Carbon–Carbon Bond Formation by Radical Cyclization: Regioselective Synthesis of Spiro Heterocyclic Compounds by n Bu3SnH‐Mediated Reaction

Several spiro heterocyclic compounds have been regioselectively synthesized in excellent yield by ⁿ Bu₃SnH‐AIBN‐mediated radical cyclization of 4‐(2′‐bromoaryloxymethyl)‐1‐methylquinolin‐2(1H)‐ones in refluxing benzene under nitrogen for 4 h.     

Regioselective Synthesis of Benzofuran‐Annulated Six‐Membered Sulfur Heterocycles by Aryl Radical Cyclization

The tin hydride–mediated cyclization of a number of sulfides and sulfones under mild and neutral conditions has been investigated. The sulfides were in turn derived from 3(2H) benzothiofuranone and 2‐bromobenzyl bromides by phase‐transfer‐catalyzed reaction, and the corresponding sulfones were prepared by treatment of the corresponding sulfides with m‐CPBA at room temperature. The sulfides and sulfones were then reacted with ⁿ Bu₃SnH‐AIBN to afford regioselectively benzofuran‐annulated six‐membered sulfur heterocycles.     

Studies in Thio‐Claisen Rearrangement: Regioselective Synthesis of Thiopyrano[2,3‐b]pyran‐2‐ones and Thieno[2,3‐b]pyran‐2‐ones

Abstract

4‐Mercapto‐6‐methyl‐2‐pyrone was alkylated with different allylic and propargylic halides under phase transfer catalyzed condition in the presence of TBAB or BTEAC catalyst in chloroform–aqueous NaOH (1%) at room temperature. The S‐alkylated thiopyran‐2‐ones were then refluxed in quinoline or in chlorobenzene to give 4‐chloromethylthiopyrano[2,3‐b]pyran‐2‐one and 4‐hydroxymethylthiopyrano[2,3‐b]pyran‐2‐one or several thieno[2,3‐b]pyran‐2‐ones.     

Aryl Radical Cyclization: Regioselective Synthesis of 6a,7,8,12b‐Tetrahydro‐6H‐chromeno[3,4‐c]quinolin‐6‐one

Regioselective synthesis of 6a,7,8,12b‐tetrahydro‐6H‐chromeno[3,4‐c]quinolin‐6‐ones 4 in good to excellent yields from 3‐(2‐bromoanilinomethyl)coumarins 3 by aryl radical cyclization is described. The cyclization precursors 3 were prepared by the reaction of 3‐chloromethyl coumarin with different 2‐bromoaniline.     

Regioselective Synthesis of 2H‐Benzothiopyrano[3,2‐c]quinolin‐7(8H)‐ones by Tri‐n‐butyltinhydride–Mediated Radical Cyclization

A number of hitherto unreported 2H‐benzothiopyrano[3,2‐c]quinolin‐7(8H)‐ones have been regioselectively synthesized in 90–96% yield by tri‐n‐butyltinhydride–AIBN–mediated radical cyclization from 4‐(2′‐bromothioarylmethyl)‐1‐methylquinolin‐2(1H)‐ones and their corresponding sulfones. 4‐(2′‐Bromothioarylmethyl)quinolin‐2(1H)‐ones were in turn prepared from 4‐bromomethylquinolin‐2(1H)‐one and o‐bromothiophenols by refluxing in acetone in the presence of anhydrous K₂CO₃. These were converted to the corresponding sulfones by oxidation with two equivalents of m‐CPBA in refluxing dichloromethane for 1 h.     

Regioselective Synthesis of Coumarin and Quinolone‐Annulated Spiro Heterocycles via Aryl Radical Cyclization

Abstract

3‐(2′‐Bromobenzyloxy)quinolin‐2‐ones and 3‐(2′‐bromobenzyloxy)benzopyran‐7‐ones undergo aryl radical cyclization in the presence of ⁿ Bu₃SnCl‐Na(CN)BH₃‐AIBN to give spiro‐quinolone and coumarin derivatives.     

Regioselective Synthesis of Coumarin‐Annulated Polyheterocycles by [3,3] Sigmatropic Rearrangement

Several coumarin‐annulated polyheterocycles have been regioselectively synthesized in 82–90% yield by anhydrous AlCl₃‐catalyzed charge‐accelerated Claisen rearrangement of 4‐aryloxymethyl [3,2‐c] pyrano benzopyran‐5‐ones in dichloromethane at rt for 0.5 h.     

Green Synthesis of Pyrano[2,3‐d]‐pyrimidine Derivatives in Ionic Liquids

Pyrano[2,3‐d]pyrimidine derivatives were synthesized in high yields by a condensation reaction between arylmethylidenemalononitrile and barbituric acid using room‐temperature ionic liquids such as 1‐n‐butyl‐3‐methylimidazolium tetrafluoroborate ([BMIm]BF₄) or 1‐butylpyridinium tetrafluoroborate ([BPy]BF₄) as solvents under neutral conditions.     

Sequential [3,3]Sigmatropic Rearrangement: Regioselective Synthesis of Dimedone‐Annulated Heterocycles

The [3,3]sigmatropic rearrangement in the 3‐(4′‐aryloxybut‐2′‐ynyl)mercapto‐5,5‐dimethyl cyclohex‐2‐enones afforded a number of 4‐aryloxymethyl‐7,7‐dimethyl‐6,7,8‐trihydrothiochrom‐3‐en‐5‐ones (70–80%), which underwent second [3,3]sigmatropic rearrangement to furnish benzofuro[3,2‐c][1]‐2,3,4,6,6a,11a‐hexahydro‐3,3,11a‐trimethylthiobenzopyran‐2‐ones (60–70%).     

Regioselective Synthesis of 1,8-Naphthyridinone-Annulated Oxygen and Sulfur Heterocycles by Tri-n-butyl Tinhydride–Mediated Aryl Radical Cyclization

The tin hydride–mediated cyclizations of a number of ethers, sulfides, and sulfones under mild, neutral conditions have been investigated. While the 2-bromobenzyloxy ethers were prepared in 62–65% yields by the alkylation of 4-hydroxy-1-phenyl-1,8-naphthyridin-2(1H)-one with 2-bromobenzyl bromides in refluxing acetone in the presence of anhydrous potassium carbonate, the sulfides were derived from 4-mercapto-1-phenyl-1,8-naphthyridin-2(1H)-one and 2-bromobenzyl bromides in 82–84% yields by a phase-transfer catalysis (PTC) reaction. The corresponding sulfones were prepared by treatment of the sulfides with m-CPBA in refluxing dichloromethane. The ethers, sulfides, and the sulfones were treated with ⁿ Bu₃SnH-AIBN to give regioselectively 1,8-naphthyridinone-annulated oxygen and sulfur heterocycles in 70–78% yields.     

Synthesis of Novel Classes of Pyrido[2,3‐d]‐pyrimidines,Pyrano[2,3‐d]pyrimidines,and Pteridines

6‐Amino‐5‐formyluracils 1 and 5‐formyl‐6‐hydroxyuracils 4 react with Meldrum's acid 2 in the presence of piperidine as catalyst under thermolytic conditions to afford 6‐carboxy‐2,4,7‐trioxopyrido[2,3‐d]pyrimidines 3 and 6‐carboxy‐2,4,7‐trioxopyrano[2,3‐d]pyrimidines 5 in good yield. Under identical conditions, 6‐amino‐5‐nitrosouracils 6 react with 2 to afford pteridine‐6‐carboxylic acids 7 in good yields.     

Synthesis of Substituted Pyrido[1,2-a]benzimidazoles by Ruthenium-Catalyzed C−H Bond Activation and Tandem Cyclization of 2-Arylimidazo[1,2-a]pyridines with Iodonium Ylides

Ruthenium-catalyzed C−H bond activation and tandem cyclization of 2-arylimidazo[1,2-a]pyridines with iodonium ylides proceed efficiently. For the first time, the easily available iodonium ylides and inexpensive ruthenium complex were employed to synthesize pyrido[1,2-a]benzimidazole derivatives in good yields under simple and easy-to-operate conditions. Several primary mechanism investigations and synthetic applications involving gram-scale preparation, derivatization reactions and the transformation of iodonium ylide generated in situ have also been conducted.     

Synthesis of Fused [5,5]‐1,2,4‐Triazoles via Tandem Thioimidate Cyclopropane Rearrangement–Cyclization

The synthesis of fused [5,5]‐1,2,4‐triazoles via a tandem cyclopropane rearrangement–cyclization sequence is described. Optimization of the cyclization reaction was achieved thermally using iPrOH as the solvent in the presence of TEA. This method was applied to the preparation of 3‐substituted‐7‐aryl‐pyrrolo‐1,2,4‐triazoles in good to excellent yields.     

Novel Method for the Synthesis of [1,2,4]Triazino[4,3‐c]quinazoline System

4‐Hydrazinoquinazoline was found to form new 2‐(3,4‐dihydro‐3oxo‐2H‐[1,2,4]triazino[4,3‐c]quinazolin‐4‐yl)acetic acid with maleic anhydride in on‐step sequence. Proposed heterocyclization includes, probably, acylation reaction followed by intramolecular uncleophilic addition.     

Synthesis of Multifluoromethylated γ-Sultines by a Photoinduced Radical Addition–Polar Cyclization

Despite the significance of sultines in synthesis, medicine, and materials science, the chemistry of sultines has remained unexplored due to their inaccessibility. Herein, we demonstrate the development of a photoredox-catalyzed multifluoromethyl radical addition/SO₂ incorporation/polar cyclization cascade approach to multifluoromethylated γ-sultines. The reactions proceed by single electron transfer induced multifluoromethyl radical addition to an alkene followed by SO₂ incorporation, and single-electron reduction for polar 5-exo-tet cyclization. Key to the success of the protocol is the use of easily oxidizable multifluoroalkanesulfinates as bifunctional reagents. The reactions proceed with excellent functional-group tolerance to deliver γ-sultines in moderate to excellent yields.     

Facile Synthesis of Pyrano[2,3‐c]pyrazol‐6‐one Derivatives Under Microwave Irradiation in Solvent‐Free Conditions

A series of substituted 1H,6H‐pyrano[2,3‐c]pyrazol‐6‐one derivatives were synthesized from one‐pot cyclocondensation of hydrazine derivatives or 1H‐pyrazol‐5‐one derivatives with various β‐keto esters under solvent‐free conditions using microwave irradiation in short time with good to excellent yields.     

Solvent‐Free,One‐Pot Synthesis of Pyrano[2,3‐c]pyrazole Derivatives in the Presence of KF·2H2O by Grinding

Abstract

A solvent‐free, one‐pot process for the preparation of 4H‐pyrans in the presence of KF?·?2H₂O by grinding was achieved. Its advantages are easy workup, mild reaction conditions, high yields, and environmental friendliness.     

Synthesis of Biodegradable Hydrogel by Radical Ring‐Opening Polymerization of 2‐Methylene‐1,3,6‐Trioxocane

2‐Methylene‐1,3,6‐trioxocane (MTC), maleic anhydride (MA), and poly(ethylene glycol diacrylate) 400 (PEGD) or divinyl adipate (DVA) were terpolymerized in the presence of a radical initiator. Though the obtained gels did not absorb deionized water, the gels could absorb deionized water and saline after hydrolyzing the MA carboxylate anhydride functionality. The absorbing ratios of deionized water and saline were high. The biodegradability of the hydrogels after hydrolysis was found to be good by a biochemical oxygen demand (BOD)‐tester using soil.     

Radical Cyclization Route to the Stereoselective Synthesis of (+)‐trans‐Cognac Lactone and (+)‐trans‐Aerangis Lactone

Stereoselective total synthesis of two chiral lactones, (+)‐trans‐cognac lactone (1b) and (+)‐trans‐aerangis lactone (2c), has been achieved from the same intermediate using a radical‐based cyclization route.