| Barton–McCombie deoxygenation | |
|---|---|
| Named after | Derek Harold Richard Barton Stuart W. McCombie |
| Reaction type | Organic redox reaction |
| Identifiers | |
| Organic Chemistry Portal | barton-mccombie-reaction |
| RSC ontology ID | RXNO:0000134 |
TheBarton–McCombie deoxygenation is anorganic reaction in which ahydroxyfunctional group in anorganic compound is replaced by ahydrogen to give analkyl group.[1][2] It is named after British chemists SirDerek Harold Richard Barton and Stuart W. McCombie.
This deoxygenation reaction is aradical substitution. In the relatedBarton decarboxylation the reactant is acarboxylic acid.
Thereaction mechanism consists of a catalytic radical initiation step and a propagation step.[3] Thealcohol (1) is first converted into a reactive carbonothioyl intermediate such as athionoester orxanthate2. Heating ofAIBN results in its homolytic cleavage, generating two 2-cyanoprop-2-yl radicals9, which each abstract a hydrogen fromtributylstannane3 to generate tributylstannylradicals4 and inactive10. The tributyltin radical abstracts the xanthate group from2 by attack of4 at the sulfur atom with concurrent homolytic cleavage of the C-S π bond. This leaves a carbon centered radical that forms a C-O π bond through homolytic cleavage of the R-O σ bond, givingalkyl radical5 and tributyltin xanthate7. Thesulfurtin bond in this compound is very stable and provides thedriving force for this reaction. The alkyl radical5 then abstracts a hydrogen atom from a new molecule of tributylstannane generating the desired deoxygenated product (6) and a new radical species ready for propagation.
Nearby radical-stabilizing moieties can capture the radical intermediate from the thionoester fission, as in atotal synthesis ofazadirachtin:[4]
Other thiocarbonyl reagents can replace thethioacyl chloride. In one variation the reagent is theimidazole1,1'-thiocarbonyldiimidazole (TCDI), for example in the total synthesis of pallescensin B.[5] TCDI is especially good to primary alcohols because there is no resonance stabilization of thethiocarbamate; the nitrogen lonepair is involved in the aromatic sextet.[citation needed]
The reaction also applies toS-alkylxanthates.[6]
The main disadvantage to Barton–McCombie deoxygenation is the toxic and expensive tributylstannane, the endproducts of which are difficult to remove from the reaction mixture. One alternative istributyltin oxide as the radical source andpoly(methylhydridesiloxane) (PMHS) as thehydrogen source.[7]
Both roles are combined in thetrialkylboranes, which can abstract the required hydrogen atoms from protic solvents, the reactor wall or even (in strictly anhydrous conditions) the borane itself.[6] Typically the reagents aretrimethylborane ortriethylborane contaminated with small amounts of water.[8]
Thecatalytic cycle begins when airoxidizes the trialkylborane3 to the borinic acid and methyl radical4. This radical methylates the xanthate2, which fragments to S-methyl-S-methyl dithiocarbonate7 and the radical intermediate5.5 abstracts a hydrogen from the borane3 to reform4 and produce the alkane6.
Theoretical calculations suggest that O-Hhomolysis in a borane-water complex isendothermic, but the energy barrier is comparable to tributylstannane and not pure water homolysis.
1,2-Diols can be converted to the bis(xanthate), which react with tributyltin hydride to give the alkene:[9]
where Bu =−C4H9. The identity of the final tin product is not well defined.