Barton-McCombie deoxygenation

The Barton-McCombie deoxygenation is an organic reaction in which an hydroxy functional group in an organic compound is replaced by a proton to an alkane. It is named for the British chemists Sir Derek Harold Richard Barton (1918–1998) and Stuart W. McCombie.



This deoxygenation reaction is a radical substitution. In the related Barton decarboxylation the reactant is a carboxylic acid.

Mechanism
The reaction mechanism consists of a catalytic radical initiation step and a propagation step. The alcohol (1) is first converted into a xanthate (2). The other reactant tributyltin hydride 3 is decomposed by AIBN 8 into a tributyltin radical 4. The tributyltin radical abstracts the xanthate group from 2 leaving an alkyl radical 5 and tributyltin xanthate (7). The sulfur tin bond in this compound is very stable and provides the driving force for this reaction. The alkyl radical in turn abstracts a proton from a new molecule of tributyltin hydride generating the desired deoxygenated product (6) and a new radical species ready for propagation.



Alternative hydride sources
Main disadvantage of this reaction is the use of the tin hydride which is toxic, expensive and difficult to remove from the reaction mixture. One alternative is the use of tributyltin anhydride as the radical source and poly(methylhydridesiloxane) (PMHS) as the hydride source. Phenyl chlorothionoformate used as the starting material ultimately generates carbonyl sulfide.



Trialkyl boranes
An even more convenient proton donor is provided by trialkylborane-water complexes such as trimethylborane contaminated with small amounts of water.



In this catalytic cycle the reaction is initiated by air oxidation of the trialkylborane 3 by air to the methyl radical 4. This radical reacts with the xanthate 2 to S-methyl-S-methyl dithiocarbonate 7 and the radical intermediate 5. The CH3B.H2O complex 3 provides a proton for recombining with this radical to the alkane 6 leaving behind diethyl borinic acid and a new methyl radical.



It is found by theoretical calculations that that a O-H homolysis reaction in the borane-water complex is endothermic with an energy similar to that of the homolysis reaction in tributyltin hydride but much lower than the homolysis reaction of pure water.

Examples
A variation of this reaction was used as one of the steps in the total synthesis of azadirachtin :


 * [[Image:AzadirachtinReactionSequence2.png|400px|Azadirachtin reaction sequence]]