Hydroacylation
Encyclopedia
Hydroacylation is a type of organic reaction
in which an aldehyde
is added over an alkene
or alkyne
bond. The reaction product is a ketone
. The reaction requires a metal catalyst and intramolecular
reaction is favored over a intermolecular one. With alkynes the reaction product is an cyclopentenone.
The reaction was discovered by K. Sakai in 1972 as part in a synthetic route to certain prostanoid
s. The reagent in this reaction was tin tetrachloride. With an stoichiometric amount of Wilkinson's catalyst
in chloroform
, acetonitrile
or benzene
an equal amount of a cyclopropane
was formed as the result of decarbonylation.
The first catalytic application was reported by Miller in 1976 in the reaction of 4-pentenal with Wilkinson's catalyst to form cyclopentanone
. In this reaction the solvent was saturated with ethylene
.
Cyclopentane ring-formation is favored, the reaction product of 5-pentenal is again a cyclopentanone. Another suitable catalyst is cationic rhodium compound Rh(dppe)ClO4
step one in hydroacylation is oxidative addition
of the metal into the aldehyde carbon-hydrogen bond followed by side-on addition of the alkene, then followed by reductive elimination. A lurking side-reaction is decarbonylation from the acyl metal hydride RCH2(CO)MH to the alkane RCH3 and M(CO) via the RCH2M(CO)H intermediate.
and a chiral diphosphine ligand. In one application the ligand is Me-DuPhos
:
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,...
in which an aldehyde
Aldehyde
An aldehyde is an organic compound containing a formyl group. This functional group, with the structure R-CHO, consists of a carbonyl center bonded to hydrogen and an R group....
is added over an alkene
Alkene
In organic chemistry, an alkene, olefin, or olefine is an unsaturated chemical compound containing at least one carbon-to-carbon double bond...
or alkyne
Alkyne
Alkynes are hydrocarbons that have a triple bond between two carbon atoms, with the formula CnH2n-2. Alkynes are traditionally known as acetylenes, although the name acetylene also refers specifically to C2H2, known formally as ethyne using IUPAC nomenclature...
bond. The reaction product is a ketone
Ketone
In organic chemistry, a ketone is an organic compound with the structure RCR', where R and R' can be a variety of atoms and groups of atoms. It features a carbonyl group bonded to two other carbon atoms. Many ketones are known and many are of great importance in industry and in biology...
. The reaction requires a metal catalyst and 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 :...
reaction is favored over a intermolecular one. With alkynes the reaction product is an cyclopentenone.
The reaction was discovered by K. Sakai in 1972 as part in a synthetic route to certain prostanoid
Prostanoid
Prostanoid is the term used to describe a subclass of eicosanoids consisting of: the prostaglandins , the thromboxanes and the prostacyclins - Biosynthesis : Cyclooxygenase catalyzes the conversion of the free essential fatty acids to...
s. The reagent in this reaction was tin tetrachloride. With an stoichiometric amount of Wilkinson's catalyst
Wilkinson's catalyst
Wilkinson's catalyst is the common name for chlorotrisrhodium, a coordination compound with the formula RhCl3 . It is named after the late organometallic chemist and 1973 Nobel Laureate, Sir Geoffrey Wilkinson who popularized its use.-Structure and basic properties:The compound is a square planar,...
in chloroform
Chloroform
Chloroform is an organic compound with formula CHCl3. It is one of the four chloromethanes. The colorless, sweet-smelling, dense liquid is a trihalomethane, and is considered somewhat hazardous...
, acetonitrile
Acetonitrile
Acetonitrile is the chemical compound with formula . This colourless liquid is the simplest organic nitrile. It is produced mainly as a byproduct of acrylonitrile manufacture...
or benzene
Benzene
Benzene is an organic chemical compound. It is composed of 6 carbon atoms in a ring, with 1 hydrogen atom attached to each carbon atom, with the molecular formula C6H6....
an equal amount of a cyclopropane
Cyclopropane
Cyclopropane is a cycloalkane molecule with the molecular formula C3H6, consisting of three carbon atoms linked to each other to form a ring, with each carbon atom bearing two hydrogen atoms...
was formed as the result of decarbonylation.
The first catalytic application was reported by Miller in 1976 in the reaction of 4-pentenal with Wilkinson's catalyst to form cyclopentanone
Cyclopentanone
Cyclopentanone is a colorless liquid organic compound with a peppermint-like odor. It is a cyclic ketone, structurally similar to cyclopentane, consisting of a five-membered ring containing a ketone functional group.-Safety:...
. In this reaction the solvent was saturated with ethylene
Ethylene
Ethylene is a gaseous organic compound with the formula . It is the simplest alkene . Because it contains a carbon-carbon double bond, ethylene is classified as an unsaturated hydrocarbon. Ethylene is widely used in industry and is also a plant hormone...
.
Cyclopentane ring-formation is favored, the reaction product of 5-pentenal is again a cyclopentanone. Another suitable catalyst is cationic rhodium compound Rh(dppe)ClO4
Reaction mechanism
In a general reaction mechanismReaction 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...
step one in hydroacylation is oxidative addition
Oxidative addition
Oxidative addition and reductive elimination are two important and related classes of reactions in organometallic chemistry. Oxidative addition is a process that increases both the oxidation state and coordination number of a metal centre...
of the metal into the aldehyde carbon-hydrogen bond followed by side-on addition of the alkene, then followed by reductive elimination. A lurking side-reaction is decarbonylation from the acyl metal hydride RCH2(CO)MH to the alkane RCH3 and M(CO) via the RCH2M(CO)H intermediate.
Asymmetric hydroacylation
Hydroacylation as an asymmetric reaction was first demonstrated by James and Young in 1983 (kinetic resolution) and by Sakai in 1989 (true asymmetric synthesis) both employing rhodiumRhodium
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...
and a chiral diphosphine ligand. In one application the ligand is Me-DuPhos
DuPhos
DuPhos is a class of asymmetric ligands for asymmetric synthesis. The name DuPhos is derived from the chemical company that developed this type of ligand and the compound class of phospholanes it belongs to. This diphosphine ligand type was introduced in 1991 by M.J...
: