A Facile Direct Route to N‐(Un)substituted Lactams by Cycloamination of Oxocarboxylic Acids without External Hydrogen

Abstract

Lactams are privileged in bioactive natural products and pharmaceutical agents and widely featured in functional materials. This study presents a novel versatile approach to the direct synthesis of lactams from oxocarboxylic acids without catalyst or external hydrogen. The method involves the in situ release of formic acid from formamides induced by water to facilitate efficient cycloamination. Water also suppresses the formation of byproducts. This unconventional pathway is elucidated by a combination of model experiments and density functional theory calculations, whereby cyclic imines (5‐methyl‐3,4‐dihydro‐2‐pyrrolone and its tautomeric structures) are found to be favorable intermediates toward lactam formation, in contrast to the conventional approach encompassing cascade reductive amination and cyclization. This sustainable and simple protocol is broadly applicable for the efficient production of various N‐unsubstituted and N‐substituted lactams.

Cycloamination strategies for renewable N-heterocycles

“…Li et al developed a generic strategy that does not require catalyst or external hydrogen by involving in situ controlledrelease of HCOOH from N-formyl species (e.g., HCONH 2 ) with H 2 O for the cycloamination of LA (22a) and other keto-acids (22), that provides access to 5-methylpyrrolidones and relevant N-(un)substituted lactams, 146 that is elucidated by a combination of model experiments and density functional theory calculations. An unconventional pathway via cyclic imines (5-methyl-3,4-dihydro-2-pyrrolone (29) and its tautomeric structures) as key intermediates is elucidated by density functional theory (DFT) calculations show yields of 5-methyl-2-pyrrolidone (30) from LA (22a) and HCONH 2 , which is different from the conventional approaches encompassing cascade reductive amination and cyclization (Scheme 10).…”

“…An unconventional pathway via cyclic imines (5-methyl-3,4-dihydro-2-pyrrolone (29) and its tautomeric structures) as key intermediates is elucidated by density functional theory (DFT) calculations show yields of 5-methyl-2-pyrrolidone (30) from LA (22a) and HCONH 2 , which is different from the conventional approaches encompassing cascade reductive amination and cyclization (Scheme 10). 146 The simple and ecofriendly protocol of Li et al 146 may open an avenue for direct synthesis of N-(un)substituted pyrrolidones/lactams by cyclic diamination of keto acids without external hydrogen gas. Besides the above-discussed reductive amination of LA (22a) and N-containing compounds, a number of other renewed synthetic routes such as ketoamides proceeding via cascade cycli-zation and ionic hydrogenation mediated by Al(OTf ) 3 and Et 3 SiH, 147 reductive transformation of itaconic acid and NH 3 over Ru/C and H 2 , 148 reductive N-alkylation and decarboxylation of glutamic acid catalyzed by Pd/Al 2 O 3 with and H 2 , 149 and Zr-catalyzed N-acylation of lactams 150 have been explored for efficient construction of pyrrolidone-type motifs.…”

Recyclable Zr/Hf-Containing Acid-Base Bifunctional Catalysts for Hydrogen Transfer Upgrading of Biofuranics: A Review

“…However, compared to the desired products especially for fuels or fuel additives, biomass-derived feedstocks generally possess higher oxygen content (Prasomsri et al, 2013;Liao et al, 2014;Li et al, 2020a;Li et al, 2020b;Wang et al, 2020a). It is still necessary to further process the biomass feedstock to upgrade its functional groups (Dabros et al, 2018;Li et al, 2019b;Iglesias et al, 2020Tan et al, 2021. In the field of biomass upgrading, the most widely used approach is to convert biomass (e.g., cellulose and hemicellulose) into a series of furan compounds via cascade reactions (Scheme 1) (Zhou and Zhang, 2016;Liu et al, 2019;Chen et al, 2021b).…”

“…Although precious metals (e.g., Ru, Pd, Ir, Pt) were widely studied for direct CTH, the prices were not suitable for industrialization (Tuteja et al, 2014;Brethauer and Studer, 2015;Cao et al, 2017;. On the other hand, non-noble metals (e.g., Fe, Co, Cu, Ni) were restricted because of relatively low activity and/or product selectivity (Hu et al, 2019a;Zhang et al, 2019b;Shi et al, 2019;Jiang et al, 2020). These disadvantages have prompted scientists to explore alternative catalysts, which can balance economy and high selectivity (Yin and Shen, 2020).…”

3-Bromopyridine-Heterogenized Phosphotungstic Acid for Efficient Trimerization of Biomass-Derived 5-Hydroxymethylfurfural with 2-Methylfuran to C21 Fuel Precursor

“…In particular, phosphotungstic acid (HPW, H 3 PW 12 O 40 ) has a tetrahedral PO 4 core in the center of the anion structure, surrounded by twelve WO 6 polyhedra via oxygen atoms to link each other, which exhibits excellent catalytic activity for upgrading biomassderived compounds into different valuable chemicals and biofuels [33,34]. However, it should be mentioned that HPW is extremely soluble into most polar solvents, difficult to separate, corrosive to reactors, and polluted to the environment [35][36][37][38][39][40][41][42][43][44][45][46][47][48]. Taking the above problems into consideration, it is highly desirable to heterogenize HPW using a high-efficiency method.…”