Editorial: Recent Advances in Synthesizing and Utilizing Nitrogen-containing Heterocycles Provisionally Accepted

Takashi Ohshima^1* Hsyueh-Liang Wu² Hyun-Joon Ha³

• ¹Kyushu University, Japan
• ²National Taiwan Normal University, Taiwan
• ³Hankuk University of Foreign Studies, Republic of Korea

The Innovative Synthetic Methods section showcases pioneering strategies for constructing nitrogen-containing heterocycles. Murakami et al. (link to #1272034) present a copper-catalyzed method for synthesizing imidazolidine and imidazolidinone by reacting aziridines with imines and isocyanates, respectively. This approach involves transforming 3-membered heterocyclic rings into 5membered ones, yielding a diverse array of 2-substituted imidazolidines and substituted imidazolidinones with high functional group compatibility. Kim et al. (link to #1267422) introduce a novel method for constructing functionalized dihydropyridinone rings via the annulation of an amide tethered with an alkyne moiety at the α-carbon. This process includes the formation of O-silyl N,Oketene acetal and silver-mediated addition, proving a new route for the total synthesis of phenanthroindolizidine and phenanthroquinolizidine alkaloids. Han et al. (link to #1255636) descrive a new single-atom deletion strategy for the late-stage conversion of alkaloids, employing oxidative ring contraction followed by chemoselective reduction to convert the 6-membered piperidine moiety of (allo)securinine into a 5-membered pyrrolidine, facilitating access to (allo)norsecurinine.In the Selectivity and Reactivity Control domain, it is demonstrated that modifications to the catalyst, reaction conditions, or substrate structure can significantly enhance selectivity and reactivity, suggesting a new control strategy in heterocyclic synthesis. Iwabuchi et al. (link to #1251299), focusing on La(OTf)3-catalyzed reactions, illuminate the efficiency and versatility of modern synthetic strategies. Their method utilizing La(OTf)3-catalyzed intramolecular regioselective aminolysis method to convert cis-3,4-epoxy amines into highly strained 4-membered ring azetidines over 5membered ring pyrrolidines. This approach achieves high yields even with acid-sensitive and Lewis basic functional groups, marking a significant advancement in synthetic organic chemistry. Ha et al.(link to #1280633) develop an innovative approach for constructing nitrogen-containing heterocycles via aziridine ring-opening reactions. In this reaction, the regioselectivity depends on the functional groups of the alkyl substituents. Employing aziridine rings substituted with ketone or silylated hydroxy group as substrates has proven to efficiently facilitate ring-opening and subsequent cyclizations, converting 3-membered heterocyclic rings into 5-or 6-membered ones. Noda and Shibasaki et al. (link to #1271896) investigate the reactivity of rhodium alkyl nitrenes derived from substituted hydroxylamine precursors for synthesizing 5-membered pyrrolidines, focusing on modulating the regioselectivity between benzylic and tertiary C-H bonds by adding of Brønsted acids or by modifying oxygen substituents. Their findings deepen the understanding of metallonitrene structures and provide valuable insights for the selective synthesis of N-heterocycles. This study underscores the profound impact of precursor structures and additives on nitrene reactivity, paving the way for substratecontrolled synthesis, which is crucial for medicinal chemistry and drug development. Hong et al. (link to #1254632) develop a novel and highly efficient strategy for the C4-selective (hetero)arylation of pyridines using N-aminopyridinium salts. This method overcomes the poor site-selectivity often encountered in conventional methods by using N-aminopyridinium salts instead of pyridine as substrates. This metal-free method proceeds at room temperature with a base, eliminating the need for catalysts or oxidants. It allows the incorporation of various electron-rich (hetero)aryl groups onto pyridines, facilitating the synthesis of valuable C4-(hetero)aryl pyridine derivatives, crucial in agrochemicals, pharmaceuticals, and functional materials. In a complementary contribution, Ohshima Further expanding the synthetic repertoire, Yoshida et al. (link to #1237878) present an efficient method for preparing organomagnesium intermediates with protected azido groups, utilizing Amphos for azide protection. This technique facilitates the synthesis of diverse functionalized azides and their subsequent conversion into a wide array of 1,2,3-triazoles through click reactions. This advancement contributes significantly to synthetic organic chemistry, pharmaceutical sciences, and materials chemistry by providing a versatile approach to synthesize azides and triazoles, pivotal as synthetic intermediates and bioactive compounds. Mohamadpour et al. (link to #1361266) introduce a groundbreaking, green photosynthesis method for synthesizing 3,4-dihydropyrimidin-2-(1H)one/thione derivatives which exhibit widespread biological applications such as antihypertensive, antiviral, antitumor, antibacterial, α-1a-antagonism, antioxidant, and anti-inflammatory actions, from aryl aldehydes, β-ketoesters, and urea/thiourea. This method employs a novel halogenated dicyanobenzene-based photosensitizer, 3DPAFIPN, as a donor-acceptor photocatalyst triggered by visible light. Utilizing blue LED technology enables a sustainable, energy-efficient reaction process in an ethanol medium at room temperature. The perspective offered by Ha (link to #1279418) brings to light the practicality and environmental benefits of using proline-derived organocatalysis and poteconomical synthesis. The synthesis of (-)-quinine serves as a prime example of overcoming synthetic challenges through organocatalysis, showcasing the method's potential in streamlining the environmentally benign production of complex organic compounds. The discussion includes various organocatalysis techniques and their success in enhancing reaction conditions, emphasizing the significance of organocatalysts in modern synthetic organic chemistry. This issue showcases the dynamic and ever-evolving landscape of research on nitrogen-containing heterocycles and lays the groundwork for future investigations. It is a testament to the collaborative spirit of the scientific community, driven by a shared commitment to unravel the complexities of chemistry for the advancement of knowledge and society.