GLYCONOTHIO-O-LACTONES .2. CYCLOADDITION TO DIENES, DIAZOMETHANE, AND CARBENOIDS

被引:16
作者
HURZELER, M
BERNET, B
MADER, T
VASELLA, A
机构
[1] F HOFFMANN LA ROCHE & CO LTD,CH-4002 BASEL,SWITZERLAND
[2] UNIV ZURICH,INST ORGAN CHEM,CH-8057 ZURICH,SWITZERLAND
关键词
D O I
10.1002/hlca.19930760434
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
The addition of dienes, diazomethane, and carbenoids to the manno- and ribo-configurated thio-gamma-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 stuctures 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-degrees), 9a/b was reduced to the cyclohexyl beta-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-degrees. At room temperature, 21 already decomposed (half-life 21.6 h) leading in CDCl3 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-degrees. Upon heating in petroleum ether at 100-degrees, 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 Rb2(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. Similarly, 33 (69%) was prepared from 2.
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页码:1779 / 1801
页数:23
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