Manuel A. Fernández-Rodríguez

A General, Efficient and Functional-Group-Tolerant Catalyst System for the Palladium-Catalyzed Thioetherification of Aryl Bromides and Iodides

The cross-coupling reaction of aryl bromides and iodides with aliphatic and aromatic thiols catalyzed by palladium complexes of the bisphosphine ligand CyPF-tBu (1) is reported. Reactions occur in excellent yields, broad scope, high tolerance of functional groups, and with turnover numbers that exceed those of previous catalysts by 2 or 3 orders of magnitude. These couplings of bromo- and iodoarenes are more efficient than the corresponding reactions of chloroarenes and could be conducted with less catalyst loading and/or milder reaction conditions. Consequently, limitations regarding scope and functional group tolerance previously reported in the coupling of aryl chlorides are now overcome.

Gold(I)‐Catalyzed Enantioselective Synthesis of Functionalized Indenes

MEC/FEDER (CTQ2007-61436/BQU, FPU grant to A.M., Ramon y Cajal and Juan de la Cierva contracts to M.A.F.-R. and P.G.-G.) and Junta de Castilla y Leon (BU021A09) for financial support. We also thank Dr. A. Mendoza (Universidad de Oviedo) for his assistance with the X-ray crystallographic analysis

Gold-Catalyzed Intermolecular Hetero-Dehydro-Diels-Alder Cycloaddition of Captodative Dienynes with Nitriles : A New Reaction and Regioselective Direct Access to Pyridines

For the first time, nitriles are used as 2pi electron component in a gold-catalyzed intermolecular hetero-dehydro-Diels-Alder cycloaddition with captodative enynes leading to the regioselective formation of pyridines.

One‐Pot Synthesis of Unsymmetrical Diaryl Thioethers by Palladium‐Catalyzed Coupling of Two Aryl Bromides and a Thiol Surrogate

Aromatic thioethers are valuable synthetic intermediates frequently found in biologically and pharmaceutically active molecules or in polymeric materials. In particular, diaryl-and aryl-heteroaryl thioethers are essential components of numerous drugs with potential application in the treatment of inflammation, cancer, human immunodeficiency virus (HIV), asthma, Alzheimer’s and Parkinson’s diseases.[1–6] Furthermore, diaryl thioethers are precursors to the corresponding sulfoxides and sulfones that also exhibit important biological activities and are contained in antifungal and anti-cancer agents as well as in potential drug candidates for Alzheimer’s disease or HIV.[7–11] Classical methods for the synthesis of such thioethers encompass thermal reaction of arenes with sulfur,[12,13] base-mediated reactions of activated chloroarenes with thiophenols,[14] and condensation of organolithium or Grignard reagents with chlorophenyl sulfide.[15] However, these reactions often require harsh reaction conditions, occur with low regioselectivity, and form disulfide and thiantrene side products.[12,13]

A Practical, One-Pot Synthesis of Highly Substituted Thiophenes and Benzo[b]thiophenes from Bromoenynes and o-Alkynylbromobenzenes

An efficient synthesis of thiophenes and benzo[b]thiophenes has been developed from easily available bromoenynes and o-alkynylbromobenzene derivatives. This novel one-pot procedure involves a Pd-catalyzed C-S bond formation using a hydrogen sulfide surrogate followed by a heterocyclization reaction. Moreover, in situ functionalization with selected electrophiles further expands the potential of this methodology to the preparation of the corresponding highly substituted sulfur heterocycles.

Synthesis of diverse indole-containing scaffolds by gold(I)-catalyzed tandem reactions of 3-propargylindoles initiated by 1,2-indole migrations: scope and computational studies.

Similar to propargylic carboxylates and sulphides, 3-propargylindoles undergo 1,2-indole migrations under cationic gold(I) catalysis. The intermediate Au-carbenoid complex may evolve through different pathways depending on the substituents at the propargylic and terminal positions of the alkyne moiety. Thus, 3-indenylindole derivatives were easily obtained through formal iso-Nazarov or Nazarov cyclizations. DFT computations support the formation of an alkylidenecyclopropane intermediate that undergoes gold-iso-Nazarov or gold-Nazarov cyclizations upon torquoselective ring opening. In addition, 3-dienylindoles could be accessed when none of the referred pathways were accessible and so the intermediate Au-carbenoid complex evolved via a 1,2-C-H insertion reaction. We have also demonstrated that the final products can be obtained in a one-pot protocol from easily available propargylic alcohols and indoles.

Approaches to the Synthesis of 2,3-Dihaloanilines. Useful Precursors of 4-Functionalized-1H-indoles

2,3-Dihaloanilines have been proved as useful starting materials for synthesizing 4-halo-1H-indoles. Subsequent or in situ functionalization of the prepared haloindoles allows the access to a wide variety of 2,4- or 2,3,4-regioselectively functionalized indoles in good overall yields. As no efficient synthetic routes to 2,3-dihaloanilines have been described in the literature, different approaches to the preparation of these 1,2,3-functionalized aromatic precursors are now presented. The most general one involves a Smiles rearrangement from the corresponding 2,3-dihalophenols and allows the preparation of 2,3-dihaloanilides in a straightforward and synthetically useful manner.

Gold(I)-catalyzed tandem cyclization-selective migration reaction of 1,3-dien-5-ynes: regioselective synthesis of highly substituted benzenes.

Highly substituted benzene derivatives have been easily prepared in a regioselective way from readily available 1,3-hexadien-5-ynes through a gold(I)-catalyzed tandem reaction. The process involves an initial cyclization followed by a selective Wagner-Meerwein shift in which the migration preference seems to be determined by the ability to stabilize a positive charge.

An unprecedented use for glycerol: chemoselective reducing agent for sulfoxides

A new application for glycerol that expands its possibilities beyond a green solvent and a precursor of value-added products has been demonstrated. Simple, easily available, and environmentally friendly dioxomolybdenum(VI) complexes are highly efficient catalysts for the chemoselective sulfoxide deoxygenation with this biomass-derived chemical feedstock. Both refined glycerol and crude glycerin can be used, thus expanding the potential application of this reaction. Subsequent transformation of glycerol during this reductive process has also been investigated.

Regioselective Synthesis of Elusive 4,9-Dihydro-1H-Carbazoles by Gold-Catalyzed Cycloisomerization of 3-Allenylmethylindoles

A general and efficient synthesis of 4,9-dihydro-1H-carbazoles from 3-allenylmethylindoles is reported. The process, catalyzed by a cationic gold(I) complex, involves a formal C2-H bond activation of the indole unit by reaction with the allene. The nature of the substituents at the allylic and terminal positions of the allene moiety has a crucial effect on the regioselectivity of the cyclization, which is also influenced by the catalyst and the solvent employed. Moreover, some evidence of the contribution of different reaction routes is provided, which led us to propose a plausible multipathway mechanism consistent with all of the results described.