Redox isomerization reactions are of particular interest because they exhibit perfect atom economy, and they often utilize the inherent reducing power of hydrogen that is embedded in molecules to effect reduction of other functional groups. [1][2][3] In doing so, redox isomerizations are able to circumvent the requirement for exogenous reducing agents, which tend to be high energy reagents. The power of redox isomerizations is arguably increased when it is used in conjunction with C-X bond-forming reactions. The Tishchenko reaction is a classic example of such a coupling reaction that has been proposed to proceed via an intermediate redox isomerization. 2 More recently, Seidel has demonstrated several intriguing reactions where an intramolecular redox reaction is used to effect a reductive amination in concert with a second C-N bond forming reaction (eq 1). 3 Herein, we report a related, acid-catalyzed intermolecular redox amination that takes advantage of the inherent reducing power of 3-pyrroline (eq 2). Ultimately, redox isomerization can be used to form N-alkyl pyrroles via reductive amination, a reaction that cannot typically occur since pyrrole is a weak N-nucleophile. Moreover, the mild conditions, atom-economy, and operational simplicity of the redox amination reported herein make redox amination a viable alternative to more standard syntheses of N-alkyl pyyroles. 4(1) Initially, we were interested in performing an intramolecular variant of a rearrangement reaction described by Murahashi. 5 However, rather than the intended product, the alkyl pyrrole 1a was isolated in 25% yield (eq 3). Since such a reductive amination to form aromatic amines is a potentially powerful synthetic method, we chose to investigate the reaction further. Literature searches reveal that Cook discovered an analogous thermal condensation of 3-pyrroline with cyclohexanone at 140 °C in xylene to produce N-cyclohexylpyrrole in 47% yield. 6,7 Unfortunately, other ketones provided even poorer yields. Since our reaction appeared to take place under milder conditions, we set our sights on developing a catalytic reaction that would have broad utility.(To begin, reactions were performed to determine which species in the original reaction mixture was responsible for catalyzing this transformation. As can be seen from Table 1, CF 3 CO 2 H effected the reaction alone (entry 3), and Pd(PPh 3 ) 4 was somewhat detrimental to the reaction (entry 2). Moreover, performing the reaction under air was problematic due to background oxidation of 3-pyrroline to pyrrole (entry 4). Having established that the reaction was catalyzed by Brønsted acids, we turned our attention to the use of milder acids. Indeed, acetic acid and benzoic acid are both competent catalysts for the transformation and can be used interchangeably. While reactions that were run with 1:1 pyrroline/aldehyde did not completely consume the aldehyde within the allotted reaction time, the yields of the reactions were still good (entries 5, 8, and 11). Ultimately, the use of 1.5 equiv of ...

Allylic esters of nitrobenzene acetic acids undergo facile palladium-catalyzed decarboxylative coupling. Both mono-and dinitroarene substrates give high yields of the coupled products. Moreover, the rates of the reactions suggest that decarboxylation is rate-limiting and substrates that sterically disfavor attainment of the reactive conformation for decarboxylation are not viable. Finally, reduction of the product nitroarenes to the corresponding anilines provides access to a variety of heterocycles including quinolines and dihydroquinolones.

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Allylic esters of heteroaromatic alkanes undergo facile palladium-catalyzed decarboxylative coupling. The resulting C−C bond is formed with high diastereoselectivity and high regioselectivity for coupling at the more substituted allyl terminus. It is proposed that this unusual combination of selectivities results from a tandem allylation/aza-Cope rearrangement sequence. After allylation, decarboxylative dearomatization produces an intermediate for the aza-Cope rearrangement. The subsequent aza-Cope rearrangement occurs under mild conditions because it is driven by rearomatization.

The cyclization of γ,δ-unsaturated tertiary hydroperoxides in the presence of a palladium(II) catalyst afforded 1,2-dioxanes resembling biologically active natural products. A variety of substrates were screened, and synthetic manipulations were accomplished to construct compounds with structural similarity to antimalarial targets.