A chiral analog of the bicyclic guanidine TBD: synthesis, structure and Brønsted base catalysis.

Starting from ()-β-phenylalanine, easily accessible by lipase-catalyzed kinetic resolution, a chiral triamine was assembled by a reductive amination and finally cyclized to form the title compound . In the crystals of the guanidinium benzoate salt the six membered rings of adopt conformations close to an envelope with the phenyl substituents in pseudo-axial positions. The unprotonated guanidine catalyzes Diels-Alder reactions of anthrones and maleimides (25-30% ee). It also promotes as a strong Brønsted base the retro-aldol reaction of some cycloadducts with kinetic resolution of the enantiomers. In three cases, the retro-aldol products (48-83% ee) could be recrystallized to high enantiopurity (≥95% ee). The absolute configuration of several compounds is supported by anomalous X-ray diffraction and by chemical correlation.