One-step Spiroannulation Using 1,2-Bis(methylene)cycloalkane-Magnesium Reagents

Article abstract of DOI:10.1021/jo00050a036

A one-step method for the synthesis of a wide variety of spirocyclic systems has been developed based on the reactions of bis-electrophiles with a series of new 1,3-diene-magnesium reagents, the magnesium complexes of 1,2-bis(methylene)cycloalkanes.The direct metalation of 1,2-bis(methylene)cycloalkanes with highly reactive magnesium in THF at ambient temperatures generates the corresponding diene-magnesium reagents in high yields.Reactions of the diene-magnesium reagents with 1,n-dibromoalkanes produce a large number of spirocarbocycles containing an exocyclic double bond.The ring sizes of the accessible spiro compounds can be any combinations of four- to seven-membered rings.In most cases, the initially alkylated intermediates can be trapped by protonation, giving the corresponding bromo olefins.Significantly, treatment of the diene-magnesium reagents with bromoalkyl nitriles leads to a one-step synthesis of keto-functionalized spirocycles.The initial adduct is believed to be a Grignard reagent containing a cyano group.When a bromo nitrile containing a cyclic moiety is used as the bis-electrophile, the approach provides a direct access to dispiroenones.