Ferrier carbocyclization

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The Ferrier carbocyclization (or Ferrier II reaction) is an

Robert J. Ferrier in 1979.[1][2] It is a metal-mediated rearrangement of enol ether pyrans to cyclohexanones. Typically, this reaction is catalyzed by mercury salts, specifically mercury(II) chloride
.

Several reviews have been published.[3][4]

Reaction mechanism

Ferrier proposed the following reaction mechanism:

In this mechanism, the terminal

Ac
group on the terminal alkene).

Ferrier also reported that the final product, compound 5, could be converted into a conjugated ketone (compound 6) by reaction with acetic anhydride (Ac2O) and pyridine, as shown below.

Modifications

In 1997, Sinaÿ and co-workers reported an alternative route to the synthesis (shown below) that did not involve cleavage of the bond at the anomeric position (the glycosidic bond).[5] In this case, the major product formed had maintained its original configuration at the anomeric position.

(Bn =
isobutyl
)

Sinaÿ proposed this reaction went through the following transition state:

Sinaÿ also discovered that titanium (IV) derivatives such as [TiCl3(O

Lewis acid, i-Bu3Al,[6]
which goes through a similar transition state involving the retention of configuration at the anomeric center.

In 1988, Adam reported a modification of the reaction that used catalytic amounts of palladium (II) salts, which brought about the same conversion of enol ethers into carbosugars in a more environmentally friendly manner.[7]

Applications

The development of the Ferrier carbocyclization has been useful for the synthesis of numerous natural products that contain the carbocycle group. In 1991, Bender and co-workers reported a synthetic route to pure

cyclohexanones in 1998.[10]

References