Buchwald–Hartwig amination of chloroheteroarenes has been a challenging synthetic process, with very few protocols promoting this important transformation at ambient temperature. The current report discusses about an efficient copper-based catalytic system (Cu/PTABS) for the amination of chloroheteroarenes at ambient temperature in water as the sole reaction solvent, a combination that is first to be reported. A wide variety of chloroheteroarenes could be coupled efficiently with primary and secondary amines as well as selected amino acid esters under mild reaction conditions. Catalytic efficiency of the developed protocol also promotes late-stage functionalization of active pharmaceutical ingredients (APIs) such as antibiotics (floxacins) and anticancer drugs. The catalytic system also performs efficiently at a very low concentration of 0.0001 mol % (TON = 980,000) and can be recycled 12 times without any appreciable loss in activity. Theoretical calculations reveal that the π-acceptor ability of the ligand PTABS is the main reason for the appreciably high reactivity of the catalytic system. Preliminary characterization of the catalytic species in the reaction was carried out using UV–VIS and ESR spectroscopy, providing evidence for the Cu­(II) oxidation state.

Commercially available Quadrol, N,N,N',N'-tetrakis(2-hydroxypropyl)ethylenediamine (THPEN), has been used for the first time as N^N- donor neutral hydrophilic ligand in the synthesis and characterization of new water soluble palladium (II) complexes...

The synthesis and characterization of new water-soluble dinuclear palladacycles of the general formula [{Pd­(R-C^N-SO3Na)­(μ-AcO)}2] (R = H (1), OMe (2), Cl (3)) incorporating an ortho-metalated sodium 4-(N-benzylideneamino)­benzenesulfonate moiety is reported. These complexes have been revealed to be excellent phosphine-free catalysts for the synthesis of functionalized nucleoside analogues involving a low-temperature Suzuki–Miyaura coupling of 5-iodo-2′-deoxyuridine with different arylboronic acids in neat water. The potential of 1–3 as synthetic precursors was also tested, and bridging acetates were cleaved by reaction with neutral PPh3, yielding the corresponding mononuclear derivatives [Pd­(R-C^N-SO3Na)­(AcO)­(PPh3)] (R = H (4), MeO (5), Cl (6)). Analytical and spectroscopic techniques confirmed the proposed formulas and reactivities reported for complexes 1–6. Structural characterization by X-ray diffraction of single crystals grown from samples of 4 and 6 produced the unexpected but valuable crystallization-mediated compounds 4cm and 6cm that also supported the results presented here.

A versatile synthetic protocol involving the room temperature direct arylation of benzothiazole with a wide variety of iodoarenes under Ag-promoted Pd-catalyzed conditions in HFIP as the reaction solvent has been...

Nucleosides modification via conventional cross-coupling has been performed using different catalytic systems and found to take place via long reaction times. However, since the pandemic, nucleoside-based antivirals and vaccines have received widespread attention and the requirement for rapid modification and synthesis of these moieties has become a major objective for researchers. To address this challenge, we describe the development of a rapid flow-based cross-coupling synthesis protocol for a variety of C5-pyrimidine substituted nucleosides. The protocol allows for facile access to multiple nucleoside analogues in very good yields in a few minutes compared to conventional batch chemistry. To highlight the utility of our approach, the synthesis of an anti-HSV drug, BVDU was also achieved in an efficient manner using our new protocol.

Modification of nucleosides via cross-coupling processes has been carried out extensively on unprotected halonucleosides to produce functionalized nucleosides that are often developed for incorporation into oligonucleotides or used as fluorescent probes. This approach requires protection of the 5 -OH with the 4,4 -dimethoxytrityl (DMTr) group, which is complicated and a common cause of reaction failure. Here we report a method for direct functionalization of 5 -O-DMTr-5-iodo-2 -deoxyuridine via Suzuki-Miyaura cross-coupling, Heck alkenylation, and carboamidation. This approach facilitates rapid synthesis of a variety of C5-substituted 5 -O-DMTr-2 -deoxyuridine derivatives. © 2022 Wiley Periodicals LLC. BasicProtocol 1: Synthesis of the SerrKap palladacycle complex Basic Protocol 2: Suzuki-Miyaura coupling of 5 -O-DMTr-5-iodo-2deoxyuridine using SerrKap palladacycle Basic Protocol 3: Heck coupling of 5 -O-DMTr-5-iodo-2 -deoxyuridine using SerrKap palladacycle Basic Protocol 4: Heck coupling of 5 -O-DMTr-5-iodo-2 -deoxyuridine with Ruth linker using Pd(OAc) 2 /PTABS Basic Protocol 5: Carbonylative amidation of 5 -O-DMTr-5-iodo-2deoxyuridine using Pd(OAc) 2 /PTABS

Etherification of chloroheteroarenes was performed at low temperatures under metal‐free, ligand‐free and base‐free conditions, that is, the reaction is promoted by the cooperative effect of DMSO (solvent) as a promoter and K3PO4 providing the catalytic surface (rather than a base). The protocol exhibits good substrate scope under mild reaction conditions and has also been explored mechanistically.

Ruth linker is a C5 pyrimidine modified nucleoside analogue widely utilized for the incorporation of a primary amine in a synthetic oligonucleotide. The increasing demand for non-radioactive labeling, detection of biomolecules, and assembly of COVID-19 test kits has triggered a need for scale-up of Ruth linker. Herein, an efficient protocol involving a palladium-catalyzed Heck alkenylation is described. The synthesis has been optimized with a goal of low catalyst concentration, column-free isolation, high product purity, reproducibility, and shorter reaction time. The scalability and utility of the process have been demonstrated successfully on a 100 g scale (starting material). Additionally, for scale-up of the Heck alkenylation protocol, 7-phospha-1,3,5-triaza-adamantanebutane sulfonate (PTABS) as the coordinating caged phosphine ligand was also synthesized on a multigram scale after careful optimization of the conditions.