(DHQD)₂PHAL – Dihydroquinidine 1,4-phthalazinediyl diether (CAS-No. 140853-10-7)

The well-known Cinchona alkaloid Dihydroquinidine based dimer (DHQD)₂PHAL (CAS. No. 140853-10-7)  as well as the Dihydroquinine based dimer (DHQ)₂PHAL (CAS No. 140924-50-1)  have been shown to be highly efficient and broadly applicable chiral catalysts for asymmetric reactions. The reactions can be performed in a operationally simple manner, and afford the desired products in high yields with good to excellent enantioselectivities. Typical applications of the chiral Cinchona alkaloid dimer catalysts are for example: allylation, amination, bromohydroxylation, bromoesterfication, bromination, chlorination, dichlorination, dihydroxylation, dithiotrifluoromethylation, fluorination, halolactonization, haloetherfications, kinetic resolution, lactonization, Mannich reaction, Michael, sulfenylation, trifluoromethylation.

Application in Asymmetric Dihydroxylation

Asymmetric Dihydroxylation of olefins is of high synthetic value because it introduces two vicinal hydroxy groups, endowing prochiral olefinic carbon(s) with chirality. Some oxo metal species of high valency, such as permanganate, ruthenium tetroxide, and osmium tetroxide undergo stereospecific cis-dihydroxylation. Among them, the osmium-mediated dihydroxylation is highly chemoselective and can be applied to a wide range of olefins. Thus, osmium-mediated asymmetric dihydroxylation has been extensively studied.

Sharpless and co-workers reported that dihydroxylation was catalytically effected, with good enantioselectivity and remarkable ligand acceleration, when Cinchona Alkaloid ligands based on DHQD or DHQ was used as the chiral auxiliary.

In this methodology, a chiral vicinal diol moiety is obtained by the reaction of an alkene with osmium tetroxide in the presence of an optically active Cinchona alkaloid ligand. Dimeric Cinchona alkaloids are employed as asymmetric ligands for the efficient synthesis of vicinal diols. K₂OsO₂(OH)₄, K₂CO₃, (DHQD)₂PHAL or (DHQ)₂PHAL, and K₃Fe(CN)₆ were found to be mandatory chemical substances for carrying out Sharpless asymmetric dihydroxylation. The mixture of these four reagents is referred to as “AD-mix”. The (DHQ)₂PHAL-containing mixture is termed “AD-mix-α”, while “AD-mix-β” includes (DHQD)₂PHAL as a ligand. The asymmetric dihydroxylation has found tremendous applications in the synthesis of a variety of fine chemicals and biologically active compounds.

More than 60 chiral application examples of (DHQD)₂PHAL and (DHQ)₂PHAL can be reviewed in our free of charge Chiral Catalyst Search Data Base.