Arylbenzo[<Emphasis Type="Italic">h</Emphasis>][1, 6]naphthyridine Derivatives: Synthesis and Photophysical Properties

Suzuki-Miyaura cross coupling was successfully used for C5-arylation in 4-amino-2-chloroquinoline-3-carbaldehyde using arylbornic acid and tetrakistriphenylphosphine palladium catalyst in water. Friedländer condensation reaction on 4-amino-2-chloro/2-arylquinoline-3-carbaldehyde and aromatic ketones gave novel aryl and diarylbenzo[h] [1, 6]naphthyridines in good yields. Fluorescence quantum yields were increased by introducing C2 and C5 π donor aryl benzo[h][1, 6]naphthyridines derivatives.

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Figure Synthesis of Fluorescent Arylbenzo[h][1, 6]naphthyridine

     

Gold-catalyzed formal [3 + 3] and [4 + 2] cycloaddition reactions of nitrosobenzenes with alkenylgold carbenoids

We report two new formal cycloaddition reactions between nitrosobenzenes and alkenylgold carbenoids. We obtained quinoline oxides 3 in satisfactory yields from the gold-catalyzed [3 + 3]-cycloadditions between nitrosobenzenes and alkenyldiazo esters 1. For propargyl esters 5, its resulting gold carbenes react with nitrosobenzene to give alkenylimine 8, followed by a [4 + 2]-cycloaddition with nitrosobenzene.     

Gold‐Catalyzed Cycloaddition Reactions of Ethyl Diazoacetate,Nitrosoarenes, and Vinyldiazo Carbonyl Compounds: Synthesis of Isoxazolidine and Benzo[b]azepine Derivatives

Gold‐catalyzed cycloadditions of ethyl diazoacetate, nitrosoarenes, and vinyldiazo carbonyl species to yield isoxazolidine derivatives stereoselectively are described. Treatment of these isoxazolidine products with the same catalyst results in a novel 1,2‐H shift/[3,3] rearrangement to give benzo[b]azepine compounds. The mechanism of this skeletal rearrangement is elucidated with deuterium‐labeling experiments.     

Identification of a nanomolar affinity α-synuclein fibril imaging probe by ultra-high throughput in silico screening

Small molecules that bind with high affinity and specificity to fibrils of the α-synuclein (αS) protein have the potential to serve as positron emission tomography (PET) imaging probes to aid in the diagnosis of Parkinson''s disease and related synucleinopathies. To identify such molecules, we employed an ultra-high throughput in silico screening strategy using idealized pseudo-ligands termed exemplars to identify compounds for experimental binding studies. For the top hit from this screen, we used photo-crosslinking to confirm its binding site and studied the structure–activity relationship of its analogs to develop multiple molecules with nanomolar affinity for αS fibrils and moderate specificity for αS over Aβ fibrils. Lastly, we demonstrated the potential of the lead analog as an imaging probe by measuring binding to αS-enriched homogenates from mouse brain tissue using a radiolabeled analog of the identified molecule. This study demonstrates the validity of our powerful new approach to the discovery of PET probes for challenging molecular targets.     

Gold‐Catalyzed Cycloaddition Reactions of Ethyl Diazoacetate,Nitrosoarenes, and Vinyldiazo Carbonyl Compounds: Synthesis of Isoxazolidine and Benzo[b]azepine Derivatives

Gold‐catalyzed cycloadditions of ethyl diazoacetate, nitrosoarenes, and vinyldiazo carbonyl species to yield isoxazolidine derivatives stereoselectively are described. Treatment of these isoxazolidine products with the same catalyst results in a novel 1,2‐H shift/[3,3] rearrangement to give benzo[b]azepine compounds. The mechanism of this skeletal rearrangement is elucidated with deuterium‐labeling experiments.     

Zinc(II)‐Catalyzed Intermolecular Hydrative Aldol Reactions of 2‐En‐1‐ynamides with Aldehydes and Water to form Branched Aldol Products Regio‐ and Stereoselectively

This work describes zinc(II)‐catalyzed hydrative aldol reactions of 2‐en‐1‐ynamides with aldehydes and water to afford branched aldol products regio‐ and stereoselectively. The anti and syn selectivity can be modulated by the sizes of sulfonamides to yield E‐ and Z‐configured zinc(II) dienolates selectively. This new reaction leads to enantiopure aldol products by using a cheap chiral sulfonamide. The mechanistic analysis reveals that the sulfonamide amides of the substrates can trap a released proton to generate dual acidic sites to activate a carbonyl allylation reaction.     

Kinetics of hydroformylation of 1-decene using carbon-supported ossified HRh(CO)(TPPTS)3 catalyst

The kinetics of hydroformylation of 1-decene has been investigated using a carbon-supported ossified HRh(CO)(TPPTS)₃/Ba catalyst in a temperature range of 343–363 K. The effect of concentration of 1-decene, catalyst loading, partial pressure of H₂ and CO, and stirring speed on the reaction rate has been investigated. A first-order dependence was observed for catalyst concentration and hydrogen partial pressure. The rate showed a typical case of substrate inhibition for high 1-decene concentration. The rate varied with a linear dependence on P_CO up to a CO partial pressure of 5–6 MPa in contrast to the general trends; for most of the rhodium-phosphine catalyzed hydroformylation reactions, severe inhibition of rate is observed with an increase in CO pressure. A rate equation has been proposed, which was found to be in good agreement with the observed rate data within the limit of experimental errors. The kinetic parameters and activation energy values have been reported.     

Kinetics of hydroformylation of camphene using rhodium-phosphite catalyst

Kinetics of hydroformylation of camphene was investigated in the presence of [Rh(CO)₂(acac)]/P(OPh)₃ catalyst in a temperature range of 363–383 K. The influence of parameters such as stirring speed, camphene, catalyst, ligand concentrations, and partial pressures of H₂ and CO on the activity and selectivity of the catalyst has been studied. The rate showed a first-order dependence with respect to catalyst and camphene concentrations. The effect of partial pressure of hydrogen showed fractional order dependence. The plots of rate versus excess ligand, that is, (P(OPh)₃) concentration and rate versus CO partial pressure passed through maxima and showed typical substrate/ligand inhibited kinetics. An empirical rate equation has been proposed and found to be in good agreement with the observed rate data. The kinetic parameters and activation energy were also evaluated.     

Gold‐Catalyzed Oxa‐Povarov Reactions for the Synthesis of Highly Substituted Dihydrobenzopyrans from Diaryloxymethylarenes and Olefins

Oxa‐Povarov reactions involving readily available diaryloxymethylarenes and aryl‐substituted alkenes are reported. Their [4+2] cycloadditions were efficiently catalyzed by IPrAuSbF₆ (IPr=1,3‐bis(diisopropylphenyl)imidazol‐2‐ylidene) with high diastereoselectivity. Product analysis revealed that the reactions likely proceed by a stepwise ionic mechanism, because both E‐ and Z‐configured β‐methylstyrene gave the same cycloadducts in the same proportions.