A convenient and general route to enantiopure 3,4-diamino-1-substituted pyrrolidines has been devised. 1-Alkyl, 1-alkanoyl, 1-cycloalkyl and 1-aryl-3,4-diaminopyrrolidines of the (3R,4R)-configurations have all been prepared, the cycloalkyl and (mono)aryl being novel derivatives. A previous difficulty in the synthesis of such compounds is the observation that dimesylates undergo two-fold displacement with sodium azide in very poor yields (<10%), if at all. However, use of lithium azide permits satisfactory yields of the diazides 5 and hence the corresponding diamines 6 and their derivatives, and avoids the generation and use of hydrazoic acid, as previously required in a Mitsunobu procedure.Enantiopure trans-vicinal diamino compounds have attracted much interest, such C 2 -symmetric diamines occupying a central role in catalytic asymmetric synthesis. 1 Whereas cyclohexane-1,2-diamine and its derivatives are well described and in enantiopure forms have found extensive use as catalysts in asymmetric synthesis, 2 1,2-diamines on a five-membered ring are much less wellknown, including 3,4-diaminopyrrolidine and its derivatives. Many amino-substituted pyrrolidines possess significant pharmacological properties, 3 including antibacterial activity, 4a and antagonistic activity toward the melanin-concentrating hormone receptor. 4b They have also found use in catalytic asymmetric synthesis. 5 3-Aminopyrrolidines have served as templates for the introduction of essential pharmacophoric groups, 6 and present a relatively conformationally rigid framework suitable for incorporation into anti-filarial agents. 7 trans-3,4-Diaminopyrrolidines have found use in the assembly of numerous systems of specific molecular recognition 8 and as catalysts in enantioselective alkylations, 9 functions that make use of their C 2 symmetry. trans-3,4-Diaminopyrrolidines are also well-suited to development in the context of combinatorial chemistry 10 and have formed the basis of some C-nucleosides. 11 Substituted 3,4-diaminopyrrolidines occupy a niche that is difficult to replace, since a wide variety of 1-substituents may be introduced without losing the essential C 2 symmetry of the molecule. A suitable 1-substituent would also permit attachment to polymeric resins or beads. Despite these applications and advantages, the literature on enantiopure 1-substituted 3,4-diaminopyrrolidines and their related 3,4-disubstituted derivatives is limited, and a general route has not yet been demonstrated. A particular limitation has been observed in attempted two-fold displacements of the corresponding pyrrolidine-trans-3,4-dimesylates with sodium azide; for example, 3,4-diazido-1-dodecylpyrrolidine could be obtained in no more than 10% yield by the use of sodium azide, either in DMF, HMPA, or under twophase conditions using phase-transfer catalysis. 12 An alternative procedure involves the generation of the highly toxic and explosive hydrazoic acid and its use under Mitsunobu conditions (e.g. with diethylacetylene dicarboxylate and triphenylphosphine), 10...