| Abstract
| - A mild oxidative workup protocol using iodine in an acetic acid−acetate buffer solution is describedfor the cleavage of borane−amine adducts arising from the borane-promoted reduction of polyamidessupported onto practical trityl-based resins. Chiral polyamines with diverse side-chain functionalitiescan be generated as free bases without premature release from the solid support and with essentiallyno racemization using this method. A series of model oligomeric secondary diamides 6 containingvarious α-amino acid residues (Val, Phe, Tyr, Ser, Cys, Met, Gln, Trp) provided triamine products8 in high yields and good to excellent purity. On the other hand, a substrate containing a tertiaryamide (15) formed a rather unusual triaminoborane intermediate that required more stringentworkup conditions to liberate the polyamine product 20. The reduction of oligomeric tertiary amidessuch as 9 was found sluggish, but these compounds could nonetheless be obtained in high purityfrom in situ reductive amination of the corresponding secondary amines. Control studies, carriedout in solution with model secondary amide 23, confirmed the efficiency of the buffered iodinesolution and highlighted several advantages (no heating necessary, no need for strong bases oracids) over existing methods for the cleavage of borane−amine adducts. A possible mechanisminvolving all buffer components (iodine, acetic acid, and acetate ion) is proposed in which borane−amine adducts are transformed first to the monoiodoborane−amine and then to the correspondingacetoxyborane−amine adduct of much weaker coordination affinity. The latter would dissociatereadily and get trapped by the acetic acid to provide the desired secondary amine. This reduction/oxidative workup protocol is useful as a general method for the facile solid-phase synthesis ofpolyamines for eventual release in solution and use in various applications. It is also potentiallyvery useful toward the synthesis and screening of bead-supported libraries of free oligoaminesassembled through split-pool methods.
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