Tungsten-catalyzed cycloisomerization of alkynyl alcohols including 8 provides only the endocyclic enol ether (11) as a key intermediate for the branched C-glycoside substructure (2) of altromycin B. A sequence of Stille cross-coupling reaction and regio-and stereoselective functional group transformations affords each C13-diastereomer of the branched C-arylglycoside (2a and 2b).Altromycin B (1, Figure 1), a member of the family of pluramycin antibiotics isolated from a South African bushveld soil, was first reported to have selective antibiotic activities against Gram-positive bacteria in the early 1990s and later reported to possess anticancer activity including in vivo activity against P388 leukemia, as well as colon, lung, and ovarian tumors. 1 The structure of altromycin B has been elucidated primarily by NMR spectroscopy, and thus the absolute stereochemistry of each of the widely separated chiral subunits has not been unambiguously assigned. Along with the studies on the biological activities, interactions between altromycin B with DNA 2 and its metal complex 3 have been reported. Despite the attractive biological activity of altromycin B and various congener natural products, none of the altromycin natural products have been prepared by total synthesis. Pasetto and Franck recently reported the synthesis of both possible C13 isomers (2a, 2b) of the northwest quadrant of altromycin B, beginning with D-glucose. 4 However, their efforts to assign C13 stereochemistry on the basis of the NMR comparison of their synthetic compounds 2a and 2b with altromycin B (1) were unsuccessful because of the complexity of the natural product structure. In support of our ongoing studies directed at the total synthesis of altromycins, we report herein a different synthesis of substructures 2a and 2b arising from non-carbohydrate precursors. 5Our retrosynthetic analysis of 2a and 2b ( Figure 1) envisioned a cross-coupling reaction 6 to form the C13 1,1-methylene linking the carbohydrate and aglycone sectors in 3, with the fmcdona@emory.edu Supporting Information Available: Experimental procedures and characterization data for new compounds, including data in CIF format. This material is available free of charge via the Internet at http://pubs.acs.org. carbohydrate coupling product 4 arising from the product of tungsten-catalyzed alkynol cycloisomerization of 5. 7 NIH Public AccessOur synthesis began with the known diol 6 (Scheme 1). 7a We observed regioselective formation of the methyl ether from the propargylic alcohol using cyclic stannylene activation of the diol, followed by silylation of the remaining alcohol and removal of the benzoate protective group with DIBAL reduction to afford alkynyl alcohol 7. Alternatively, protection of diol 6 with 2,2-dimethoxypropane in the presence of catalytic p-TsOH, followed by DIBAL reduction of the benzoate ester provided the cyclic acetonide-protected alkynol 8.The tungsten-catalyzed cycloisomerization was initially conducted with substrate 7 (Table 1). In contrast to other alk...

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The tungsten-catalyzed cycloisomerization of alkynyl alcohols can be conducted without using photochemistry, using a stable tungsten Fischer carbene as the precatalyst for this transformation. A variety of alkynyl alcohols undergo cycloisomerization under these conditions to provide endocyclic enol ethers of 5, 6, and 7-membered ring sizes. The utility of this method is further demonstrated in the stereoselective synthesis of the disaccharide substructure of altromycin B.The importance of cyclic enol ethers in synthetic organic chemistry has been demonstrated in several contexts, including the efficient synthesis of a variety of biologically important carbohydrate and oligosaccharide-containing natural products, in which carbohydratederived cyclic enol ethers (glycals) are valuable electrophilic partners for a variety of glycoside synthesis processes. 1 Our laboratory has developed group VI transition metalcatalyzed processes for the synthesis of structurally diverse carbohydrates arising from noncarbohydrate-derived alkynyl alcohols, which has greatly expanded the scope of available substrates for glycal-based approaches to glycoconjugate synthesis. 2 The various methods reported by our laboratory for catalytic cycloisomerization have utilized photochemical activation of molybdenum or tungsten carbonyl in the presence of a tertiary amine, with molybdenum catalysis preferred for the formation of five-membered rings 3 and tungsten catalysis proving more effective for the synthesis of six 4 -and seven-membered ring cyclic enol ethers 5 (Figure 1). However, we are aware that the requirement for photochemical activation has limited the exploration and application of this methodology to laboratories that have specialized photochemical equipment. Thus we describe herein a new catalytic system which does not require photochemical activation, based on (methoxymethylcarbene)pentacarbonyl tungsten (3) 6 as a stable and easily prepared precatalyst for the Correspondence to: Frank E. McDonald, fmcdona@emory.edu. Supporting Information Available: Experimental procedures, characterization and spectral data on new compounds. This material is available free of charge via the Internets at http://pubs.acs.org. Fischer carbene-catalyzed cycloisomerizations of alkynyl alcohols 20 with C3 and C4-oxygen substituents 9b required additional optimization relative to the photochemical procedure (Table 2), as substantial amounts of the exocyclic glycal were produced from substrate 20b. As reported by others, 15 sterically bulky propargylic substituents are required for high endo-regioselectivity, but we observed that reduced steric bulk in the O4 methoxymethyl (MOM) protective group required increasing the steric bulk at O3 to the triisopropylsilyl ether 20c to obtain good endo-regioselectivity. The formation of exocyclic glycal 22b from substrate 20b was rationalized as the action of tungsten pentacarbonyl as a Lewis acid to promote cyclization to 25 (figure 2), but increasing the steric bulk at O3 in substrate 20c would increase...

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halogen compoundshalogen compounds (benzene compounds) Q 0090 -101Bromodecarbonylation and Bromodecarboxylation of Electron-Rich Benzaldehydes and Benzoic Acids with Oxone r and Sodium Bromide. -Benzaldehydes and benzoic acids bearing o-or p-electron donating substituents having an unshared electron pair undergo a rather unexpected bromodecarbonylation or bromodecarboxylation, resp., on treatment with NaBr in the presence of Oxone r .