Metallated 2-Alkenyl Sulfoximines in Asymmetric Synthesis: Regio- and Stereoselective Synthesis of Highly Substituted Oxabicyclic Ethers and Studies Towards the Total Syntheses of the Euglobals G1 and G2 and Arenaran A

Abstract

2‐Cyclopentenyl‐ and 2‐cyclohexenylmethyl sulfoximines can be converted into angular carbon‐functionalised, highly substituted, isomerically pure (ds ≥ 98%) 2‐oxabicyclo[3.3.0]octanes and 2‐oxabicyclo[3.4.0]nonanes in high yields by a convenient one‐pot sequence. Molecular frameworks such as these can be found in many biologically active natural products. In addition to the methodological work, we report on studies towards the total synthesis of the euglobals G1 and G2 and arenaran A.

The Julia Reaction

“…These allylic anions can lead to either aor g-adducts. The regio-and diastereocontrolled formation of g-addition products has been reported by Reggelin et al [176][177][178][179], and Gais elegantly extended this methodology to the preparation of a-hydroxy-sulfoximines.…”

Preparation of oxocene terpenes. The first enantiospecific synthesis of cytotoxic arenaran A

“…These considerations, together with the possibility of preparing large quantities of arenaran A (1) in order to conduct an in-depth study of its biological activity, encouraged us to develop a synthetic route to compound 1 and related terpenes. In this respect, the only relevant antecedent is a study aimed at the synthesis of arenaran A reported by Reggelin et al 3 These authors essayed the construction of the bicyclic oxocene structure of 1 based on the intramolecular attack of an allyl alcohol on an alkenyl sulfoximine. The failure of their attempt highlights the difficulty in forming an eight-membered ring.…”

2-Hydroxy-4,6-dimethoxy-3-(3-methylbutanoyl)benzaldehyde

“…The title compound, (I), was obtained by a Friedel±Crafts acylation reaction of 4,6-dimethoxysalicylaldehyde with 3-methylbutyric acid chloride (Reggelin et al, 1999). Only one of two possible regioisomers was obtained.…”