Synthesis of Enantioenriched α,α-Dichloro- and α,α-Difluoro-β-Hydroxy Esters and Amides by Ruthenium-Catalyzed Asymmetric Transfer Hydrogenation

A mild and convenient approach was developed to prepare a series of α,α-dihalogeno β-hydroxy esters or amides by using commercially available Noyori’s complex [RuCl­(<i>p</i>-cymene)­(<i>R</i>,<i>R</i>)-TsDPEN] as a catalyst (S/C = 100−200) in the asymmetric transfer hydrogenation of the corresponding ketones. Moderate to high yields (up to 99%) and excellent enantioselectivities (up to >99% ee) were achieved for a series of variously substituted dichloro and difluoro β-hydroxy esters and amides

Ruthenium-Catalyzed [2 + 2 + 2] Cycloaddition Reaction Forming 2‑Aminopyridine Derivatives from α,ω-Diynes and Cyanamides

A novel, efficient, and mild synthetic route for the preparation of 2-aminopyridines via ruthenium-mediated [2 + 2 + 2] cycloaddition of α,ω-diynes and cyanamides has been developed. This atom-economical catalytic process demonstrated remarkable regioselectivities to access pyridine derivatives of high synthetic utility

HNTf₂‑Catalyzed Regioselective Preparation of Polysubstituted Naphthalene Derivatives Through Alkyne–Aldehyde Coupling

We report herein the preparation of polysubstituted naphthalene derivatives by the original Brønsted-acid-catalyzed benzannulation reaction of phenylacetaldehydes with alkynes. This reaction, which was usually performed with Lewis acids under thermal activation, is efficiently promoted by 15 mol % of triflimide (HNTf₂) at room temperature under metal-free and mild reaction conditions and leads with a perfect regioselectivity to a wide variety of diversely functionalized naphthalenes in 41–78% yield. A catalytic cycle is proposed together with some further applications of this catalytic system in the related benzannulation transformations of epoxide and acetal derivatives

Access toward Fluorenone Derivatives through Solvent-Free Ruthenium Trichloride Mediated [2 + 2 + 2] Cycloadditions

An efficient and practical route for the preparation of highly substituted fluorenones and analogues via solvent-free ruthenium trichloride mediated [2 + 2 + 2] cycloaddition of α,ω-diynes and alkynes has been developed. This green chemistry approach involves a solventless and atom-economical catalytic process to generate densely functionalized fluorenones and related derivatives of high synthetic utility

Enantioselective Synthesis of 1-Aryl-tetrahydroisoquinolines through Iridium Catalyzed Asymmetric Hydrogenation

Asymmetric hydrogenation of 1-aryl-3,4-dihydroisoquinolines using the [IrCODCl]₂/(<i>R</i>)-3,5-diMe-Synphos catalyst is reported. Under mild reaction conditions, this atom-economical process provides easy access to a variety of enantioenriched 1-aryl-1,2,3,4-tetrahydroisoquinoline derivatives, which are important pharmacophores found in several pharmaceutical drug candidates, in high yields and enantiomeric excesses up to 99% after a single crystallization

Synthesis and Antiproliferative and Metabolic Evaluations of Novel Securinine Derivatives

New securinine analogues have been prepared by semisynthesis. Two series were developed using either Suzuki or Sonogashira cross coupling reactions. The <i>in vitro</i> cytotoxicity of the compounds was assayed against HCT-116 colon cancer cells. The most potent derivatives showed promising growth inhibition on four tumoral cell lines giving a valuable insight on the structure–activity relationship (SAR) of securinine. Moreover, high antiproliferative effect against A-375 (melanoma) was observed with IC₅₀ up to 60 nM

Palladium-Catalyzed Efficient Enantioselective Synthesis of Chiral Allenes: Steric and Electronic Effects of Ligands

Asymmetric synthesis of chiral allenes starting from prochiral substrates under mild reaction conditions promoted by Pd-SYNPHOS catalyst is reported. This protocol provides an efficient access to various enantioenriched aryl- and alkyl- substituted allenes, which are versatile building blocks of high utility to both organic and medicinal chemists, in excellent isolated yields (up to 96%) and high enatiomeric ratio values (up to 95:5). In addition, a comparative study using several <i>C</i>₂-symmetric atropisomeric diphosphine ligands revealed the overwhelming impact of the steric and electronic properties of the ligands for the catalytic efficiency of this process

Enantioselective Rhodium-Catalyzed Synthesis of α-Chloromethylene-γ-Butyrolactams from <i>N</i>-Allylic Alkynamides

The first enantioselective cycloisomerization with intramolecular halogen migration of various 1,6-enynes promoted by a cationic Rh-Synphos catalyst is reported. This method provides an efficient route to enantiomerically enriched γ-butyrolactam derivatives, which are important core scaffolds found in numerous natural products and biologically active molecules. Good yields and enantiomeric excesses up to 96% are achieved

Heck Coupling Using a Vinyliodo-MIDA Boronate: An Efficient and Modular Access to Polyene Frameworks

A simple Heck coupling between an alkenyl iodo-boronate and a variety of terminal olefins is disclosed. This method gives access to a wide range of dienic moieties including valuable bis-functionalized dienes. The synthetic potential of the coupling reaction is demonstrated by a short and modular preparation of several tetraenic compounds

Palladium(0)-Catalyzed Dearomative [3 + 2] Cycloaddition of 3‑Nitroindoles with Vinylcyclopropanes: An Entry to Stereodefined 2,3-Fused Cyclopentannulated Indoline Derivatives

The palladium(0)-catalyzed diastereoselective dearomative cyclopentannulation of 3-nitroindoles with vinylcyclopropanes is described. This straightforward and highly atom-economical method leads to a wide range of functionalized indolines in good yields and diastereoselectivities and represents an unprecedented entry toward the valuable 2,3-fused cyclopentannulated indoline scaffold