Synthesis of Substituted 1‐Alkylidenephthalanes via Lithium‐Promoted 5‐exo‐dig Cyclization

A one-pot synthesis of 1-alkylidenephthalanes from 3-(2-bromophenyl)propyne derivatives has been developed. 3-(2-Bromophenyl)propynal acetals 9 and corresponding orthoester 19 were treated successively with n-butyllithium and various aldehydes and ketones at low temperature to obtain 1-alkylidenephthalanes 10 and 20 with various functional groups at the exocyclic methylene moiety. Halogen-metal exchange, nucleophilic addition to various carbonyl compounds, regioselective 5-exo-dig cyclization of the respective intermediate lithium alcoholate and hydrolysis represent the key steps in this Domino reaction. A two-step mechanism involving at first a synchronous cyclization to form a vinyllithium intermediate and then a methoxide elimination leading to the respective 1-methoxy allenes is suggested based on DFT-calculations.