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A strategy that enables resin-bound bismuth to be utilized as a multidirectional linker in SPOS is presented. For solid-phase organic synthesis and as a resin-bound arylation reagent resin-bound bismuth has been used as part of a multidirectional linker system for the fist time.

Research has been conducted on the range of pyrazole 1-oxides. The preparation of these oxides has been carried out via the regioselective deprotonation or bromine-magnesium exchange and transmetalation with ZnCl (sub)2 and palladium(0)-catalyzed cross-coupling.

Research has been conducted on the electrophiles. Results indicate that these electrophiles have been introduced regioselectively at the 5-position of 1-(benzyloxy)imidazole via lithiation at C-5 after the C-2 protection with the chloro or trimethylsilyl group

Research demonstrates that 4-substituted pyrazolo[4,3-c]quinolines, 9-substituted pyrazolo[3,4-c]quinolines, and 1,4-dihydrochromenol[4,3-c]pyrazoles can be synthesized from C-4 and C-5 aryl-substituted 1-(bezyloxy)pyrazoles. Results point out that the synthetic route of these tricyclic pyrazoles uses readily available monocyclic precursors, which are functionalized to heteroaromatic frameworks.

Research was conducted to examine two protocols for introduction of electrophiles at the 4-position of 1-hydroxypyrazoles. One involves the deprotonation of 4-bromo-1-((tert-butyldiphenylsilyl)oxy)pyrazole with LDA to generate the 5-lithio derivative. The other involves the treatment of 4-bromo-1-hydroxypyrazole with excess LDA and trimethylsilyl chloride to produce 3,5-bis(trimethylsilyl)4-bromo-1-hydroxypyrazole. Results indicate that 4-lithio-1-lithoxypyrazoles can be generated by bromine-lithium exchange in the presence of silyl protecting groups at C-5 or at C-3 and C-5.

A new method for the introduction of several substituents in 1-hydroxyimidazole after the imidazole ring was formed is presented. The new approach was based on deprotonation which was followed by reaction with an electrophile. Debenzylation yielded 2-substituted 1-hydroxyimidazoles which could be deoxygenated to generate 2-substituted imidazoles. Results indicate that the new method is seemingly better than the previous approaches used for the preparation of 1-(benzyloxy)imidazole.

A study was conducted to characterize the synthesis of 5-substituted 1-hydroxy-1,2,3-triazoles by selective benzylation. O-Benzyl and O-carbamoyl-protected N-hydroxypyrazoles were prepared in good yields and were utilized in the metalation reactions while benzyl azide was reacted with acetylenedicarboxylic acid. Results indicated that hydrogen bonding to N-7 increased the catalytic effect of 7-aza 1-hydroxybenzotriazoles.

The lithiation of 1-(benzyloxy)pyrazole with n-BuLi followed by a electrophile reaction results in the formation of 5-substituted 1-(benzyloxy)pyrazole indicating that the N(benzyloxy) group is suitable for directed metalation stabilizing of the pyrazol-5-yllithium motif. The elimination of the benzyl protecting group results in the formation of 5-substituted hydroxypyrazoles indicating that the addition of electrophiles at 5-position can be achieved by using activating the groups.

A multistep solid-phase organic synthesis with resin-bound bismuth linker is described. The flexibilities inherent in this system through novel chemoselective cross-coupling reactions, in conjunction with multidirectional and/or traceless cleavage methodologies, are exploited.

Research has been conducted on the pyrazoles possessing C-aryl substituents. The convergent preparation of the 3-arylated 1-hydroxypyrazoles based on the 2-(4-methoxybenzyl)-pyrazole-1-oxide formation which undergoes monobromination at C-3 and bromine-magnesium exchange is discussed.

A procedure for preparing 4-substituted 1-(benzyloxy)pyrazoles without protection groups at C-5 is introduced. The synthetic approach permits the introduction of aryl- and heteroaryl substituents by combining iodine-magnesium exchange, transmetalation with zinc chloride and palladium-catalyzed cross-coupling. The method also allows regiospecific introduction of electrophiles in the 4-position of 1-(benzyloxy)pyrazoles via iodine-magnesium exchange of 1-(benzyloxy)-4-iodopyrazole.

Directed ortho-lithiation of resin-bound 1-hydroxyimidazole on a solid-state protocol at C-2 with n-butyllithium was investigated. Resin-bound 1-hydroxyimidazole was obtained by alkylation of the sodium salt of 1-hydroxyimidazole with chloromethyl polystyrene. Experimental results showed that subsequent treatment with halogen, carbon or sulfur electrophiles followed by detachment from the solid support by heating with trifluoracetic acid at 100 degrees Celsius for 20 hours produced 2-substituted 1-hydroxyimidazoles in 52-93% yields.

1-Substituted 2-, 4- and 5-cyanoimidazoles were synthesized by reaction of 3-cyclohexyl or 3-p-tolylimidazole 1-oxide and trimethylsilyl cyanide in the presence of triethylamine. The product composition depended on reaction temperature and solvent polarity. By choosing the proper parameters, each isomer could be produced selectively in reasonable yield.

The synthesis of substituted 2-cyanoarylboronic esters is described using lithiation/in situ trapping of the corresponding methoxy-, trifluoromethyl-, fluoro-, chloro- and bromobenzonitriles. The crude arylboronic esters are obtained in high yields and purities and with good regioselectivities.

A noncryogenic protocol, which provides a synthesis of 2,3-substituted thienylboronic acids and esters, is introduced. The process includes a combination of halogen-magnesium followed by trapping with an electrophile and a palladium-catalyzed borylation.

The authors decribe bromine-lithium exchance. They report that this exchange has taken place via the use of tert-butyl-lithium, initiating a cascade process in order to produce xanthone derivatives or pentacyclic 13-azadibenzo[a,de]anthacenes.

Research has been conducted on hapten derivatives of 1alpha,25-dihydroxy-vitamin D (sub)3 and its 20-epimer. The synthesis and conjugation of these compounds to a carrier protein for raising polyclonal antibodies are described.

The pyridine ring of pyrazoloquinolines 14 and 18 was formed via cyclization of a formyl group at C-4 or C-5 and an amino group of a 2-aminophenyl substituent at C-5 or C-4 in 1-benzyloxypyrazole. The order of reactions and use of protecting groups in the individual sequences have been optimized.

Ortho-substituted arylboronic esters are efficiently coupled with carbamoyl chlorides under Pd-catalysis to give tertiary benzamides. A series of different carbamoyl chlorides are coupled with selected arylboronic esters to investigate the scope of the reaction with respect to the carbamoyl chlorides.