Research
Our main focus is on Organic Synthesis, developing new approaches to molecular skeletons, and building complexity rapidly yet selectively. In our laboratory, we develop such transformations catalyzed by metal salts and organocatalysts to achieve the above goals. Our interests include element-element coupling/addition reactions (element being -B, -Si, -F, -C, -N, -X, etc.), Redox chemistry involving radicals, and so on.
Transition Metal Catalysis - General Overview
The approach to complex molecular skeletons has transformed with a growing arsenal of efficient synthetic methodologies. Metals play an important role in this due to their diverse reactivity at their various oxidation states. Our group will focus on developing new, interesting multifunctionalization reactions utilizing this diversity. Some of the major areas that we currently focus on are:
1. Nickel(0)-Catalyzed Cycloaddition Reactions
2. Metal-Catalyzed Introduction of Main Group Functionalities & Their Reactivity
3. Organocatalysis
4. Aromaticity and Soft Materials with Optoelectronic Properties
Nickel(0)-Catalyzed Cycloaddition Reactions
Nickel(0) catalyzed cycloaddition reactions represent a powerful tool in contemporary synthetic chemistry, offering a versatile and efficient approach to building complex organic molecules. Our research focuses on enhancing the accessibility and applicability of this chemistry.
We explored the potential of Ni(COD)(DQ), a stable Ni(0) complex, as a catalyst for the reductive coupling of aldehydes with alkynes and ynamides, yielding silylated allyl alcohols with high yields and regioselectivities. We elucidated the mechanism using mass spectrometric identification of intermediates and DFT studies. Notably, Ni(COD)(DQ) exhibited exceptional stability and catalytic activity on the bench for over six months, suggesting its suitability for user-friendly Ni(0) chemistry. Furthermore, we introduced a modular approach for the in situ generation of Ni(NHC)(EDO) complexes, facilitating rapid ligand screening for enantioselective catalysis.
Additionally, we demonstrated a regioselective [2+2+2] cyclotrimerization of 1,3-diynes catalyzed by Ni(0) to produce hexa-substituted benzenes (HSBs), which find applications as functional materials and pharmaceuticals. Our protocol displayed remarkable versatility, accommodating diverse alkyl, aryl, and heterocyclic groups on 1,3-diynes to generate corresponding HSBs. Control experiments and DFT calculations provided insights into the reaction mechanism and regioselectivity.
We first introduced a nickel-catalyzed diastereoconvergent reductive coupling of heteroatom-attached allyl moieties with aldehydes, yielding syn-chromanols exclusively. This transformation proceeds via a [2 + 2 + 1] oxidative cycloaddition mechanism involving the active catalyst. Notably, our method is applicable to both terminal and internal olefin substrates. We showcased the utility of this approach through formal syntheses of CP-199.330, CP-199.331, and CP-85.958, supported by control experiments, mass spectrometric analysis, and DFT studies elucidating the plausible mechanism and the origin of exclusive syn-selectivity.
Ghosh, S. et al. Org. Lett. 2024, (Accepted)
Metal-Catalyzed Introduction of Main Group Functionalities & Their Reactivity
We are interested in introducing Main group functionalities that are challenging on various systems. We employ transition metals and organocatalysts to achieve such transformations.
Our interest was in developing the protoboration of 1,3-diynes as a platform for the iterative functionalization of various groups on enynes and dienes. An operationally simple, regioselective protoboration of 1,3-diynes using a mixed diboron reagent and Cu(I)/phosphine catalyst provided enynylboronates and 1,4-diboryl-1,3-dienes in good yields. The iterative coupling capabilities of the products have been demonstrated along with other downstream transformations offering a range of value-added skeletons.
Organophosphorus Catalysis
We use the versatility and commercial availability of a large number of phosphorus compounds towards the introduction of main-group elements in organic substrates to achieve our larger goal of simultaneous multifunctionalizations.
We disclosed an operationally simple route to delta-valerolactones through an organophosphorus-catalyzed borylative ring-opening/allylation of vinylcyclopropanes providing delta-hydroxy esters stereoselectively. The delta-hydroxy esters were lactonized to obtain densely substituted delta-valerolactones. The present methodology exhibited enhanced functional group tolerance compared to the existing metal-mediated methods.
Aromaticity and Soft Materials with Optoelectronic Properties
The cyclic non-benzenoid compounds show interesting aromaticity characteristics, which impart special molecular and optoelectric properties. We have contributed to the understanding of their mechanism of action using computational and experimental techniques.
Mondal, S. et al. Adv. Synth. Catal. 2024, In Press
Mondal, S. et al. Org. Lett. 2023, 25, 3941–3945
