Calix[4]arenes with four different “lower rim” substituents were synthesized following six-stepsequences. The first alkyl group (R1) was introduced using R1X and CH3ONa, and then reactionwith R2X and K2CO3 led to the introduction of a second alkyl group (R2) at the 3-position. Benzoatewas introduced as a protecting group at the 1,3-O-disubstituent stage and was removed underbasic conditions after the incorporation of the third alkyl group (R3) with R3X and NaH. The finalalkyl group (R4) was introduced with R4X and NaH to give the chiral title compounds.