Barton-McCombie protocol

The keto group of the trisubstituted dioxanone 133 generated by ozonolysis was removed by radical deoxygenation according to the Barton-McCombie protocol [80] via the alcohols 134 and the corresponding xanthate, leading after deben-zylation to the dioxane 135 in excellent yield. After conversion to the tosylate, cleavage of the acetonide and protection of the secondary alcohol function as a TBS ether provided access to oxirane 128 by cyclization with NaH in 99% yield and in virtually diastereo- and enantiomerically pure form (de, ee > 96%). 

With the formation of the entire colombiasin skeleton accomplished through the successful generation of 40 (Scheme 7), including the two quaternary carbon atoms and the additional three stereocenters present in the target molecule, only a few minor details remained before arriving at colombiasin A (1). First, the extraneous hydroxyl group at C-5 was reductively removed through the use of the Barton—McCombie protocol in which the initial for-... 

In the asymmetric synthesis of the C1-C19 fragment of kabiramide C, to complete the stereochemical array, J. Panek and co-workers used, among other methods, the Barton-McCombie deoxygenation protocol. ... 

The original discovery synthesis of the P2 domain of telaprevir utilized bicycloproline derivative 56 (Scheme 10),"° which was prepared in racemic form using a four-step, two-pot protocol starting from 2-cyclopentenone, as described by Monn and Valli." In this approach, enantiomerically pure 56 was obtained via chiral HPLC separation." Reduction of the ketone of 56 produced secondary alcohol 57, which was further reduced to 58 under Barton-McCombie deoxygenation conditions. The synthesis of P2 fragment 59 was completed by hydrogenolysis of the benzyl carbamate. 

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. 

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