Gerald B. Hammond

Synthesis and Structural Characterization of Stable Organogold(I) Compounds. Evidence for the Mechanism of Gold-Catalyzed Cyclizations

The vast majority of homogeneous Au-catalyzed reactions have exploited the propensity of Au to activate unsaturated carbon-carbon bonds as electrophiles. It is generally assumed that a nucleophile attacks a gold-activated carbon-carbon multiple bond to give an alkenyl Au intermediate, notwithstanding the fact that these intermediates are hitherto unknown. We have obtained room temperature stable gamma-lactone gold(I) complexes through the reaction of cationic Au(I) reagents with allenoates, under mild conditions. The reactions of one such complex with electrophiles yielded the expected products of Au-catalyzed cyclizations. These results furnish experimental evidence for the mechanism of Au-catalyzed cyclizations.

Ligand Effects and Ligand Design in Homogeneous Gold(I) Catalysis

Gold catalysis is considered one of the most important breakthroughs in organic synthesis during the past decade, but a rational understanding of ligand effects in gold catalysis is lacking. Most gold-catalyzed reactions go through three major stages: (i) electronic activation of alkyne (or allene) to generate a vinyl gold intermediate; (ii) protodeauration to generate the product and regenerate the cationic gold catalyst; (iii) decay of the active gold catalyst. Our research provides a clearer understanding of how ligands influence each of the three stages in the gold catalytic cycle. What is even more important, by not focusing on a particular gold-catalyzed reaction, we have been able to categorize most gold-catalyzed reactions and propose a ligand design protocol for each category of gold-catalyzed reactions.

Evaluation of the wound-healing activity of selected traditional medicinal plants from Perú

Folk medicine practitioners in Perú employ plant preparations as wound-healing agents on superficial and internal wounds (gastric ulcers). The results of a scientific evaluation of the wound-healing activity of nine plants found in the Amazon jungle near Iquitos and in the Andes mountains is presented. The species studied were: Peperomia galioides, Mentzelia cordifolia, Mutisia acuminata, Himatanthus sucuuba, Spondias mombin, Eleutherine bulbosa, Muehlenbeckia tamnifolia, Anredera diffusa and Jatropha curcas. These plants have also been examined for their toxicological properties, their effect on blood pressure, smooth muscle and capillary permeability. Significant wound-healing activity was detected in Peperomia galioides, Anredera diffusa and Jatropha curcas. Extracts from Peperomia galioides and Anredera diffusa had no effect on cell proliferation and did not exhibit mutagenic activity.

A survey of traditional medicinal plants from the Callejón de Huaylas, Department of Ancash, Perú

The medicinal uses of local flora from the Callejón de Huaylas, Department of Ancash, northeastern Perú, are reported. This geographical area has an old tradition of herbal healing. A total of 33 species have been documented through interactions with village elders, traditional doctors and herbalists. Of the 33 medicinal plant species surveyed in the Callejón de Huaylas, six have not been previously reported, seven have received only minor phytochemical coverage in the literature, and the medicinal uses of seven other plants have not been corroborated with traditional medicinal reports from around the world. The traditional medicinal uses of six medicinal plants have been corroborated with previously published reports but their biological activities have yet to be confirmed in the laboratory. The medicinal uses of four other plants have been corroborated with previously published reports and their biological activities have been confirmed in the laboratory. The purported medicinal use of three plant species could not be confirmed in the laboratory.

Designer HF-based fluorination reagent: highly regioselective synthesis of fluoroalkenes and gem-difluoromethylene compounds from alkynes.

Hydrogen fluoride (HF) and selected nonbasic and weakly coordinating (toward cationic metal) hydrogen-bond acceptors (e.g., DMPU) can form stable complexes through hydrogen bonding. The DMPU/HF complex is a new nucleophilic fluorination reagent that has high acidity and is compatible with cationic metal catalysts. The gold-catalyzed mono- and dihydrofluorination of alkynes using the DMPU/HF complex yields synthetically important fluoroalkenes and gem-difluoromethlylene compounds regioselectively.

Efficient Synthesis of γ-Keto Esters through Neighboring Carbonyl Group-Assisted Regioselective Hydration of 3-Alkynoates

The Au(III)-catalyzed hydration of 3-alkynoates led to a practical one-step synthesis of gamma-keto esters in high yields, through a carbonyl group participation enabled by a favored 5-endodig cyclization. This mild-aqueous ethanol, room temperature, and atom-economical method has been used effectively with a wide range of substrates. Using the same conditions, a 2-alkynoate produced the corresponding beta-keto ester in high yield.

Reactions of Cationic Gold(I) with Allenoates: Synthesis of Stable Organogold(I) Complexes and Mechanistic Investigations on Gold-Catalyzed Cyclizations

The reaction of allenoates with cationic gold(I)-generated in situ from a phosphine gold chloride and a silver salt-formed unusual, room temperature stable vinyl gold(I) lactones under very mild conditions. The scope and limitations for the synthesis of this novel organogold complex was investigated. DFT calculations on the highest occupied molecular orbitals (HOMOs) of allenoates and the natural bond orbital (NBO) charge densities provided an explanation for the limitations. A plausible mechanism for its formation was proposed based on in situ (1)H and (31)P NMR spectroscopic analyses. Controlled experiments for the cleavage of the gold-carbon bond by electrophiles indicated that this vinyl gold(I) complex is the likely intermediate in the gold-catalyzed reaction of carbon-carbon multiple bonds.

Highly efficient Cu(I)-catalyzed synthesis of N-heterocycles through a cyclization-triggered addition of alkynes.

An aminoalkyne (terminal or internal) and a terminal alkyne furnish functionalized five-, six-, and seven-membered N-heterocycles in excellent yields via a Cu(I)-catalyzed, one-pot, tandem hydroamination/alkynylation process.

Cationic Gold Catalyst Poisoning and Reactivation

High gold affinity impurities (halides, bases) in solvents, starting materials, filtration, or drying agents could affect the reactivity of gold catalyst adversely, which may significantly reduce the TON of cationic gold-catalyzed reactions. Use of a suitable acid activator (e.g., HOTf, In(OTf)3) reactivates the gold catalyst and makes the reaction proceed smoothly at low gold catalyst loading.

Antibacterial activity of some Peruvian medicinal plants from the Callejon de Huaylas.

Extracts of eight medicinal plants from the Callejon de Huaylas in Peru were screened for antibacterial activity in eighteen bacterial strains by the agar-diffusion method; six of these were active against a variety of bacteria.