Synthesis of Azabicycles via Cascade Aza-Prins Reactions: Accessing the Indolizidine and Quinolizidine Cores

The first detailed studies of intramolecular aza-Prins and aza-silyl-Prins reactions, starting from acyclic materials, are reported. The methods allow rapid and flexible access toward an array of [6,5] and [6,6] aza-bicycles, which form the core skeletons of various alkaloids. On the basis of our findings on the aza-Prins and aza-silyl-Prins cyclizations, herein we present simple protocols for the intramolecular preparation of the azabicyclic cores of the indolizidines and quinolizidines using a one-pot cascade process of <i>N</i>-acyliminium ion formation followed by aza-Prins cyclization and either elimination or carbocation trapping. It is possible to introduce a range of different substituents into the heterocycles through a judicial choice of Lewis acid and solvent(s), with halo-, phenyl-, and amido-substituted azabicyclic products all being accessed through these highly diastereoselective processes

Electron Transfer Reactions: KO<i>t</i>Bu (but not NaO<i>t</i>Bu) Photoreduces Benzophenone under Activation by Visible Light

Long-standing controversial reports of electron transfer from KO<i>t</i>Bu to benzophenone have been investigated and resolved. The mismatch in the oxidation potential of KO<i>t</i>Bu (+0.10 V vs SCE in DMF) and the first reduction potential of benzophenone (of many values cited in the literature, the least negative value is −1.31 V vs SCE in DMF), preclude direct electron transfer. Experimental and computational results now establish that a complex is formed between the two reagents, with the potassium ion providing the linkage, which markedly shifts the absorption spectrum to provide a tail in the visible light region. Photoactivation at room temperature by irradiation at defined wavelength (365 or 400 nm), or even by winter daylight, leads to the development of the blue color of the potassium salt of benzophenone ketyl, whereas no reaction is observed when the reaction mixture is maintained in darkness. So, <i>no</i> electron transfer occurs in the ground state. However, when photoexcited, electron transfer occurs within a complex formed from benzophenone and KO<i>t</i>Bu. TDDFT studies match experimental findings and also define the electronic transition within the complex as n → π*, originating on the butoxide oxygen. Computation and experiment also align in showing that this reaction is selective for KO<i>t</i>Bu; no such effect occurs with NaO<i>t</i>Bu, providing the first case where such alkali metal ion selectivity is rationalized in detail. Chemical evidence is provided for the photoactivated electron transfer from KO<i>t</i>Bu to benzophenone: <i>tert</i>-butoxyl radicals are formed and undergo fragmentation to form (acetone and) methyl radicals, some of which are trapped by benzophenone. Likewise, when KOC­(Et)₃ is used in place of KO<i>t</i>Bu, then ethylation of benzophenone is seen. Further evidence of electron transfer was seen when the reaction was conducted in benzene, in the presence of <i>p-</i>iodotoluene; this triggered BHAS coupling to form 4-methylbiphenyl in 74% yield

KO<i>t</i>Bu: A Privileged Reagent for Electron Transfer Reactions?

Many recent studies have used KO<i>t</i>Bu in organic reactions that involve single electron transfer; in the literature, the electron transfer is proposed to occur either directly from the metal alkoxide or indirectly, following reaction of the alkoxide with a solvent or additive. These reaction classes include coupling reactions of halobenzenes and arenes, reductive cleavages of dithianes, and S_RN1 reactions. Direct electron transfer would imply that alkali metal alkoxides are willing partners in these electron transfer reactions, but the literature reports provide little or no experimental evidence for this. This paper examines each of these classes of reaction in turn, and contests the roles proposed for KO<i>t</i>Bu; instead, it provides new mechanistic information that in each case supports the <i>in situ</i> formation of organic electron donors. We go on to show that direct electron transfer from KO<i>t</i>Bu can however occur in appropriate cases, where the electron acceptor has a reduction potential near the oxidation potential of KO<i>t</i>Bu, and the example that we use is CBr₄. In this case, computational results support electrochemical data in backing a direct electron transfer reaction