Intermolecular Amination of Unactivated C(sp3)−H Bonds with Cyclic Alkylamines: Formation of C(sp3)−N Bonds through Copper/Oxygen‐Mediated C(sp3)−H/N−H Activation

The first example of intermolecular amination of unactivated C(sp³)?H bonds by cyclic alkylamines mediated by Cu(OAc)₂/O₂ is reported. This method avoids the use of benzoyloxyamines as the aminating reagent, which are normally prepared from alkylamines in extra steps. A variety of unnatural β^{2, 2}‐amino acid analogues are synthesized by this simple and efficient procedure. This approach offers a solution to the previous unmet challenge of C(sp³)?H/N?H activation for the formation of C(sp³)?N bonds.     

Highly Chemoselective Synthesis of Indolizidine Lactams by SmI2‐Induced Umpolung of the Amide Bond via Aminoketyl Radicals: Efficient Entry to Alkaloid Scaffolds

Samarium(II) iodide enables a wide range of highly chemoselective umpolung radical transformations proceeding by electron transfer to carbonyl groups; however, cyclizations of important nitrogen‐containing precursors have proven limited due to their prohibitive redox potential. Herein, we report the first reductive cyclizations of unactivated cyclic imides onto N‐tethered olefins using SmI₂/H₂O. This new umpolung protocol leads to the rapid synthesis of nitrogen‐containing heterocycles that are of particular significance as precursors to pharmaceutical pharmacophores and numerous classes of alkaloids. The reaction conditions tolerate a wide range of functional groups. Excellent chemoselectivity is observed in the cyclization over amide and ester functional groups. Such unconventional reactivity has important implications for the design and optimization of new bond‐forming reactions by umpolung radical processes. The reaction advances the SmI₂ cyclization platform to the challenging unactivated N‐tethered acyl‐type radical precursors to access nitrogen‐containing architectures.     

Anodic and Cathodic CC-Bond Formation

Electrolysis allows the reactivity of a substrate to be changed, or its polarity to be reversed (“redox umpolung”). The carbon skeleton and the functional groups of a synthetic building block can thus be utilized more economically, and at the same time the number of reaction steps in multistage syntheses can be reduced. The tools necessary for an electrolytic process are a cell, a power source, electrodes, and an electrolyte, the latter being chosen in accordance with the reduction or oxidation potential of the substrate. A series of electroanalytical methods provides information on the electrode reaction mechanisms. At the anode, arenes, phenolic ethers, and electron-rich olefins dimerize via intermediate radical cations. In the Kolbe electrolysis, carboxylic acid anions decarboxylate to form radicals which can couple to form e.g. long chain alkene derivatives having pheromone activity, or add to ole-fins. At the cathode, activated olefins hydrodimerize via radical anions or, in the presence of appropriate reagents, can be acylated, alkylated, and carboxylated. Pinacols, crossed hydrodimers, and cyclic and arylated compounds are accessible via the cathodically produced radicals, while the formation of strained small rings or the reductive addition of halides to carbonyl compounds takes place through intermediate carbanions.     

Synthetic and Mechanistic Aspects of Inorganic Insertion Reactions. Insertion of Carbon Monoxide

The synthetic potential and the mechanistic aspects of inorganic insertion reactions of carbon monoxide, especially into metal-carbon σ-bonds, are considered. Reactions of this type are encountered among most 3d, 4d, and 5d elements. In one case it has been demonstrated that the CO insertion proceeds by alkyl migration; this is likely to be a general feature of all such reactions. If an alkyl migration takes place, then insertion of CO into the M? C bond is governed kinetically by the cleavage of that bond. CO abstraction from RCO? M bonds most commonly proceeds by rate-determining vacation of a coordination position. Both CO insertion and abstraction are usually highly stereospecific.     

gem-Diol-Type Intermediate in the Activation of a Ketone on Sn-β Zeolite as Studied by Solid-State NMR Spectroscopy

Lewis acid zeolites have found increasing application in the field of biomass conversion, in which the selective transformation of carbonyl-containing molecules is of particular importance due to their relevance in organic synthesis. Mechanistic insight into the activation of carbonyl groups on Lewis acid sites is challenging and critical for the understanding of the catalytic process, which requires the identification of reaction intermediates. Here we report the observation of a stable surface gem-diol-type species in the activation of acetone on Sn-β zeolite. ¹³C, ¹¹⁹Sn, and ¹³C–¹¹⁹Sn double-resonance NMR spectroscopic studies demonstrate that only the open Sn site ((SiO)₃Sn-OH) on Sn-β is responsible for the formation of the surface species. ¹³C MAS NMR experiments together with density functional theory calculations suggest that the gem-diol-type species exhibits high reactivity and can serve as an active intermediate in the Meerwein—Ponndorf–Verley–Oppenauer (MPVO) reaction of acetone with cyclohexanol. The gem-diol-type species offers an energy-preferable pathway for the direct carbon-to-carbon hydrogen transfer between ketone and alcohol. The results provide new insights into the transformation of carbonyl-containing molecules catalyzed by Lewis acid zeolites.     

Oxidative Coupling via Organocopper Compounds

The type of reaction described here, which achieved preparative importance before the turn of the century in the form of the Glaser reaction, has found new applications in recent years: Syntheses of 1,3-dienes, 2,3,6,7-tetraaza-1,3,5,7-tetraenes, 2,3-diaza-1,3-dienes, hydrazine derivatives, bis(heteroallyl) compounds, hetarenes, polyhetarenes, cyclopolyarenes, protophanes, phanes, and heteraprotophanes. The reaction, which consists in the metalation of the starting substance followed by oxidative coupling of the metal derivative, merits special preparative interest when several successive coupling processes are possible (e. g. polyyne, polyarene, cyclopolyarene, and protophane syntheses). The main factors limiting its applicability are the high thermal stability of some organic copper compounds and the disproportionation of the ligands that frequently occurs as a competing reaction. Selective asymmetric linkages are not generally possible by this method.