Radical cyclizations to imino acceptors directed toward the total syntheses of aminosugars

Two natural products were examined for total synthesis utilizing 5- exo and 6-exo radical cyclization reactions. Cyclizations of silicon tethered vinyl groups onto hydrazone acceptors resulted in the stereoselective formation of 1,2-hydrazinoalcohols as the key formation of the chiral alpha-branched amine of L-daunosamine. A reverse regiocontrolled Wacker oxidation converted the inserted olefin to an aldehyde, completing the synthesis of N-TFA methyl acetal of L-daunosamine.; Additionally, 6-exo radical cyclizations of silicon tethered vinyl groups towards the diastereoselective formation of 1,3-aminoalcohols were explored. Unfortunately, it was discovered that the reaction resulted in only addition across the vinyl group, rather than the expected addition-cyclization. Increasing the rate of cyclization, vinyl radicals generated from silicon tethered alpha-bromovinyl groups were employed, successfully forming 1,3-hydrazinoalcohols. The stereoselectivity, however, was much lower than observed in the 5- exo radical cyclization of silicon tethered vinyl groups.; Upon further investigations into the synthesis of (-)-dysiherbaine, 6- exo radical cyclizations utilizing a silicon tethered vinyl group were successful. Interestingly, the cyclization produced one diastereomer. In previously studied 5-exo radical cyclizations, the stereoselectivity of the reaction was successfully realized following the Beckwith-Houk model. The 6-exo cyclization towards the synthesis of (-)-dysiherbaine afforded one diastereomer which was opposite to the Beckwith-Houk model prediction suggesting additional stereocontrol elements. Evaluation of the substrate revealed the possible dipole-dipole interaction with an alpha-oxygen functionality. This hypothesis was examined further to reveal the importance of a cyclic compound with an alpha-oxygen on the reactivity and stereocontrol.; Further developments towards the synthesis of (-)-dysiherbaine included the use of a propargyl ether for radical cyclization. This cyclization was successful in the formation of the cyclic core of C8-epi-dysiherbaine with high efficiency. Attempts to reverse stereocontrol are ongoing.