A broadly applicable method has been demonstrated for the efficient synthesis of chiral bicyclic guanidines such as 1 from chiral a-amino acids. Compounds containing the guanidine unit are of considerable biological interest because of the hydrogen-bond mediated interaction of guanidinium ions with phosphate-containing biomolecules* and because of a range of biological activities, including hypotensive and adrenergic neuron blocking effects.2 The cyclic marine-derived guanidines saxitoxin, ptilocaulin and tetrodotoxin are potent ion-channel blockers which have stimulated noteworthy research both in neuroscience and chemical synthesis.3 A number of rigid, achiral, cyclic guanidine& and sterically hindered guanidines6 have been synthesized and used as basic synthetic reagents. This paper describes the first general synthetic route to chiral C2 symmetric bicyclic guanidines as exemplified by 3R,7R-dicyclohexyl-l.4,6-triazabicyclo[3.3.0]oct-4-ene (1). The method provides access to chiral products without the need for resolution starting from readily available a-ammo acids. It is also capable of producing unsymmetrically substituted guanidines starting from two different a-amino acids. D-(-)-a-phenylglycine methyl ester (R enantiomer, 2) was converted to the trityl-protected diamine 3 by the sequence: (1) amide formation with saturated ammonia in methanol at O'C for 3 h and 22OC for 16 h (84%, mp 127-131ยฐC, [CIjz2D -103" (c=1.2, EtOH)); (2) hydrogenation of phenyl to cyclohexyl using 5227