1 -Benzyl-2,4,5-tris- methylthio

Aus l-Benzyl-2,4,5-tribrom-irnidazol erhalt man in einer Eintopfsynthese durch Umsetzung mit zunachst zwei Aquivalenten Butyl-lithium und Dimethyldisulfan und anschlieBender noch-maliger Umsetzung mit je einem Aquivalent dieser Reagentien 1-Benzyl-2,4,5-tris-[methylthio]-imidazol (67%)1040 ... 

By careful control of metallating agent, blocking groups and reaction conditions, it is possible to make 2-alkyl(aryl)thio- and 4(5)-alkyl(aryl)thioimidazoles in high yields, e.g. l-trityl-2-phenylthio- [3], 4(5)-methylthio- [4] and l-benzyl-2,4,5-tris(methylthio)-imidazole [5]. 

A convenient base-mediated strategy to synthesize 3-aroyl-4-methyl-(or benzyl)-2-methylthio furans (tri-substituted furans) was developed through domino coupling/annulation between readily available a-oxo ketene dithioacetals and propargyl alcohols (140BC8947). 

Monomolar benzylation of methyl 2,3-di-0-benzyl-a-D-galactopyranoside in DMF gave 2,3,6-tri-O-benzyl derivative in 73% yield [52], The primary 6-benzyl ether also forms the major part of the monobenzyl fraction obtained from methyl a-D-galactopyranoside or from its p-anomer [53]. Interestingly, position 6 becomes less reactive than position 2 if 3,4-0-isopropylidene acetals is used to protect the other two secondary hydroxyl groups. The ratio of 2- and 6-benzyl ethers was found to be 11 1 in the a-anomer and 2.5 1 in the p-anomer [53] (see also, Ref. [54]). Uridine [55], cyti-dine [56], and 4-(methylthio)uridine [56] also prefer OH-2 over the primary position when benzylated in dimethyl sulfoxide (for other benzylations in this solvent, see Refs. [35, 57]). 

Abbreviations Ac acetyl Bn benzyl BSP 1-benzenesulfinyl piperidine BTIB bis(trifluoroacetoxy)iodobenzene DAST (diethylamino)sulfur trifluoride DDQ 2,3-dichloro-5,6-dicyano-/)-benzoquinone DMDO dimethyldioxirane DMTSF dimethyl(methylthio)sulfonium tetrafluoroborate DMTST dimethyl(methylthio)sulfonium triflate DTBMP 2,6-Ai-tert-butyl-4-methylpyridine DTBP 2,6-di-tert-butylpyridine DTBPl 2,6-di-tert-butylpyridinium iodide FDCPT l-fluoro-2,6-dichloropyridinium triflate FTMPT l-fluoro-2,4,6-trimethylpyridinium triflate IDCP iodonium dicollidine perchlorate IDCT idonium dicollidine triflate LPTS 2,6-lutidinium p-toluenesulfonate LTMP lithium tetramethylpiperidide Me methyl MPBT S-(4-methoxyphenyl) benzenethiosulflnate NBS A-bromosuccinimide NIS A-iodosuccinimide NlSac A-iodosaccharin PPTS pyridinium p-toluenesulfonate TBPA tris(4-bromophenyl)ammoniumyl hexachloroantimonate Tf trifluoromethanesulfonyl TMTSB methyl-bis(methylthio)sulfonium hexachloroantimonate TMU tetramethylurea Tr trityl TTBP 2,4,6-tri-tert-butylpyrimidine. 

Illustrative of the fusion method, 6-methylthio-8-azapurine and 1-0-ace-tyl-2,3,5-tri-0-benzoyl-a-D-arabinofuranose, when fused at 200 C, gave the 7-, 8-, and 9-arabinosides in 5,24, and 37% yields, respectively. A similar reaction to make the ribofuranoside benefited from the catalytic action of bis-p-nitrophenyl phosphate. In an attempt to obtain the anomer, 6-methylthio-8-azapurine and 2,3,5-tri-O-benzyl- D-arabinofuranosyl chloride were fused (120 C, 45 min). Even under these mUder conditions, much anomerization to the unwanted a isomer occurred. In a modificaction of the fusion reaction, tetra-O-acetyl-D-ribofuranose was heated with 6-nonan-oylamino-8-azapurine to give azaadenosine in 14% yield. ... 

In a third variant on this theme, methyl 3,4,6-tri-O-benzyl-l-thio-a-D-mannopyranoside is converted into a p-methoxybenzyl acetal by first etherifying the 2-OH group with p-methoxyben/yl bromide and then treating the resulting p-methoxybenzyl ether with a hydroxyl compound in the presence of 2,3 -dichloro-5,6-dicyano-l,4-benzoquinone (DDQ). Activation of the methylthio anomeric center with methyl triflate then produces the (3-D-mannopyranoside as the only possible glycoside, again because of the acceptor being tethered to the (3 side of the mannopyranoside.56... 

The alcohols used were ethanol, methyl 2,3,4-tri-O-benzyl-a-D-glucopyranoside, and 4-nitrophenylethyl 2-azido-2-deoxy-4,6-0-benzylidene-a-D-mannopyranoside. A range of promoters were tried dimethyl(methylthio)-sulfonium triflate, methyl triflate, iodonium dicollidine perchlorate, and iodonium dicollidine triflate. Yields were in the 30-70% range. 

Protected P-thioglycosides have been converted rapidly and efficiently by dimethyl (methylthio)sulfonium tetrafluoroboiate into the corresponding a-glycosyl fluorides, while tetra-0-acetyl-glucopyranosyl fluoride has been rearranged in anhydrous HF to the 2,3 5,6 diacetoxonium ion of a-D-mannofuranosyl fluoride. The synthesis of 3,4,5-tri-<9-benzyl-7-0-r-butyldiphenylsilyl-l-0-(2,2,2-triphenyl)ethyl-D-g/Mco-2-heptulopyranosyl fluoride has been described. ... 

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