Mark L. Trudell

Palladium-bisimidazol-2-ylidene complexes as catalysts for general and efficient Suzuki cross-coupling reactions of aryl chlorides with arylboronic acids

A series of bisimidazolium salts 1–6 were synthesized and evaluated as precursors to bisimidazol-2-ylidene ligands in palladium-catalyzed Suzuki cross-coupling reactions with aryl chlorides and arylboronic acids. The bisimidazolium salt 6 was found to be superior over imidazolium and other bisimidazolium salts affording high yields of biaryl products employing a wide variety of substrates.

A NEW [4 + 2] CYCLOADDITION STRATEGY FOR THE SYNTHESIS OF N-ACYL-7-AZABICYCLO[2.2.1]HEPTAN-2-ONES: A FORMAL SYNTHESIS OF (±)-EPIBATIDINE

Abstract N -Acyl-7-azabicyclo[2.2.1]heptan-2-one derivatives were prepared from N -acyl pyrroles via a [4 + 2] cycloaddition reaction with allenes. This represents a new synthetic approach for the synthesis of epibatidine and related analogs.

Synthesis of optically pure epibatidine analogs: (1R, 2R, 5S)-2β-(2-chloro-5-pyridinyl)-8-azabicyclo[3.2.1]octane and (1R, 2S, 5S)-2α-(2-chloro-5-pyridinyl)-8-azabicyclo[3.2.1]octane from (−)-cocaine

Abstract Two optically pure epibatidine analogs, 4 and 5 , which contain the 8-azabicyclo[3.2.1]octane ring system were synthesized from (−)-cocaine. The nicotinic receptor binding affinity and the stimulant activity of 4 and 5 were measured to be significantly lower than racemic epibatidine (± -1 ).

Synthesis of 2,6-Diethyl-3-Methacroyloxymethyl-1,5,7,8-Tetramethylpyrromethene-BF2 for the Preparation of New Solid-State Laser Dyes.

The synthesis of 2,6-diethyl-3-methacroyloxymethyl-1,5,7,8-tetramethylpyrromethene-BF2 (2) was carried out in straightforward fashion from 2,6-diethyl-1,3,5,7,8-pentamethylpyrromethene-BF2 (1) in three steps. The monomer unit 2 has been shown to be useful for copolymerization with methyl methacrylate for the synthesis of new solid-state optical materials. In addition, the synthesis of 1 has been modified to give greater yields of this useful laser dye.

Enantioselective Syntheses of Both Enantiomers of Noranabasamine

Both the R and S enantiomers of the amphibian alkaloid noranabasamine were prepared in >30% overall yield with 80% ee and 86% ee, respectively. An enantioselective iridium-catalyzed N-heterocyclization reaction with either (R)- or (S)-1-phenylethylamine and 1-(5-methoxypyridin-3-yl)-1,5-pentanediol was employed to generate the 2-(pyridin-3-yl)-piperidine ring system in 69-72% yield.

A mild and efficient oxidation of alcohols to aldehydes and ketones with periodic acid catalyzed by chromium(III) acetylacetonate

Chromium(III) acetylacetonate was found to be an efficient catalyst (10 mol%) for the oxidation of alcohols to aldehydes and ketones with periodic acid (1.5 equiv.) in acetonitrile at room temperature.

Synthesis and CB1 Cannabinoid Receptor Affinity of 4-Alkoxycarbonyl-1,5-diaryl-1,2,3-triazoles

A series of 4-alkoxycarbonyl-1,5-diaryl-1,2,3-triazoles were synthesized regioselectively using click chemistry and evaluated at CB1 cannabinoid receptors. The n-propyl ester 11 (K(i)=4.6 nM) and phenyl ester 14 (K(i)=11 nM) exhibited the most potent affinity of the series.

A Simplified Method for the Preparation of Ethynyl P-Tolyl Sulfone and Ethynyl Phenyl Sulfone

Abstract Silica gel mediated desilylation of aryl 2-(trimethylsilyl)ethynyl sulfones was found to greatly simplify the synthesis of the acetylenic sulfones, ethynyl ptolyl sulfone 1 and ethynyl phenyl sulfone 2. Each were easily prepared in good yield and high purity on a multigram scale from bis(trimethylsilyl)acetylene 3.

SYNTHESIS OF NEW DIPYRIDOTETRAAZAPENTALENES

The new heteroaromatic compounds, dipyridotetraazapentalenes 3–5, were synthesized in two steps from readily available triazolopyridines 6 and 10. N-Arylation of 6 and 10 followed by subsequent reductive cyclization of the N-(nitropyridyl)-triazolopyridines with triethylphosphite in toluene afforded 3, 4 and 5, respectively, in good yields. Nitration of 3 afforded the new energetic tetranitrotetraazapentalene derivative 15 in 58% yield.

Spinally mediated analgesia and receptor binding affinity of epibatidine analogs

Two epibatidine derivatives, (1R, 2R, 5S)-A-(2-chloropyridinyl) azabicyclo [3.2.1] octane; A=2 beta: analog 1, 2 alpha: analog 2, were investigated for their spinally mediated analgesic effects and binding affinity to nicotinic acetylcholine receptors. The tail flick response and behavioral side effects were studied after intrathecal agents in rats. The membrane preparations of the Torpedo Californica and rat cerebral cortices were used for radioligand binding utilizing [3H] epibatidine displacement. Their affinity to muscular and neuronal nicotinic acetylcholine receptors and spinally mediated analgesic potencies were 15, 20, and 3.8 times (analog 1) and 2000, 30,000, and 3.3 times (analog 2) less than epibatidine, respectively. Two times the analgesic 50% effective doses (ED(50)s) of the analogs did not induce side effects, while one-third of that of epibatidine induced motor disturbance. In summary, the two epibatidine analogs have higher potency ratio of spinally mediated analgesia/side effects than epibatidine.