Base-Controlled Reactions through an Aldol Intermediate Formed between 2‑Oxoaldehydes and Malonate Half Esters

A practical, atom-economical, base-directed, and highly efficient method for the generation of different selective products through a common aldol intermediate of 2-oxoaldehydes and malonate half esters is successfully developed. The addition of a strong basic environment (potassium <i>tert</i>-butoxide) catalyzed the synthesis of stable decarboxylative aldol products (α-hydroxy ketones), while the Doebner modification procedure resulted in decarboxylative elimination to (<i>E</i>)-α,β-unsaturated esters in good yields. The application of this method in one pot and one pot/two steps with azoles helped to develop regioselective α- and β-azolated products in appreciable yields

2‑Oxo-Driven N₂ Elimination Induced Decarbonylative Cyclization Reaction in Benzotriazoles to 6‑Aminophenanthridines

An efficient functional group induced strategy for the synthesis of 6-aminophenanthridines (6AP) has been developed as a result of an in situ generated novel system “CO–CH­(N₁N₂)”. This reaction presents a new mode of N₂ extrusion in benzotriazoles that later result in decarbonylative cyclization to 6AP. This method offers an easier protocol for the synthesis of 6AP from readily available inexpensive substrates

2‑Oxo Driven Unconventional reactions: Microwave Assisted Approaches to Tetrahydro­furo[3,2‑<i>d</i>]­oxazoles and Furanones

A highly efficient, novel, microwave-assisted, metal-free, diastereoselective synthesis of tetrahydro­furo­[3,2-<i>d</i>]­oxazole is disclosed. The synthesis of napthoxazoles is achieved for the first time without the aid of an external catalyst. On the contrary, our reactions generated naphthofuranones when treated in the presence of metals in microwave/thermal conditions. The unusual behavior of our reactions has further been explored in the generation of furanones from tetrahydro­furo­[3,2-<i>d</i>]­oxazole through the use of metals

Tf₂O‑Promoted Regioselective Heteronucleophilic Ring-Opening Approaches of Tetrahydrofuran

The ring-opening functionalization strategy in tetrahydrofuran (THF) represents an ideal approach to access different valuable structures. Herein, we report different operationally simple, efficient, unique, and practical regioselective heteronucleophilic ring-opening strategies for the THF system. Tf2O, which is a strong electrophilic activator, was found to generate a THF triflate intermediate that triggers the nucleophilicity of nitriles (Nu1) and led to regioselective ring opening in the presence of different nucleophiles (Nu2). Furthermore, the synthesis of different heteronucleophilic ring-opening dimerization products was attributed to the nucleophilicity of Nu2. We also demonstrated that use of borane–tetrahydrofuran (BTHF) can achieve challenging hydride addition in a similar manner

Divergent Reactivity of Amino Acid Alkyl Ester Hydrochlorides with 2‑Oxoaldehydes: Role of Selenium Dioxide To Promote Regioselective Synthesis of Imidazoles

Novel amino acid substituted imidazoles engendered from amino acid alkyl ester hydrochlorides and 2-oxoaldehydes as a result of selenium dioxide promoted unconventional reaction in a basic environment is presented for the first time. Despite the nature of the 2-oxoaldehydes/amino acids used, the imidazoles generated had a functional core structure, and all of the reactions meticulously retained regioselectivity. The imperative feature of these reactions was the uniqueness of selenium dioxide in fixing two nitrogen atoms from amino acids through an in situ generated ArCOCHN₁N₂ system

One-Pot Tandem Approach to Functionalized 3‑Hydroxy-2-furanyl-acrylamides

A novel one-pot tandem process involving Knoevenagel condensation, Michael addition, selective amidation, and Paal–Knorr cyclization to diverse functionalized 3-hydroxy-2-furanyl-acrylamides from simple 2-oxoaldehydes and aroylacetonitriles was presented. Attempts were also made to expand the scope of the reaction to different 2-heteroarylfurans. The packing diagram of the molecules viewed down along the α-axis of the unit cell showed a characteristic intramolecular classical O–H···O hydrogen bond between hydroxyl and carbonyl O atoms leading to self-associated (<i>Z</i>)-2-furanyl-acrylamides

One-Pot Tandem Approach to Functionalized 3‑Hydroxy-2-furanyl-acrylamides

A novel one-pot tandem process involving Knoevenagel condensation, Michael addition, selective amidation, and Paal–Knorr cyclization to diverse functionalized 3-hydroxy-2-furanyl-acrylamides from simple 2-oxoaldehydes and aroylacetonitriles was presented. Attempts were also made to expand the scope of the reaction to different 2-heteroarylfurans. The packing diagram of the molecules viewed down along the α-axis of the unit cell showed a characteristic intramolecular classical O–H···O hydrogen bond between hydroxyl and carbonyl O atoms leading to self-associated (<i>Z</i>)-2-furanyl-acrylamides

One-Pot Tandem Approach to Functionalized 3‑Hydroxy-2-furanyl-acrylamides

A novel one-pot tandem process involving Knoevenagel condensation, Michael addition, selective amidation, and Paal–Knorr cyclization to diverse functionalized 3-hydroxy-2-furanyl-acrylamides from simple 2-oxoaldehydes and aroylacetonitriles was presented. Attempts were also made to expand the scope of the reaction to different 2-heteroarylfurans. The packing diagram of the molecules viewed down along the α-axis of the unit cell showed a characteristic intramolecular classical O–H···O hydrogen bond between hydroxyl and carbonyl O atoms leading to self-associated (<i>Z</i>)-2-furanyl-acrylamides

Amino Catalytic Oxidative Thioesterification Approach to α‑Ketothioesters

An efficient metal-free method for the synthesis of α-ketothioesters is described for the first time. This reaction features the ability of pyrrolidine to fine-tune the reaction between 2-oxoaldehyde and thiols through iminium to the desired product in moderate to good yields. As an advantage, no external oxidants or metal catalysts are required in our method. Reactions performed under modified conditions lead to an apparent balance in reactivity of secondary amine and thiols toward 2-oxoaldehydes

Four-Component Domino Strategy for the Combinatorial Synthesis of Novel 1,4-Dihydropyrano[2,3‑<i>c</i>]pyrazol-6-amines

An efficient one-pot four-component domino protocol for the combinatorial synthesis of novel 1,4-dihydropyrano­[2,3-<i>c</i>]­pyrazol-6-amines has been achieved. This transformation presumably occurs via cyclization–Knoevenagel condensation–Michael addition–tautomerism–intramolecular <i>O</i>-cyclization–elimination sequence of reactions. The significant features of this reaction include expedient one-pot process, short reaction time, no column chromatographic purification, excellent yield, and readily available starting materials