Glyconothio-O-lactones Part II. Cycloaddition to Dienes,Diazomethane, and Carbenoids

The addition of dienes, diazomethane, and carbenoids to the manno- and ribo-configurated thio-γ-O-lactones 1 and 2 was investigated. Thus, 1 (Scheme 1) reacted with 2,3-dimethylbutadiene (→ 4 , 73%), cyclopentadiene (→ 5a/b 1:1, 70%), cyclohexa- 1,3-diene (→ 9a/b 2:3, 92%), and the electron-rich butadiene 6 (→ 7a/b 3:1, 82%). Wheras 5a/b was separated by flash chromatography, 7a/b was desilylated leading to the thiapyranone 8 . Selective hydrolysis of one isopropylidene group of 9a/b and flash chromatography gave 10a and 10b . The structures of the adducts were elucidated by X-ray analysis ( 4 ), by NOE experiments ( 4 , 5a , 5b , 7a/b , 10a , and 10b ), and on the basis of a homoallylic coupling ( 7a/b ). The additions occurred selectively from the ‘exo’ -side of 1 . Only a weak preference for the ‘endo’-adducts was observed. Hydrogenation of 9a/b with Raney-Ni (EtOH, room temperature) gave the thiabicyclo 2.2.2]octane 11 . Under harsher conditions (dioxane, 110°), 9a/b was reduced to the cyclohexyl ß-D C-glycoside 12 which was deprotected to 13 . X-Ray analysis of 13 proved that the desulfuration occurred with inversion of the anomeric configuration. The regioselective addition of the dihydropyridine 14 to 1 (Scheme 2) and the methanolysis of the crude adduct 15 gave the lactams 16a (32%) and 16b (38%). Desilylation of 15 with Bu₄NF · 3H₂O, however, gave the unsaturated piperidinedione 17 (92%) which was deprotected to the tetrol 18 (65%). Similarly, 2 was transformed via 19 (62%) into the triol 20 (74%). The cycloaddition of 1 with CH₂N₂ (Scheme 3) gave a 35:65 mixture of the 2,5-dihydro- 1,3,4-triazole 21 and the crystalline 4,5-dihydro 1,2,3-triazole 22 . Treatment of 21 and 22 with base gave the hydroxytriazoles 23 and 24 , respectively. The structure of 24 was established by X-ray analysis. The triazole mixture 21/22 was separated by prep. HPLC at 5°. At room temperature, 21 already decomposed (half-life 21.6 h) leading in CDCI₃ solution to a complex mixture (containing ca. 20–25% of the spirothiirane 27 and ca. 7–10% of its anomer) and in MeOH solution exclusively to the O,O,S-ortholactone 26 . Crystals of 22 proved be stable at 105°. Upon heating in petroleum ether at 100°, 22 was transformed into a ca. 1:1 mixture of 27 and the enol ether 28 . The reaction of 1 with ethyl diazoacetate (Scheme 4) in the presence of Rh₂(OAc)₄. 2H₂O gave the unsaturated esters 29 (33%) and 30 (26%), whereas the analogous reaction with diethyl diazomalonate afforded the spirothiirane 31 (68%) and the enol ether 32 (29%). Complete transformation of 31 into 32 was achieved by the treatment with P(NEt₂)₃. Similary, 33 (69%) was prepared from 2 .