Despite tremendous progress of dienamine catalysis along with its application in enantioselective synthesis over nearly two decades, certain limitations, especially with respect to the regioselectivity in the dienamine generation step, continue to persist. To overcome these shortcomings of classical dienamine catalysis, we now introduce the concept of alkoxy-directed dienamine catalysis and apply it to the enantioselective de novo arene construction by desymmetrizing meso-enediones through [4 + 2]-cycloaddition. Catalyzed by a diphenylprolinol silyl ether, this reaction utilizes γ-alkoxy α,β-unsaturated aldehydes as the substrate and proceeds in a highly regioselective fashion through the intermediacy of δ-alkoxy dienamine. Besides carrying out mechanistic elucidation through density functional theory (DFT) calculation, the utility of this newly developed strategy is demonstrated for the concise enantioselective synthesis of a benzo-analogue of the natural ladderane phospholipid component (+)-[3]-ladderanol. Designed as a functional analogue of natural [3]-ladderanol, this unnatural benzo-[3]-ladderanol was found to impart lower proton permeability and higher stability to the membrane compared to its natural counterpart.