Controlled Double-Bond Migration in Palladium-Catalyzed Intramolecular Arylation of Enamidines

Palladium-catalyzed intramolecular cyclization of N-(N'-tert-butylformimidoyl)-6-[2-(2-iodophenyl)ethyl]-1,2,3,4-tetrahydropyridine (1a) and N-(N'-tert-butylformimidoyl)-6-[3-(2-iodophenyl)propyl]-1,2,3,4-tetrahydropyridine (1b) respectively results in formation of spiro compounds 1'-(N-tert-butylformimidoyl)-3',4'-dihydrospiro[indan-1,2'(1'H)-pyridine] (4a), 1'-(N-tert-butylformimidoyl)-1',6'-dihydrospiro[indan-1,2'(3'H)-pyridine] (5a), and 1'-(N-tert-butylformimidoyl)-5',6'-dihydrospiro[indan-1,2'(1'H)-pyridine] (6a) and 1'-(N-tert-butylformimidoyl)-3,3',4,4'-tetrahydrospiro[naphthalene-1(2H),2'(1'H)-pyridine] (4b), 1'-(N-tert-butylformimidoyl)-1',3,4,6'-tetrahydrospiro[naphthalene-1(2H),2'(3'H)-pyridine] (5b), and 1'-(N-tert-butylformimidoyl)-3,4,5',6'-tetrahydrospiro[naphthalene-1(2H),2'(1'H)-pyridine] (6b). The double-bond migration process can be controlled, and any of the three double-bond isomers can be prepared by employing proper ligands. A combination of BINAP and the amidine function was required to obtain the isomers 5a and 5b with the double bond in the homoallylic position relative to the aryl group. An electrospray ionization mass spectrometric study was conducted to support suggested reaction intermediates.     

Mass spectral fragmentation patterns of heterocycles. VI. Carbazole and 1,8-dideuteriocarbazole

The mass spectral fragmentation of carbazole was reinvestigated using metastable ion studies, exact mass measurements and 1,8-dideuteriocarbazole. 1,8-Dideuteriocarbazole was prepared by successive metalations and deuterations of carbazole. The ¹H- and ¹³C-nmr spectra of 1,8-dideuteriocarbazole confirmed earlier assignments for carbazole.     

Dimethylformamide as a carbon monoxide source in fast palladium-catalyzed aminocarbonylations of aryl bromides

Dimethylformamide (DMF) acts as an efficient source of carbon monoxide and dimethylamine in the palladium-catalyzed aminocarbonylation (Heck carbonylation) of p-tolyl bromide to provide the dimethylamide. Addition of amines to the reaction mixture in excess delivers the corresponding aryl amides in good yields. The amines employed, benzylamine, morpholine, and aniline, all constitute good reaction partners. The reaction proceeds smoothly with bromobenzene and more electron-rich aryl bromides, but electron-deficient aryl bromides fail to undergo aminocarbonylation. The reactions are conducted at 180-190 degrees C for 15-20 min with microwave heating in a reaction mixture containing imidazole and potassium tert-butoxide: the latter is required to promote decomposition of the DMF solvent at a suitable rate. The beneficial effects of controlled microwave irradiation as an energy source for the rapid heating of the carbonylation reaction mixture are demonstrated. The carbonylation procedure reported herein, which relies on the in situ generation of carbon monoxide, serves as a convenient alternative to other carbonylation methods and is particularly applicable to small-scale reactions where short reaction times are desired and the direct use of carbon monoxide gas is impractical.     

Mass spectral fragmentation patterns of heterocycles. IV . Tetracyclic phenothiazines. IX. Electron impact promoted mass spectral fragmentation of pyrrolo[3,2,1-kl]phenothiazine

The mass spectral fragmentation patterns of pyrrolo[3, 2, 1-kl]phenothiazine ( 1 ) and its 1, 10-dideuterioderi-vative [2] are reported. The site of deuterium substitution in 2 was established by examination of its ¹³C nuclear magnetic resonance spectrum. The heteroaromatic stability of 1 to electron impact is exemplified by the occurrence of the molecular ion as the base peak and the formation of a reasonably intense M²⁺ ion. An intense M-1 ion is also observed. The more abundant fragment ions appear to result from sulfur ionization. Fragment ions arising from ionization of the nitrogen constitute only a small fraction of the total ion current. Proposed fragmentation pathways of 1 are supported by the detection of appropriate metastable ions, exact mass measurements, and electron impact spectrum of 2 .     

Regiochemical Control and Suppression of Double Bond Isomerization in the Heck Arylation of 1-(Methoxycarbonyl)-2,5-dihydropyrrole

Arylation of 1-(methoxycarbonyl)-2,5-dihydropyrrole under standard Heck reaction conditions produces a mixture of compounds. The olefin undergoes two types of palladium-catalyzed reactions: (a) arylation to provide C-3 arylated derivatives and (b) competing double bond isomerization. Addition of silver carbonate and thallium acetate fully suppressed the isomerization, and good yields of C-3 substituted compounds were achieved after arylation with aryl halides. With regard to aryl triflates as arylating agents, addition of lithium chloride was necessary to promote the Heck reaction. This additive excluded the use of silver and thallium salts, but high regioselectivity and good yields could be obtained by employing tri-2-furylphosphine as ligand. Arylation was rendered both regioselective and enantioselective (58% ee) with 1-naphthyl triflate as substrate utilizing a (R)-BINAP/thallium acetate combination. The C-3 arylated enamides were converted further into the corresponding 3-arylpyrrolidines.     

N-Aryl Isoleucine Derivatives as Angiotensin?II AT2 Receptor Ligands

A novel series of ligands for the recombinant human AT₂ receptor has been synthesized utilizing a fast and efficient palladium-catalyzed procedure for aminocarbonylation as the key reaction. Molybdenum hexacarbonyl [Mo(CO)₆] was employed as the carbon monoxide source, and controlled microwave heating was applied. The prepared N-aryl isoleucine derivatives, encompassing a variety of amide groups attached to the aromatic system, exhibit binding affinities at best with K_i values in the low micromolar range versus the recombinant human AT₂ receptor. Some of the new nonpeptidic isoleucine derivatives may serve as starting points for further structural optimization. The presented data emphasize the importance of using human receptors in drug discovery programs.     

Detection of topological transitions by transport through molecules and nanodevices

We analyze the phase transitions of an interacting electronic system weakly coupled to free-electron leads by considering its zero-bias conductance. This is expressed in terms of two effective impurity models for the cases with and without spin degeneracy. Using the half-filled ionic Hubbard ring, we demonstrate that the weight of the first conductance peak as a function of external flux or of the difference in gate voltages between even and odd sites allows one to identify the topological charge transition between a correlated insulator and a band insulator.     

Regioselective palladium-catalyzed synthesis of beta-arylated primary allylamine equivalents by an efficient Pd-N coordination.

A highly regioselective Heck arylation, utilizing aryl triflates and a palladium/dppf catalytic system, can be performed at the internal, beta-carbon of Boc- and phthalimido-protected allylamines, yielding arylated primary allylamine equivalents. The very high regioselectivity obtained with secondary Boc-protected allylamides is suggested to be caused by an efficient coordination between an anionic nitrogen and palladium. Single-mode microwave irradiation has been utilized to shorten the reaction times and, in the case of Boc-protected allylamides, to improve the yields of two electron-poor aryl triflates.     

Total assignment of the 13C-NMR spectra of 5H-indolo[1,7-ab][1]benzazepine and 6,7-dihydro-5H-indolo[1,7-ab][1]benzazepine using two-dimensional proton-carbon chemical shift correlation experiments

¹³C-nmr chemical shift assignments for 5H-Indolo[1,7-ab][1]benzazepine and 6,7-Dihydro-5H-indolo-[1,7-ab][1]benzazepine, made on the basis of two-dimensional ¹H-¹³C chemical shift correlation experiments are reported.