Asymmetric Aldol−Ring-Closing Metathesis Strategy for the Enantioselective Construction of Six- to Nine-Membered Oxygen Heterocycles

摘要: The ring closing metathesis reaction has rapidly become an important transformation in organic synthesis.1 Examples of many sizes with a variety functional appendages2 have been constructed by this powerful method, largely because the advent functionally tolerant ruthenium3 and molybdenum4 carbene complexes. Even kinetically thermodynamically disfavored eight-membered rings prepared ringclosing metathesis. However, virtually all5 successful closures required incorporation cyclic conformational constraints6 or rigid acyclic control elements to avoid formation dimers oligomers.7 It is noteworthy that constrained dienes underwent more efficient form when two olefinic chains were positioned trans on constraint than they cis.7 Grubbs6a attributed effect greater difference energy between diene olefin cissubstituted substrate. We reasoned appropriate bias might allow eight (or nine)-membered additional strain imposed fused attached newly formed olefin. recently reported asymmetric aldol-ring-closing strategy for enantioselective synthesis carbocyclic fragment nucleoside analogue 1592U89.8 In view importance approaches ethers all sizes, particularly eightand nine-membered metabolites are abundant marine algae,9 extension aldol-metathesis oxygen heterocycles seemed order. report here efficient, general sixto ethers.10