Probing the scope of the asymmetric dihydroxylation of polymer-bound olefins : monitoring by HRMAS NMR allows for reaction control and on-bead measurement of enantiomeric excess

Abstract

The aim of this study was (I) to define the scope and limitations of the Sharpless asymmetric dihydroxylation (AD) for polymer-bound olefins of different structural types and (II) to elaborate HRMAS NMR methods for the direct on-bead monitoring of the asymmetric dihydroxylation, including the on-bead determination of enantiomeric excess (ee). (I) 2-Methoxy-4-(2-propenyl)phenol (eugenol, E), 10-undecenoic acid (U), and (E)-4-hydroxystilbene (S) were bound to Wang-resin or TentaGel S-OH. These olefins gave low (E, 32%), intermediate (U, 88%), and very high enantiomeric excesses (S, >99%) when treated with AD mix β in solution. When bound to the polymers, the trend of the enantioselectivities remained the same [S (97%) > U (20−45%) > E (0−3%)]. However, the absolute ee values demonstrate that only the most selective types of substrates in homogeneous solution have practical potential for enantioselective AD on solid phase. (II) HRMAS NMR was successfully used for on-bead monitoring and for the first time for the ee measurement of the polymer-bound dihydroxylation product. As an example, the full assignment of all resonances of polymer-bound 10-undecenoic acid (U) and its dihydroxylation product is presented. For the ee measurement, the polymer-bound dihydroxylation product was derivatized with Mosher's acid. The integration of seven different pairs of resonances in the 13C HRMAS NMR of the diastereomeric Mosher esters gave (in each case) an ee value that agreed within <1% with that determined by chiral HPLC after cleavage of the AD product