Deevi basavaiah, bhavanam sekhara reddy, and satpal singh badsara. Traditional moritabaylishillman reaction of aldehydes with methyl vinyl ketone cocatalyzed by triphenylphosphine and nitrophenol min shi and yinghao liu state key laboratory of organometallic chemistry, shanghai institute of organic chemistry, chinese academy of sciences, 354 fenglin lu, shanghai 200032, china, email. An activated alkene, an electrophile and a nucleophilic. The morita baylis hillman mbh type reactions possess the two most important requirements atom economy and generation of multifunctional groups. This investigation into the chemistry of chromone derivatives focuses largely on their use in the moritabaylishillman reaction.
Here, we describe our studies on the thioureacatalyzed moritabaylishillman mbh reaction. Singh1, kishorchandrabharadwaj1 anddharmendrakumartiwari2 full research paper open access address. In the course of our research interest meier et al. Hillman reaction and its applications with the main objective of developing this reaction into a useful and powerful synthetic tool in organic chemistry. This reaction is also known as the moritabaylishillman reaction or mbh reaction k. Jun 22, 2012 dabcocatalyzed dimerization of moritabaylishillman acetates to synthesize a series of 3alkyl4ealkenylcyclohex1ene1,4dicarbonyl compounds in excellent yields with modest to excellent diastereoselectivity is reported.
Applications of moritabaylishillman reaction to the synthesis of natural products and drug molecules. However the synthesis of natural product mimics using mbh chemistry is beyond the scope of this article. Method for the preparation of acrylic compounds from the reaction between. Pdf moritabaylishillman reaction in waterionic liquids under. Recent developments in the asymmetric organocatalytic. Under the appropriate reaction conditions, sodium borohydride is a highly chemoselective reducing agent. Application of 7azaisatins in enantioselective morita baylis. Abstract an efficient protocol for the evaluation of catalysts for the asymmetric moritabaylishillman mbh reaction was developed. Pdf the moritabaylishillman reaction of acrylamide, as an activated alkene, has seen little development due to its low reactivity. Application of 7azaisatins in enantioselective morita. This reaction represents the first direct transformation of mbh alcohols into hydrazines. Zwitterionic dienolates generated from morita baylis hillman carbonates of cyclohexen2one and a phenolic tertiary amine catalyst underwent divergent cyclization reactions with isatylidene malononitriles.
Carboncarbon bond formations and functional group transformations are the most fundamental reactions for the construction of molecular frameworks and are at the forefront of organic chemistry research. Batra, applications of moritabaylishillman reaction to the synthesis of natural products and drug molecules, current organic chemistry, vol. The tandem reaction of moritabaylishillman mbh alcohols 1a1l derived from acrylic nitrile with 2aminobenzimidazole 2 in ionic iquid il bmimclh 2 o without additional catalyst was developed for the efficient synthesis of benzimidazol1,2apyrimidin78himine compounds. Since the first elegant work on the enantioselective mbh reaction between isatins and acrolein catalyzed by. Chiral thiourea derivatives as organocatalyts in the. Stereoselective construction of entire diastereomeric. The reaction at room temperature under neat conditions no solvent with quinuclidine as an amine nucleophil synthetic methodology in obc. Aug 21, 2014 the morita baylis hillman reaction is a type of carboncarbon bond forming reactions between aldehydesimines and electron deficient alkenes promoted by nucleophilic catalysts.
Dmap catalyst in moritabaylishillman mbh reactions of nitroalkenes with ethyl glyoxylate, which result in excellent conversions and short reaction times with, importantly, very low catalyst loading. Cyclopropenation of alkylidene carbenes derived from. The moritabaylishillman reaction is an organocatalyzed chemical transformation that allows access to small polyfunctionalized molecules and has considerable synthetic potential and promising biological profiles. Moritabaylishillman reaction, stereochemical control, organic synthesis, catalytic cycle. Baylis celanese corporation north plainfield, nj claims. Diastereoselective synthesis of multisubstituted chroman. A highly regioselective s n 2 mitsunobu reaction between moritabaylishillman mbh alcohols, azodicarboxylates, and triphenylphosphine is developed, which provides an easy access to. Magee, same ratshonka, jessica mcconaghy, maggie hood. Haxell and chitaru hirosawa department of chemistry and biochemistry, florida state university, tallahassee, florida, 32306 experimental section. In 1968, morita and coworkers described an elegant reaction between. General features of the moritabaylishillman reaction. Tandem reaction of moritabaylishillman alcohols derived.
Applications of morita baylis hillman reaction current organic chemistry, 2014, vol. A novel asymmetric azaspirocyclisation using a morita. Carboncarbon bond formations and functional group transformations are the most fundamental reactions for the construction of molecular frameworks and. Chiral nphosphonyl imines for azamoritabaylishillman. General features of the morita baylis hillman reaction. The strategy is based on a onepot sequence involving an oxidative cleavage of the double bond of silylated moritabaylishillman adducts, followed by. Employing a nucleophilic catalyst, such as a tertiary amine and phosphine, this reaction provides a densely functionalized product e. Organic chemistry portal traditional morita baylis hillman reaction of aldehydes. It is named for the japanese chemist kenichi morita, the british chemist anthony b.
Applications of moritabaylishillman reaction current organic chemistry, 2014, vol. For simplicity, the unsaturated component is presented as the fundamental, nonsubstituted version. Hillman reactions reported since the beginning of 20. Phosphines can also be used in this reaction, and enantioselective reactions may be carried out if the amine or phosphine catalyst is asymmetric. The first onepot synthesis of moritabaylis hillman adducts starting directly from alcohols l.
In this reaction, three transformations iminium formationmoritabaylishillman reactionoxamichael reaction occurred successively to afford multisubstituted chroman derivatives in moderate chemical yields with excellent. Chiral phosphine lewis bases in catalytic, asymmetric aza. The first onepot synthesis of moritabaylishillman adducts starting directly from alcohols l. Applications in the azamoritabaylishillman reaction and anion sensing jenny diep master of science department of chemistry university of toronto 20 abstract selfassembly is an efficient method for generating large numbers of structurally diverse catalysts for screening.
Synthesis and characterization of new chiral ketopinic. Herein, we wish to report the catalytic, asymmetric azamoritabaylishillman reaction using a chiral phosphine lewis base in which high enantioselectivities 90 % ee can also be realized. The reaction is organocatalytic, atomically economical and operationally simple in nature. Recent developments in the asymmetric organocatalytic morita. As a consequence moritabaylishillman reactions that employ nitroalkenes can now be performed with great efficiency through catalysis with remarkably low amounts of super. We also acknowledge previous national science foundation support under grant numbers. A novel asymmetric azaspirocyclisation using a moritabaylishillmantype reaction novel asymmetric azaspirocyclisation using a moritabaylishillmantype reactionjonathan c. Esimsms investigation with charge tags and ionic liquid e. Canadian journal of chemistry canadian science publishing. Applications of moritabaylis hillman reaction to the synthesis of natural products and drug molecules. Regioselective sn2 mitsunobu reaction of moritabaylis. Hillman chemistry and applications after the publication of the last.
Chemistry a european journal 2016, 22 49, 1759517599. The baylishillman reaction is a carboncarbon bond forming reaction between the. In particular, the direct formation of stereogenic quater. Enantioselective synthesis of polycyclic indole derivatives. The chemistry of the moritabaylishillman reaction by. Pdf moritabaylishillman reaction of acrylamide with isatin. Lewis acids, carbonates, catalysts, catalytic activity, chemical structure, cyclization reactions, organic compounds, zwitterions abstract. Hillman adducts, illustrating that they constitute synthetically important. Concise and efficient methods for the syntheses of functionalized indene and indanone derivatives from morita. Baylis hillman mbh alcohols via palladium catalyzed annulations are described. Divergent cyclization reactions of moritabaylishillman. Aggarwal a a school of chemistry, university of bristol, cantocks close, bristol bs8 1ts, uk. An enantioselective organocatalytic approach for the synthesis of cyclopenta b annulated arenes and heteroarenes.
Chemistry of the moritabaylishillman reaction book. Request pdf chiral nphosphonyl imines for azamoritabaylishillman reaction via groupassisted purification gap chemistrytechnology seventeen examples of. Moritabaylishillman reaction of acrylamide with isatin. The chemistry of the moritabaylishillman reaction rsc. Catalyst development and mechanistic insights based on mass spectrometric backreaction screening. The moritabaylishillman reaction is known to be dominant tool for the construction of densely functionalized alcohols and isatin derivatives which serve as promising electrophile in this reaction.
Mueller department of chemistry, hampdensydney college, hampdensydney, va 23943 introduction the morita baylishillman reaction is a process that has been related to increasing the. Synthesis of various catalysts for the moritabaylishillman. Antimicrobial activity of allylic thiocyanates derived. Neto, laboratory of medicinal and technological chemistry. Angewandte chemie international edition 2016, 55 5, 17771781.
A simple primarytertiary diamine has been explored as a novel catalyst for the moritabaylis hillman reaction of mvk and aryl aldehydes, and moderate to good chemical yields were obtained. Pc bond formation in reactions of moritabaylishillman. Catalytic systems for the moritabaylishillman reaction meixin zhao, yin wei, min shi transformations of functional groups in moritabaylishillman adducts meixin zhao, yin wei, min shi moritabaylishillman adducts or derivatives for the construction of cyclic frameworks feijun wang, yin wei, min shi application of morita. It presents a clear picture of how the senior author db has i uncovered the bh reaction, whi.
His research group has been working for the last 26 years and continues to work on various aspects of the baylis. Morita baylis hillman, heterocycles, drugs, acrylates, mass spectrometry, natural products. Organic chemistry portal sila morita baylis hillman reaction of arylvinyl. The chemistry of the moritabaylishillman reaction ebook.
Traditional moritabaylishillman reaction of aldehydes. The chemistry of the moritabaylishillman reaction by james. The baylishillman reaction is an organic reaction used to form a cc bond between an unsaturated carbonyl compound and an aldehyde, activated ketone, or other carbon electrophiles. Morita baylis hillman reaction, stereochemical control, organic synthesis, catalytic cycle.
A chiral phosphinecatalyzed asymmetric azamoritabaylishillman reaction between indolederived sulfonyl imines and bis3chlorophenylmethyl acrylate has been developed, giving the desired adducts in good yields and enantiomeric excess values along with the further transformations to polycyclic indoles such as dihydropyrido1,2aindole and. The last decade has seen exponential growth of the mbh reaction and its applications. Stereoselective construction of entire diastereomeric stereotetrads based on an asymmetric moritabaylishillman reaction hikaru yoshimura graduate school of biomedical sciences, nagasaki university, 1. A study of the effect of michael acceptor stereochemistry on the efficiency of intramolecular morita. Baylishillman reaction an overview sciencedirect topics. Those amino aldehydes were converted into allylic alcohols by the classical moritabaylishillman reaction or by condensation with seleniumstabilized. In contrast, the corresponding reaction with acrylate and. Synthesis of various catalysts for the moritabaylishillman reaction benjamin w. Hillman or moritabaylishillman mbh reaction is a very useful and versatile one. The moritabaylishillman mbh type reactions possess the two most important requirements atom economy and generation of multifunctional groups. The reaction tends to be slow under classical conditions. The morita baylis hillman reaction is known to be dominant tool for the construction of densely functionalized alcohols and isatin derivatives which serve as promising electrophile in this reaction. Singh and batra, 2008 and the antimicrobial activity of synthetic derivatives silveira et al.
The moritamoritabaylis hillman reaction mmbhr is one of the most important carbon carbon bond forming reactions, and involves the selective atomeconomical construction of a carbon carbon bond at the. The major potential of the morita baylis hillman reaction is in its opportunity to provide practically unlimited structural combinations of readily available substrates. This coupling of an activated alkene derivative with an aldehyde is catalyzed by a tertiary amine for example. This reaction is most commonly catalyzed by dabco but other tertiary amines or phosphines can also be used as catalysts. A bronsted acid and lewis base organocatalyst for the azamoritabaylishillman reaction k. The morita baylis hillman reaction is an organocatalyzed chemical transformation that allows access to small polyfunctionalized molecules and has considerable synthetic potential and promising. A onepot, highly diastereoselective synthesis of chroman derivatives with three contiguous stereogenic centers is described. The asymmetric moritabaylishillman mbh reaction is one of the most powerful synthetic methods in organic chemistry, as it directly constructs carboncarbon bonds in an atomeconomical manner and provides densely functionalized molecules 14. Application of 7azaisatins in enantioselective moritabaylis. Synthesis of various catalysts for the moritabaylis.
The asymmetric moritabaylishillman mbh reaction is one of the most powerful synthetic methods in organic chemistry, as it directly constructs carboncarbon bonds in. The tandem reaction included azamichael addition and intramolecular addition of an amino group. The major potential of the moritabaylishillman reaction is in its opportunity to provide practically unlimited structural combinations of readily available substrates. The formation and nature of the product was based on the mbh adduct used and the reaction conditions established after detailed optimization studies. Synthesis and evaluation of baylishillman reaction. Chemoselective activation of carbonyl compounds via hydrogen bonding to thiourea as a catalyst is the key to drastic rate acceleration of this reaction. Cyclic tertiary amines like dabco, dmap, and dbu and phosphines are usually used as the nucleophilic catalyst.
Apart from the previous reported dephosphoration to access reductive aldol. However, the aza version of the reaction with nphenylacrylamide as a substrate was not successful and led to a complicated reaction mixture. The morita baylis hillman reaction is an organocatalyzed chemical transformation that allows access to small polyfunctionalized molecules and has consider. Thioureacatalyzed moritabaylishillman reaction sciencedirect.
What follows is a brief survey of the known chemistry of chromones, and cromone3carbaldehyde in particular, and a detailed account of earlier research on the moritabaylishillman reaction. Vilsmeier haack reaction mechanism scope application for iit jam tifr ugc csir net set gate duration. A plausible reaction mechanism is also proposed on the basis of previous literature and preliminary investigation the asymmetric version of the reaction. The baylishillman reaction is a successful, useful, and atomeconomical carboncarbon bond forming reaction, which has grown from an obscure level to the level of high synthetic popularity due to its operational simplicity and also due to the enormous applications of the baylishillman adducts in organic synthesis. Morita baylis hillman reaction pdf wikipedia baylis hillman reaction organic chemistry. It involves the coupling of an activated alkene with an electrophile usually aldehydes or imines in the presence of a catalyst fig. Chiral catalysis is another important area of his research interest. Detailed mechanism study indicated that the diamine acted as a bifunctional cooperation catalyst via a bicyclic enaminoquaternary ammonium intermediate. Hillman or morita baylishillman mbh reaction is a very useful and versatile one. Moritabaylishillman reaction of a chiral aziridine. Sulfonated imines with methyl vinyl ketone in the presence of chiral bifunctional phosphane lewis bases zhi. The baylishillman reaction is an organic reaction of an aldehyde and an. Ebru aydin hatay mustafa kemal university department of chemistry, tayfur sokmen campus 31040 hatay, turkey email.
Alkylation of enones using saturated alkyl halides marie e. The reactions were catalyzed by a phosphine, and the reaction substrates studied were enones containing a pendant aldehyde moiety attached at the. Moritabaylishillman reaction pdf wikipedia baylishillman reaction baylishillman reaction wikipedia azabaylishillman reaction wikipedia baylishillman reaction. Journal of the american chemical society 2011, 3 21, 883. The chemistry of the moritabaylishillman reaction rsc publishing. Organocatalytic tandem threecomponent reaction of imine, alkyl vinyl ketone, and imide via azabaylishillman reaction s. Jump to content jump to main navigation jump to main navigation. Pdf the present work describes a new experimental protocol of the morita baylishillman reaction in h2o ionic liquid media under microwave. It also includes the asymmetric organocatalysed transformations of racemic azamorita. The moritabaylishillman mbh reaction is an important carboncarbon bondforming reaction. 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. The moritabaylishillman mbh type reactions possess the two most important requirements atom economy and generation of multifunctional.
It is a carboncarbon bondforming transformation of an electronpoor alkene with a carbon electrophile. Dielsalder dimerization of moritabaylishillman acetates. Unprecedented reactivity in the moritabaylishillman reaction. Recent advances in the moritabaylishillman reaction. Of those important cc bond forming reactions, the baylis. As a consequence morita baylis hillman reactions that employ nitroalkenes can now be performed with great efficiency through catalysis with remarkably low amounts of super. The moritabaylishillman reaction of r1r1phenylethylaziridine2carbaldehyde with alkyl acrylate was carried out under various conditions by changing solvents, bases, and alcohol additives. The morita baylis hillman reaction is an organocatalyzed chemical transformation that allows access to small polyfunctionalized molecules and has considerable synthetic potential and promising biological profiles. We have developed the moritabaylishillman reaction of acrylamide with isatin derivatives. A chiral phosphinecatalyzed asymmetric azamoritabaylishillman reaction between indolederived sulfonyl imines and bis3chlorophenylmethyl acrylate has been developed, giving the desired adducts in good yields and enantiomeric excess values along with the further transformations to polycyclic indoles such as dihydropyrido1,2aindole and dihydropyrazino1,2aindole skeleton. The measured kinetic data indicates that the effects of solvent and protic co. Electronpoor alkenes include acrylic esters, acrylonitriles, vinyl ketones, vinyl sulfones, and acroleins. Unprecedented reactivity in the moritabaylishillman.
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