Markó–Lam deoxygenation explained

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.

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.

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]

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

Scope

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

Notes and References

1. Web site: Alkane synthesis by deoxygenation . Organic-chemistry.org. 2010-01-01.
2. http://www.chem-station.com/odos/2010/06/-marko-lam-deoxygenation.html マルコ・ラム脱酸素化 Marko-Lam Deoxygenation – ODOOS -合成反応データベース- by Chem-Station
3. Bouveault. L.. Louis Bouveault. Blanc. G. L.. Bull. Soc. Chim. Fr.. 1904. 31. 666–672. Transformation des acides monobasiques saturés dans les alcools primaires correspondants. French. Transforming saturated monobasic acids into the corresponding primary alcohols.
4. Web site: Home . lamresearchgroup.com.
5. Lam, K. . Markó, I.E. . Org. Lett.. 2008. 10. 13. 2773–2776. 10.1021/ol800944p. 18507394. Using toluates as simple and versatile radical precursors.
6. Lam, K. . Markó, I.E. . . 2009 . 2009 . 1 . 95–97 . 10.1039/b813545b . 19082010 . Organic electrosynthesis using toluates as simple and versatile radical precursors.
7. Lam, K.. Markó, I.E.. Org. Lett.. 2009. 11. 13. 2752–2755. 10.1021/ol900828x. 19492803. Chemoselective chemical and electrochemical deprotections of aromatic esters.
8. Lam, K. . Markó, I.E. . . 2009 . 65 . 52. 10930–10940 . 10.1016/j.tet.2009.09.111 . Toluates: Unexpectedly versatile reagents.
9. Takahashi, K. . Akao, R. . Honda, T. . amp . . 2009 . 74 . 9. 3424–3429 . 10.1021/jo900369t . 19334700 . Efficient diastereoselective synthesis of trifarane-type sesquiterpenes, trifarienols A and B .