875140-33-3Relevant academic research and scientific papers
Functionalised monocyclic five- to seven-membered exo-glycals by alkynol cycloisomerisation of hydroxy buta-1,3-diynes and 1-haloalkynols
Xu, Ming,Miao, Zhiwei,Bernet, Bruno,Vasella, Andrea
, p. 2918 - 2937 (2007/10/03)
Base-promoted (KOH or MeONa in MeOH, or NaH in THF) Cycloisomerisation of partially benzylated, 1-substituted (R = Ph-C≡C, pyridin-2-yl, or Br) ald-1-ynitols leads to (Z)-configured five-, six-, and seven-membered exo-glycals. The reactivity of the ald-1-ynitols depends upon their configuration. The ald-1-ynitols were derived from 2,3,5-tri-O-benzyl-D- ribofuranose 1, and the corresponding, partially O-benzylated galactose, glucose, and mannose hemiacetals by ethynylation. The hex-1-ynitol 2 derived from 1 (61%) was transformed via the 1-phenylbuta-1,3-diyne 3 and the 1-(pyridin-2-yl)acetylene 5 into the five-membered exo-glycals 4 and 6 (in 66 and 72% yields, resp., from 2). The analoguous ethynylation of 2,3,4,6-tetra-O-benzyl-D-galactose 8 was accompanied by elimination of one benzyloxy (BnO) group to the hept-3-en-1-ynitol 9 (71%), which was transformed into the non-5-ene-1,3-diynitol 10 and further into the six-membered exo-glycal 11 (50% from 9). Addition Of Me3SiC≡CH to the galactose 8 and to the gluco- and manno-analogues 16 and 24 gave epimeric mixtures of the silylated oct-1-ynitols (86% of 12L/12D 45:55, 94% of 17L/17D 7:3, and 86% of 25L/25D 55:45), which were separated by flash chromatography, and individually transformed into the corresponding 1-bromooct-1-ynitols. Upon treatment with NaH in THF, only the minor epimers 13L, 18D, and 26D cyclised readily to form the seven-membered hydroxy exo-glycals. They were acetylated to the more stable monoacetates 14L, 23D, and 28D (82-89% overall yield). Under the same conditions, the epimers 13D, 18L, and 26L decomposed within 12 h mostly to polar products. The difference of reactivity was rationalised by analysing the consequences of an intramolecular C(3)O-H ...-OC(7) H-bond of the intermediate alkoxides on the orientation of -O-C(7) of 13L, 18D, and 26D and its proximity to the ethynyl group.
