Synthesis of (±)-Emtricitabine and (±)-Lamivudine by Chlorotrimethylsilane–Sodium Iodide-Promoted Vorbrüggen Glycosylation

By simple combination of water and sodium iodide (NaI) with chlorotrimethylsilane (TMSCl), promotion of a Vorbrüggen glycosylation en route to essential HIV drugs emtricitabine (FTC) and lamivudine (3TC) is achieved. TMSCl–NaI in wet solvent (0.1 M water) activates a 1,3-oxathiolanyl acetate donor for N-glycosylation of silylated cytosine derivatives, leading to cis-oxathiolane products with up to 95% yield and 20:1 dr. This telescoped sequence is followed by recrystallization and borohydride reduction, resulting in rapid synthesis of (±)-FTC/3TC from a tartrate diester.

Automated On-Demand Titration of Organometallic Reagents in Continuous Flow,

The use of strong organometallic bases and nucleophiles is commonplace in modern organic synthesis. That they react with a wide range of functional groups requires accurate and precise stoichiometry in reactions that utilize them. For best results, these bases are titrated prior to use, and such titrations can be time-consuming and variable due to human error near the end point. Herein, we describe an automated method for titrations of multiple commercial organometallic reagents enabled by continuous flow. Through utilizations of continuous monitoring via UV–vis spectroscopy and a feedback loop developed within LabVIEW, titrations with enhanced reproducibility were provided over current batch procedures

Anion-Selective Redox-Electrodes: Electrochemically-Mediated Separation with Heterogeneous Organometallic Interfaces

Redox species have been explored extensively for catalysis, energy storage, and molecular recognition. It is shown that nanostructured pseudocapacitive electrodes functionalized with ferrocene-based redox polymers are an attractive platform for the selective sorptive separation of dilute organic anions from strong aqueous and organic electrolyte solutions, and subsequent release of the sorbed ions to a stripping phase through electrochemical control of the specific binding processes. A remarkable degree of selectivity is shown for carboxylates (–COO–), sulfonates (–SO3−), and phosphonates (–PO3−2) over inorganic anions such as PF6− and ClO4− (separation factor 140 in aqueous and 3000 in organic systems), and between carboxylates with various substituents, based on differences in electronic structure and density of the adsorbates, beyond size, and charge. Our organometallic redox electrodes are a promising platform for targeting aqueous and organic systems requiring high separation factors and fast throughput, such as in the recovery of value-added products from organic synthesis and isolation of dilute yet highly toxic organic contaminants. The combination of spectroscopic experiments and quantum chemistry sheds light on a selective binding mechanism based on redox-enhanced hydrogen bonding between the cyclopentadienyl ligand and the carboxylate functional group, with broader implications for molecular design, supramolecular recognition, and metallocene catalysis.

Continuous Flow Synthesis of Ketones from Carbon Dioxide and Organolithium or Grignard Reagents

We describe an efficient continuous flow synthesis of ketones from CO2 and organolithium or Grignard reagents that exhibits significant advantages over conventional batch conditions in suppressing undesired symmetric ketone and tertiary alcohol byproducts. We observed an unprecedented solvent-dependence of the organolithium reactivity, the key factor in governing selectivity during the flow process. A facile, telescoped three-step–one-flow process for the preparation of ketones in a modular fashion through the in-line generation of organometallic reagents is also established.

A Broadly Applicable Strategy for Entry into Homogeneous Nickel(0) Catalysts from Air-Stable Nickel(II) Complexes

A series of air-stable nickel complexes of the form L2Ni(aryl) X (L = monodentate phosphine, X = Cl, Br) and LNi(aryl)X (L = bis-phosphine) have been synthesized and are presented as a library of precatalysts suitable for a wide variety of nickel-catalyzed transformations. These complexes are easily synthesized from low-cost NiCl2·6H2O or NiBr2·3H2O and the desired ligand followed by addition of 1 equiv of Grignard reagent. A selection of these complexes were characterized by single-crystal X-ray diffraction, and an analysis of their structural features is provided. A case study of their use as precatalysts for the nickel-catalyzed carbonyl-ene reaction is presented, showing superior reactivity in comparison to reactions using Ni(cod)2. Furthermore, as the precatalysts are all stable to air, no glovebox or inert-atmosphere techniques are required to make use of these complexes for nickel-catalyzed reactions.