Phil Ho Lee

Synthesis of Pyrroles from Terminal Alkynes, N-Sulfonyl Azides, and Alkenyl Alkyl Ethers through 1-Sulfonyl-1,2,3-triazoles

A method for synthesis of substituted pyrroles has been developed. 1-Sulfonyl-1,2,3-triazoles generated from terminal alkynes gave α-imino rhodium carbene complexes, which when reacted with alkenyl alkyl ethers afforded substituted pyrroles. The method can be efficiently applied to a one-pot sequential reaction starting from terminal alkynes.

Palladium-Catalyzed Carbon−Sulfur Cross-Coupling Reactions with Indium Tri(organothiolate) and Its Application to Sequential One-Pot Processes

It was found that indium tri(organothiolate) is an effective nucleophilic coupling partner in Pd-catalyzed C-S cross-coupling reactions to produce the functionalized sulfides in excellent yields with high atom efficiency and complete regio- and chemoselectivity. The present method was efficiently applied to the sequential one-pot processes composed of selective double C-S cross-coupling reactions and addition of allylindium or allenylindium to aldedyde to give the functionalized sulfides and bis(sulfides).

3-Hydroxymorphinan, a metabolite of dextromethorphan, protects nigrostriatal pathway against MPTP-elicited damage both in vivo and in vitro

We investigated the neuroprotective property of analogs of dextromethorphan (DM) in lipopolysaccharide (LPS) and 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP) models to identify neuroprotective drugs for Parkinsons disease (PD). In vivo studies showed that daily injections with DM analogs protected dopamine (DA) neurons in substantia nigra pars compacta and restored DA levels in striatum using two different models for PD. Of the five analogs studied, 3‐hydroxymorphinan (3‐HM), a metabolite of DM, was the most potent, and restored DA neuronal loss and DA depletion up to 90% of the controls. Behavioral studies showed an excellent correlation between potency for preventing toxin‐induced decrease in motor activities and neuroprotective effects among the DM analogs studied, of which 3‐HM was the most potent in attenuating behavioral damage. In vitro studies revealed two glia‐dependent mechanisms for the neuroprotection by 3‐HM. First, astroglia mediated the 3‐HM‐induced neurotrophic effect by increasing the gene expression of neurotrophic factors, which was associated with the increased acetylation of histone H3. Second, microglia participated in 3‐HM‐mediated neuroprotection by reducing MPTP‐elicited reactive microgliosis as evidenced by the decreased production of reactive oxygen species. In summary, we show the potent neuroprotection by 3‐HM in LPS and MPTP PD models investigated. With its high efficacy and low toxicity, 3‐HM may be a novel therapy for PD.—Zhang, W., Shin, E‐J., Wang, T., Lee, P. H., Pang, H., Wie, M. B., Kim, W‐K., Kim, S‐J., Huang, W‐H., Wang, Y., Zhang, W., Hong, J‐S., Kim, H‐C. 3‐Hydroxymorphinan, a metabolite of dextromethorphan, protects nigrostriatal pathway against MPTP‐elicited damage both in vivo and in vitro. FASEB J. 20, 2496–2511 (2006)

Rhodium-catalyzed oxidative coupling through C–H activation and annulation directed by phosphonamide and phosphinamide groups

Rhodium-catalyzed oxidative coupling reactions via C-H activation and annulation directed by phosphonamide and phosphinamide groups were developed under aerobic conditions, which produced benzazaphosphole 1-oxides and phosphaisoquinolin-1-oxides.

Synthesis of Phosphaisocoumarins through Rhodium-Catalyzed Cyclization Using Alkynes and Arylphosphonic Acid Monoesters

A rhodium-catalyzed cyclization using alkynes and arylphosphonic acid monoesters for the synthesis of phosphaisocoumarins is reported. A number of arylphosphonic acid monoesters were selectively cyclized in high yields with functional group tolerance. In addition, unsymmetrical alkynes are applied in high regioselectivity.

Synthesis of 2-aryl-2H-benzotrizoles from azobenzenes and N-sulfonyl azides through sequential rhodium-catalyzed amidation and oxidation in one pot.

An efficient synthetic method of 2-aryl-2H-benzotriazoles from nonprefunctionalized azobenzenes and N-sulfonyl azides via sequential Rh-catalyzed amidation (C-N bond formation) and oxidation (N-N bond formation) with PhI(OAc)2 in one pot is reported.

Synthesis of Cinnolin-3(2H)-one Derivatives from Rh-Catalyzed Reaction of Azobenzenes with Diazotized Meldrum’s Acid

A synthetic method of a wide range of cinnolin-3(2H)-one derivatives is developed from the reaction of symmetrical as well as unsymmetrical azobenzenes with diazotized Meldrums acid via Rh-catalyzed C-H alkylation followed by cyclization.

Rhodium-Catalyzed Oxidative Cyclization of Arylphosphonic Acid Monoethyl Esters with Alkenes: Efficient Synthesis of Benzoxaphosphole 1-Oxides

Rhodium-catalyzed tandem oxidative alkenylation and an intramolecular oxy-Michael reaction were developed using arylphosphonic acid monoethyl esters and alkenes under aerobic conditions, which produced benzoxaphosphole 1-oxides in good to excellent yields.

Synthesis of Pyrazines from Rhodium-Catalyzed Reaction of 2H-Azirines with N-Sulfonyl 1,2,3-Triazoles

An efficient synthetic route to a wide range of trisubstituted pyrazines is developed from Rh-catalyzed reaction of 2H-azirines with N-sulfonyl-1,2,3-triazoles through the elimination of nitrogen molecule and arylsulfinic acid. The present reaction proceeds through formation of in situ generated dihydropyrazines.

Palladium-Catalyzed C–H Arylation Using Phosphoramidate as a Directing Group at Room Temperature

This communication describes the first phosphoramidate directing group for synthetically useful arylation. Remarkably, the nature of a new directing group drives selective C-H bond activation to afford diverse N-aryl phosphoramidates in good to excellent yields at room temperature.