Markó–Lam deoxygenation

The Markó–Lam deoxygenation is an organic chemistry reaction where the hydroxy functional group in an organic compound is replaced by a hydrogen atom to give an alkyl group.^[1][2] The Markó-Lam reaction is a variant of the Bouveault–Blanc reduction^[3] and an alternative to the classical Barton–McCombie deoxygenation. It is named for the Belgian chemists István Markó and Kevin Lam.^[4]

The main features of the reaction are:

• short reaction time (5 seconds to 5 minutes).
• the use of a stable toluate derivative.
• the use of SmI₂/HMPA system or electrolysis instead of the classical and difficult to remove tributyltin hydride.

The Marko-Lam deoxygenation

Mechanism

A hydroxyl group is first derivitised into a stable and very often crystalline toluate derivative. The aromatic ester is submitted to a monoelectronical reduction, by the use of SmI₂/HMPA^[5] or by electrolysis,^[6] to yield the a radical-anion which decomposes into the corresponding carboxylate and into the radical of the alkyl fragment.

The Marko-Lam deoxygenation

This radical could be used for further chemical reactions or can abstract a hydrogen atom to form the deoxygenated product.

Variations

In presence of methanol or isopropanol, the reduction lead to the selective deprotection of the aromatic esters.^[7]

The Markó-Lam deoxygenation

In presence of ketones, allylic derivatives lead to the coupling product when treated in Barbier's conditions with samarium diiodide.^[8]

The Marko-Lam deoxygenation

Scope

The Markó-Lam reaction was used as a final step in the total synthesis of Trifarienol B:^[9]

Synthesis of Trifarienol B employing the Marko-Lam deoxygenation