Antiproliferative in Vitro Evaluation of Terpenic Amines Synthesized via a Rhodium-catalyzed Hydroaminomethylation.

Terpene-derived alkaloids show a variety of biological activities, including antioxidant, anti-inflammatory, antimicrobial and cytotoxicity effects. In this work, homologated monoterpene amines have been prepared via a rhodium-catalyzed hydroaminomethylation of biomass-based alkenes, such as (R)-limonene, linalool, myrcene and camphene, in combination with secondary amines of aliphatic and aromatic nature, namely morpholine and N-methylaniline, leading to highly chemo- and regioselective processes. The as-prepared amines were obtained in 50-99 % overall yields, and in vitro tested on a human colon cancer cell line (HCT-116) to evaluate their cytotoxic potential. The lead compound of the series (3 a) showed cytotoxicity in the micromolar range (IC50 52.46 µM) via the induction of cell death by apoptosis, paving the way towards further structure-activity relationship studies.

Tandem Catalysis Utilizing Olefin Metathesis Reactions.

Since olefin metathesis transformation has become a favored synthetic tool in organic synthesis, more and more distinct non-metathetical reactions of alkylidene ruthenium complexes have been developed. Depending on the conditions applied, the same olefin metathesis catalysts can efficiently promote isomerization reactions, hydrogenation of C=C double bonds, oxidation reactions, and many others. Importantly, these transformations can be carried out in tandem with olefin metathesis reactions. Through addition of one portion of a catalyst, a tandem process provides structurally advanced products from relatively simple substrates without the need for isolation of the intermediates. These aspects not only make tandem catalysis very attractive from a practical point of view, but also open new avenues in (retro)synthetic planning. However, in the literature, the term "tandem process" is sometimes used improperly to describe other types of multi-reaction sequences. In this Concept, a number of examples of tandem catalysis involving olefin metathesis are discussed with an emphasis on their synthetic value.

Direct C-H amidation of benzoic acids to introduce meta- and para-amino groups by tandem decarboxylation.

The Ir-catalyzed mild C-H amidation of benzoic acids with sulfonyl azides was developed to give reactions with high efficiency and functional-group compatibility. Subsequent protodecarboxylation of ortho-amidated benzoic acid products afforded meta- or para-substituted (N-sulfonyl)aniline derivatives, the latter being inaccessible by other C-H functionalization approaches. The decarboxylation step was compatible with the amidation conditions, enabling a convenient one-pot, two-step process.

Asymmetric allylation of ketones and subsequent tandem reactions catalyzed by a novel polymer-supported titanium-BINOLate complex.

By using a novel, simple, and convenient synthetic route, enantiopure 6-ethynyl-BINOL (BINOL = 1,1-binaphthol) was synthesized and anchored to an azidomethylpolystyrene resin through a copper-catalyzed alkyne-azide cycloaddition (CuAAC) reaction. The polystyrene (PS)-supported BINOL ligand was converted into its diisopropoxytitanium derivative in situ and used as a heterogeneous catalyst in the asymmetric allylation of ketones. The catalyst showed good activity and excellent enantioselectivity, typically matching the results obtained in the corresponding homogeneous reaction. The allylation reaction mixture could be submitted to epoxidation by simple treatment with tert-butyl hydroperoxide (TBHP), and the tandem asymmetric allylation epoxidation process led to a highly enantioenriched epoxy alcohol with two adjacent quaternary centers as a single diastereomer. A tandem asymmetric allylation/Pauson-Khand reaction was also performed, involving simple treatment of the allylation reaction mixture with Co2(CO)8/N-methyl morpholine N-oxide. This cascade process resulted in the formation of two diastereomeric tricyclic enones in high yields and enantioselectivities.