Browsing by Author "Kishor Chandra Bharadwaj"

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Acryl Activation by Intramolecular Hydrogen Bond: Morita Baylis Hillman Reaction of Acrylamide with Broad Substrate Scope
(Wiley-Blackwell, 2017) Kishor Chandra Bharadwaj
Use of acrylamide as an activated alkene in largely recognized Morita Baylis Hillman (MBH) reaction has been least explored owing to less reactivity of acrylamide as Michael acceptor. Contrary acrylamide have profound applications in synthetic, medicinal and polymer chemistry. An intramolecular Hydrogen bond activated, MBH reaction of N-(2-hydroxyphenyl) acrylamide has been developed. With various control experiments, role of ortho hydroxy was found to be as an activator and was critical for success of reaction. Under the influence of DABCO, designed acrylamides gave wide substrate scope including a number of less reactive aldehydes and chemo selective MBH reactions. Such mode of activation can be helpful in design of other reactions too. An example has been presented by successful Michael addition reaction. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Acrylamide in Rauhut-Currier reaction; intramolecular isomerization of activated alkenes for quinolone synthesis
(Elsevier Ltd, 2017) Kishor Chandra Bharadwaj
Acrylamides are fundamental Michael acceptors which have been used profoundly in synthetic, medicinal and polymer chemistry. However, due to their lower reactivity they have been least used in Morita-Baylis-Hillman (MBH) reaction and have been out of its vinylogus version Rauhut Currier (RC) reaction. Herein, use of acrylamide in RC reaction is being presented. Intramolecular RC reaction followed by [1,3]-H shift led to the synthesis of quinolone moiety. DABCO catalyzed IRC reaction of acrylamide at 80 °C in presence of water, was found to work on a number of precursors. En route chemo selective, gram scale method for ambiphilic, versatile precursor 2-amino chalcone is also reported. Chemoselective and economical conversion of 2-nitro chalcone to 2-aryl quinoline has also been developed. © 2017 Elsevier Ltd
Alkaloid group of Cinchona officinalis: structural, synthetic, and medicinal aspects
(Elsevier, 2018) Kishor Chandra Bharadwaj; Tanu Gupta; Radhey M. Singh
Of the various natural products isolated so far, cinchona alkaloids hold the supreme position for their various medicinal, synthetic, and catalytic applications. The diverse array of structural features studded with a complete spectrum of biological properties makes them a valuable class of natural products. This chapter summarizes their isolation and structural aspects. Subsequently, important synthesis followed by medicinal properties has been discussed. © 2018 Elsevier Ltd. All rights reserved.
Cascade SN2′–SNAr, Elimination, and 1,5-Hydride Shift Reactions by Acetylacetone/Acetoacetic Esters: Synthesis of 9,10-Dihydroacridines
(Wiley-VCH Verlag, 2016) Tanu Gupta; Kishor Chandra Bharadwaj; Radhey M. Singh
A reaction involving the use of acetylacetone/methyl acetoacetate and Morita–Baylis–Hillman acetates for the efficient, one-pot, metal-free synthesis of 9,10-dihydroacridines at room temperature was developed. The cascade of reactions involved sequential SN2′–SNAr reactions, elimination, and reduction through ketene generation and hydride transfer. Evidence for hydride shift via a ketene intermediate was also discussed. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Catalytic trifluoromethylation of aldehyde and potential application for pyrano[4,3-b]quionline synthesis
(Elsevier Ltd, 2018) Kalpana Mishra; Kishor Chandra Bharadwaj; Radhey M. Singh
We have described CsF-catalyzed trifluoromethylation of heteroaromatic aldehydes at room temperature to afford trifluoromethyl group containing alcohols in very good yields. Using catalytic amount of CsF (0.2 eq.) in toluene, trifluoromethylated products were achieved in good yields at rt. The substrate scope has been exemplified by a large number of substrates. As an application, iodo etherification/cyclization has also been demonstrated for the synthesis of trifluoromethyl pyrano[4,3-b]quinoline from o-alkynyltrifluoro methyl alcohol, in very good yield. © 2018
Chemoselective and Highly Rate Accelerated Intramolecular Aza-Morita-Baylis-Hillman Reaction
(American Chemical Society, 2018) Kishor Chandra Bharadwaj
Despite being a very useful C-C bond forming and highly applicative reaction, Morita-Baylis-Hillman (MBH) reaction has been limited by its excessive slow reaction rate, including its intramolecular version. In certain cases, reaction time may even go to weeks and months. A highly chemoselective and rate accelerated intramolecular MBH reaction of just 15 min has been developed. The product dihydroquinoline, being unstable, was converted to an important quinoline framework. In some cases IMBH adducts were isolable, thus confirming the reaction path. Control experiments toward mechanism investigation have been carried out. Use of sodium sulfide has emerged as a rate accelerating catalyst in DMF-EtOH solvent system. Reaction intermediate for IMBH pathway was isolated and characterized. Other aspects such as the application of IMBH adduct for Michael addition and amidation have also been carried out. Copyright © 2018 American Chemical Society.
Chemoselective Intramolecular Morita-Baylis-Hillman Reaction; Acrylamide and Ketone as Sluggish Reacting Partners on a Labile Framework
(American Chemical Society, 2024) Kishor Chandra Bharadwaj
Chemoselectivity is an important issue frequently encountered while working over labile precursors. Carbonyl compounds with a heteroatom at the β carbon are sensitive precursors because they are prone to elimination under different conditions. Morita-Baylis-Hillman (MBH) reaction, although a widespread method for C-C bond formation, has its own limitations. Acrylamide and ketone are such limitations of the MBH reaction. Using them together for an intramolecular MBH (IMBH) reaction on a labile framework prone to elimination is a significant 2-fold synthetic challenge. A highly chemoselective IMBH reaction on such precursors has been established using 1,4-diazabicyclo[2.2.2]octane (DABCO) as a promoter. The protocol leads to quick access to a diversely substituted and functionalized piperidone framework in high yields. Various substitution patterns in the form of 34 successful examples have been studied. A diastereoselective version and tolerance to various functional and protecting groups are the added advantages of the developed methodology. A tertiary carbon at the β position of ketone, however, led to complete reversal of selectivity and gave only the elimination product. Control experiments toward a better understanding of the substitution pattern, role of catalyst, and mechanistic study have been carried out. As an application of the IMBH adduct, a one-step allylic rearrangement for the dihydropyridone framework has also been demonstrated. © 2024 American Chemical Society.
Chemoselective Intramolecular Rauhut-Currier Reaction on a Labile Framework of Enone and Acrylamide: Tricyclohexylphosphine as a Stable and Economical Catalyst
(John Wiley and Sons Inc, 2024) Rakesh Kumar Verma; Mansingh Bairwa; Kishor Chandra Bharadwaj
Intramolecular Rauhut-Currier (IRC) reaction is an atom-economical way of making carbocyclic and heterocyclic rings. However, its sensitivity towards electronic and steric parameters limits the reaction and stems the need for further development. Acrylamides have been one such left out of their sensitivity. Herein we report an IRC reaction, using acrylamide as a source of initial enolate. The cyclization has been achieved on a labile and challenging framework, prone to decomposition. Different control experiments have addressed the instability of the precursor. Protocol was further extendable to annulation for benzo analogs. We also report tricyclohexylphosphine (PCy3) as a stable, commercial, and easy-to-use nucleophilic catalyst in the field of IRC reactions as compared to earlier well-established trimethyl and tributyl phosphines. Me3P and Bu3P although useful, are sensitive, prone to oxidation, and need careful handling. The protocol leads to the synthesis of piperidone and dihydroquinolone frameworks. A quick study to test the feasibility of catalyzing the Morita-Baylis-Hillman (MBH) reaction by PCy3 was also done successfully, although in moderate yields. © 2024 Wiley-VCH GmbH.
Domino Sequence of Ketimization and Electrophilic Amination for an Inverse Aza Intramolecular Morita-Baylis-Hillman Adduct
(American Chemical Society, 2024) Mansingh Bairwa; Rakesh Kumar Verma; Kishor Chandra Bharadwaj
Morita-Baylis-Hillman (MBH) reaction, typically catalyzed by a Lewis base, is a popular and useful method for C-C bond formation. Unfortunately, it is limited by a slow reaction rate and has sensitivity toward steric and electronic parameters. Despite tremendous efforts, the versatility of the reaction keeps the quest open for new mechanistic and catalytic pathways. Here, we have reported a Bro̷nsted acid-catalyzed, electrophilic amination (Umpolung of imine) as a method for an inverse Aza Intramolecular MBH adduct in the form of 2-acylindole. Umpolung of imine with nitrogen acting as an electrophilic center has been achieved. Interestingly, the reaction was also shown to occur under catalyst-free conditions also. The expected products of ketimine formation, 6π electrocyclization, or quinoline formation were least/not observed. A large number of examples have demonstrated the reaction strength. β-aryl-substituted acrylate and acrylamide (cinnamates and cinnamides), which are extremely sluggish in conventional MBH chemistry, are the highlights of the developed methodology. The annulated product exhibited keto-enol tautomerism, which was proven by 1H NMR integrals. As an application, another tandem reaction in the form of Michael addition on a highly complex amine was carried out to provide spiro-annulated indole. © 2024 American Chemical Society.
Double Morita-Baylis-Hillman (MBH) strategy; An intermolecular and a chemo selective intramolecular MBH reactions for 5/6 substituted, functionalized piperidine unit
(Elsevier Ltd, 2016) Kishor Chandra Bharadwaj; Dharmendra Kumar Tiwari
A novel approach utilizing dual Morita-Baylis-Hillman (MBH) reactions in form of intermolecular and a chemo selective intramolecular version, has been developed. With three electrophilic and a nucleophilic site in precursor, selective condition for intramolecular MBH reaction has been optimized. Role of water was found to be crucial. The dual strategy was applicable for synthesis of a variety of medicinally and synthetically important piperidine unit whose 5/6 atoms of ring were substituted, featuring a stereo defined trisubstituted olefin, a Michael acceptor (with a methylene moiety), trivalent nitrogen and a tertiary alcohol. © 2015 Elsevier Ltd. All rights reserved.
Intramolecular Morita-Baylis-Hillman and Rauhut-Currier reactions. A catalytic and atom economic route for carbocycles and heterocycles
(Royal Society of Chemistry, 2015) Kishor Chandra Bharadwaj
Intramolecular Morita-Baylis-Hillman and Rauhut-Currier reactions are important tools which have constantly grown over several years. This review summarizes and highlights their various aspects such as development of activated alkenes, electrophiles and catalysts both in achiral and chiral fashion, use of non conventional electrophiles, applications in total synthesis. Selected miscellaneous reports of internal promoters, cycloadditions, and non conventional routes for IMBH adduct have also been presented, along with future projections. © 2015 The Royal Society of Chemistry.
Ligand-free palladium-catalyzed facile construction of tetra cyclic dibenzo[b,h][1,6]naphthyridine derivatives: Domino sequence of intramolecular C-H bond arylation and oxidation reactions
(Royal Society of Chemistry, 2016) Jay Bahadur Singh; Kishor Chandra Bharadwaj; Tanu Gupta; Radhey M. Singh
A ligand-free Pd-catalyzed approach has been developed for the synthesis of dibenzo-fused naphthyridines. The reaction involves a one-pot domino sequence of reactions involving C-H functionalisation and oxidation. The reaction was applicable to a wide range of substrates, giving the required product. Further fluorescence studies were performed where the Stoke's shift was found to be dependent on the polarity of the solvent. © 2016 The Royal Society of Chemistry.
Morita-Baylis-Hillman reaction of acrylamide with isatin derivatives
(Beilstein-Institut Zur Forderung der Chemischen Wissenschaften, 2014) Radhey M. Singh; Kishor Chandra Bharadwaj; Dharmendra Kumar Tiwari
The Morita-Baylis-Hillman reaction of acrylamide, as an activated alkene, has seen little development due to its low reactivity. We have developed the reaction using isatin derivatives with acrylamide, DABCO as a promoter and phenol as an additive in acetonitrile. The corresponding aza version with acrylate and acrylonitrile has also been developed resulting in high product yields. © 2014 Singh et al; licensee Beilstein-Institut. License and terms: see end of document.
Na2S-mediated synthesis of terminal alkynes from: Gem -dibromoalkenes
(Royal Society of Chemistry, 2017) Radhey M. Singh; Durgesh Nandini; Kishor Chandra Bharadwaj; Tanu Gupta; Raj Pal Singh
The Na2S-mediated facile synthesis of terminal alkynes from gem-dibromoalkenes, at 20/40 °C under open flask conditions has been developed. Various precursors derived from heteroaromatic/aromatic/aliphatic aldehydes were found compatible. The reaction is proposed to proceed through the Fritsch-Buttenberg-Wiechell (FBW) rearrangement involving the corresponding vinyl carbene. Using mild reaction conditions with inexpensive Na2S·9H2O under air atmosphere has significant advantages over earlier routes. © 2017 The Royal Society of Chemistry.
Pd catalyzed facile synthesis of cyclopenta[: B] quinolin-1-one via sequential Sonogashira coupling and annulation. An unusual mode of ring closure, using sulphur as a soft nucleophile
(Royal Society of Chemistry, 2016) Radhey M. Singh; Ritush Kumar; Kishor Chandra Bharadwaj; Tanu Gupta
Pd mediated one pot sequential Sonogashira coupling followed by annulation using o-alkynyl aldehyde is reported. Contrary to the established modes of ring closures, an unusual mode of the initial attack of sulphur across the triple bond occurs leading to a cascade of reactions. The protocol requires just single column chromatography, delivering cyclopenta[b]quinolin-1-one in high yields. Furthermore chemoselective transformations were carried out across annulated precursors. © the Partner Organisations 2016.