Construction of chiral complex molecules continues to be a challenge for organic chemists all over the world and to address this challenge numerous methodologies have been developed. 1,3-Dipolar cycloaddition reactions is one such simple and elegant method, which can be employed towards the construction of chiral heterocycles. The ability to construct multiple stereocenters in one operation is one of the salient features of dipolar cycloaddition reaction. Asymmetric dipolar cycloaddition via chiral Lewis or Bronsted acid catalyzed processes is aided by the development of various templates, which provide points of attachment for these catalyst. Application of acyl imidazoles as multifunctional templates has been investigated for Lewis and Bronsted acid catalyzed 1,3-dipolar cycloaddition of azomethine imines and nitrones. Chapter 1. A review of 1,3-dipolar cycloaddition towards to construction of chiral nitrogen containing heterocycles is discussed in this chapter. This chapter intends to provide the reader a current state of asymmetric 1,3-dipolar cycloaddition. Chapter 2. Development of exo and enantioselective Cu(II) catalyzed azomethine imine cycloaddition to pyrazolidinone acrylates is discussed in this chapter. The key issues approached in this chapter includes impact of metal geometry on diastereoselectivity as well as effect of N-l and C-5 substitution on enantioselectivity of cycloadducts. Investigation into the scope and limitation of azomethine imines and dipolarophiles has also been discussed. Chapter 3. This chapter introduces acyl imidazoles as multifunctional template for asymmetric azomethine imine cycloaddition. Limitation of substrate scope for azomethine imine cycloaddition encountered in the previous chapter has been resolved by the use of acyl imidazoles as templates. Synthesis of complementary diastereomers of azomethine imine cycloadducts via Lewis acid and Bronsted acid catalyzed reactions has been discussed in this chapter. Chapter 4. This chapter highlights the application of acyl imidazoles as template for first Bronsted acid catalyzed exo and enantioselective nitrone cycloaddition to electron deficient olefins. Study of appropriate chiral Bronsted acid and investigation of breadth and scope of nitrones and dipolarophiles has also been discussed here. Chapter 5. This chapter address one of the most challenging aspect of synthetic organic chemistry namely the construction of chiral quaternary stereocenters. This study highlights chiral Bronsted catalyzed nitrone cycloaddition to p,|3-disubstituted-a,P-unsaturated acyl imidazole leading to the formation of isoxazolidines with chiral quaternary stereocenter. This methodology is useful for the construction of chiral fluorinated heterocycles.

No description available.

published_or_final_version / abstract / Chemistry / Doctoral / Doctor of Philosophy

published_or_final_version / abstract / Chemistry / Doctoral / Doctor of Philosophy

published_or_final_version / abstract / Chemistry / Doctoral / Doctor of Philosophy

published_or_final_version / abstract / Chemistry / Doctoral / Doctor of Philosophy

Graduate

No description available.

From a review of the published work in the field of cycloadditions, it is evident that further research is needed to establish the mechanism of ketene cycloadditions. This work was initiated with the intent of obtaining kinetic data which will contribute to the elucidation of the mechanism of ketene cycloadditions.

One objective of this study was to explore the intramolecular [2+2] cycloadditions of phenoxyketenes to carbonyl groups with isoflavones and benzofurans as target compounds. The other objective was to investigate the eyeloaddition reactions of rarely studied aminoketenes. The conversion of 2-(carboxyalkoxy)benzils to the corresponding phenoxyketenes leads to an intramolecular [2+2] cycloaddition to ultimately yield isoflavones and/or 3-aroylbenzofurans. The product distributions are dependent upon the substitution pattern in the original benzil acids. The initial cycloaddition products, β-lactones, are isolated in some instances while some β-lactones spontaneously underwent decarboxylation and could not be isolated. The ketene intermediate was demonstrated in the intramolecular reaction of benzil acids or ketoacids with sodium acetate and acetic anhydride. It is suggested that sodium acetate and acetic anhydride could serve as a source for the generation of ketenes directly from certain organic acids. The treatment of ketoacids with acetic anhydride and sodium acetate provides a simpler procedure to prepare benzofurans than going through the acid chloride with subsequent triethylamine dehydrochlorination to give the ketenes. N-Ary1-N-alkylaminoketenes were prepared for the first time from the corresponding glycine derivatives by using p-toluenesulfonyl chloride and triethylamine. These aminoketenes underwent in situ cycloadditions with cyclopentadiene, cycloheptene and cyclooctenes to yield only the endo -bicyclobutanones. The cycloheptene and cyclooctene cycloaddition products underwent dehydrogenation under the reaction conditions to yield bicycloenamines. A mechanism is proposed for this dehydrogenation involving a radical cation of the arylalkylamine. (N-Phenyl-N-methyl) aminomethylketene was also prepared and found to undergo an intramolecular Friedel-Crafts type acylation to yield an indole derivative when prepared by the acetic anhydride, sodium acetate method. The in situ cycloaddition of N-aryl-N-alkyl aminoketenes with various imines was found to form predominately cis-3-amino-2-azetidinones. A mechanism involving a dipolar intermediate is provided whereby the structure of the intermediate is determined by both electronic and steric effects. The stereochemistry of the resulting β-lactams is dependent upon the structure of the dipolar intermediate.