Synthesis of Poly( α -aminoketones) through Pd-Catalyzed C(sp3)–C(sp3) Cleavage of Azetidinol Monomers

Abstract

Herein we describe a synthetic route to poly(α-aminoketones) based on the Pd-catalyzed C(sp3)–C(sp3) bond cleavage of N-protected 3-azetidinol monomers containing a haloaryl group. The reactivity of the azetidinols was sensitive to the nature of the N-protecting group. Thus, substrates with N-tert-butyloxycarbonyl or N-phenyl polymerized in the presence of catalytic amounts of Pd(OAc)2 and PPh3 to give the corresponding poly(α-aminoketones) in moderate to good yields, whereas the N-tosyl, N-benzoyl or N-acetyl substrates were unproductive. Azetidinols containing the linkers 1,4- or 1,3-phenylene, 9,9-dimethyl-2,7-fluorenylene or 4,4′-biphenylene between the two reactive sites of the monomer (azetidinol and halogen) gave polymers containing these moieties in the polymeric chain. Furthermore, the organometallic nature of the mechanism was confirmed by the isolation and characterization of an aryl–Pd(II) catalytic intermediate. This methodology represents a complementary strategy to classic polyamine synthesis via cationic or anionic ring-opening polymerization of azaheterocycles, which allows the inclusion of different arylene linkers in the polymer main chain. Among the groups evaluated, the Boc group provides the most favorable reactivity while also allowing facile deprotection to afford polyammonium salts of potential biotechnological interest.