Barton s deoxygenation

In the laboratory of V. Singh a novel and efficient stereospecific synthesis of the marine natural product capnellene from p-cresol was developed. After rapidly assembling the desired carbon framework, it was necessary to remove the carbonyl group from the tricyclic intermediate which was accomplished using Barton s deoxygenation procedure. 

Deoxykanamycin A, an antibiotic resistant to 3 -phosphotransferase-modifying enzymes [(APH)3 -la s], has been prepared via two different routes. One route used Barton s deoxygenation protocol [87], and in another a mixture of 2, 3 - and 3, 4 -epoxy intermediates of kanamycin A derivatives resulted in the formation of a single product (3 -deoxy derivative) upon reduction with Raney nickel or sodium borohydride [88]. 

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. 

The Barton deoxygenation (or Barton-McCombie deoxygenation) is a two-step reaction sequence for the reduction of an alcohol to an alkane. The alcohol is first converted to a methyl xanthate or thioimidazoyl carbamate. Then, the xanthate or ihioimidazoyl carbamate is reduced with a tin hydride reagent under radical conditions to afford the alkane. Trialkylsilanes have also been used as the hydride source. Reviews (a) McCombie, S. W. In Comprehensive Organic Synthesis Trost, B. M. Fleming, I., Eds. Pergamon Press Oxford, U. K., 1991 Vol. 8, Chapter 4.2 Reduction of Saturated Alcohols and Amines to Alkanes, pp. 818-824. (b) Crich, D. Quintero, L. Chem. Rev. 1989, 89, 1413-1432. 

The preparation34 of the left half of cephalostatin 7 was more straightforward. Compound 56, the minor product of the stannane addition (Scheme 25, vide supra) was deoxygenated by Barton s xanthate procedure (Scheme 28) to give 60, which was stereoselectively dihydroxylated using the Sharpless AD-mix-a reagent35 to yield 61 and its inseparable C-25 epimer in a 2.5 1 ratio. 

Two important reactions were introduced by Barton s group. The radical deoxygenation of secondary alcohols via thiono esters is a selective and mild replacement of hydroxy groups by hydrogen [22-25]. The deoxygenation at 2 -position of adenosine via the thionocarbamate derivative has been chosen as an example (Eq. 6)... 

Radical addition-fragmentation processes have been exploited in synthetic organic chemistry since the early 1970 s. Ally transfer reactions with allyl stannancs and the Barton-McCombic deoxygenation process with xanthates arc two examples of reactions known to involve a S[j2 mechanism. However, the first reports of addition-fragmentation transfer agents in polymerization appeared in the... 

Alternate procedures were also developed using Barton s reagent. In the first of these, coupling of the xanthate 3.1.4.3 obtained from 10-deacetylbaccatin III with protected side chain, followed by free radical deoxygenation and deprotection, gave 10-deacetoxy taxol (3.1.4.4) or 10-dehydroxydocetaxel (3.1.4.5), depending on the side-chain used (83). 

Barton s radical deoxygenation procedure has been applied to methyl xanthate derivatives of sugars to prepare methyl 2-deoxy-B-D-... 

---