Formates, Barton-McCombie deoxygenation

The initiation of the Barton Decarboxylation ( Bu3Sn-H -> Bu3Sn-) is effected with a radical initiator, and as with the Barton-McCombie Deoxygenation, the driving force for the reaction itself is the formation of the stable S-Sn bond. 

Ammonium formate hydrogenolysis of 7t-allyl-palladium(II) complexes formed via oxidative addition of Pd(0) to propargylic carbonate esters is a useful method for preparing disubstituted alkynes, as depicted below. This method of deoxygenation avoids the use of expensive and toxic reagents often associated with the free-radical Barton-McCombie deoxygenation. °... 

Scheme 4. Side reactions in the Barton-McCombie deoxygenation an example of methyl ether formation...

The addition of silyl radicals to thiocarbonyl derivatives is a facile process leading to a-silylthio adducts (Reaction 5.37). This elementary reaction is the initial step of the radical chain deoxygenation of alcohols or Barton McCombie reaction (see Section 4.3.3 for more details). However, rate constants for the formation of these adducts are limited to the value for the reaction of (TMS)3Si radical with the xanthate c-C6HuOC(S)SMe (Table 5.3), a reaction that is also found to be reversible [15]. Structural information on the a-silylthio adducts as well as some kinetic data for the decay reactions of these species have been obtained by EPR spectroscopy [9,72]. 

Radical deoxygenation of alcohols is important, and the reduction of xanthates prepared from alcohols, with Bu3SnH in the presence of AIBN is called the Barton-McCombie reaction (eq. 2.13) [37-51]. The driving force for the reaction is the formation of a strong C=0 bond from the C=S bond, approximately 10 kcal/mol stronger. This reaction can be used for various types of substrates such as nucleosides and sugars. Though methyl xanthates, prepared from alcohols with carbon disulfide and methyl iodide under basic conditions are very frequently used, other thiocarbonates, as shown in eq. 2.14, can also be employed. 

Examination of the various steps in the above sequence provides considerable insight. From a thermodynamic standpoint several factors are important. In the first instance, the conceptual link between acylthiohydroxamate chemistry and the elegant Barton-McCombie reductive deoxygenation of xanthates and similar thiocarbonyl derivatives is immediately apparent, inasmuch as the reaction involves formation of the strong carbonyl bond at the expense of a weak thiocarbonyl moiety. The enhancement of the aromatic character which occurs when the pyridine nucleus... 

Since the deoxygenation of compound 38 was well characterized using classical Barton-McCombie conditions, Roberts chose this same model substrate to illustrate the viability of silane/thiol reduction protocol. Reduction with this system gave a good yield of 39, however, it was observed that minor diasteromer 40, resulting from radical-induced epimerization at C-5, could also be isolated. The rationale for the formation of 38 was potentially due to the thiyl catalyst abstracting H from the substrate faster than from the silane. The authors propose that the use of a better donor, such as diphenylsilane, could prevent such side-products from occurring. 

Radical Chemistry. Treatment of secondary alcohols with 1 equiv of TCDI affords an imidazole-1-thiocarbonyl derivative (imidazolide), which can be reduced to a CH2 unit under Tri-n-butylstannane (TBTH) radical chain reaction conditions. - The deoxygenation of secondary alcohols by way of an imidazolide or other thiocarbonyl derivative is called the Barton-McCombie reaction (eq 4). Since imidazolide formation (TCDI, reflux, 65 °C) and the subsequent radical chemistry are done under neutral or near-neutral conditions, the overall reduction is tolerant of the presence of many sorts of functional groups. Furthermore, the low solvation requirements of radical species permits deoxygenation in sterically congested environments (eq 5). ... 

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