Carbene C-H insertion
Encyclopedia
Carbene C−H insertion in organic chemistry
concerns the insertion reaction
of a carbene
into a carbon–hydrogen bond. This organic reaction
is of some importance in the synthesis of new organic compounds . Simple carbenes such as methylene
and dichlorocarbene
are not regioselective towards insertion. When the carbene is stabilized by a metal the selectivity increases. The compound dirhodium tetraacetate is found to be especially effective. In a typical reaction ethyl diazoacetate
(a well-known carbene precursor) and dirhodium tetraacetate react with hexane
with 1% insertion into one of the methyl C−H bonds, 63% insertion into the alpha-methylene group and 33% into the beta-methylene group. The fist such reaction was reported in 1981 by Teyssié
In a general reaction mechanism
for this reaction as proposed by Doyle in 1993 the metal that stabilizes the carbene, dissociates at the same time but not to the same degree as carbon–carbon bond formation and hydrogen atom migration. The reaction is distinct from a metal catalyzed C−H activation reaction where the metal actually inserts itself between carbon and hydrogen.
The metal employed as a catalyst in this reaction historically was copper
until superseded by rhodium
. Other metals stabilize the carbene too much (e.g. molybdenum
as in Fischer carbenes) or result in carbenes too reactive (e.g. gold
, silver
). Many dirhodium carboxylates and carboxamidates exist, including chiral
ones. An effective chiral dirhodium catalyst is Rh2(MPPIM)4 with MPPIM (Methyl PhenylPropyl IMidazolidinecarboxylato) asymmetric ligand.
Most successful reactions are intramolecular
within geometrically rigid systems, as pioneered by Wenkert (1982) and Taber (1982) .
Wee compared the use of different catalysts :
Organic chemistry
Organic chemistry is a subdiscipline within chemistry involving the scientific study of the structure, properties, composition, reactions, and preparation of carbon-based compounds, hydrocarbons, and their derivatives...
concerns the insertion reaction
Insertion reaction
An insertion reaction is a chemical reaction where one chemical entity interposes itself into an existing bond of typically a second chemical entity e.g.:...
of a carbene
Carbene
In 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 RR'C:, but the carbon can instead be double-bonded to one group. The term "carbene" may also merely refer to the compound H2C:, also called...
into a carbon–hydrogen bond. This organic reaction
Organic reaction
Organic reactions are chemical reactions involving organic compounds. The basic organic chemistry reaction types are addition reactions, elimination reactions, substitution reactions, pericyclic reactions, rearrangement reactions, photochemical reactions and redox reactions. In organic synthesis,...
is of some importance in the synthesis of new organic compounds . Simple carbenes such as methylene
Methylene
Methylene is a chemical species in which a carbon atom is bonded to two hydrogen atoms. Three different possibilities present themselves:* the -CH2- substituent group: e.g., dichloromethane ....
and dichlorocarbene
Dichlorocarbene
Dichlorocarbene is a carbene commonly encountered in organic chemistry. This reactive intermediate with chemical formula CCl2 is easily available by reaction of chloroform and a base such as potassium t-butoxide or sodium hydroxide dissolved in water...
are not regioselective towards insertion. When the carbene is stabilized by a metal the selectivity increases. The compound dirhodium tetraacetate is found to be especially effective. In a typical reaction ethyl diazoacetate
Ethyl diazoacetate
Ethyl diazoacetate is a diazo compound and a reagent in organic chemistry. It was discovered by Theodor Curtius in 1883. The compound can be prepared by reaction of the ethyl ester of glycine with sodium nitrite and sodium acetate in water....
(a well-known carbene precursor) and dirhodium tetraacetate react with hexane
Hexane
Hexane is a hydrocarbon with the chemical formula C6H14; that is, an alkane with six carbon atoms.The term may refer to any of four other structural isomers with that formula, or to a mixture of them. In the IUPAC nomenclature, however, hexane is the unbranched isomer ; the other four structures...
with 1% insertion into one of the methyl C−H bonds, 63% insertion into the alpha-methylene group and 33% into the beta-methylene group. The fist such reaction was reported in 1981 by Teyssié
In a general reaction mechanism
Reaction mechanism
In chemistry, a reaction mechanism is the step by step sequence of elementary reactions by which overall chemical change occurs.Although only the net chemical change is directly observable for most chemical reactions, experiments can often be designed that suggest the possible sequence of steps in...
for this reaction as proposed by Doyle in 1993 the metal that stabilizes the carbene, dissociates at the same time but not to the same degree as carbon–carbon bond formation and hydrogen atom migration. The reaction is distinct from a metal catalyzed C−H activation reaction where the metal actually inserts itself between carbon and hydrogen.
The metal employed as a catalyst in this reaction historically was copper
Copper
Copper is a chemical element with the symbol Cu and atomic number 29. It is a ductile metal with very high thermal and electrical conductivity. Pure copper is soft and malleable; an exposed surface has a reddish-orange tarnish...
until superseded by rhodium
Rhodium
Rhodium is a chemical element that is a rare, silvery-white, hard and chemically inert transition metal and a member of the platinum group. It has the chemical symbol Rh and atomic number 45. It is composed of only one isotope, 103Rh. Naturally occurring rhodium is found as the free metal, alloyed...
. Other metals stabilize the carbene too much (e.g. molybdenum
Molybdenum
Molybdenum , is a Group 6 chemical element with the symbol Mo and atomic number 42. The name is from Neo-Latin Molybdaenum, from Ancient Greek , meaning lead, itself proposed as a loanword from Anatolian Luvian and Lydian languages, since its ores were confused with lead ores...
as in Fischer carbenes) or result in carbenes too reactive (e.g. gold
Gold
Gold is a chemical element with the symbol Au and an atomic number of 79. Gold is a dense, soft, shiny, malleable and ductile metal. Pure gold has a bright yellow color and luster traditionally considered attractive, which it maintains without oxidizing in air or water. Chemically, gold is a...
, silver
Silver
Silver is a metallic chemical element with the chemical symbol Ag and atomic number 47. A soft, white, lustrous transition metal, it has the highest electrical conductivity of any element and the highest thermal conductivity of any metal...
). Many dirhodium carboxylates and carboxamidates exist, including chiral
Chirality (chemistry)
A chiral molecule is a type of molecule that lacks an internal plane of symmetry and thus has a non-superimposable mirror image. The feature that is most often the cause of chirality in molecules is the presence of an asymmetric carbon atom....
ones. An effective chiral dirhodium catalyst is Rh2(MPPIM)4 with MPPIM (Methyl PhenylPropyl IMidazolidinecarboxylato) asymmetric ligand.
Most successful reactions are intramolecular
Intramolecular
Intramolecular in chemistry describes a process or characteristic limited within the structure of a single molecule, a property or phenomenon limited to the extent of a single molecule.- Examples :...
within geometrically rigid systems, as pioneered by Wenkert (1982) and Taber (1982) .
Wee compared the use of different catalysts :