A new methodology to synthesize 2,6-di-, and 2,2′,6-trisubstituted morpholines via the reduction of oxabicyclic tetrazoles under mild conditions is described. The reaction proved successful for a wide range of tetrazoles, including sterically encumbered ones harboring gem-substituents on tertiary carbon centers. The mechanism for the decades-old reduction of tetrazoles to secondary amines is elucidated.

A practical two-step synthesis of N,N′-disubstituted cyanamides consists in the low-temperature metalation of Nsubstituted 5H-tetrazoles that undergo spontaneous cycloreversion at 0 °C releasing dinitrogen, and forming N-metalated cyanamides that can be reacted in situ with a variety of electrophiles. Remarkably, the N-substituted Li and K cyanamides are air stable white solids at room temperature. Addition of lithium organometallics to the N,N′-disubstituted cyanamides provides a new method for accessing N,N′-disubstituted amidines.

We report the synthesis of two novel azaperhydroazulene tropane-hederacine chimeras A and B, which contain an 8-azabicyclo[3.2.1]octane ring and a 7-azabicyclo[4.1.1]octane ring, respectively. The synthesis of both chimeras was achieved by epoxide ring opening and was governed by the stereochemistry of the hydroxy-epoxide unit. Finally, a density functional theory study was conducted to explain the regioselectivity of the cyclization and the importance of the stereochemistry of the hydroxyl group.

Polygonapholine was isolated in 1997 from the Polygonatum alte-lobatum rhizome. Based on spectroscopic data, it was assigned a structure comprising an unusual cis-2,6-disubstituted bis-aryl morpholine ring to which is attached a (Z)-4-hydroxycinnamate as an amide and an (E)-4-hydroxycinnamate as an ester. Being a meso compound, polygonapholine should not exhibit an optical rotation as reported. A total synthesis of the purported morpholine alkaloid presented herein reveals discrepancies between the synthetic and the natural product casting doubt on the originally proposed structure.