Asymmetrically Substituted s-Triazine Phosphonates by One-Step Synthesis.

Asymmetrically substituted s-triazine phosphonates with up to three different phosphonate groups C3 N3 RR'R" with R, R', R"=PO(OR"') and R"'=for example, methyl, ethyl, isopropyl or n-butyl are interesting as polymer additives like flame retardants. Typically, these compounds are obtained by multiple synthesis steps. However, this leads to high production costs, which are a disadvantage for commercial use. Here we report the one-step synthesis of mixtures of asymmetrical s-triazine phosphonates which is an easy way to adjust the thermal behaviour and other properties such as viscosities of the compounds. The synthesis is based on a Michaelis-Arbuzov reaction. A complete conversion of the reactants to the target compounds is observed which was proofed by detailed 1 H, 13 C and 31 P NMR investigations and elemental analysis. The thermal behaviour was compared with thermogravimetric analysis (TGA).

Access to Unexplored 3D Chemical Space: cis-Selective Arene Hydrogenation for the Synthesis of Saturated Cyclic Boronic Acids.

A new class of saturated boron-incorporated cyclic molecules has been synthesized employing an arene-hydrogenation methodology. cis-Selective hydrogenation of easily accessible, and biologically important molecules comprising benzoxaborole, benzoxaborinin, and benzoxaboripin derivatives is reported. Among the various catalysts tested, rhodium cyclic(alkyl)(amino)carbene [Rh-CAAC] (1) pre-catalyst revealed the best hydrogenation activity confirming turnover number up to 1400 with good to high diastereoselectivity. A broad range of functional groups was tolerated including sensitive substituents such as -F, -CF3 , and -silyl groups. The utility of the synthesized products was demonstrated by the recognition of diols and sugars under physiological conditions. These motifs can have a substantial importance in medicinal chemistry as they possess a three-dimensional structure, are highly stable, soluble in water, form hydrogen bonds, and interact with diols and sugars.

Synthesis of Saturated N-Heterocycles via a Catalytic Hydrogenation Cascade.

Saturated N-heterocycles are prominent motifs found in various natural products and pharmaceuticals. Despite the increasing interest in this class of compounds, the synthesis of saturated bicyclic azacycles requires tedious multi-step syntheses. Herein, we present a one-pot protocol for the synthesis of octahydroindoles, decahydroquinolines, and octahydroindolizines through a cascade reaction.

Bipyridinium and Phenanthrolinium Dications for Metal-Free Hydrodefluorination: Distinctive Carbon-Based Reactivity.

The development of novel Lewis acids derived from bipyridinium and phenanthrolinium dications is reported. Calculations of Hydride Ion Affinity (HIA) values indicate high carbon-based Lewis acidity at the ortho and para positions. This arises in part from extensive LUMO delocalization across the aromatic backbones. Species [C10 H6 R2 N2 CH2 CH2 ]2+ (R=H [1 a]2+ , Me [1 f]2+ , tBu [1 g]2+ ), and [C12 H4 R4 N2 CH2 CH2 ]2+ (R=H [2 a]2+ , Me [2 b]2+ ) were prepared and evaluated for use in the initiation of hydrodefluorination (HDF) catalysis. Compound [2 a]2+ proved highly effective towards generating catalytically active silylium cations via Lewis acid-mediated hydride abstraction from silane. This enabled the HDF of a range of aryl- and alkyl- substituted sp3 (C-F) bonds under mild conditions. The protocol was also adapted to effect the deuterodefluorination of cis-2,4,6-(CF3 )3 C6 H9 . The dications are shown to act as hydride acceptors with the isolation of neutral species C16 H14 N2 (3 a) and C16 H10 Me4 N2 (3 b) and monocationic species [C14 H13 N2 ]+ ([4 a]+ ) and [C18 H21 N2 ]+ ([4 b]+ ). Experimental and computational data provide further support that the dications are initiators in the generation of silylium cations.

Substituted Dihydropyridine Synthesis by Dearomatization of Pyridines.

Dearomatization is an effective method to transform readily available N-heterocycles into partially saturated motifs. Manipulation of dihydro-derivatives holds great potential and provides access to a variety of semi-saturated N-heterocyclic building blocks. However, current strategies are limited in scope and the use of sensitive reagents restricts the applicability in synthetic laboratories. Herein, we report the synthesis of a broad variety of N-substituted 1,4- and 1,2-dihydropyridines by very mild and selective reduction with amine borane for the first time.

Enantio- and Diastereoselective, Complete Hydrogenation of Benzofurans by Cascade Catalysis.

We report an enantio- and diastereoselective, complete hydrogenation of multiply substituted benzofurans in a one-pot cascade catalysis. The developed protocol facilitates the controlled installation of up to six new defined stereocenters and produces architecturally complex octahydrobenzofurans, prevalent in many bioactive molecules. A unique match of a chiral homogeneous ruthenium-N-heterocyclic carbene complex and an in situ activated rhodium catalyst from a complex precursor act in sequence to enable the presented process.

Interrupted Pyridine Hydrogenation: Asymmetric Synthesis of δ-Lactams.

Metal-catalyzed hydrogenation is an effective method to transform readily available arenes into saturated motifs, however, current hydrogenation strategies are limited to the formation of C-H and N-H bonds. The stepwise addition of hydrogen yields reactive unsaturated intermediates that are rapidly reduced. In contrast, the interruption of complete hydrogenation by further functionalization of unsaturated intermediates offers great potential for increasing chemical complexity in a single reaction step. Overcoming the tenet of full reduction in arene hydrogenation has been seldom demonstrated. In this work we report the synthesis of sought-after, enantioenriched δ-lactams from oxazolidinone-substituted pyridines and water by an interrupted hydrogenation mechanism.

Design of Ru(II)-NHC-Diamine Precatalysts Directed by Ligand Cooperation: Applications and Mechanistic Investigations for Asymmetric Hydrogenation.

A modular synthesis of Ru(II)-NHC-diamine complexes from readily available chiral N-heterocyclic carbenes (NHCs) and chiral diamines is disclosed for the first time. The well-defined Ru(II)-NHC-diamine complexes show unique structure and coordination chemistry including an unusual tridentate coordination effect of 1,2-diphenylethylenediamine. The isolated air- and moisture-stable Ru(II)-NHC-diamine complexes act as versatile precatalysts for the asymmetric hydrogenation of isocoumarines, benzothiophene 1,1-dioxides, and ketones. Moreover, on the basis of the identification of reaction intermediates by stoichiometric reactions and NMR experiments, together with the DFT calculations, a possible catalytic cycle was proposed.

Accessing (Multi)Fluorinated Piperidines Using Heterogeneous Hydrogenation.

Fluorinated piperidines are desirable motifs for pharmaceutical and agrochemical research. Nevertheless, general synthetic access remains out of reach. Herein, we describe a simple and robust cis-selective hydrogenation of abundant and cheap fluoropyridines to yield a broad scope of (multi)fluorinated piperidines. This protocol enables the chemoselective reduction of fluoropyridines while tolerating other (hetero)aromatic systems using a commercially available heterogenous catalyst. Fluorinated derivatives of important drug compounds are prepared, and a straightforward strategy for the synthesis of enantioenriched fluorinated piperidines is disclosed.