Two Contrasting Asymmetric Approaches to Muscarine Based on 5‐ endo ‐trig Cyclisations

5‐ endo ‐trig cyclisation of the ( Z )‐hydroxyalkenoate 17 using iodine as the electrophile gave a good yield of the β‐hydroxytetrahydrofuran 18 , probably via the corresponding iodohydrin. A variety of one‐carbon degradation methods were then used to generate precursors to (−)‐muscarine ( 25d ). An alternative strategy featured control of a 5‐ endo ‐trig iodocyclisation by an allylic hydroxyl group, which can be used for the highly stereocontrolled synthesis of hydroxy‐iodotetrahydrofurans 28 . Application of this strategy to the ( Z )‐alkenediol derivative 38 led to an excellent yield of the tetrahydrofuran 39 when iodine monobromide was used as the electrophile. Two simple and efficient transformations then gave the (+)‐muscarine precursor 40b . (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)