Rapid Assembly of Functionalized 2-Chromenes and 1,2-Dihydroquinolines via Microwave-Assisted Secondary Amine-Catalyzed Cascade Annulation of 2-/-Propargylarylaldehydes with 2,6-Dialkylphenols.

An efficient, secondary amine-catalyzed cascade annulation of 2-/-propargylarylaldehydes with 2,6-dialkylphenols was established to access biologically relevant functionalized 2-chromenes and 1,2-dihydroquinolines tethered with a synthetically useful -quinone methide scaffold in high yields under microwave irradiation and conventional heating conditions. The microwave-assisted strategy was convenient, clean, rapid, and high yielding in which the reactions were completed in just 15 min, and the yields obtained were up to 95%. This highly atom-economical domino process constructed two new C-C double bonds and a six-membered O/N-heterocyclic ring in a single synthetic operation.

Diversity-Oriented Synthesis of Benzo[][1,4]oxazepine-, 2-Chromene-, and 1,2-Dihydroquinoline-Fused Polycyclic Nitrogen Heterocycles under Microwave-Assisted Conditions.

An efficient, diversity-oriented synthesis of oxazepino[5,4-]quinazolin-9-ones, 6-chromeno[4,3-]quinolines, and dibenzo[,][1,6]naphthyridines was established involving a substrate-based approach under microwave-assisted and conventional heating conditions in high yields (up to 88%). The CuBr-catalyzed, chemoselective cascade annulation of -propargylated 2-hydroxybenzaldehydes and 2-aminobenzamides delivered oxazepino[5,4-]quinazolin-9-ones involving a 6-- cyclization-air oxidation-1,3-proton shift-7- cyclization sequence. This one-pot process showed excellent atom economy (-HO) and constructed two new heterocyclic rings (six- and seven-membered) and three new C-N bonds in a single synthetic operation.

Palladium-catalyzed intramolecular oxypalladation-initiated cascade: solvent-dependent chemodivergent approach to functionalized benzazepines and tetrahydroquinolines.

Palladium-catalyzed, solvent-dependent intramolecular oxypalladation-triggered domino sequences of internal alkynes bearing tethered nucleophilic carboxylic ester and electrophilic enone functionalities were developed for the chemodivergent synthesis of two completely distinct biologically significant complex molecules including isochromenone-fused benzazepines and isobenzofuranone-fused tetrahydroquinolines/chromanes in a single synthetic operation.

A microwave-assisted intramolecular aminopalladation-triggered domino sequence: an atom economical route to 5,10-dihydroindeno[1,2-]indoles.

A microwave-assisted, palladium(II)-catalyzed cascade reaction of 2-alkynylanilines tethered with an α,β-unsaturated carbonyl moiety was established to access 5,10-dihydroindeno[1,2-]indoles in high yields (up to 84%) in a short reaction time. This operationally simple cascade process shows 100% atom economy and allows the construction of two new five-membered rings and two new (1 C-C and 1 C-N) bonds in a single synthetic attempt. The mechanistic pathway of this reaction is visualized involving intramolecular aminopalladation (5-) followed by carbopalladation (olefin insertion) and protonolysis steps.

Microwave-assisted one-pot two-step imine formation-hetero-Diels-Alder-detosylation/aromatization sequence: direct access to dibenzo[,][1,6]naphthyridines.

A microwave-assisted, copper-catalyzed, one-pot, two-step reaction is established to access functionalized [1,6]naphthyridines in high yields (up to 96%) starting from 2-(-propargylamino)benzaldehydes and arylamines. This rapid and operationally simple sequential reaction allowed the construction of two new heterocyclic rings and three new (2 C-C and 1 C-N) bonds in a single synthetic operation. This reaction tolerated various electron-donating and electron-withdrawing substituents well and delivered the desired products in a shorter reaction time under microwave irradiation.

Microwave-Assisted Copper(II)-Catalyzed Cascade Cyclization of 2-Propargylamino/Oxy-Arylaldehydes and -Phenylenediamines: Access to Densely Functionalized Benzo[]Imidazo[1,2-][1,4]Oxazepines and Benzo[]Imidazo[1,2-][1,4]Diazepines.

A highly efficient microwave-assisted copper(II)-catalyzed cyclization cascade was established starting from readily accessible /-propargylated 2-hydroxy or 2-aminobenzaldehydes and -phenylenediamines to synthesize densely functionalized imidazo[1,2-][1,4]oxazepines and imidazo[1,2-][1,4]diazepines in high yields (up to 93%). This one-pot two-step process was found to be highly atom economical (-HO, -H) and operationally simple and enabled the generation of two new heterocycle rings (seven- and five-membered) and three new C-N bonds in a single synthetic operation. These reactions well tolerated a variety of substituents including electron-donating and electron-withdrawing groups and furnished the desired fused heterocycles in high yields under microwave irradiation in a very short reaction time.

Regioselective synthesis of tetrahydroquinolines via syn- and anti-nucleopalladation-initiated cascade processes.

Palladium(ii)-catalyzed regioselective syn-chloropalladation and anti-acetoxypalladation-initiated cascade processes were developed for the synthesis of functionalized tetrahydroquinolines. A series of N-propargyl arylamines tethered with an α,β-unsaturated carbonyl scaffold underwent atom economical cascade reactions to deliver chloro- and acetoxy-substituted tetrahydroquinolines bearing an exocyclic double bond in high yields. A mechanism is proposed for these cascade processes involving a sequential syn-chloropalladation or anti-acetoxypalladation of alkynes followed by intramolecular olefin insertion (6-exo-trig) and protonolysis steps.

Direct Access to Bridged Tetrahydroquinolines and Chromanes via an InCl-Catalyzed Sequential Three-Component Cascade.

A sequential three-component cascade process was developed for the synthesis of bridged tetrahydroquinolines and chromanes bearing 2,6-methanobenzo[][1,3]diazocine and 2,6-methanobenzo[][1,3]oxazocine scaffolds, respectively, in good yields from readily available materials. The InCl-catalyzed reaction progressed via enamine formation, Michael addition, intramolecular cyclization, and intramolecular iminium ion cyclization steps. Notably, this high atom economic approach (-2HO) allowed the generation of four new bonds (1 C-C and 3 C-N or 1 C-C, 1 C-O and 2 C-N) and two heterocyclic rings in a single operation.

Oxidant-free, three-component synthesis of 7-amino-6-benzo[]chromen-6-ones under green conditions.

An oxidant-free three-component synthesis of biologically significant 7-amino-6-benzo[]chromen-6-ones was established involving a Sc(OTf) catalyzed three-component reaction between primary amines, β-ketoesters and 2-hydroxychalcones under green conditions. In this strategy, both the B and C rings of 6-benzo[]chromen-6-ones were constructed simultaneously starting from acyclic precursors by generating four new bonds including two C-C, one C-N and one C-O in a single synthetic operation. The mechanism of this sequential cascade process involves the initial formation of a β-enaminone intermediate followed by Michael addition with 2-hydroxychalcone, intramolecular cyclization, dehydration, lactonization and aromatization steps.

Direct Access to 9-Chloro-1-benzo[]furo[3,4-]azepin-1-ones via Palladium(II)-Catalyzed Intramolecular -Oxypalladation/Olefin Insertion/sp-C-H Bond Activation Cascade.

An efficient Pd(II)-catalyzed cascade approach was established for the synthesis of 9-chloro-1-benzo[]furo[3,4-]azepin-1-ones starting from -propargyl arylamines having a pendant α,β-unsaturated ester scaffold. The mechanism of this sequential process involved intramolecular -oxypalladation followed by olefin insertion and sp-C-Cl bond formation reactions. This high atom- and step-economical cascade sequence generated two heterocycle rings and three new bonds in a single synthetic operation.

Heterogeneous Amberlyst-15-catalyzed synthesis of complex hybrid heterocycles containing [1,6]-naphthyridine under metal-free green conditions.

An efficient green protocol for the synthesis of complex hybrid heterocycles containing [1,6]-naphthyridine and coumarin/pyrazole moieties was established, involving an intramolecular [4 + 2] hetero Diels-Alder reaction as the key step. The biologically significant 12,13-dihydro-6H-benzo[h]chromeno[3,4-b][1,6]naphthyridin-6-ones and 6,10-dihydro-5H-benzo[h]pyrazolo[3,4-b][1,6]naphthyridines were synthesized starting from 2-(N-propargylamino)-arylaldehydes and 3-aminocoumarins or 3-methyl-1-aryl-1H-pyrazol-5-amines in the presence of an Amberlyst-15 catalyst in PEG-200 in good yields. The easy access to diverse complex molecules in a single operation from readily available starting materials, a commercially available, transition metal-free and recyclable catalyst, the use of a green solvent, a very high atom economy and the release of water as the only side product are the highlights of this protocol.

Palladium-Catalyzed Regioselective Syn-Chloropalladation-Olefin Insertion-Oxidative Chlorination Cascade: Synthesis of Dichlorinated Tetrahydroquinolines.

A palladium catalyzed cascade process involving syn-chloropalladation, intramolecular olefin insertion, and oxidative C-Cl bond formation reactions was demonstrated for the synthesis of dichlorinated tetrahydroquinolines in high yields (up to 93%). The N-propargyl arylamines having a tethered α,β-unsaturated carbonyl moiety underwent a regioselective syn-chloropalladation followed by a Heck-type reaction to deliver the tetrahydroquinoline scaffold. The rare insertion of the second chlorine atom was rationalized comprising a Pd catalytic cycle and oxidative cleavage of the C-Pd bond.

Diastereoselective ABB' Three-Component Synthesis of Highly Functionalized Spirooxindoles Bearing Five Consecutive Asymmetric Carbons.

The synthesis of spirooxindoles bearing tetrahydro-4 H-cyclopenta[ b]furan framework was established starting from isatin-derived aldehydes and 2 equiv of 1,3-dicarbonyl compounds involving a piperidine-catalyzed ABB' three-component domino process. This reaction was highly diastereoselective affording a single diastereomer of spirooxindoles with five consecutive asymmetric carbons including spiro and tetrasubstituted carbon centers. In addition, this waste-free (-2HO) reaction showed high atom economy and step economy by creating four new bonds, including three C-C bonds and one C-O bond, and two rings (one carbo- and one heterocyclic) in a single operation.

Synthesis of 6,12-Epiminodibenzo[b,f][1,5]diazocines via an Ytterbium Triflate-Catalyzed, AB Three-Component Reaction.

An efficient and selective procedure for the synthesis of epiminodibenzo[b,f][1,5]diazocines involving a AB three-component reaction is developed. Two equivalents of suitably substituted 2-aminoarylaldehydes reacted with arylamines in the presence of Yb(OTf) to afford the desired products in high yields. The reaction is highly atom-economic and waste-free, in addition to allowing the generation of two heterocyclic rings and four C-N bonds in a single operation.

The effect of postretrieval extinction of nicotine pavlovian memories in rats trained to self-administer nicotine.

Introduction: Retrieval (reactivation) of smoking-related memories is a potent trigger of relapse among ex-smokers, and manipulation of smoking-related memories is considered to be a promising target for therapeutic intervention. Recent studies have shown that postreactivation extinction attenuates drug-related memories and relapse to drug-seeking both in rodents and in humans. We investigated the effect of postreactivation extinction in a rat model of relapse to nicotine-seeking.