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

Abstract 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)