The Dieckmann Condensation (Including the Thorpe‐Ziegler Condensation)

Abstract: Incorporation of nitrile groups into fine chemicals is of particular interest through C(sp3)-H bonds activation of alkyl nitriles in the synthetic chemistry due to the highly efficient atom economy. However, the direct α-functionalization of alkyl nitriles is usually limited to its enolate chemistry. Here we report an electro-oxidative C(sp3)-H bond functionalization of acetonitrile with aromatic/aliphatic mercaptans for the synthesis of sulfur-containing β-enaminonitrile derivatives. These tetrasubstituted olefin products are stereoselectively synthesized and the stereoselectivity is enhanced in the presence of a phosphine oxide catalyst. With iodide as a redox catalyst, activation of C(sp3)-H bond to produce cyanomethyl radicals proceeds smoothly at a decreased anodic potential, and thus highly chemoselective formation of C-S bonds and enamines is achieved. Importantly, the process is carried out at ambient temperature and can be easily scaled up.

Abstract: The induction of strain in carbocycles, thereby increasing the amount of s-character in the C−H bonds and the acidity of these protons, has been probed with regard to its effect on the rate constan...

Abstract: Computational power and quantum chemical methods have improved immensely since computers were first applied to the study of reactivity, but the de novo prediction of chemical reactions has remained challenging. We show that complex reactions can be efficiently and autonomously predicted using chemical activation imposed by simple geometrical constraints. Our approach is demonstrated on realistic and challenging chemistry, such as a triple cyclization cascade involved in the total synthesis of a natural product and several oxidative addition reactions of complex drug-like molecules. Notably and in contrast with traditional hand-guided computational chemistry calculations, our method requires minimal human involvement and no prior knowledge of products or mechanisms. Imposed activation can be a transformational tool to screen for chemical reactivity and mechanisms as well as to study byproduct formation and decomposition.

Abstract: The mechanism of the Wolff rearrangement of some deprotonated diazocarbonyl compounds has been studied using density functional calculations, for both the gas and aqueous phases. The anionic rearrangement of the deprotonated analogues proceeds in a similar manner to the neutral counterparts. In the gas phase, the syn and anti conformers form the deprotonated ketene product concertedly. In certain analogues, the reaction of the anti conformer occurs non-concertedly, involving a deprotonated carbene-like intermediate. The migratory aptitude is similar to that in the neutral rearrangement, except that methoxy and amino substituents exchange positions.