M.; Dixon, Darren J. (2020). "Bifunctional Iminophosphorane Superbase Catalysis: Applications in Organic Synthesis". Accounts of Chemical Research. 53 (10): 2235–2247. doi:10.1021/acs.accounts.0c00369. PMID 32886474.
  9. ^ Pozharskii, Alexander F.; Ozeryanskii, Valery A. (2012). "Proton Sponges and Hydrogen Transfer Phenomena". Mendeleev Communications. 22 (3): 117–124. doi:10.1016/j.mencom.2012.05.001.
  10. ^ Barić, Danijela; Dragičević, Ivan; Kovačević, Borislav (2013-04-19). "Design of Superbasic Guanidines: The Role of Multiple Intramolecular Hydrogen Bonds". The Journal of Organic Chemistry. 78 (8): 4075–4082. doi:10.1021/jo400396d. ISSN 0022-3263.
  11. ^ Klett, Jan (2021). "Structural Motifs of Alkali Metal Superbases in Non‐coordinating Solvents". Chemistry – A European Journal. 27 (3): 888–904. doi:10.1002/chem.202002812. PMC 7839563. PMID 33165981.
  12. ^ Caubère, P (1993). "Unimetal Super Bases". Chemical Reviews. 93 (6): 2317–2334. doi:10.1021/cr00022a012.
  13. ^ Verkade, John G.; Urgaonkar, Sameer; Verkade, John G.; Urgaonkar, Sameer (2012). "Proazaphosphatrane". Encyclopedia of Reagents for Organic Synthesis. doi:10.1002/047084289X.rn00702.pub2.
  14. ^ Kovačević, Borislav; Maksić, Zvonimir B. (2006). "High basicity of phosphorus–proton affinity of tris-(tetramethylguanidinyl)phosphine and tris-(hexamethyltriaminophosphazenyl)phosphine by DFT calculations". Chemical Communications (14): 1524. doi:10.1039/b517349c. ISSN 1359-7345.
  15. ^ Ullrich, Sebastian; Kovačević, Borislav; Xie, Xiulan; Sundermeyer, Jörg (2019). "Phosphazenyl Phosphines: The Most Electron-Rich Uncharged Phosphorus Brønsted and Lewis Bases". Angewandte Chemie International Edition. 58 (30): 10335–10339. doi:10.1002/anie.201903342. ISSN 1521-3773.
  16. ^ Mehlmann, Paul; Mück-Lichtenfeld, Christian; Tan, Tristan T. Y.; Dielmann, Fabian (2017-05-02). "Tris(imidazolin-2-ylidenamino)phosphine: A Crystalline Phosphorus(III) Superbase That Splits Carbon Dioxide". Chemistry - A European Journal. 23 (25): 5929–5933. doi:10.1002/chem.201604971.
  17. ^ Ullrich, Sebastian; Kovačević, Borislav; Koch, Björn; Harms, Klaus; Sundermeyer, Jörg (2019). "Design of non-ionic carbon superbases: second generation carbodiphosphoranes". Chemical Science. 10 (41): 9483–9492. doi:10.1039/C9SC03565F. ISSN 2041-6520. PMC 6993619. PMID 32055322.
  18. ^ Jianshe Kong, Tao Meng, Pauline Ting, and Jesse Wong (2010). "Preparation of Ethyl 1-Benzyl-4-Fluoropiperidine-4-Carboxylate". Organic Syntheses. 87: 137. doi:10.15227/orgsyn.087.0137.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  19. ^ Schlosser, M. (1988). "Superbases for organic synthesis". Pure Appl. Chem. 60 (11): 1627–1634. doi:10.1351/pac198860111627.
  20. ^ MacMillan, David W. C. (2008). "The advent and development of organocatalysis". Nature. 455 (7211): 304–308. Bibcode:2008Natur.455..304M. doi:10.1038/nature07367.