- Source: Hydroacylation
Hydroacylation is a type of organic reaction in which an electron-rich unsaturated hydrocarbon inserts into a formyl C-H bond. With alkenes, the product is a ketone:
RCHO + CH2=CHR' → RC(O)CH2CH2R'
With an alkyne instead, the reaction produces an α,β-unsaturated ketone.
The reaction requires a metal catalyst or a radical initiator. It is almost invariably practiced as an intramolecular reaction using homogeneous catalysts, often based on rhodium phosphines.
History
The reaction was discovered in the 1970s as part of a synthetic route to certain prostanoids. The reaction required tin tetrachloride and a stoichiometric amount of Wilkinson's catalyst:
An equal amount of a cyclopropane was formed as the result of decarbonylation.
The first catalytic application involved cyclization of 4-pentenal to cyclopentanone using (again) Wilkinson's catalyst. In this reaction the solvent was saturated with ethylene.
CH2=CHCH2CH2CHO → (CH2)4CO
Reaction mechanism
Labeling studies establish the following regiochemistry:
RCDO + CH2=CHR' → RC(O)CH2CHDR'
In terms of the reaction mechanism, hydroacylation begins with oxidative addition 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, 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. A competing side-reaction is decarbonylation of the aldehyde. This process also proceeds via the intermediacy of the acyl metal hydride:
R"C(O)-MLn-H → R"-M(CO)Ln-H
This step can be followed by reductive elimination of the alkane:
R"-M(CO)Ln-H → R"-H + M(CO)Ln
Asymmetric hydroacylation
Hydroacylation as an asymmetric reaction was demonstrated in the form of a kinetic resolution. A true asymmetric synthesis was also described. Both conversions employed rhodium catalysts and a chiral diphosphine ligand. In one application the ligand is Me-DuPhos: