Preparation dithioacetal, oxidation

MacDonald and H. O. L. Fischer372 oxidized D-glucose diethyl dithioacetal pentaacetate (24) and its D-manno isomer with mono-peroxyphthalic acid in ether, isolating not the epimeric disulfones but a common product, to which they assigned the structure 3,4,5,6-tetra- O - acetyl -1,2- dideoxy-1,1 -bis (ethylsulfonyl)-D-arabtno-hex-1-enitol (176). Ammonolysis of 176 and reacetylation afforded 177, which was also prepared by oxidation of 2-acetamido-3,4,5,6-tetra-0-acetyl-2-deoxy-D-glucose diethyl dithioacetal, whereas the action of hydrazine in methanol on 176 produced a retroaldol reaction (and saponification) affording D-arabinose (179, 40% yield) and bis(ethyl-sulfonyl)methane (178). The latter reaction accords with earlier ob-... 

D-Arabinose 88 l-Deoxy-l,l-bis(ethylsulfonyl)-D-mannitol (1 g) (prepared by oxidation of D-mannose diethyl dithioacetal with peroxypropionic acid in dioxan) is made into a slurry with water (10 ml), and then concentrated aqueous ammonia solution (1 drop) is added. The sulfone dissolves rapidly and after 30 min the precipitated diethyl methylene disulfone is filtered off. The filtrate is extracted four times with chloroform (10-ml portions), and the aqueous phase is evaporated in a vacuum at 40°. The residue is treated with hot methanol (5 ml) and after being kept for 24 h at 4° affords / -D-arabinose (0.32 g, 86%), [a]D20 —102° (c 3.5 at equilibrium in water). 

Oxidation of cyclic phosphonoformaldehyde dithioacetal, using the Modena protocol, yields the trans disulfoxide 121 in excellent enantiomeric excess. Then 121, via HWE olefination and oxidation of the double bond has been used for the diastereoselective preparation of spirocyclic his-sulfinyl oxiranes (new versatile intermediates in asymmetric synthesis) [79] (Scheme 37). 

Triazoline imino sugar derivatives 297 that are prospective glycosidase inhibitors have been prepared as single diastereomers in high yield via an lAOC reaction of in situ generated azido alkene 296 (Eq. 32) [78]. m-CPBA oxidation of the dithioacetal groups in the 0-acetylated 5-azido-5-deoxydibenzyl dithio-acetal of o-xylose or D-ribose 294 to the bis-sulfone 295, followed by loss of HOAc between C-1 and C-2 provided the lAOC precursor 296. 

These problems were circumvented by protecting the C(4),C(5) diol prior to Wittig olefination step (Figure 3). Thus, treatment of 10b (a mixture of pyranose and furanose anomers prepared by hydrolysis of 8 with aqueous trifluoroacetic acid) with excess EtSH and concentrated HCI (as solvent) at provided dithioacetal 9 in 50% yield, along with 25% of a mixture of thiopyranosides and thiofuranosides that was recycled to 10b in high yield by treatment with HgCIa and CaCOa in aqueous CH3CN. Finally, the diol unit was protected as a cyclohexylidene ketal, and then the thioacetal was hydrolyzed under oxidative conditions to arrive at the key aldehyde intermediate 3. 

The second route involves the palladium catalyzed coupling of iodoaniline 51 with the acyl silane 54 in the presence of DABCO to give the 2-trimethylsilyl indole 55. The acyl silane 54 was prepared by alkylation of 1,3-dithianyl-trimethylsilane with (3-bromopropyl)-dimethylamine to give 56, followed by removal of the dithioacetal with mercuric oxide and mercuric chloride. Finally, desilylation of 55 in aqueous HCl and methanol afforded rizatriptan (4). 

The orf/to-formylation of 2-aminopyridines can be effected via the rearrangement of the azasulfonium salt prepared from a 2-aminopyridine, 1,3-dithiane, f-butyl hypochlorite and sodium methoxide (74CC685). The crude sulfilimine (815) was refluxed in f-butanol containing potassium f-butoxide to yield the dithioacetal (816). Hydrolysis of (816) with mercury(II) oxide/boron trifluoride etherate gave the aldehyde (817 Scheme 191). This method should be applicable to the formylation of other heterocyclic amines. 

Wolfrom and coworkers88-71 were able to prepare various 1-thio-a-D-galactofuranosides, generally isolated as the acetates, after purification by column chromatography. Thus, the Pacsu and Wilson method gave sirupy ethyl 1-thio-a-D-galactofuranoside, and a crystalline acetate. This product was also obtained by treatment of the dithioacetal with dilute hydrochloric acid and then mercuric oxide. Ethyl 2-acetamido-2-deoxy-l-thio-a-D-galactofuranoside was prepared in 32% yield, and the /3-d anomer in 3% yield. 

Whereas ethyl l-thio-d-D-arabinofuranoside cannot be prepared directly, the 5-O-benzoyl diethyl dithioacetal gave 38% of ethyl 5-O-benzoyl-l-thio-0-D-arabinofuranoside, which was debenzoylated to the desired product. The 5-benzoate of ethyl 1-thio-a-D-ribofuranoside was similarly prepared.88 Two other compounds, ethyl 2-acetamido-2-deoxy-l-thio-/3-L-arabino-furanoside72 and ethyl 2-acetamido-2-deoxy-l-thio-a-D-xylofuranoside,73 were prepared from the corresponding d-galacto and d-gluco analogs by periodate oxidation, and subsequent borohydride reduction of the product. 

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