Given that carboxylic acid derivatives and alcohols are abundant in a wide range of building blocks and complex molecules, catalytic diversification of these functional groups is highly sought-after. To this end, recently employing a deoxygenative approach for modifying these oxygenated species has gained momentum. However, to date, asymmetric variants of these methods have been underdeveloped and often require precious metal…
The Nacsa Group uses electron transfer techniques to address challenges in organic synthesis. Our lab works in two main areas. The first uses electrochemistry to develop new approaches for dehydration reactions, such as the synthesis of amides and esters from carboxylic acids, with an emphasis on catalysis. Dehydrative transformations are workhorse operations in pharmaceutical R&D, but owing to the wasteful reagents overwhelmingly used to…
Fluorine has quickly become an atom of great importance in pharmaceutical development. Fluorine, being the element with the highest electronegativity, can impart substantial changes to a molecule’s chemical and physical properties. Incorporation of fluorine into a given framework can be divided into both nucleophilic and electrophilic fluorinating reagents. Particularly, nucleophilic fluorination has the distinct advantage over…
Nucleophilic dearomatization receives attention for its ability to install stereogenicity within a molecule using few steps. Whilst using aromatic substrates as a starting material can be difficult due to the low reactivity, methods have been developed to utilized them as building blocks. Exploring into pharmaceuticals and natural products will show a common moiety in di/tetrahydro pyridine and piperidines. These moieties can be synthesized via…
Diels–Alder (DA) reactions featuring furan as diene have often been plagued with a variety of challenges due to the ease of reversibility.[1] Factors that contribute to this trend stem from a large HOMO–LUMO gap between furan and the dienophile as well as the greater ring-strain of the newly furnished oxa-norbornene cycloadduct in contrast to cyclopentadiene, its carbo-congener. To address these shortcomings, highly activated furans and/or…
Ring-closing alkyne metathesis (RCAM) has received considerable attention over the last 20 years for its utility in synthesizing macrocycles[1]. While its more widely studied counterpart—alkene metathesis—has become a cornerstone of modern synthetic methodology for macrocycle formation, alkyne metathesis remains comparatively unexplored[2]. However, recent studies have highlighted the synthetic potential of cycloalkynes as versatile…
Late-stage functionalization, a transformative strategy in medicinal chemistry, enables precise modification of molecular frameworks through atom insertion, deletion, or exchange, offering rapid access to novel pharmacophores and enhancing drug discovery efforts. Nitrogen-containing heterocycles, such as indoles, pyrroles, and pyridines, are pivotal in pharmaceuticals.[1] Yet, existing methods for their diversification by nitrogen insertion…