Conventional solid phase organic synthesis (SPOS) involves covalent attachment of substrates to an insoluble matrix, from which after the reaction cycles products are released by the chemoselective cleavage of a linker moiety. The major problem of this technology is the difficulty of analytical characterization (and impossibility of purification) of synthetic intermediates. Herein I describe the developed of a novel strategy to overcome the problems of SPOS by the freely reversible attachment of substrates to a solid matrix. The concept relies on the fact that anchoring of substrates by hydrophobic interactions can be controlled by solvent polarity. Substrates immobilized to a hydrophobic matrix by a hydrophobic anchor unit in a highly polar, protic solvent (e.g., water) can be released by simple switching to a nonpolar organic solvent. Additionally, total recovery of supports (matrix and anchor) is facile and efficient (Sustainable SPOS). Further motivation came from environmental and economic considerations (“green chemistry”) with further development of catalytic and asymmetric reactions. We have realized the concept by using common commercial reversed-phase silica gel (RP) as the matrix. As exemplary anchors, N-alkylated acridone derivatives were established. The advantages of acridone as tag, besides its hydrophobic nature, are its bright fluorescence. Thus, rapid sensitive screening of reactions by TLC (detection limit ca. 1 pmol) can be performed with very small amounts of material. As for our reversible attachment principle, I have investigated a number of such reaction types that are compatible with aqueous conditions (e.g. Diels-Alder reactions, 1,3-cycloadditions, aldol, Michael, allylation and Pd-catalyzed conversions) towards the new strategy and therefore prove of the concept for the reversible solid phase syntheses principle.