Asymmetric Pd(II)-catalyzed C−O, C−N, C−C bond formation using alkenes as substrates : insight into recent enantioselective developments

This Review summarizes the advances in the catalytic enantioselective mono- and difunctionalization of alkenes, highlighting the fundamental role of ligands. Several types of asymmetric reactions have been developed involving different bonds formation, C−O, C−N and C−C, highlighting the urgency to go ahead in the search for new ligands and synthetic methodologies in order to improve the control over the reaction selectivity and activity and thus, to increase the applications in the synthesis of heterocyclic scaffolds and biologically active compounds. The Review is organized into paragraphs, which discuss the type of bond formed during the nucleopalladation, C−O, C−N, C−C bonds, and the type of reaction involved

Non-Decarboxylative Ruthenium-Catalyzed Rearrangement of 4-Alkylidene-isoxazol-5-ones to Pyrazole- and Isoxazole-4-carboxylic Acids

Treatment of 4-(2-hydroaminoalkylidenyl)- and 4-(2-hydroxyalkylidenyl)-substituted isoxazol-5(4H)-ones with catalytic amounts of [RuCl2(p-cymene)]2, without any additive, afforded pyrazole- and isoxazole-4-carboxylic acids, respectively. The presence of an intramolecular H-bond in these substrates was the key to divert the classical mechanism toward a ring-opening non-decarboxylative path that is expected to generate a vinyl Ru-nitrenoid intermediate, the cyclization of which affords the rearranged products. A gram scale protocol demonstrated the synthetic applicability of this transformation

Methanol as a C1 Source for the Synthesis of 1,3‐Polyheterocyclic Systems

A very attractive approach toward 1,3-polyheterocyclic systems was provided exploiting the copper-catalyzed reaction of aminoalcohols and diaminoalkanes, in oxidative conditions and in the presence of methanol. The synthetic pathway showed the involvement of methanol both as solvent and as a reagent, making the procedure particularly efficient and sustainable for the synthesis of five-, six-, and seven-membered polyheterocyclic rings.A simple, efficient and low-cost procedure for the synthesis of 1,3-polyheterocyclic systems was reported, starting from the easily accessible aminoalcohols or diaminoalkanes, using CuCl2 as catalyst, H2O2, as inexpensive oxidant agent, and methanol acting both as solvent and reagent, proceeding under mild reaction conditions.imag

Selective 7- endo -Cyclization of 3-Aza-5-alkenols through Oxidative Pd(II)-Catalyzed Olefin Oxyarylation

3-Aza-5-alkenols undergo selective 7- endo - trig cyclization when treated with a catalytic Pd(II) species, CuCl2and ArSnBu3giving 7-aryl-substituted oxazepanes. The intramolecular alkoxylation occurs with formation of a seven-membered ring only when associated with an arylating step. Otherwise, 6- exo-trig reactions, providing morpholine derivatives, were observed

Ruthenium-Catalyzed Hydroamination of Aminoallenes: an Approach to Vinyl Substituted Heterocycles

Heterosubstituted aminoallenes underwent smooth ruthenium-catalyzed intramolecular exo-hydroamination reactions yielding the corresponding five-, six-, or seven-membered 1,3-diaza- or 1,3-oxaza-heterocyclic structures. This procedure is a valuable and less expensive alternative to the already known transition metal-catalyzed hydroamination reactions of aminoallenes

Divergent Palladium- and Platinum-Catalyzed Intramolecular Hydroamination/Hydroarylation of O-Propargyl-2-aminophenols

A fruitful divergent cyclization of terminal alkynes arising from 2-aminophenols depending on the transition metal employed is reported. Under palladium- and platinum-catalysis, the total regioselective carbon\u2013nitrogen or carbon\u2013carbon bonds formation afforded 1,4-benzoxazines or benzopyrans, through different reaction pathways. The subsequent functionalization of the benzopyran scaffold paved the way for a new synthesis of the tricyclic pyrano[3,2-h]quinolines

Copper-Catalyzed Alkoxylation as Key Step to Convert Isatin to Oxazinoindol-2-one Derivatives

The treatment of N-alkyl-5,7-dibromoisatin derivatives through the copper-catalyzed sequential processes consisting of intra/intermolecular alkoxylation/amination or double alkoxylation provided the pyrrolo[1, 2,3-de]-1,4-benzoxazine derivatives. Moreover, the alkoxylation/arylation process proceeded in a one-pot fashion under tandem copper-palladium catalysis affording 5-(hetero)aryl substituted hetero-tricyclic systems. Biological evaluation of the synthesized compounds showed antiproliferative activity on the low micromolar range

A new scaffold of topoisomerase I inhibitors: Design, synthesis and biological evaluation

The synthesis of a new hexacyclic system was realized starting from tryptamines and exploiting as a key step a sequential Pd-catalyzed N-arylation/acylation reaction. Having topoisomerases as biological target and the campthotecins class as benchmark, the new scaffold was decorated with substituents having different polarity and tested as Topoisomerase I inhibitors