Optimization. Interestingly, 2-oxabicyclo[2.2.2]octane core was known in the literature before. Chemists used it as a starting material in organic synthesis, and even in medicinal chemistry 26 as an analogue of 4-aminopiperidine 27 or cyclohexane. Preparation of 2-oxabicyclo[2.2.2]octane was also reported. In 2014, Singh and Fukuda obtained compound 2 from diethyl malonate (1) in 15 steps using alkylation as a key reaction (Scheme 2). In 2019, Harrison synthesized compound 4 from ester 3 already in six steps employing an intramolecular Michael addition. The latter approach was limited only to aromatic substituents. We, however, needed a general modular method that would give 2-oxabicyclo[2.2.2]octanes with two functional groups that could be subsequently modified to obtain a wide variety of derivativesbioisosteres of para-substituted benzenes.