Natural products Barton-McCombie deoxygenation

Barton-McCombie deoxygenation is not always stereoselective the diastereo-meric ratios strongly depends on the nature of the protecting groups and of the ester moiety. However, in 2-C-trifluoromethyl-2-deoxyfuranose, the a compound is the major product of the reaction, due to steric hindrance of this a side. In 3-C-trifluoromethyl-3-deoxyfuranose, deoxygenation by tributyltin hydride yields only the a product, if it is performed with oxalate instead of thiocarbonate. Another possibility to obtain this selectivity is to perform the reaction with 1,2,5,6-di-O-isopropylidene-a-D-glucofuranose (Figure 6.34). ... 

Alcohols are ubiquitous in natural products or as intermediates in organic synthesis, and the Barton-McCombie deoxygenation has been applied hundreds of times on all kinds of molecules, and several reviews have already appeared [1]. Three examples, illustrating its tremendous synthetic potential, are set out in Scheme 3 they represent a deoxygenation of secondary thiocarbonyl imidazolide... 

Audran and colleagues described two syntheses of furanosesqui-terpene natural products employing similar synthetic pathways, culminating in the use of the Barton-McCombie deoxygenation as a key step. The ester unit in bicyclic lactones 65 and 66 is used to set stereochemistry of the C-2 center. After further elaboration, the ester stereocontrol element is then reductively cleaved and cyanated to yield the diols 67 and 68, from 65 and 66, respectively. Then, in a one-pot, two-step process, activation and double deoxygenation was performed to yield reduced compounds 69 and 70, which are the intermediates in the synthesis of (-i-)-ricciocarpin A (71) and (+)-ancistrofuran (72), respectively. 

Ramana et al. [89] opted for a Pd(II) catalyst for the intramolecular hydroalkoxylation of alkyne 186 in their synthesis of the enantiomeric cephalosporolides 189a and 189b (Scheme 44). The spirocyclization afforded a 1 1 mixture of the spiroacetals 187, which were then elaborated to the ent-natural products via hydrolysis of the isopropylidene acetal, followed by oxidation and Barton-McCombie deoxygenation. 

A relevant reductive process, which has found wide application in organic synthesis, is the deoxygenation of alcohols introduced in 1975 by Barton and McCombie [58]. Reaction (4.28) shows that the thiocarbonyl derivatives, easily obtained from the corresponding alcohol, can be reduced in the presence of BusSnH under free radical conditions. The reactivity of xanthates and thiocarbonyl imidazolides [58] was successfully extended to 0-arylthiocarbonates [59] and (9-thioxocarbamates [60]. Several reviews have appeared on this subject, thus providing an exhaustive view of this methodology and its application in natural product synthesis [61-64]. 

Scheme 4 gives the endgame from Corey s cyclization product 4 (Scheme 1) to the marine natural product scalarenedial (20, [15]), which is a strong fish feeding deterrent. The Barton-McCombie process [16] was employed to deoxygenate at C3, followed by conversion of the ketone to the vinyl triflate 18 with PhNTf2 (McMurry s method [17]). After hydroxy-desilylation of 18, the carbonylation to 19 was catalyzed by Pd(dppp) (see above). The vicinal... 

S.J. Danishefsky and co-workers developed a synthetic route to the neurotrophic illicinones and a total synthesis of the natural product tricycloillicinone. Illicinones were found to enhance the action of choline acetyltransferase, which catalyzes the synthesis of acetylcholine from its precursors. The application of Corey-Snider oxidative cycHzation and the Barton-McCombie radical deoxygenation provided a direct route to tricycloillicinone. 

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