Oligosaccharide Analogues of Polysaccharides. Part 9. Synthesis and Thermolysis of Acetylenosaccharide-Derived 1,2-Dialkynylbenzenes

Thermolysis of the 1,2-bis(glucosylalkynyl)benzenes 6 and 16 was studied to evaluate the effects of intramolecular H-bonding on the activation energy of the Bergman-Masamune-Sondheimer cycloaromatization, and to evaluate the use of the cycloaromatization for the synthesis of di-glycosylated naphthalenes. The dialkynes were prepared by cross-coupling of the O-benzylated or O-silylated glucosylalkynes 1 and 4 (Scheme 1). Thiolysis of the known 1 , or acetolysis of 1 , followed by deacetylation ( →2→3 ) and silylation gave 4 . Cross-coupling of 1 or 4 with iodo- or 1,2-diiodobezene depended upon the nature of the added amine and on the protecting group, and led to the mono- and dialkynylbenzenes 5 and 6 , or 12, 13 , and 15 , respectively. The benzyl ethers 5 and 6 gave poor yields upon acetolysis catalyzed by BF₃ · OEt₂, while Ac₂O/CoCl₂ · 6 H₂O transformed 6 in good yields into the regioselectively debenzylated 10 . Desilylation of 7 and 13 gave the alcohols 8 and 14 , respectively. Thermolysis of 6 in PhCl gave 22 and 23 , independently of the presence or absence of 1,4-cyclohexadiene; 23 was formed from 22 (Scheme 2). Acetolysis of 22 gave the hexaacetate 24 that was completely debenzylated by thiolysis, yielding the diol 26 and trans-stilbene, evidencing the nature and position of the bridge between the glucosyl moieties (Scheme 3). Thiolysis of 22 yielded the unprotected 2,3-diglucosylnaphthalene 28 , a new type of C-glycosides. Depending upon conditions, hydrogenation of 22 led to 29 (after acetylation), 30 , or 32 . NMR and particularly NOE data evidence the threo-configuration of the bridge. The structure of 23 was confirmed by hydrolysis to the diol 34 and diphenylacetaldehyde, and by correlation of 23 with 22 via the common product 31 . Formation of 22 is rationalized by a Bergman cyclization to a diradical, followed by regioselective abstraction of a H-atom from the BnO? C(2) group, and diastereoselective combination of the doubly benzylic diradical (Scheme 4). While thermolysis of 3 in EtOH sets in around 140°, 16 did not react at 160° and decomposed at 180–220°. No evidence for intramolecular H-bonds of 16 , as compared to 14 , were found.