| Rhodium catalyzed asymmetric hydroformylation (AHF) generates chirality and a versatile functional group in a single atom-economic reaction, yet remains underutilized in the synthesis of fine chemicals and pharmaceuticals. Bis-3,4-diazaphospholanes have already been demonstrated as highly selective and active ligands for this process with a range of substrates. However, continued improvements to these ligands expand the scope of substrates, allow for rapid optimization with new substrates, and facilitate the development of industrial-scale processes. This work describes the synthesis of a library of bisdiazaphospholanes, immobilization on solid supports to facilitate recycling, and synthesis of primary phosphines to develop bisdiazaphospholanes containing additional electron withdrawing groups. In order to improve optimization of AHF reactions, libraries of easily synthesized bisdiazaphospholanes are required. A tetraacyl fluoride bisdiazaphospholane was prepared which can be used to generate previously examined as well as previously inaccessible tetracarboxamide bisdiazaphospholanes. This library was applied to the hydroformylation of vinyl acetate, styrene, allyloxy-t-butyldimethylsilane, (E)-1-phenyl-1,3-butadiene, 2,3-dihydrofuran, and 2,5-dihydrofuran. Tertiary carboxamide bisdiazaphospholanes synthesized for this library allowed for AHF of 2,3- and 2,5-dihydrofuran with simultaneously high rates and selectivities. Bisdiazaphospholanes that demonstrated high selectivity were then immobilized on resin supports via the same amide coupling method used to generate the previous ligand library. Bisdiazaphospholanes immobilized on Tentagel resins give selectivities similar to the homogenous catalyst and show similar reactivity trends for styrene and 2,3-dihydrofuran AHF. While the activities of the immobilized catalyst are three to four times slower compared to the homogenous catalyst, they can be recycled without loss of selectivity and minimal rhodium leaching, ultimately leading to higher productivity. The immobilized bisdiazaphospholanes were used in a plug flow reactor with similar selectivity and recyclability as in batch reactors. Attempts to synthesize bisdiazaphospholanes with a fluorinated backbone were carried out using tetrafluorobisphosphinobenzene. The synthesis of tetrafluorobisphosphinobenzene was performed using phenylsilane as a safe alternative to lithium aluminum hydride. Unfortunately, purification of the desired primary phosphine was low yielding and could not be improved. NMR analysis indicates that the desired bisdiazaphospholanes could be generated using standard procedures, but these new ligands have not yet been applied to hydroformylation. |
