Clemmensen reduction

The two-step sequence of Friedel-Crafts acylation followed by Clemmensen reduction constitutes a classical strategy for the primary alkylation of arenes.

[9][11] Highly symmetrical hydrocarbon compounds have attracted much interest due to their beautiful structure and potential applications, but the challenges in the synthesis persist.

Importantly, the reaction effectively reduced the two ketones, alcohol, and the methoxycarbonyl group while avoiding any by-products, giving the product in high yield (61%).

A modified condition, involving activated zinc dust in an anhydrous-solution of hydrogen chloride in diethyl ether or acetic anhydride, results in a more effective reduction.

The modified Clemmensen reduction allows for the selective deoxygenation of ketones in molecules that contain stable groups such as cyano, amido, acetoxy, and carboalkoxy.

The Clemmensen reduction
Scheme 1: Reaction scheme of Clemmensen Reduction.
Scheme 2: A mechanism of Clemmensen reduction was proposed in 1975. [ 7 ] [ 8 ] The carbonyl is first converted to radical anion (shown as blue), then to zinc carbenoid (shown as red), and then reduced to alkane.
Scheme 3: The synthesis of Dibarrelane. [ 12 ]
Scheme 4: Reducing cholestane-3-one to cholestane using Clemmensen reduction. [ 13 ]