An efficient, atomeconomic and green approach to synthesizing enamines was developed by intermolecular hydroamination of activated alkynes with high yields under catalyst and solventfree conditions. Reductive deoxygenation occurs in the particular case of aryl ketones. Nitrogencontaining molecules are ubiquitous in both natural products and pharmaceutical drugs, thus an efficient method for. While the reaction has been intensely studied, concerns still exist over its amenability to organic synthesis. Herein, we report a novel protocol that directly converted 22propynylaniline derivatives 1 into tetrahydroquino. Catalyzed intramolecular asymmetric hydroamination. Catalytic activity of gold nanoclusters in intramolecular. The goldcatalyzed, sevenmembered ring forming, intramolecular hydroamination of alkynic sulfonamides has been investigated. Rhodiumcatalyzed asymmetric intramolecular hydroamination. Catalyzed intramolecular hydroamination of alkynes.
Intramolecular hydroamination of alkynes catalyzed by pdpph34. The clean formation of products allowed for a facile synthesis and isolation of 23 examples of secondary amines in yields of 3399%. Amines are common in finechemical, pharmaceutical, and agricultural industries. Intramolecular hydroamination of unactivated alkenes with. A study on the gold icatalyzed intramolecular hydroamination of trichloroacetimidates derived from propargyl and homopropargyl alcohols is described. Request pdf isoindoles and dihydroisoquinolines by goldcatalyzed intramolecular hydroamination of alkynes. The journal of organic chemistry 2008, 73 24, 96989709. Pdf hydroamination of aromatic alkynes to imines catalyzed by. Mechanism, origin of enantioselectivity, and role of additives c. Intramolecular hydroamination of alkynes catalyzed by silver.
This chapter deals with hydroamination reactions catalyzed by s. Use of group 4 bissulfonamido complexes in the intramolecular hydroamination of alkynes and allenes lutz ackermann, robert g. In recent years hydroamination has received an increasing amount of attention as a direct and atomefficient method to access nitrogencontaining compounds. Intramolecular hydroamination of alkynes catalyzed by. Goldicatalyzed intramolecular hydroamination of alkyne. Intramolecular hydroamination of unactivated alkenes nitrogencontaining heterocycles are to be found in a large number of natural products of interest.
The familiar intramolecular alkyne hydroamination was reported by crabtrees group to be catalyzed by an iridium hydride catalyst 1. Department of chemistry, national university of singapore, 3 science drive 3, singapore 117543. An orthogonality of the current catalytic protocol with those using a. However, if it is necessary for the discussion, older results and intramolecular reactions, which can be achieved more easily, will be mentioned as well. Intramolecular copetype hydroamination of alkenes and alkynes using hydrazides.
Amines are invaluable precursors and necessary chemical components in industrial settings as well as pharmaceutical industries, making methods for efficient formation of cn bonds a vital chemical process. The reaction condi tions and the scope of the process are examined. Chapter 2a basemediated hydroamination of symmetrical. In this paper, we describe the intramolecular hydroamination of tolenesulfonamides to substrates with carboncarbon multiple bonds including unactivated alkenes and alkynes, along with some additional results to provide insight into the reaction mechanism. Andy horb and king kuok mimi hii,a department of chemistry, imperial college london, south kensington, london sw7 2az, u. Directed organocatalytic intermolecular copetype hydroamination of alkenes by peter joseph ng thesis submitted to the faculty of graduate and postdoctoral studies university of ottawa in partial fulfillment of the requirements for the m. The first rhodiumcatalyzed asymmetric intramolecular hydroamination of unactivated olefins was developed by using dialkylbiaryl phosphine ligands see scheme. Frustrated lewis pairs flps based on sterically encumbered anilines and the lewis acid bc 6 f 5 3 were found to react with terminal alkynes effecting intermolecular hydroamination affording iminium alkynylborate species of the form rphn cr.
Organometallic catalysts for intramolecular hydroamination. Intramolecular hydroamination of unactivated alkenes. Request pdf palladiumcatalyzed intramolecular asymmetric hydroamination, hydroalkoxylation, and hydrocarbonation of alkynes a. Intramolecular hydroamination of internal alkyne with primary amine 11 yielding imine 12 and terminal alkyne with secondary amine yielding enamine 14 using the same samarium catalyst. Jan, 2006 read isoindoles and dihydroisoquinolines by gold. Palladiumcatalyzed intramolecular asymmetric hydroamination. Metalcatalyzed enantioselective intramolecular hydroamination of olefins 1 is one of the most conceptually simple and atomeconomical approaches to the construction of enantioenriched nitrogen heterocycles, 2 which are valuable synthons in the preparation of natural products and biologically active molecules. In the synthetic process of the derivatives, n,ndimethylformamidedmf pretreated with metal na, was used. Silvercatalysed intramolecular hydroamination of alkynes with trichloroacetimidates. Intramolecular metalcatalyzed hydroamination of alkynes, leading to.
The introduction of nonchelating nitrogeneous ligands suppresses competitive bronsted acid catalys. In the ideal case, hydroamination is atom economical and green. Consecutive intramolecular hydroaminationasymmetric. The catalytic hydrogenation of the resulting enamines leads. Catalytic hydroaminations of alkenes, allenes, and dienes which may be inter or intramolecular afford amines, imines, and enamines eq. This strategy is efficient to build complex structures from simple starting materials in an environmentally compatible fashion. Hydrogenation and hydroamination reactions using boron. Intra and intermolecular hydroamination of alkynes catalyzed by. Rhodium catalyzed asymmetric hydroamination of internal alkynes with indoline. Of these methods, the hydroamination of alkenes and alkynes, specifically the addition of an nh bond across a carboncarbon. Dean toste department of chemistry, university of california, berkeley, california 94720 received december 9, 2006. Sequential intermolecular hydroamination of alkynes and. Mungra, jin zhu department of polymer science and engineering, school of chemistry and chemical engineering, state key laboratory of coordination chemistry, nanjing national laboratory of microstructures, nanjing university, nanjing 210093, p.
Gold nanoclusters stabilized by a hydrophilic polymer, polynvinyl2pyrrolidone au. The intramolecular hydroamination reaction is among the more versatile means of forming nitrogencontaining hetereocycles, compounds of interest in a variety of chemical disciplines. Mechanism of the intramolecular hydroamination of alkenes. Intramolecular alkyne hydroalkoxylation and hydroamination. Goldi catalysed regio and stereoselective intermolecular hydroamination of internal alkynes was developed for the effective synthesis of a series of zfunctionalised vinylazoles under solvent free conditions. Hydroamination is the addition of an nh bond of an amine across a carboncarbon multiple bond of an alkene, alkyne, diene, or allene. However, older results and intramolecular reactions will be. Rareearth metal complexes are highly efficient catalysts for intramolecular hydroamination of various cc unsat urations such as alkenes, alkynes, allenes. Organometallic catalysts for intramolecular hydroamination of. Highly regioselective agntf 2catalyzed intermolecular hydroamination of alkynes with anilines xu zhang, bin yang, guangzhao li, xin shu, divyesh c. Finally, the lewis acid bc 6f53 is found to enable the intermolecular hydroamination of various terminal alkynes giving iminium alkynylborate complexes of.
Sunoj the journal of organic chemistry 2018 83 5, 26272639. Intramolecular hydroamination of unactivated alkenes 31102006 2. Hydroamination reactions of alkenes organic reactions wiki. As for the c6d6 solvent, the intramolecular hydroamination reaction was. Intramolecular copetype hydroamination of alkenes and. Intra and intermolecular hydroamination of alkynes. Catalyzed intramolecular asymmetric hydroamination, hydroalkoxylation, and hydrocarbonation of alkynes. Unlimited viewing of the articlechapter pdf and any associated supplements and figures. Abstract ircodcl 2 is an effective precatalyst for the intramolecular hydroamination of a range of unactivated alkenes with pendant secondary amines. Coupled with the limitations of traditional cn bond formation reactions, there is much interest in catalytic hydroamination as a route to nitrogen heterocycles.
Phasetransfercatalyzed intramolecular hydroaryloxylation. In the hydroamination, unsaturated molecules including alkenes, alkynes, allenes. The catalytic hydrogenation of the resulting enamines leads to substituted saturated azoles in good yields. Silveri complexes catalyse the intramolecular addition of trichloroacetimidates to alkynes. Silvercatalysed intramolecular hydroamination of alkynes. Palladiumcatalyzed intramolecular asymmetric hydroamination, hydroalkoxylation, and hydrocarbonation of alkynes. Catalytic asymmetric intramolecular hydroamination of alkynes in the presence of a catalyst system consisting of pd0methyl norphos or tolyl renorphosbenzoic acid. Some late transition metal complexes have been investigated for enantioselective hydroamination, with good results for alkynes, 8 allenes, 9 dienes, 10 and vinylarenes.
The use of agntf 2 as catalyst enables a facile, economic, regioselective, and highyielding protocol for the hydroamination of unsymmetrical internal alkynes under mild reaction conditions. The catalyst can be used at relatively low loadings and without the need for added ligands or other cocatalysts. Hydrogenation and hydroamination reactions using boronbased. Goldi catalysed regio and stereoselective intermolecular. Consecutive intramolecular hydroaminationasymmetric transfer. The intramolecular hydroamination of alkynes tethered with amino group 1 in the presence of catalytic amounts of pdpph34 and pph3 in benzene at 100 c proceeded smoothly without the use of any additional acid source to afford five and sixmembered nitrogen heterocycles 2 in good to excellent yields. Intramolecular hydroamination of alkenes early main. Jun 25, 2015 frustrated lewis pairs flps based on sterically encumbered anilines and the lewis acid bc 6 f 5 3 were found to react with terminal alkynes effecting intermolecular hydroamination affording iminium alkynylborate species of the form rphn cr. Silvercatalyzed intramolecular hydroamination of alkynes in. Silvercatalysed intramolecular hydroamination of alkynes with trichloroacetimidates valerie h. A variety of 2methylpyrrolidines have been synthesized with high enantioselectivities. Intramolecular hydroamination of alkynic sulfonamides. Rhodiumcatalyzed asymmetric intramolecular hydroamination of. The ratedetermining step in the catalytic cycle for alkyne hydroamination with lanthanide catalysts is binsertion, as it was for alkenes.
Silvercatalyzed intramolecular hydroamination of alkynes. The catalytic synthesis of linear secondary amines using the schafer titanium catalyst was accomplished through an intermolecular hydroamination of terminal alkynes followed by a pdc hydrogenation. Dimethylaminoacrylate derivatives were also obtained with high yields. Palladiumcatalyzed intramolecular asymmetric hydroamination of alkynes article in journal of the american chemical society 1266. Under 100, with cucl as catalyst, intermolecular and intramolecular double hydroamination reaction has generated between 1,3butadiyne and primary amine 24 scheme 27, 1,4two substituted 1,3butadiyne and alkynes through selective intermolecular hydroamination to form 1, 2, 5three substituted pyrroles with a high yield. Loy contribution from the department of chemistry and center for new directions in organic synthesis, university of california, berkeley, california 947201460. Intramolecular hydroalkoxylation and hydroamination of. Zeises dimercatalyzed regioselective hydration of homopropargyl tertiary ether. The direct addition of a nh bond across a carboncarbon multiple bond, the hydroamination reaction, constitutes an atomeconomical method for the synthesis of substituted amines. The catalytic intermolecular hydroamination of alkynes is more difficult to accomplish than the intramolecular version, thus requiring higher tempera ture. In the absence of a ligand, the selectivity of the reaction is dependent upon the nature of the counteranion and solvent. Similar alkyne hydroaminations using iridium catalysis were. C bonds is an atom economical strategy to construct n.
Intramolecular hydroamination of alkynes catalyzed by silverphenanthroline complexes doctoral dissertation. The reaction proceeds via antiaddition of toluenesulfonamide to the alkenes assisted by. The protocol, with a semihollowshaped triethynylphosphine as a ligand for gold, allowed the synthesis of a variety of azepine derivatives, which are difficult to access by other methods. Developing transitionmetal catalysts for the intramolecular hydroamination of alkynes. An efficient and green approach to synthesizing enamines. Gold i catalyzed enantioselective intramolecular hydroamination of allenes rebecca l. Intramolecular hydroamination of alkynes catalyzed by pd. Hydroamination, the addition of hnr 2 across a carboncarbon. The intramolecular hydroamination of alkynes tethered with amino group 1 in the presence. Silvercatalyzed intramolecular hydroamination of alkynes in aqueous media.
The title compounds are enantioselectively synthesized in just two preparative steps. Basemediated hydroamination of symmetrical internal alkynes 25 scheme 2a. For the intermolecular alkynes hydroamination synthesis of the. In these cases, the reagent ratio of borane, aniline, and alkyne is 1. Highly regioselective agntf 2 catalyzed intermolecular. Nitrogencontaining molecules are ubiquitous in both natural products and pharmaceutical drugs, thus an efficient method for the formation of these motifs is of great importance. Pvp, catalyzed the intramolecular hydroamination of toluenesulfonamides to unactivated alkenesalkynes in etoh under aerobic and basic conditions. Intramolecular addition of o h and nh bonds across carboncarbon triple bonds to form 5 or 6membered rings with exocyclic methylene groups for ether products and exocyclic methyl groups for imine products is catalyzed by iprcume ipr 1,3bis2,6diisopropylphenylimidazol2ylidene.
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