Hydroacylation is a type of

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, Mechanistic Organ ...

in which an

alkene In organic chemistry, an alkene is a hydrocarbon containing a carbon–carbon double bond. Alkene is often used as synonym of olefin, that is, any hydrocarbon containing one or more double bonds.H. Stephen Stoker (2015): General, Organic, an ...

is inserted into the a formyl C-H bond. The product is a

ketone In organic chemistry, a ketone is a functional group with the structure R–C(=O)–R', where R and R' can be a variety of carbon-containing substituents. Ketones contain a carbonyl group –C(=O)– (which contains a carbon-oxygen double bo ...

. The reaction requires a metal

catalyst Catalysis () is the process of increasing the rate of a chemical reaction by adding a substance known as a catalyst (). Catalysts are not consumed in the reaction and remain unchanged after it. If the reaction is rapid and the catalyst recyc ...

. It is almost invariably practiced as an

intramolecular reaction 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 * intramolecular hydride transfer (transfer of a hy ...

using

homogeneous catalyst In chemistry, homogeneous catalysis is catalysis by a soluble catalyst in a solution. Homogeneous catalysis refers to reactions where the catalyst is in the same phase as the reactants, principally in solution. In contrast, heterogeneous catalysis ...

s, often based on rhodium phosphines. :RCHO + CH₂=CHR' → RC(O)CH₂CH₂R' With an alkyne in place of alkenes, the reaction produce an α,β-unsaturated ketone.

Examples

The reaction was discovered as part of a synthetic route to certain

prostanoid Prostanoids are active lipid mediators that regulate inflammatory response. Prostanoids are a subclass of eicosanoids consisting of the prostaglandins (mediators of inflammatory and anaphylactic reactions), the thromboxanes (mediators of vasoconst ...

s. The reaction required

tin tetrachloride Tin(IV) chloride, also known as tin tetrachloride or stannic chloride, is an inorganic compound with the formula Sn Cl4. It is a colorless hygroscopic liquid, which fumes on contact with air. It is used as a precursor to other tin compounds. It w ...

and a stoichiometric amount of

Wilkinson's catalyst Wilkinson's catalyst is the common name for chloridotris(triphenylphosphine)rhodium(I), a coordination complex of rhodium with the formula hCl(PPh3)3(Ph = phenyl). It is a red-brown colored solid that is soluble in hydrocarbon solvents such as ...

. An equal amount of a

cyclopropane Cyclopropane is the cycloalkane with the molecular formula (CH2)3, consisting of three methylene groups (CH2) linked to each other to form a ring. The small size of the ring creates substantial ring strain in the structure. Cyclopropane itself ...

was formed as the result of decarbonylation. : HydroacylationSakai1972

The first

catalytic Catalysis () is the process of increasing the rate of a chemical reaction by adding a substance known as a catalyst (). Catalysts are not consumed in the reaction and remain unchanged after it. If the reaction is rapid and the catalyst recyc ...

application involved cyclization of 4-pentenal to

cyclopentanone Cyclopentanone is the organic compound with the formula (CH2)4CO. This cyclic ketone is a colorless volatile liquid. Preparation Upon treatment with barium hydroxide at elevated temperatures, adipic acid undergoes ketonization to give cyclopenta ...

using with

. In this reaction the solvent was saturated with

ethylene Ethylene (IUPAC name: ethene) is a hydrocarbon which has the formula or . It is a colourless, flammable gas with a faint "sweet and musky" odour when pure. It is the simplest alkene (a hydrocarbon with carbon-carbon double bonds). Ethylene i ...

. :CH₂=CHCH₂CH₂CHO → (CH₂)₄CO

Reaction mechanism

Labeling studies establish the following regiochemistry: :RCDO + CH₂=CHR' → RC(O)CH₂CHDR' In terms of the

reaction mechanism In chemistry, a reaction mechanism is the step by step sequence of elementary reactions by which overall chemical change occurs. A chemical mechanism is a theoretical conjecture that tries to describe in detail what takes place at each stage of ...

, hydroacylation begins with

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. Oxidat ...

of the aldehydic carbon-hydrogen bond. The resulting acyl hydride complex next binds the alkene. The sequence of oxidative addition and alkene coordination is often unclear. Via

migratory insertion In organometallic chemistry, a migratory insertion is a type of reaction wherein two ligands on a metal complex combine. It is a subset of reactions that very closely resembles the insertion reactions, and both are differentiated by the mechanism ...

, the alkene inserts into either the metal-acyl or the metal-hydride bonds. In the final step, the resulting alkyl-acyl or beta-ketoalkyl-hydride complex undergoes

reductive elimination Reductive elimination is an elementary step in organometallic chemistry in which the oxidation state of the metal center decreases while forming a new covalent bond between two ligands. It is the microscopic reverse of oxidative addition, and is ...

. A competing side-reaction is decarbonylation of the aldehyde. This process also proceeds via the intermediacy of the acyl

metal hydride In chemistry, a hydride is formally the anion of hydrogen( H−). The term is applied loosely. At one extreme, all compounds containing covalently bound H atoms are called hydrides: water (H2O) is a hydride of oxygen, ammonia is a hydride of ...

: :R"C(O)-ML_n-H → R"-M(CO)L_n-H This step can be followed by reductive elimination of the alkane: :R"-M(CO)L_n-H → R"-H + M(CO)L_n : Hydroacylation reactionMechanism

Asymmetric hydroacylation

Hydroacylation as an

asymmetric reaction Enantioselective synthesis, also called asymmetric synthesis, is a form of chemical synthesis. It is defined by IUPAC as "a chemical reaction (or reaction sequence) in which one or more new elements of chirality are formed in a substrate molecu ...

was demonstrated in the form of a kinetic resolution. A true asymmetric synthesis was also described. Both conversions employed

rhodium Rhodium is a chemical element with the symbol Rh and atomic number 45. It is a very rare, silvery-white, hard, corrosion-resistant transition metal. It is a noble metal and a member of the platinum group. It has only one naturally occurring isoto ...

catalysts and a chiral

diphosphine ligand Diphosphines, sometimes called bisphosphanes, are organophosphorus compounds most commonly used as bidentate phosphine ligand, phosphine ligands in inorganic chemistry, inorganic and organometallic chemistry. They are identified by the presence of ...

. In one application the ligand is Me-DuPhos:''Synthesis of D- and L-Carbocyclic Nucleosides via Rhodium-Catalyzed Asymmetric Hydroacylation as the Key Step'' Patricia Marce, Yolanda Dıaz, M. Isabel Matheu, Sergio Castillon

Org. Lett. ''Organic Letters'' is a biweekly peer-reviewed scientific journal covering research in organic chemistry. It was established in 1999 and is published by the American Chemical Society. In 2014, the journal moved to a hybrid open access publishin ...

, 2008, 10 (21), pp 4735–4738 : AsymmetrichydroAcylationMarce2008

References

{{Reflist Organic reactions