Abstract:
This thesis describes the synthesis of chiral aminotetrahydropyran derivatives from the biomass-derived building block levoglucosenone (LGO). The diastereoselective aza-Michael addition of various anilines to LGO was performed under aqueous conditions to give a suite aminolevoglucosenone derivatives; electron-rich and electron-poor anilines, as well as heteroaromatic amines were all capable substrates in this reaction. A Wolff-Kishner reductive elimination of the aza-Michael adduct (Ar=C6H5) afforded a trans-3-aminodihydropyran, as well as the cis-3-aminodihydropyran, the latter resulting from base-mediated epimerisation. Reduction of the aminodihydropyrans afforded the corresponding aminotetrahydropyrans, demonstrating that these valuable heterocycles can be prepared in enantiopure form from biomass. In a complementary study, LGO was readily converted to dihydrolevoglucosenone, which was subjected to a reductive amination study. After a significant amount of investigation, it was found that the reductive amination proceeded with the best diastereoselectivity using sodium borohydride in acetic acid at room temperature to give a 1:4 ratio of the (R)- to (S)- aminolevoglucosenone derivative. The reductive amination study has laid foundations for the future preparation of 5-aminotetrahydropyran derivatives from biomass.
