Carbene
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 or where the R represents substituents or hydrogen atoms.
The term "carbene" may also refer to the specific compound, 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 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: α-elimination and small-molecule extrusion.Α Elimination
In α elimination, two substituents eliminate from the same carbon atom. Α-elimination typically occurs when strong bases act on acidic protons with no good vicinal leaving groups. For example, phenyllithium will abstract HX from a haloform. Such reactions often require phase-transfer conditions.Molecules with no acidic proton can still be induced to α-eliminate. A geminal dihalide exposed to organolithiums can undergo metal-halogen exchange and then eliminate a lithium salt:
Zinc metal abstracts halogens similarly in the Simmons–Smith reaction.
Mercuric and organomercury halides can stably store a wide variety carbenes as the α-halomercury adduct until a mild thermolysis. For example, the "Seyferth reagent" releases CCl2 upon heating:
It remains uncertain which of such metallated reagents form truly free carbenes, instead of a reactive metal-carbene complex. Nevertheless, reactions with such metallocarbenes generally give the same organic products as with other carbene sources.
Small-molecule extrusion
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 to inert nitrogen gas. 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 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 decompose diazoalkanes to a carbene and gaseous nitrogen; such are the Bamford–Stevens reaction and Wolff rearrangement. As with metallocarbenes, some reactions of diazoalkanes that formally proceed via carbenes may instead form a 1,3-Dipolar cycloaddition| cycloadduct intermediate that extrudes nitrogen.
To generate an alkylidene carbene a ketone can be exposed to trimethylsilyldiazomethane and then a strong base: image:alkylidene carbene.svg|frameless|alt=Alkylidene carbene synth|center|upright=2
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, 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. Bond angles 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 more stable than singlet carbenes, comparable to nitrogen inversion. The stabilization is in part attributed to Hund's rule of maximum multiplicity. Only few persistent triplet carbenes are known, either stabilized by a metal substituent such as lead, palladium or platinum, or two aryl groups for efficient resonance stabilization. 9-Fluorenylidene has been shown to be a rapidly equilibrating mixture of singlet and triplet states with an approximately 1.1 kcal/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 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
At a very high level of generality, carbenes behave like 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 intermediate with two unpaired electrons.
Singlet carbenes can 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
are another common type of carbene reaction, a form of oxidative addition. Insertions may or may not occur in single step. The end result is that the carbene interposes itself into an existing bond, preferably X–H, else C–H or a C–C bond. Alkyl carbenes insert much more selectively than methylene, which does not differentiate between primary, secondary, and tertiary C-H bonds.image:carbene intra.svg|left|frame|Carbene intramolecular reaction
image:Carbene_intermolecular_insertion.svg|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. 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. 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. 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. 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.
- 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.
- Image:Grubbs_catalyst_Gen2.svg|thumb|right|220px|The "second generation" of the Grubbs catalysts for alkene metathesis features an NHC ligand.N-Heterocyclic, 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
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 but there is a whole family of carbene dyes.