Barton s procedure

Another stereospecific synthesis of2-deoxy-DL-en/tfiro-pentose was based10 on cis-l-(tetrahydropyran-2-yloxy)-2-penten-5-ol (156) as the substrate. cts-Hydroxylation of 156, followed by oxidation of the unprotected, primary hydroxyl group to an aldehyde group according to Barton s procedure, yielded the desired sugar 2 in low yield. 

In some examples, the stereochemistry of radical reactions was controlled by chiral carbohydrate auxiliaries. As a radical counterpart to the ionic conjugate additions discussed above, Garner et al. [169] prepared carbohydrate linked radicals that were reacted with a,P-unsaturated esters. The radical precursor, the carboxylic acid 256, generated by the addition of ( Sj-methyl lactate to tri-O-benzyl-D-glucal and subsequent ester hydrolysis, was decarboxylated by Barton s procedure (Scheme 10.84) [170]. Trapping of the chiral radical 258 with methyl acrylate furnished the saturated ester 259 in 61% yield and with high diastereoselectivity (11 1). The auxiliary caused a preferential addition to the si-facQ of radical 258, probably due to entropic effects. The ester 259 was transformed in acceptable yield to the y-butyrolactone 261 by reductive removal of the thiopyridyl group followed by acid hydrolysis. 

Much more critical, however, is the introduction of the 2 -deoxy function. This can be achieved after selective 3 -0-benzoylation to 170, xanthation at the 2 position to 171 and reductive cleavage (Bu3SnH) to 172 following Barton s method [91]. Further radical ring opening by the Hullar-Hanessian procedure and final reduction leads to the D-C disaccharide 173 [92],... 

Cubane- 1,2-dicarboxylic acid 12 (see Fig. 2.19), a precursor for 1,2-dihalocubanes was prepared from commercially available cubane-1,4-dicarboxylic acid in 65% yield. The other acids 14a and 14c were similarly prepared from the cubane-l,4-dicarboxylic acid 14b according to the literature procedures. 1H NMR spectra of the compound 13a showed a broad singlet at 4.41 for the clibyl protons, whereas compound 13b showed two multiplets. Conversion of bridgehead carboxylic acids to the corresponding halides using Pb(OAc)4 and iodine in refluxing benzene under illumination is reported. This is considered to be an alternative to Barton s method, because of its simplicity and ease of preparation, but it involves toxic lead compounds. 

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. 

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. 

A construction of the carbazole framework involving copper(ll)-catalyzed aryla-mine arylation and palladium(ll)-mediated oxidative cyclization has been reported by Menendez et al. (Scheme 41) [190, 191]. The diarylamines 95 were obtained by copper(ll) acetate-catalyzed N-arylation of arylamines 31 with phe-nyllead triacetate (183) using Barton s conditions [192]. Subsequent oxidative cyclization using palladium(ll) acetate under microwave irradiation afforded the carbazoles 32. This procedure was applied to the synthesis of murrayafoline A (188) [190]. 

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-... 

Further modifications and applications of Barton s radical deoxygenation procedure have been reported. The use of l,l -thio-carbonyldi-2,2 -pyrldone has been promoted for derivatizlng secondary hydroxy groups, since the blproduct in the subsequent reduction (with Bu SnH-AIBN) is the neutral and water soluble 2-pyrldone. In this way dlacetoneglucose was converted to the thlono ester (6) and... 

New methods have been reported for the deoxygenation of carbohydrate derivatives. One such procedure reported by Barton s group has been noted in Chapter 6 (see Scheme 25). This group has also shown that ring-opening reactions of diol thiocarbonates can be usefully applied to the synthesis of 6-deoxy-sugars (Scheme 75) 374 Thus, the diol thiocarbonate (201) was transformed into the iodo-thio-... 

In 1983, Barton et al. described a new procedure for the oxidation of saturated hydrocarbons [1] by the use of metallic iron, adamantane, hydrogen sulfide or sodium sulfide, pyridine, acetic acid and a small amount of water. The reactions were run under air and afforded adamant-l-ol together with a mixture of adamant-2-ol and adamantanone. The substrate scope could be extended to other hydrocarbons. However, all of them led to product mixtures of the corresponding alcohol(s) and ketone (Scheme 3.1). 

The Ireland s)mthetic intermediate 176 was deoxygenated by the Barton procedure to provide 194 (O Scheme 22). Stepwise deprotection and protection of hydroxy groups in 194 afforded 195. De-O-tritylation and Swem oxidation of 195 gave the C10-C15 segment 192. As shown in Scheme 22, this aldehyde was transformed into the C10-C20 segment 197. 

Sharpless s successful use of his chiral epoxidation technology has been discussed in Section 2, Scheme 2,15. Using the Sharpless procedure, Corey, Hashimoto, and Barton also described an analogous, though somewhat longer. 

The introduction of 0-acyl thiohydroxamates (mixed anhydrides of carboxylic acids with thiohydroxamic acids) by the Barton group in 1983 [1] has provided one of the mildest and most convenient and versatile sources of carbon-centered radicals which fulfill the above criteria, and can hence, in Sir Derek s own words, be described as disciplined . Since their preparation from carboxylic acids is extremely straightforward, and since they have demonstrated a rapacious radicophilicity in a wide variety of very useful transformations, it is no surprise that these derivatives are commonly named either as Barton esters or by the acronym PTOC (pyridine thiocarbonyl) esters. The ongoing development of this chemistry has been summarized over the years in several useful reviews [2], and some of the tried and tested experimental procedures have also been collated [3]. 

Since we have emphasized second-order perturbation theory in this section, it might be useful to point out that the effect of the Bi j i(s) nonadiabatic coupling elements could also be included by second-order perturbationtheory, using a procedure analogous to that of Barton and Howard.87... 

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