Hydroformylation of m-diisopropenylbenzene and 1-isopropyl-3-isopropenylbenzene for the preparation of the fragrance Florhydral®

An hydroformylation-based approach to the synthesis of the odorant Florhydral® has been investigated. The hydroformylation of m-diisopropenylbenzene (2) in the presence of rhodium catalysts leads to mixtures of 3-(3-isopropenylphenyl)butyraldehyde (3), which is an immediate precursor of Florhydral® and of the dialdehyde 3-[3-(1-methyl-3-oxopropyl)phenyl]butyraldehyde (4), which is a useless side product. The 3/4 ratio is dependent on the substrate conversion: when it is pushed over 40%, the formation of 4 becomes increasingly important. Interestingly, the reaction can be carried out in aqueous biphasic systems using a rhodium catalyst precursor either in the presence of sulphonated triphenyl phosphine or human serum albumin (HSA) as the ligands. Good results were also obtained using rhodium complexes immobilized on silica; in this case it was possible to exclusively obtain the sought aldehyde 3 by limiting the substrate conversion at about 41%.As an alternative approach, 1-isopropyl-3-isopropenylbenzene (8) was synthesized and hydroformylated. In both homogeneous and biphasic systems, in the presence of rhodium catalysts, the reaction leads to the formation of Florhydral® with high reaction rates and complete chemo- and regioselectivity. The use of chiral phosphino ligands, in order to obtain enantiomerically enriched Florhydral®, gave very poor ees.

Graphical abstractThe rhodium catalyzed hydroformylation of 2 affords a mixture of aldehyde 3, a precursor of the valuable fragrance Florhydral®, and 4. The formation of the useless dialdehyde 4 becomes increasingly important at substrate conversions higher than 30%. Alternatively, the hydroformylation of olefin 8 is chemo- and regioselective affording Florhydral® in almost quantitative yield. Figure optionsDownload full-size imageDownload as PowerPoint slide