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In organic chemistry, a carbene is a molecule containing a neutral carbon atom with a valence of two and two unshared valence electrons. The general formula is R−:C−R' or R=C: where the R represents substituents or hydrogen atoms.

The term "carbene" may also refer to the specific compound :CH₂, also called methylene, the parent hydride from which all other carbene compounds are formally derived.

There are two types of carbenes: singlets or triplets, depending upon their electronic structure. The different classes undergo different reactions.

Most carbenes are extremely reactive and short-lived. A small number (the dihalocarbenes, carbon monoxide, and carbon monosulfide) can be isolated, and can stabilize as metal ligands, but otherwise cannot be stored in bulk. A rare exception are the persistent carbenes, which have extensive application in modern organometallic chemistry.

Generation

There are two common methods for carbene generation.

In α elimination, two substituents eliminate from the same carbon atom. This occurs with reagents with no good leaving groups vicinal to an acidic proton are exposed to strong base; for example, phenyllithium will abstract HX from a haloform (CHX₃). Such reactions typically require phase-transfer conditions.

Molecules with no acidic proton can also form carbenes. A geminal dihalide exposed to organolithiums can undergo metal-halogen exchange and then eliminate a lithium salt to give a carbene, and zinc metal abstracts halogens similarly in the Simmons–Smith reaction.

R₂CBr₂ + BuLi → R₂CLi(Br) + BuBr

R₂CLi(Br) → R₂C + LiBr

It remains uncertain if these conditions form truly free carbenes or a metal-carbene complex. Nevertheless, metallocarbenes so formed give the expected organic products. In a specialized but instructive case, α-halomercury compounds can be isolated and separately thermolyzed. The "Seyferth reagent" releases CCl₂ upon heating:

C₆H₅HgCCl₃ → CCl₂ + C₆H₅HgCl

Separately, carbenes can be produced from an extrusion reaction with a large free energy change. Diazirines and epoxides photolyze with a tremendous release in ring strain to carbenes. The former extrude inert nitrogen gas, but epoxides typically give reactive carbonyl wastes, and asymmetric epoxides can potentially form two different carbenes. Typically, the C-O bond with lesser fractional bond order (fewer double-bond resonance structures) breaks. For example, when one substituent is alkyl and another aryl, the aryl-substituted carbon is usually released as a carbene fragment.

Ring strain is not necessary for a strong thermodynamic driving force. Photolysis, heat, or transition metal catalysts (typically rhodium and copper) decompose diazoalkanes to a carbene and gaseous nitrogen; this occurs in the Bamford–Stevens reaction and Wolff rearrangement. As with the case of metallocarbenes, some reactions of diazoalkanes that formally proceed via carbenes may instead form a cycloadduct intermediate that extrudes nitrogen.

To generate an alkylidene carbene a ketone can be exposed to trimethylsilyl diazomethane and then a strong base.

Structures and bonding

The two classes of carbenes are singlet and triplet carbenes. Triplet carbenes are diradicals with two unpaired electrons, typically form from reactions that break two σ bonds (α elimination and some extrusion reactions), and do not rehybridize the carbene atom. Singlet carbenes have a single lone pair, typically form from diazo decompositions, and adopt an sp orbital structure. Bond angles (as determined by EPR) are 125–140° for triplet methylene and 102° for singlet methylene.

Most carbenes have a nonlinear triplet ground state. For simple hydrocarbons, triplet carbenes are usually only 8 kcal/mol (33 kJ/mol) more stable than singlet carbenes, comparable to nitrogen inversion. The stabilization is in part attributed to Hund's rule of maximum multiplicity. However, strategies to stabilize triplet carbenes at room temperature are elusive. 9-Fluorenylidene has been shown to be a rapidly equilibrating mixture of singlet and triplet states with an approximately 1.1 kcal/mol (4.6 kJ/mol) energy difference, although extensive electron delocalization into the rings complicates any conclusions drawn from diaryl carbenes. Simulations suggest that electropositive heteroatoms can thermodynamically stabilize triplet carbenes, such as in silyl and silyloxy carbenes, especially trifluorosilyl carbenes.

Lewis-basic nitrogen, oxygen, sulphur, or halide substituents bonded to the divalent carbon can delocalize an electron pair into an empty p orbital to stabilize the singlet state. This phenomenon underlies persistent carbenes' remarkable stability.

Reactivity

Carbenes behave like very aggressive Lewis acids. They can attack lone pairs, but their primary synthetic utility arises from attacks on π bonds, which give cyclopropanes; and on σ bonds, which cause carbene insertion. Other reactions include rearrangements and dimerizations. A particular carbene's reactivity depends on the substituents, including any metals present.

Singlet-triplet effects

Singlet and triplet carbenes exhibit divergent reactivity.

Triplet carbenes are diradicals, and participate in stepwise radical additions. Triplet carbene addition necessarily involves (at least one) intermediate with two unpaired electrons.

Singlet carbenes can (and do) react as electrophiles, nucleophiles, or ambiphiles. Their reactions are typically concerted and often cheletropic. Singlet carbenes are typically electrophilic, unless they have a filled p orbital, in which case they can react as Lewis bases. The Bamford–Stevens reaction gives carbenes in aprotic solvents and carbenium ions in protic ones.

The different mechanisms imply that singlet carbene additions are stereospecific but triplet carbene additions stereoselective. Methylene from diazomethane photolysis reacts with either cis- or trans-2-butene to give a single diastereomer of 1,2-dimethylcyclopropane: cis from cis and trans from trans. Thus methylene is a singlet carbene; if it were triplet, the product would not depend on the starting alkene geometry.

Cyclopropanation

Carbenes add to double bonds to form cyclopropanes, and, in the presence of a copper catalyst, to alkynes to give cyclopropenes. Addition reactions are commonly very fast and exothermic, and carbene generation limits reaction rate.

In Simmons-Smith cyclopropanation, the iodomethylzinc iodide typically complexes to any allylic hydroxy groups such that addition is syn to the hydroxy group.

C—H insertion

Insertions are another common type of carbene reaction, a form of oxidative addition. Insertions may or may not occur in single step (see above). The end result is that the carbene interposes itself into an existing bond, preferably X–H (X not carbon), else C–H or (failing that) a C–C bond. Alkyl carbenes insert much more selectively than methylene, which does not differentiate between primary, secondary, and tertiary C-H bonds.

The 1,2-rearrangement produced from intramolecular insertion into a bond adjacent to the carbene center is a nuisance in some reaction schemes, as it consumes the carbene to yield the same effect as a traditional elimination reaction. Generally, rigid structures favor intramolecular insertions. In flexible structures, five-membered ring formation is preferred to six-membered ring formation. When such insertions are possible, no intermolecular insertions are seen. Both inter- and intra-molecular insertions admit asymmetric induction from a chiral metal catalyst.

Electrophilic attack

Carbenes can form adducts with nucleophiles, and are a common precursor to various 1,3-dipoles.

Carbene dimerization

Carbenes and carbenoid precursors can dimerize to alkenes. This is often, but not always, an unwanted side reaction; metal carbene dimerization has been used in the synthesis of polyalkynylethenes and is the major industrial route to Teflon (see Carbene § Industrial applications). Persistent carbenes equilibrate with their respective dimers, the Wanzlick equilibrium.

Ligands in organometallic chemistry

In organometallic species, metal complexes with the formulae L_nMCRR' are often described as carbene complexes. Such species do not however react like free carbenes and are rarely generated from carbene precursors, except for the persistent carbenes. The transition metal carbene complexes can be classified according to their reactivity, with the first two classes being the most clearly defined:

• Fischer carbenes, in which the carbene is bonded to a metal that bears an electron-withdrawing group (usually a carbonyl). In such cases the carbenoid carbon is mildly electrophilic.
• Schrock carbenes, in which the carbene is bonded to a metal that bears an electron-donating group. In such cases the carbenoid carbon is nucleophilic and resembles a Wittig reagent (which are not considered carbene derivatives).
• Carbene radicals, in which the carbene is bonded to an open-shell metal with the carbene carbon possessing a radical character. Carbene radicals have features of both Fischer and Schrock carbenes, but are typically long-lived reaction intermediates.

• 

  N-Heterocyclic (NHC), Arduengo or Wanzlick carbenes are C-deprotonated imidazolium or dihydroimidazolium salts. They often are deployed as ancillary ligands in organometallic chemistry. Such carbenes are usually very strong σ-donor spectator ligands, similar to phosphines.

Industrial applications

A large-scale application of carbenes is the industrial production of tetrafluoroethylene, the precursor to Teflon. Tetrafluoroethylene is generated via the intermediacy of difluorocarbene:

CHClF₂ → CF₂ + HCl

2 CF₂ → F₂C=CF₂

The insertion of carbenes into C–H bonds has been exploited widely, e.g. the functionalization of polymeric materials and electro-curing of adhesives. Many applications rely on synthetic 3-aryl-3-trifluoromethyldiazirines (a carbene precursor that can be activated by heat, light, or voltage) but there is a whole family of carbene dyes.

History

Carbenes had first been postulated by Eduard Buchner in 1903 in cyclopropanation studies of ethyl diazoacetate with toluene. In 1912 Hermann Staudinger also converted alkenes to cyclopropanes with diazomethane and CH₂ as an intermediate. Doering in 1954 demonstrated their synthetic utility with dichlorocarbene.

See also

• Transition metal carbene complexes
• Atomic carbon a single carbon atom with the chemical formula :C:, in effect a twofold carbene. Also has been used to make "true carbenes" in situ.
• Foiled carbenes derive their stability from proximity of a double bond (i.e. their ability to form conjugated systems).
• Carbene analogs and carbenoids
• Carbenium ions, protonated carbenes
• Ring opening metathesis polymerization

References

1. Hoffmann, Roald (2005). Molecular Orbitals of Transition Metal Complexes. Oxford. p. 7. ISBN 978-0-19-853093-0.
2. IUPAC, Compendium of Chemical Terminology, 2nd ed. (the "Gold Book") (1997). Online corrected version: (2006–) "carbenes". doi:10.1351/goldbook.C00806
3. Grossman, Robert B. (2003). The Art of Writing Reasonable Organic Reaction Mechanisms (2nd ed.). New York: Springer. p. 84. ISBN 0-387-95468-6.
4. ^ Grossman 2003, p. 35.
5. For detailed reviews on stable carbenes, see: (a) Bourissou, D.; Guerret, O.; Gabbai, F. P.; Bertrand, G. (2000). "Stable Carbenes". Chem. Rev. 100 (1): 39–91. doi:10.1021/cr940472u. PMID 11749234. (b) Melaimi, M.; Soleilhavoup, M.; Bertrand, G. (2010). "Stable cyclic carbenes and related species beyond diaminocarbenes". Angew. Chem. Int. Ed. 49 (47): 8810–8849. doi:10.1002/anie.201000165. PMC 3130005. PMID 20836099.
6. Grossman 2003, pp. 84–85.
7. ^ Grossman 2003, p. 85.
8. Grossman 2003, p. 84.
9. Grasse, P. B.; Brauer, B. E.; Zupancic, J. J.; Kaufmann, K. J.; Schuster, G. B. (1983). "Chemical and physical properties of fluorenylidene: equilibration of the singlet and triplet carbenes". Journal of the American Chemical Society. 105 (23): 6833. doi:10.1021/ja00361a014.
10. Nemirowski, A.; Schreiner, P. R. (November 2007). "Electronic Stabilization of Ground State Triplet Carbenes". J. Org. Chem. 72 (25): 9533–9540. doi:10.1021/jo701615x. PMID 17994760.
11. Smith, Michael B.; March, Jerry (2007), Advanced Organic Chemistry: Reactions, Mechanisms, and Structure (6th ed.), New York: Wiley-Interscience, ISBN 978-0-471-72091-1
12. Contrariwise, Grossman 2003, p. 85 states: "The reactivities of carbenes and carbenoids are the same no matter how they are generated." Grossman's analysis is not supported by modern physical organic chemistry texts, and likely refers to rapid equilibration between carbene states following most carbene generation methods.
13. Skell, P. S.; Woodworth, R. C. (1956). "Structure of Carbene, Ch2". Journal of the American Chemical Society. 78 (17): 4496. doi:10.1021/ja01598a087.
14. Grossman 2003, pp. 85–86.
15. Grossman 2003, pp. 86–87.
16. ^ Grossman 2003, p. 87.
17. For a concise tutorial on the applications of carbene ligands also beyond diaminocarbenes, see Munz, D (2018). "Pushing Electrons—Which Carbene Ligand for Which Application?". Organometallics. 37 (3): 275–289. doi:10.1021/acs.organomet.7b00720.
18. Contrariwise, Grossman 2003: "Diazo compounds are converted to singlet carbenes upon gentle warming and to carbenoids by treatment with a Rh(II) or Cu(II) salt such as Rh₂(OAc)₄ or CuCl₂. The transition-metal-derived carbenoids, which have a metal –– C double bond, undergo the reactions typical of singlet carbenes. At this point you can think of them as free singlet carbenes, even though they’re not."
19. For a general review with a focus on applications with diaminocarbenes, see: Hopkinson, M. N.; Richter, C.; Schedler, M.; Glorius, F. (2014). "An overview of N-heterocyclic carbenes". Nature. 510 (7506): 485–496. Bibcode:2014Natur.510..485H. doi:10.1038/nature13384. PMID 24965649. S2CID 672379.
20. S. P. Nolan "N-Heterocyclic Carbenes in Synthesis" 2006, Wiley-VCH, Weinheim. Print ISBN 9783527314003. Online ISBN 9783527609451. doi:10.1002/9783527609451
21. Marion, N.; Diez-Gonzalez, S.; Nolan, S. P. (2007). "N-heterocyclic carbenes as organocatalysts". Angew. Chem. Int. Ed. 46 (17): 2988–3000. doi:10.1002/anie.200603380. PMID 17348057.
22. Bajzer, W. X. (2004). "Fluorine Compounds, Organic". Kirk-Othmer Encyclopedia of Chemical Technology. John Wiley & Sons. doi:10.1002/0471238961.0914201802011026.a01.pub2. ISBN 978-0471238966.
23. Yang, Peng; Yang, Wantai (2013-07-10). "Surface Chemoselective Phototransformation of C–H Bonds on Organic Polymeric Materials and Related High-Tech Applications". Chemical Reviews. 113 (7): 5547–5594. doi:10.1021/cr300246p. ISSN 0009-2665. PMID 23614481.
24. ^ Ping, Jianfeng; Gao, Feng; Chen, Jian Lin; Webster, Richard D.; Steele, Terry W. J. (2015-08-18). "Adhesive curing through low-voltage activation". Nature Communications. 6: 8050. Bibcode:2015NatCo...6.8050P. doi:10.1038/ncomms9050. ISSN 2041-1723. PMC 4557340. PMID 26282730.
25. Nakashima, Hiroyuki; Hashimoto, Makoto; Sadakane, Yutaka; Tomohiro, Takenori; Hatanaka, Yasumaru (2006-11-01). "Simple and Versatile Method for Tagging Phenyldiazirine Photophores". Journal of the American Chemical Society. 128 (47): 15092–15093. doi:10.1021/ja066479y. ISSN 0002-7863. PMID 17117852.
26. ^ Blencowe, Anton; Hayes, Wayne (2005-08-05). "Development and application of diazirines in biological and synthetic macromolecular systems". Soft Matter. 1 (3): 178–205. Bibcode:2005SMat....1..178B. doi:10.1039/b501989c. ISSN 1744-6848. PMID 32646075.
27. ^ Liu, Michael T. H. (1982-01-01). "The thermolysis and photolysis of diazirines". Chemical Society Reviews. 11 (2): 127. doi:10.1039/cs9821100127. ISSN 1460-4744.
28. Elson, Clive M.; Liu, Michael T. H. (1982-01-01). "Electrochemical behaviour of diazirines". Journal of the Chemical Society, Chemical Communications (7): 415–416. doi:10.1039/c39820000415. ISSN 0022-4936.
29. Buchner, E.; Feldmann, L. (1903). "Diazoessigester und Toluol". Berichte der Deutschen Chemischen Gesellschaft. 36 (3): 3509. doi:10.1002/cber.190303603139.
30. Staudinger, H.; Kupfer, O. (1912). "Über Reaktionen des Methylens. III. Diazomethan". Berichte der Deutschen Chemischen Gesellschaft. 45: 501–509. doi:10.1002/cber.19120450174.
31. Von E. Doering, W.; Hoffmann, A. K. (1954). "The Addition of Dichlorocarbene to Olefins". Journal of the American Chemical Society. 76 (23): 6162. doi:10.1021/ja01652a087.

External links

• Media related to Carbenes at Wikimedia Commons

• Carbenes
• Reactive intermediates
• Functional groups