Olga García Mancheño

TEMPO Oxoammonium Salt-Mediated Dehydrogenative Povarov/Oxidation Tandem Reaction of N-Alkyl Anilines

The synthesis of a variety of substituted quinolines from N-alkyl anilines by a one-pot dehydrogenative Povarov/oxidation tandem reaction with mono- and 1,2-disubstituted aryl and alkyl olefins was developed. A simple protocol using cheap and benign iron(III)chloride as the Lewis acid catalyst and a TEMPO oxoammonium salt as a nontoxic, mild, efficient oxidant is reported.

Iron-Catalyzed Oxidative Tandem Reactions with TEMPO Oxoammonium Salts: Synthesis of Dihydroquinazolines and Quinolines

A straightforward iron-catalyzed divergent oxidative tandem synthesis of dihydroquinazolines and quinolines from N-alkylanilines using a TEMPO oxoammonium salt as a mild and nontoxic oxidant has been developed. Fe(OTf)2 was the Lewis acid catalyst of choice for the formation of dihydroquinazolines, whereas FeCl3 led to better results for the synthesis of quinolines. This divergent approach implies that, for both syntheses, direct oxidative functionalization of a α-C(sp(3))-H bond of the N-alkylanilines occurs, leading to C-N bond formation or C-C bond formation upon homocondensation or reaction with simple olefins, respectively. Cyclization followed by a final oxidation generates these classes of interesting bioactive heterocycles in one synthetic transformation. Additionally, the one-pot multicomponent synthesis of quinolines from anilines, aldehydes, and olefins has also been successfully developed under these mild oxidative conditions.

Mild metal-free tandem α-alkylation/cyclization of N-benzyl carbamates with simple olefins.

Easy does it! The chemoselective oxidative α-C(sp(3))-H alkylation/cyclization reaction of N-benzyl carbamates using simple mono-, di-, and trisubstituted olefins provides functionalized N-heterocycles such as oxazinones. A TEMPO oxoammonium salt serves as the oxidant, making it possible to carry out the reaction at low temperatures. Neither a metal catalyst nor preactivation in the α-position to the nitrogen group are needed.

Iron-catalyzed imination of sulfoxides and sulfides.

[reaction: see text] The Fe(III)-catalyzed imination of sulfoxides and sulfides with sulfonylamides in the presence of iodinanes has been investigated. The best results were obtained when Fe(acac)(3) was used as a catalyst in combination with iodosylbenzene, providing an effective alternative (stereospecific) access to sulfoximines and sulfilimines.

Catalyzed Selective Direct α- and γ-Alkylation of Aldehydes with Cyclic Benzyl Ethers by Using T+BF4− in the Presence of an Inexpensive Organic Acid or Anhydride†

The cross dehydrogenative coupling (CDC) of cyclic benzyl ethers with aliphatic and α,β-unsaturated aldehydes has been developed. The mild reaction conditions, in which an N-oxoammonium salt derived from TEMPO (2,2,6,6-tetramethyl-1-piperidinoxyl) is employed as the oxidant in combination with a Cu catalyst, allow the use of relatively redox-unstable aldehydes under oxidative CDC conditions. The addition of a catalytic amount of trifluoroacetic acid (TFA) or Ac(2)O facilitates the reaction and increases the efficiency and selectivity. In contrast to the expected α-alkylation obtained with aliphatic aldehydes, α,β-unsaturated aldehydes led preferentially to the more challenging γ-alkylated products. The utility of the developed methodology was demonstrated by the synthesis of isochromane-derived bioactive compounds, such as the dopamine antagonist sonepiprazole.

H-Donor Anion Acceptor Organocatalysis—The Ionic Electrophile Activation Approach

Hydrogen bonds are key interactions in nature, which create cooperative non-covalent networks that support highly efficient molecular transformations. These non-covalent interactions are characteristic for the high selective substrate recognition, activation, and elevated stereocontrol in enzyme catalysis. Molecular recognition, which relies on specific binding-sites, is hence essential in life-processes and anions are ubiquitous in biological systems. Indeed, most cofactors and enzyme-substrates are anionic species (>70 %), which makes the recognition and binding of anions indispensable. Therefore, and inspired by nature, considerable effort has been set for the development of man-made small organic molecules as anion receptors and catalysts. Those synthetic anion receptors are often based on neutral bior multi-H-bond donor compounds, such as (thio)ureas, squarimides, (macrocyclic)amides, or calixarenes, which can host important classes of anions like phosphates, sulfates, carboxylates, cyanide, or halide anions through H-bonding. These can bind in a mono-, bior multidentate fashion depending on both the nature and geometry of the H-bond donor and the anion (Figure 1).

New Trends towards Well‐Defined Low‐Valent Iron Catalysts

In the past few years iron catalysis has emerged as an important and challenging research area for the development of alternative, more affordable, and sustainable methods. Besides the traditional applications of iron catalysts as Lewis acids and for reduction/oxidation processes in organic synthesis, organoiron species have been shown to be suitable catalysts for a broad range of nonrelated transformations such as cross-coupling reacions, allylations, and hydrogenations. Simple and stable commercially available iron compounds such as iron(II) or (III) chlorides, [Fe(acac)3] (acac = acetylacetonate), and [Fe(CO)5] have been largely employed for these purposes. However, the complexity of the reaction mixtures makes it extremely difficult to identify the active iron species and the reaction mechanisms, thus hampering the rational design and modification of the catalytic systems. In view of the rapidly growing interest in highly reactive lowvalent organoiron catalysts, 3] the preparation of such wellcharacterized iron compounds is essential for a better understanding and the further development of modern iron catalysis. Much progress has been made in this direction, from which the reduction of iron(II) species, typically with alkali-metal and more recently zinc reagents, has become an established method to generate low-valent iron catalysts. Following the first report on cross-coupling reactions by using in situ formed low-valent iron catalysts by Tamura and Kochi, several research groups have utilized this approach to broaden the scope of low-valent iron catalysis (Figure 1). Although the enormous potential of low-valent iron catalysts is already known, there is still a necessity to generate well-defined species to obtain more mechanistic insight and enlarge the synthetic applicability. F rstner et al. have contributed significantly in this regard, not only by the development of a number of iron-catalyzed transformations and their application in total synthesis but also by the systematic mechanistic study of several isolable low-valent ferrate complexes (for example, Scheme 1, left and middle). It was proposed that interconnected Fe /Fe, Fe/Fe, and Fe/ Fe redox cycles may be operative within these systems. The research groups of Chirik and Wieghardt have joined forces to understand the character and performance of welldefined formal low-valent iron species with bis(imino)pyridine ligands (e.g. Scheme 1, right). A more complex scenario is envisioned in this case, since these tridentate ligands can also participate actively in the reduction/oxidation steps. Consequently, the ligand might preferentially take part in the redox processes while the iron atom retains its oxidation state. Recently, Ritter and co-workers developed an effective new method to obtain well-defined and relatively stable lowvalent iron catalysts (Scheme 2). In their approach, the wellknown two-electron reductive elimination reaction of transition metals (such as Pd, Rh, Ru, or Ni) was applied to iron complexes for the first time. To accomplish this transformation, the carefully designed new bis(aryl)iron(II) complex 1 was prepared from inexpensive FeCl2, pyridine, and (2-[(N,Ndimethylamino)methyl]phenyl)lithium. The use of the chelating amino aryl ligand, which places the C donors in a pseudo-trans conformation, was crucial to prevent reductive elimination at this stage and allow the isolation of the stable intermediate 1. The low-valent iron complexes 2 were achieved in a clever manner by the subsequent addition of Figure 1. Overview of the reaction scope of low-valent iron catalysts.

Iron(II) triflate as an efficient catalyst for the imination of sulfoxides.

The challenging imination of benzyl-, sterically demanding alkyl-, and heteroaryl-substituted sulfoxides has been studied. Iron(II) triflate was identified as a highly efficient and robust catalyst for sulfur imination reactions. A variety of sulfoxides and sulfides were efficiently iminated with sulfonyliminoiodinanes (PhI=NSO(2)R) at room temperature to give the corresponding sulfoximines and sulfilimines in good yields and with short reaction times.

Chiral Helical Oligotriazoles: New Class of Anion-Binding Catalysts for the Asymmetric Dearomatization of Electron-Deficient N-Heteroarenes

Helical chirality and selective anion-binding processes are key strategies used in nature to promote highly enantioselective chemical reactions. Although enormous efforts have been made to develop simple helical chiral systems and thus open new possibilities in asymmetric catalysis and synthesis, the efficient use of synthetic oligo- and polymeric helical chiral catalysts is still very challenging and rather unusual. In this work, structural unique chiral oligotriazoles have been developed as C-H bond-based anion-binding catalysts for the asymmetric dearomatization of N-heteroarenes. These rotational flexible catalysts adopt a reinforced chiral helical conformation upon binding to a chloride anion, allowing high levels of chirality transfer via a close chiral anion-pair complex with a preformed ionic substrate. This methodology offers a straightforward and potent entry to the synthesis of chiral (bioactive)heterocycles with added synthetic value from simple and abundant heteroarenes.

Highly Enantioselective Nucleophilic Dearomatization of Pyridines by Anion‐Binding Catalysis

The asymmetric dearomatization of N-heterocycles is an important synthetic method to gain bioactive and synthetically valuable chiral heterocycles. However, the catalytic enantio- and regioselective dearomatization of the simplest six-membered-ring N-heteroarenes, the pyridines, is still very challenging. The first anion-binding-catalyzed, highly enantioselective nucleophilic dearomatization of pyridines with triazole-based H-bond donor catalysts is presented. Contrary to other more common NH-based H-bond donors, this type of organocatalyst shows a prominent higher C2-regioselectivity and is able to promote high enantioinductions via formation of a close chiral anion-pair complex with a preformed N-acyl pyridinium ionic intermediate. This method offers a straightforward and useful synthetic approach to chiral N-heterocycles from abundant and readily available pyridines.