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Visible advance: A mild, one-pot Stadler-Ziegler process for C-S bond formation has been developed. The method employs the photoredox catalyst [Ru(bpy)3Cl2]⋅6 H2O irradiated with visible light. A variety of aryl-alkyl and diaryl sulfides were prepared from readily available arylamines and aryl/alkylthiols in good yields. The use of a photo microreactor led to a significant improvement with respect to safety and efficiency.

Optimized reaction conditions are established for an intramolecular SRN1 type cyclization of 2-(2-haloarylamino)pyridines (I) to give pyrido[1,2-a]benzimidazoles in good yield.

An intramolecular palladium(0)-mediated α-arylation of ketones applied to the synthesis of various substituted tetracyclic indoles is reported. Most significantly, the efficiency of the transformation was enhanced by the use of monoligated Pd(0) complexes. This methodology was extended to double α-arylation of ketones using one-pot reactions with either simultaneous addition or sequential addition of two aryl halides for producing aryl substituted tetracyclic indoles.

An efficient microwave assisted one-pot synthesis of substituted 3-(phenylmethylene)isoindolin-1-ones is reported via a copper-free Sonogashira coupling and a regioselective 5-exo-dig cycloisomerization. This domino reaction was also extended to other related heterocycles.

It provides a convenient method to prepare all four carboline regioisomers in good to high yields.

Ring opening cross-metathesis (ROM) of bicyclic alkenes with terminal aryl alkenes on solid support was accomplished. A select group of resin-bound bicyclic alkenes underwent highly regioselective ROM with electron rich styrenes. The influence of both electronic and steric factors on regioselectivity was examined.

The solution-phase ring opening cross-metathesis (ROM) of bicyclic alkenes with styrene derivatives is described. The influence of bicyclic alkene substituents on the rate and product distribution of solution-phase ROM reactions with styrene derivatives is discussed. In addition, a method for the “resin capture” of solution-phase ROM products by resin-bound amines is also illustrated.

The reaction of 7,9-dibromo-5-tribromornethyl-2-t-butyl-4-cyano-1,3,6,9b-tetraazaphenalene (1a) with p-toluidine is shown to give 4,6-dibromo-2-t-butyl-8,13-dihydro-13-imino-11-methyl-1,3,7,8,13c-pentaazabenzo[de]naphthacene (4) in two steps with 7,9 dibromo-2-t-butyl-4-cyano-5-p-toluidino-1,3,6,9b-tetraazaphenalene (2b) as the intermediate product. A related annulation reaction of 1a with N-(5-amino-2,4-dimethylphenyl)trimethylacetamide (8) leads in two steps to 9,11-dibromo-2,13-di-t-butyl-4,6-dimethyl-7H-1,3,7,8,11b,12,14-heptaazadibenzo[de,hi]naphthacene (6) with 7,9-dibromo-2-t-butyl-4-cyano-5N-(2,4-dimethyl-5-trimethylacetamidophenyl)amino-1,3,6,9b-tetraazaphenalene (2d) as the intermediate product. In a similar fashion the reaction of 1a with o-phenylenediamine forms 14-amino-4,6-dibromo-2-t-butyl-8H-1,3,7,8,13,14c-hexaazobenzo[4,5]cyclohepta[1,2-a]-phenalene (12) by way of the intermediate 5-N-(2-aminophenyl)amino-7,9-dibromo-2-t-butyl-4-cyano-1,3,6,9b-tetraazaphenalene (2e). The preparation of N-(2,4-dimethyl-5-nitrophenyl)-trimethylacetamide (11) and its reduction to N-(5-amino-2,4-dimethylphenyl)trimethylacetamide (8) is also described.

The photostimulated intramolecular ortho-arylation reactions of bromoarenes linked with pendant phenoxy containing N-substituted tetrahydroisoquinolines in liquid ammonia afforded aporphine (54−82% yield) alkaloid derivatives via SRN1 reactions. This strategy was extended for the first time to the synthesis of a homoaporphine derivative (40% yield). Tetrahydroisoquinoline precursors that contained electron-withdrawing groups on nitrogen (i.e., amides, sulfonamides, and carbamates) gave cyclized products, whereas precursors with basic nitrogens (i.e., NH or NMe) either failed to yield cyclized products or gave aporphines in only low yield.

Thieno[2,3-d]pyrimidin-4-one acylhydrazide derivatives were discovered as moderately potent inhibitors of TGase 2 (tissue transglutaminase) utilizing a fluorescence-based assay that measured TGase 2 catalyzed incorporation of the dansylated Lys derivative alpha-N-Boc-Lys-CH(2)-CH(2)-dansyl into the protein substrate N,N-dimethylated-casein. A SAR study revealed that the acylhydrazide thioether side-chain and the thiophene ring were critical to inhibitory activity.

A new route to substituted β -carbolines and carbazoles is described. Diketoindole intermediates, prepared by Friedel–Crafts acylations of 3-substituted indoles, have been converted to 3-hydroxycarbazoles and β -carbolines in good yields, 51–96% and 82–97%, respectively. This method also allows for the formation of 4-substituted β -carbolines. The application of this methodology to the synthesis of the natural products hyellazole and 6-chlorohyellazole is also described.

A synthesis of the alkaloid (±)-aporphine is reported. The initial key step of the synthesis involves a Pictet–Spengler cyclization of N-tosyl tyramine with 2-bromophenylacetaldehyde in trifluoroacetic acid. This step was followed by the second strategic transformation a palladium-mediated intramolecular phenol ortho -arylation reaction utilizing tricyclohexylphosphine as co-catalysts in the presence of cesium carbonate. Finally, de-oxygenation of the phenol, removal of the tosyl group and methylation gave the desired alkaloid.

A palladium-mediated intramolecular phenol ortho -arylation reaction applied to the construction of aporphine alkaloids is reported. Most significantly, the efficiency of this transformation was enhanced by the utilization of trialkylphosphine (i.e. tricyclohexylphosphine) or trialkylphosphonium salts (i.e. di- tert -butylmethyl-phosphonium tetrafluoroborate) as co-catalysts in the presence of cesium carbonate. This methodology was employed in the syntheses of the aporphine alkaloids (±)-lirinidine and (±)-nuciferine.

The reaction of N-cyano-N′-(6-amino-2-pyridyl)acetamidine (5a) and homophthalic anhydride followed by ring closure of the 2-[2-(carboxymethyl)phenyl]-5-methyl-1,3,4,6,9b-pentaazaphenalene intermediate (4a) gave 5-methyl-13-oxo-13H-4,6,7,13a,13c-pentaazabenzo[hi]chrysene (8a). An analogous series starting with 3-N-(6-amino-2-pyridyl)amino-2-cyano-2-butenenitrile (5b) in place of 5a gave in two steps 5-methyl-13-oxo-13-H-4,7,13a,13c-tetraazabenzo[hi]chrysene-6-carbonitrile (8b). Elemental analysis, ir and pmr spectra of 8a, 8b and several new model compounds aided in confirming the structures of 8a and 8b. The synthesis of one of these model compounds for 5b and phenylacetic anhydride led surprisingly to 2-methyl-9-phenyl-7H-3,7,-10,10b-tetraazacyclohepta[de]naphthalene (10) in addition to the expected 2-benzyl-4-cyano-5-methyl-1,3,-6,9b-tetraazaphenalene (7b).