Research Projects

This proposal primarily explores the synthetic utility of an isolable cyclic dienamine for the synthesis of biologically relevant scaffolds. Dienamines are inherently nucleophilic species that have enjoyed a tremendous rise in popularity as transiently generated species for enantioselective transformations since the advent of asymmetric organocatalysis. On the other hand, preformed or isolable dienamines remain comparatively much less explored presumably owing to their labile nature. The dienamine in reference is regiochemically a cyclic 1-amino-1,3-butadiene frozen in the s-cis conformation, which makes it an optimal substrate for Diels–Alder cycloadditions with a variety of dienophiles. Dienamines can also be functionalized at the gamma-position with suitable electrophiles, giving rise to new molecular architectures. Beyond the reactivity of dienamines, the core of the project involves the synthesis of heterocyclic scaffolds that are fundamental to a vast array of biologically active compounds and therapeutics. Evidently, the significance of these motifs has spurred the research community to devise a plethora of methods for accessing them. Nonetheless, there has rarely been an instance of a single molecule as a common platform for the construction of a variety of such scaffolds. The core idea behind the present proposal addresses this challenge by presenting a cyclic dienamine as an easily accessible template to construct a large number of heterocyclic skeletons including acridines, dibenzodiazepines, carbazoles, dibenzofurans apart from other motifs such as triarylmethanes and biphenyls. A series of transformations aimed at accessing these diverse architectures has been designed, based on the functional modification of the cyclic dienamine core. Thus, the rationale for the present work can be outlined on the basis of the following: • The availability of a stable cyclic dienamine, an inherently nucleophilic entity with a variety of possibilities for synthetic maneuvering. • The feasibility of transformations such as the Diels-Alder reaction and gamma-functionalization of the dienamine that give rise to the possibility of developing molecules with promising applications. The scientific objectives of the proposed work comprise: • Development of a pot-efficient access to acridines and dibenzodiazepines. • Synthesis of carbazoles, dibenzo[1,4]diazepinones, and dibenzo[1,4]oxaazepinones by an intramolecular Diels-Alder reaction strategy. • Access to biphenyls, substituted benzo-/ naphthoquinones and triarylmethanes by gamma-functionalization of the dienamine. • Studies on trapping of iminium ion intermediates generated from the dienamine species for the construction of dibenzofurans as well as bicyclo[2.1.1]hexanes by formal [3+2] cycloadditions. • Generation of other interesting molecular frameworks such as terphenyls and quaterphenyls. The major experiments to be studied include: • Inter- and intramolecular Diels-Alder reactions on the cyclic dienamine; a sequential one-pot Diels-Alder-retro-Diels-Alder strategy shall also be deployed, followed by cyclization to reveal the desired motif. • Functionalization of the cyclic dienamine at gamma-position by use of suitable electrophiles. • Combining the nucleophilicity and electrophilicity of the dienamine and iminium ion respectively to bring about [3+2] cycloadditions and dimerizations. The significance of the proposed constitutes: • Deeper insight into the fascinating reactivity of cyclic dienamines, creating opportunities for further mechanistic studies and development of new synthetic transformations. • Straightforward pot-efficient approach to heterocycles with having a significant biological activity profile. • Potential applications of the developed methods for the total synthesis of natural products. Overall, the proposal aims to traverse the two domains of dienamine chemistry and the construction of pharmaceutically significant molecular frameworks.