Defense Date


Graduation Date

Fall 2011


Immediate Access

Submission Type


Degree Name



Chemistry and Biochemistry


Bayer School of Natural and Environmental Sciences

Committee Chair

Tomislav Pintauer

Committee Member

Partha Basu

Committee Member

Jeffrey D. Evanseck

Committee Member

Nicolay V. Tsarevsky


Atom transfer radical reactions, Catalyst regeneration, Click chemistry, Copper, Cyclopropanation, Organic catalysis


Copper-catalyzed regeneration in atom transfer radical addition (ATRA) utilizes reducing agents, which continuously regenerate the activator (CuI) from the deactivator (CuII) species. This technique was originally found for mechanistically similar atom transfer radical polymerization (ATRP) and its application in ATRA and ATRC has allowed significant reduction of catalyst loadings to ppm amounts. In order to broaden the synthetic utility of in situ catalyst regeneration technique, this was applied in copper-catalyzed atom transfer radical cascade reaction in the presence of free radical diazo initiators such as 2, 2'-azobis(isobutyronitrile) (AIBN) and (2, 2'-azobis(4-methoxy-2, 4-dimethyl valeronitrile) (V-70), which is the first part of this dissertation. This methodology can be translated to sequential ATRA/ATRC reaction, in which the addition of CCl4 to 1, 6-dienes results in the formation 5-hexenyl radical intermediate, which undergoes expedient 1, 5-ring closure in the exo- mode to form 1, 2-disubstituted cyclopentanes. When [CuII(TPMA)Cl][Cl] complex was used in conjunction with AIBN at 60 0C, cyclic products derived from the addition of CCl4 to 16-heptadiene, diallyl ether and N, N­-diallyl-2, 2, 2-trifluoroacetamide were synthesized in nearly quantitative yields using as low as 0.02 mol% of the catalyst (relative to 1, 6-diene). Even more impressive were the results obtained utilizing tert­-butyl-N, N-diallylcarbamate and diallyl malonate using only 0.01 mol% of the catalyst. Cyclization was also found to be efficient at ambient temperature when V-70 was used as the radical initiator. High product yields ( 80%) were obtained for mixtures having catalyst concentrations between 0.02 and 0.1 mol%. Similar strategy was also conducted utilizing unsymmetrical 1, 6-diene esters. It was found out that dialkyl substituted substrates (dimethyl-2-propenyl acrylate and ethylmethyl-2-propenyl acrylate) underwent 5-exocyclization producing halogenated g-lactones after the addition of CCl4 in the presence of 0.2 mol% of [CuII(TPMA)Cl][Cl]. Based on calculations using density functional theory (DFT) and natural bond order (NBO) analysis, cyclization of 1, 6-diene esters was governed by streoelectronic factors.

As a part of broadening the synthetic usefulness of in situ copper(I) regeneration, scope was further extended to sequential organic transformations. Based on previous studies, copper(I) catalyzed [3+2] azide-alkyne cycloaddition is commonly conducted via in situ reduction of CuII to CuI species by sodium ascorbate or ascorbic acid. At the same time, ATRA reactions have been reported to proceed efficiently via in situ reduction of CuII complex to the activator species or CuI complex has been fulfilled in the presence of ascorbic acid. Since the aforementioned reactions share similar catalyst in the form of copper(I), a logical step was taken in performing these reactions in one-pot sequential manner. Reactions involving azidopropyl methacrylate and 1-(azidomethyl)-4-vinylbenzene in the presence of a variety of alkynes and alkyl halides, catalyzed by as low as 0.5 mol-% of [CuII(TPMA)X][X] (X=Br-, Cl-) complex, proceeded efficiently to yield highly functionalized (poly)halogenated esters and aryl compounds containing triazolyl group in almost quantitative yields ( 90%). Additional reactions that were carried out utilizing tri-, di- and monohalogenated alkyl halides in the ATRA step provided reasonable yields of functionalized trriazoles. A slightly different approach involving a ligand-free catalytic system (CuSO4 and ascorbic acid) in the first step followed by addition of the TPMA ligand in the second step was applied in the synthesis of polyhalogened polytriazoles. Sequential reactions involving vinylbenzyl azide, tripropargylamine and polyhalogenated methane (CCl4 and CBr4) provided the desired products in quantitative yield in the presence of 10 mol% of the catalyst. Modest yields of functionalized polytriazoles were obtained from the addition of less active tri- and dihalogenated alkyl halides utilizing the same catalyst loading.

The last part focuses on copper(I) complexes, which were used catalysts in cyclopropanation reaction. One class represented cationic copper(I)/2, 2-bipyridine complexes with p-coordinated styrene [CuI(bpy)(p-CH2CHC6H5)][A] (A = CF3SO3- (1) and PF6- (2) and ClO4- (3). Structural data suggested that the axial coordination of the counterion in these complexes observed in the solid state weak to non-coordinating (2.4297(11) Å 1, 2.9846(12) Å 2, and 2.591(4) Å 3). When utilized in cyclopropanation, complexes 1-3 provided similar product distribution suggesting that counterions have negligible effect on catalytic activity. Furthermore, the rate of decomposition of EDA in the presence of styrene catalyzed by 3 (kobs=(7.7±0.32)´10-3 min-1) was slower than the rate observed for 1 (kobs=(1.4±0.041)´10-2 min-1) or 2 (kobs=(1.0±0.025)´10-2 min-1). On the other hand, tetrahedral copper(I) complexes with bipyridine and phenanthroline based ligands have been reported to have strongly coordinated tetraphenylborate anions. CuI(bpy)(BPh4), CuI(phen)(BPh4) and CuI(3, 4, 7, 8-Me4phen)(BPh4) complexes are the first examples in which BPh4- counterion chelates a transition metal center in bidentate fashion through h2 p-interactions with two of its phenyl rings. The product distribution revealed that the mole percent of trans and cis cyclopropanes were very similar. The observed rate constants (kobs) shown in for decomposition of EDA in the presence of externally added styrene were determined to be kobs=(1.5±0.12)´10-3 min-1, (6.8±0.30)´10-3 min-1 and (5.1±0.19)´10-3 min-1.