UC Berkeley

This dissertation describes studies toward the core modification of cyclic aliphatic amines aimed at late-stage structural diversification. The main strategy involves oxidative C–N and/or C–C bond cleavage to open the cyclic amine core, and this work explores mild methods for ring opening in order to provide wide functional group tolerance, as well as opportunities for bond formation following ring opening. These investigations are contingent on the use of peroxydisulfate (persulfate) as a versatile oxidant that can be paired with metal or non-metal oxidative mediators for a set of distinct outcomes involving transformation of the cyclic amine framework. Specifically, Chapter 1 discusses mild, oxidative ring opening of cyclic amines to access linear aldehydes using flavin-derived photoredox catalysis. Linear carboxylic acids are also accessed with copper salts as a mediator. The mechanisms of these two reactions are investigated by computation. The computations suggest that the flavin-mediated oxidation is initiated by hydrogen-atom transfer from the cyclic amine to the photocatalyst, whereas the copper-mediated process begins instead with single-electron oxidation of the cyclic amine with concomitant reduction of persulfate. Chapter 2 describes ring opening of cyclic amines and subsequent C–C and C–O bond formation in one-pot reactions, enabled by the intermediacy of a primary alkyl radical. Ring opening followed by radical decarboxylation with Ag(I) and persulfate enables a Minisci-type Csp3–Csp2 coupling to form alkylamine-substituted pyridines. Additionally, Cu(II) oxidation of the alkyl radical arising from N-acylated cyclic amines leads to a C–O bond-forming cyclization event producing oxazines, constituting a heterocycle replacement of the cyclic amine core. While Cu(II) oxidations of radicals typically favor elimination pathways leading to olefins, computational studies into the cyclization indicate that cyclization is kinetically preferred over elimination in this instance.