Research Program

Our research group at the OCS Lab at IISERB has been focused on the development of new synthetic avenues towards the total synthesis of biologically-relevant organic molecules. Our group focuses on the following research themes:

• Organic synthesis via transition metal catalysis.

• Enantioselective synthesis of substituted heterocyclic natural products using C-H functionalization as the key step.

• Synthesis of natural products using transition metal catalyzed C-C bond forming reactions as the key steps.

• Synthesis of macrocyclic peptides.

• Synthesis of peptides using unnatural amino acids.

Some selected areas of our research are depicted below:

(1)          In the area of organic synthesis via transition-metal catalysis, we employ two approaches to achieve our goals:

(A)  Low-valent transition-metal catalysis in C-C bond formation.

(B) High-valent transition metal catalysis in C-H and C-C bond functionalizations.

(A)          Low-valent transition metal catalysis:

In this area of research, our research group has been the first to generalize an approach towards the regioselective C(sp3)-H arylation of enones, dienones and trienones. We have successfully employed this approach in the synthesis of several N-heterocycles and employed it twice over in the synthesis of an important building block of the drug molecule Fluvastatin. Recently, we have employed this methodology in site-selective remote functionalizations to achieve the gamma-arylations of dienones and epsilon-arylations of trienones. Additionally, we have successfully executed this idea in remote alkylation, allenylation as well as propargylation. Currently, this methodology is being employed in the stereoselective synthesis of several alkaloids.

(B)      High-valent transition metal catalysis in C-H and C-C bond functionalizations:

In this area of research our primary focus has been the development of new synthetic methodologies for C-C bond formation via catalyst-controlled site-specific C-H bond functionalization. The goal that we pursue in our research is to achieve a site-specific C-H functionalization in a substrate capable of undergoing multiple C-H bond functionalizations at the same time. The idea is to achieve C-H bond functionalizations which are in the near proximity of Lewis-basic heteroatom based directing groups. In the same molecule, distal C-H bond functionalization can be achieved if a heteroatom with an available non-bonded pair of electrons is conjugated to an extended pi-system. 

In addition to this, as a part of our contribution to the field of heteroatom-directed C-H functionalization, we have employed a novel methodology for the utilization of allylic alcohols as coupling partners, which is a rare and very difficult approach utilized only by a handful of research groups around the world. We have utilized this approach in the synthesis of a variety of N-heterocycles. 

We have also utilized the heteroatom-directed approach to achieve unique C-H nitrations and halogenations of substrates which are very prone to SEAr reactions. We also developed methods where regiodivergent outcomes could be obtained with strained ring molecules as coupling partners, utilizing C-H and C-C activations in tandem.

In another approach we have achieved the C-H alkylation reactions of pi-deficient N-heterocycles and have utilized this carbene migratory insertion approach in the synthesis of a variety of fused bicyclic N-heterocycles. Additionally, we have also developed methodologies for the rapid assembly of fluorescent molecules which have several significant applications such as organic materials.

In a recent study, we have developed a directing group-controlled, palladium-catalyzed, regio-, stereo-, and enantiospecific anti-carboxylation of unactivated, internal allenes enabled via the synergistic interplay of a rationally designed bidentate directing group, palladium catalyst, and a multifunctional acetate ligand. The potential of this concept has been demonstrated by the development of the chiral version of this transformation by using axial-to-central chirality transfer with good yields and enantioselectivities.

We also developed the distal C-H functionalization of ferrocenes using an easily removable directing group with precise selectivity under a Pd(II)/ MPAA ligand catalytic system via a highly strained ferrocene appended 12-membered palladacycle intermediate. We have also achieved a regio-and stereoselective synthesis of ferrocene-1,3-derivatives by a Catellani-type reaction. The resulting metallocene derivatives can be readily derivatized to yield planar chiral ligands and catalysts for asymmetric catalysis as well as the building blocks for other applications.

(2)             Synthesis of peptides capable of acting as anti-mycobacterial agents:

 Our group has been interested in applying a Trojan-horse approach in dealing with MDR-mycobacterium tuberculosis. To achieve this goal, our group has been developing the total synthesis of several metabolites of mycobacterium such as Mycobactin J, lasso-peptides Lariatins A & B as well as interesting natural products such as ralsolamycin, fusaripeptides to name a few.