skip to main content

Title: Recent advances in the synthesis and reactivity of azetidines: strain-driven character of the four-membered heterocycle
Azetidines represent one of the most important four-membered heterocycles used in organic synthesis and medicinal chemistry. The reactivity of azetidines is driven by a considerable ring strain, while at the same the ring is significantly more stable than that of related aziridines, which translates into both facile handling and unique reactivity that can be triggered under appropriate reaction conditions. Recently, remarkable advances in the chemistry and reactivity of azetidines have been reported. In this review, we provide an overview of the synthesis, reactivity and application of azetidines that have been published in the last years with a focus on the most recent advances, trends and future directions. The review is organized by the methods of synthesis of azetidines and the reaction type used for functionalization of azetidines. Finally, recent examples of using azetidines as motifs in drug discovery, polymerization and chiral templates are discussed.  more » « less
Award ID(s):
Author(s) / Creator(s):
Date Published:
Journal Name:
Organic & Biomolecular Chemistry
Page Range / eLocation ID:
3274 to 3286
Medium: X
Sponsoring Org:
National Science Foundation
More Like this
  1. The importance and prevalance of O-, N-, and S-atom containing saturated four-membered ring motifs in biologically active molecules and potential therapeutics continues to drive efforts in their efficient synthetic preparation. In this review, general and recent strategies for the synthesis of these heterocycles are presented. Due to the limited potential bond disconnections, retrosynthetic strategies are broadly limited to cyclizations and cycloadditions. Nonetheless, diverse approaches for accessing cyclization precursors have been developed, ranging from nucleophilic substitution to C–H functionalization. Innovative methods for substrate activation have been developed for cycloadditions under photochemical and thermal conditions. Advances in accessing oxetanes, azetidines, and thietanes remain active areas of research with continued breakthroughs anticipated to enable future applications. 
    more » « less
  2. Cerium oxide nanoparticles (CeNPs) are versatile materials with unique and unusual properties that vary depending on their surface chemistry, size, shape, coating, oxidation states, crystallinity, dopant, structural and surface defects. This review details advances made over the past twenty years in the development of CeNPs and ceria-based nanostructures, the structural determinants affecting their activity, and translation of these distinct features into applications. The two-oxidation states of nanosized CeNPs (Ce3+/Ce4+) coexisting at the nanoscale level, facilitate formation of oxygen vacancies and defect states which confer extremely high reactivity and oxygen buffering capacity, and the ability to act as catalysts for oxidation and reduction reactions. However, the method of synthesis, surface functionalization, surface coating and defects are important factors in determining their properties. This review highlights the key properties of CeNPs, their synthesis, interactions and reaction pathways, and provides examples of emerging applications. Due to their unique properties, CeNPs have become quintessential candidates for catalysis, chemical mechanical planarization (CMP), sensing, biomedical applications and environmental remediation, with tremendous potential to create novel products and translational innovations in a wide range of industries. This review highlights the timely relevance and the transformative potential of these materials in addressing societal challenges and driving technological advancements across these fields. 
    more » « less
  3. Naphthopyran molecular switches undergo a ring-opening reaction upon external stimulation to generate intensely colored merocyanine dyes. Their unique modularity and synthetic accessibility afford exceptional control over their properties and stimuli-responsive behavior. Commercial applications of naphthopyrans as photoswitches in photochromic ophthalmic lenses have spurred an extensive body of work exploring naphthopyran–merocyanine structure–property relationships. The recently discovered mechanochromic behavior of naphthopyrans has led to their emergent application in the field of polymer mechanochemistry, enabling advances in the design of force-responsive materials as well as fundamental insights into mechanochemical reactivity. The structure–property relationships established in the photochemical literature serve as a convenient blueprint for the design of naphthopyran molecular force probes with precisely tuned properties. On the other hand, the mechanochemical reactivity of naphthopyran diverges in many cases from the conventional photochemical pathways, resulting in unexpected properties and opportunities for deeper understanding and innovation in polymer mechanochemistry. Here, we highlight the features of the naphthopyran scaffold that render it a powerful platform for the design of mechanochromic materials and review recent advances in naphthopyran mechanochemistry. 
    more » « less
  4. Abstract

    α‐Diimine ligands have contributed extensively to the coordination chemistry of the majority of the transition metals; bis(arylimino)acenaphthene ligands (BIANs) have been widely studied and found to offer great versatility in their application as supporting ligands in catalytic transformations. In recent years, BIAN‐based iron complexes have proven effective in mediating a number of reductive transformations which includes hydrosilylation, hydroboration and hydrogenation chemistries. This review highlights the most recent contributions to the field. In our initial 2015 communication, we disclosed that the arene‐capped Fe(0) speciesArBIAN−Fe(toluene) mediates aldehyde and ketone hydrosilylation with exceptional activity under solvent‐free conditions. This led us to the discovery that such systems were capable of the hydrosilylation of imines and esters, the hydroboration of imines, aldehydes, ketones, alkenes, and alkynes and even the ring‐opening polymerization ofrac‐lactide. Spectroscopic and computational studies have firmly established the importance of redox non‐innocence in BIAN complexes and detailed mechanistic studies have revealed the importance of spin‐state‐crossing in catalysis. Although this work represents only a small component of advances in iron catalysis, our efforts have proven influential in Fe‐based approaches to reductive transformations and is likely to continue to inform the design of Fe‐based catalysts.

    more » « less
  5. The synthesis of ATP, life’s “universal energy currency,” is the most prevalent chemical reaction in biological systems and is responsible for fueling nearly all cellular processes, from nerve impulse propagation to DNA synthesis. ATP synthases, the family of enzymes that carry out this endless task, are nearly as ubiquitous as the energy-laden molecule they are responsible for making. The F-type ATP synthase (F-ATPase) is found in every domain of life and has facilitated the survival of organisms in a wide range of habitats, ranging from the deep-sea thermal vents to the human intestine. Accordingly, there has been a large amount of work dedicated toward understanding the structural and functional details of ATP synthases in a wide range of species. Less attention, however, has been paid toward integrating these advances in ATP synthase molecular biology within the context of its evolutionary history. In this review, we present an overview of several structural and functional features of the F-type ATPases that vary across taxa and are purported to be adaptive or otherwise evolutionarily significant: ion channel selectivity, rotor ring size and stoichiometry, ATPase dimeric structure and localization in the mitochondrial inner membrane, and interactions with membrane lipids. We emphasize the importance of studying these features within the context of the enzyme’s particular lipid environment. Just as the interactions between an organism and its physical environment shape its evolutionary trajectory, ATPases are impacted by the membranes within which they reside. We argue that a comprehensive understanding of the structure, function, and evolution of membrane proteins—including ATP synthase—requires such an integrative approach.

    more » « less