Sachin Handa

Sustainable Fe–ppm Pd nanoparticle catalysis of Suzuki-Miyaura cross-couplings in water

Iron lends power to traces of palladium Palladium (Pd) is a mainstay of chemical catalysis. The precious metal has a knack for forging carbon-carbon (C-C) bonds. Handa et al. now report that when mixed in a specific preparation with iron, just parts per million of Pd suffice to catalyze the C-C bond–forming Suzuki coupling reaction. The addition of surfactants allowed the reaction to proceed in water. The protocol bodes well for conserving Pd in pharmaceutical and agrochemical synthesis. Science, this issue p. 1087 An iron preparation substantially lowers the quantity of palladium needed to catalyze a common reaction that forms C-C bonds. Most of today’s use of transition metal–catalyzed cross-coupling chemistry relies on expensive quantities of palladium (Pd). Here we report that nanoparticles formed from inexpensive FeCl3 that naturally contains parts-per-million (ppm) levels of Pd can catalyze Suzuki-Miyaura reactions, including cases that involve highly challenging reaction partners. Nanomicelles are employed to both solubilize and deliver the reaction partners to the Fe–ppm Pd catalyst, resulting in carbon-carbon bond formation. The newly formed catalyst can be isolated and stored at ambient temperatures. Aqueous reaction mixtures containing both the surfactant and the catalyst can be recycled.

Aerobic Oxidation in Nanomicelles of Aryl Alkynes, in Water at Room Temperature†

On the basis of the far higher solubility of oxygen gas inside the hydrocarbon core of nanomicelles, metal and peroxide free aerobic oxidation of aryl alkynes to β-ketosulfones has been achieved in water at room temperature. Many examples are offered that illustrate broad functional group tolerance. The overall process is environmentally friendly, documented by the associated low E Factors.

Safe and Selective Nitro Group Reductions Catalyzed by Sustainable and Recyclable Fe/ppm Pd Nanoparticles in Water at Room Temperature

As a result of a unique synergy between ligand-free Fe/ppm Pd nanoparticles and PEG-containing designer surfactants, a facile and selective reduction of nitro-containing aromatics and heteroaromatics can be effected in water at room temperature in the presence of NaBH4 . This new nanotechnology involves low catalyst loadings, is highly chemoselective, and tolerates a wide variety of functional groups. The process, which includes recycling of the entire aqueous medium, offers a general, environmentally responsible, and notably safe approach to highly valued reductions of nitro-containing compounds.

HandaPhos: A General Ligand Enabling Sustainable ppm Levels of Palladium‐catalyzed Cross‐Couplings in Water at Room Temperature

The new monophosphine ligand HandaPhos has been identified such that when complexed in a 1:1 ratio with Pd(OAc)2, enables Pd-catalyzed cross-couplings to be run using ≤1000u2005ppm of this pre-catalyst. Applications to Suzuki-Miyaura reactions involving highly funtionalized reaction partners are demonstrated, all run using environmentally benign nanoreactors in water at ambient temperatures. Comparisons with existing state-of-the-art ligands and catalysts are discussed herein.

Nanonickel-catalyzed Suzuki-Miyaura cross-couplings in water.

Nickel nanoparticles, formed inu2005situ and used in combination with micellar catalysis, catalyze Suzuki-Miyaura cross-couplings in water under very mild reaction conditions.

Asymmetric Gold‐Catalyzed Lactonizations in Water at Room Temperature

Asymmetric gold-catalyzed hydrocarboxylations are reported that show broad substrate scope. The hydrophobic effect associated with inu2005situ-formed aqueous nanomicelles gives good to excellent ees of product lactones. In-flask product isolation, along with the recycling of the catalyst and the reaction medium, are combined to arrive at an especially environmentally friendly process.

Access to 2′-Substituted Binaphthyl Monoalcohols via Complementary Nickel-Catalyzed Kumada Coupling Reactions under Mild Conditions: Key Role of a P,O Ligand

Two complementary Kumada coupling methods for the conversion of monotriflated 1,1-binaphthalene-2,2-diol (BINOL) into 2-substituted binaphthyl monoalcohols under mild conditions are reported. A protocol using NiCl2(dppe), in combination with an improved preparation of the monotriflate, is effective for 1,1-binaphthalene-2-ols containing unsubstituted or electron-poor aryl or benzyl 2-substituents. An alternative procedure, using a potentially hemilabile-bidentate phosphinan-4-ol ligand, is superior for products containing neopentyl or electron-rich aryl 2-substituents. The obtained binaphthyl alcohols represent potentially useful synthons for chiral ligands and auxiliaries.

Enantiomeric separation of isochromene derivatives by high-performance liquid chromatography using cyclodextrin based stationary phases and principal component analysis of the separation data

Isochromene derivatives are very important precursors in the natural products industry. Hence the enantiomeric separations of chiral isochromenes are important in the pharmaceutical industry and for organic asymmetric synthesis. Here we report enantiomeric separations of 21 different chiral isochromene derivatives, which were synthesized using alkynylbenzaldehyde cyclization catalyzed by chiral gold(I) acyclic diaminocarbene complexes. All separations were achieved by high-performance liquid chromatography with cyclodextrin based (Cyclobond) chiral stationary phases. Retention data of 21 chiral compounds and 14 other previously separated isochromene derivatives were analyzed using principal component analysis. The effect of the structure of the substituents on the isochromene ring on enantiomeric resolution as well as the other separation properties was analyzed in detail. Using principal component analysis it can be shown that the structural features that contribute to increased retention are different from those that enhance enantiomeric resolution. In addition, principal component analysis is useful for eliminating redundant factors from consideration when analyzing the effect of various chromatographic parameters. It was found that the chiral recognition mechanism is different for the larger γ-cyclodextrin as compared to the smaller β-cyclodextrin derivatives. Finally this specific system of chiral analytes and cyclodextrin based chiral selectors provides an effective format to examine the application of principal component analysis to enantiomeric separations using basic retention data and structural features.

Sustainable HandaPhos-ppm Palladium Technology for Copper-Free Sonogashira Couplings in Water under Mild Conditions

Complexation of ca. 1000 ppm Pd(OAc)2 with the ligand HandaPhos (1-1.5:1) leads to a precatalyst that efficiently mediates Sonogashira couplings in aqueous nanomicelles under very mild conditions. Neither copper nor organic solvent is required in the reaction medium, and the product can be isolated directly from the reaction flask, leaving behind a reaction mixture that can be recycled without additional additives.

Micelle-Enabled Clean and Selective Sulfonylation of Polyfluoroarenes in Water Under Mild Conditions

Proline-based designer surfactant FI-750-M has been demonstrated to enable selective nucleophilic aromatic substitution of polyfluoro(hetero)arenes by sulfinate salts in water under mild micellar conditions. Resultant sulfones were obtained from diverse substrates in good yields without side product formation and could usually be purified by simple filtration. The nature of micelles of FI-750-M and the solubility of coupling partners in different micellar regions has been supported by dynamic light scattering, cryo-TEM, and DFT calculations.