The term "carbene" may also refer to the specific compound :CH 2, also called methylene, the parent hydride from which all other carbene compounds are formally derived.[1][2]
There are two types of carbenes: singlets or triplets, depending upon their electronic structure.[3] The different classes undergo different reactions.
Molecules with no acidic proton can also form carbenes. A geminal dihalide exposed to organolithiums with 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.[7]
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.[7] 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 [3+2] cycloadduct intermediate that extrudes nitrogen. frame|Alkylidene carbeneTo generate an alkylidene carbene a ketone can be exposed to trimethylsilyldiazomethane and then a strong base.
Structures and bonding
Singlet and triplet carbenes
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 sp2 orbital structure.[8] 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.[9] Simulations suggest that electropositive heteroatoms can thermodynamically stabilize triplet carbenes, such as in silyl and silyloxy carbenes, especially trifluorosilyl carbenes.[10]
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
right|frame|Carbene addition to alkenes
Singlet and triplet carbenes exhibit divergent reactivity.[11][page needed][12]
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.[4] Their reactions are typically concerted and often cheletropic.[citation needed] Singlet carbenes are typically electrophilic,[4] 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.[13]
thumb|right|Carbene cyclopropanation
Carbenes add to double bonds to form cyclopropanes,[14] 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.
thumb|Carbene insertion
Insertions are another common type of carbene reaction,[15] 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.
left|frame|Carbene intramolecular reaction
left|frame|Carbene intermolecular reaction
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.[16] 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.[16]
right|frame|Wanzlick equilibrium
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 Chemistry: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 LnMCRR' are often described as carbene complexes.[17] Such species do not however react like free carbenes and are rarely generated from carbene precursors, except for the persistent carbenes.[citation needed][18] 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.
The "second generation" of the Grubbs catalysts for alkene metathesis features an NHC ligand.N-Heterocyclic (NHC), Arduengo or Wanzlick carbenes[19] 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.[20][21]
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:[22]
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[23] and electro-curing of adhesives.[24] Many applications rely on synthetic 3-aryl-3-trifluoromethyldiazirines[25][26] (a carbene precursor that can be activated by heat,[27] light,[26][27] or voltage)[28][24] but there is a whole family of carbene dyes.
↑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 Society105 (23): 6833. doi:10.1021/ja00361a014.
↑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. PMID17994760.
↑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.
↑Skell, P. S.; Woodworth, R. C. (1956). "Structure of Carbene, Ch2". Journal of the American Chemical Society78 (17): 4496. doi:10.1021/ja01598a087.
↑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?". Organometallics37 (3): 275–289. doi:10.1021/acs.organomet.7b00720.
↑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."
↑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". Nature510 (7506): 485–496. doi:10.1038/nature13384. PMID24965649. Bibcode: 2014Natur.510..485H.
↑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 Society128 (47): 15092–15093. doi:10.1021/ja066479y. ISSN0002-7863. PMID17117852.
↑ 27.027.1Liu, Michael T. H. (1982-01-01). "The thermolysis and photolysis of diazirines" (in en). Chemical Society Reviews11 (2): 127. doi:10.1039/cs9821100127. ISSN1460-4744.
↑Von E. Doering, W.; Hoffmann, A. K. (1954). "The Addition of Dichlorocarbene to Olefins". Journal of the American Chemical Society76 (23): 6162. doi:10.1021/ja01652a087.
