Functionalised Bicyclic exo-Glycals by Alkynol Cycloisomerisation of Hydroxy 1,3-Diynes and Hydroxy Haloalkynes

• Published in: Helvetica chimica acta 2005-07, Vol.88 (7), p.1885-1912
• Main Authors: Miao, Zhiwei, Xu, Ming, Hoffmann, Barbara, Bernet, Bruno, Vasella, Andrea
• Format: Article
• Language: English
• ISSN: 0018-019X; 1522-2675
• DOI: 10.1002/hlca.200590145

Functionalised bicyclic exo‐glycals are readily obtained by base‐catalysed (typically MeONa in MeOH) alkynol cycloisomerisation of ethynylated cyclic saccharides. Thus, base treatment of the phenylethynyl‐ and halogenoethynylated 1‐O‐acetyl‐ribofuranoses 22–24 and the 4‐ethynylated 1‐thioglucopyranosides 30–33 gave – after deacetylation – selectively the (Z)‐configured exocyclic enol ethers 26–28 (84–91%) and 34–37 (63–76%), respectively, resulting from a trans‐5‐exo‐dig cyclisation. The ring closure to the trans‐dioxahexahydroindans 34–37 is favoured by a concerted intramolecular protonation of the intermediate vinyl anion by the neighbouring HOC(3). Cycloisomerisation of the 6‐O‐acetyl‐4‐(phenylethynyl)‐1‐thio‐α‐D‐glucopyranoside 39 occurred via the corresponding phenylethynylated allenes to provide the galacto‐configured (Z)‐ and (E)‐cis‐dioxahexahydroindans 40 (30%) and 41 (51%). Surprisingly, the HOC(4) unprotected α‐d‐galactopyranosyl‐buta‐1,3‐diyne 15 and the β‐D‐glucopyranosyl‐buta‐1,3‐diyne 51 (and its 2‐bromoethynyl analogue) undergo a 6‐exo‐dig ring closure to the 2,5‐dioxabicyclo[2.2.2]octanes 16–19 and 52/53, respectively, the ring closure requiring a boat conformation (B1,4 for 15, 1,4B for 51). Ring strain (anti‐reflex effect) prevents an alkynol cycloisomerisation of 4‐(phenylbuta‐1,3‐diynyl, bromoethynyl, or iodoethynyl)levoglucosan 56–59, and 56 reacted by elimination to the hex‐1‐ene‐3,5‐diyne 59 (82%), while isomerisation of 57 and 58 led to epimeric mixtures of the haloallenes 60 (82%) and 61 (68%).