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Incorporating enzymatic reactions into natural product synthesis can significantly improve synthetic efficiency and selectivity. In contrast to the increasing applications of biocatalytic functional‐group interconversions, the use of enzymatic C−C bond formation reactions in natural product synthesis is underexplored. Herein, we report a concise and efficient approach for the synthesis of [7.7]paracyclophane natural products, a family of polyketides with diverse biological activities. By using enzymatic Friedel–Crafts alkylation, cylindrocyclophanes A and F and merocyclophanes A and D were synthesized in six to eight steps in the longest linear sequence. This study demonstrates the power of combining enzymatic reactions with contemporary synthetic methodologies and provides opportunities for the structure–activity relationship studies of [7.7]paracyclophane natural products. [ABSTRACT FROM AUTHOR]