Journal of the american chemical society 2003, 125 41, 1258412605. New mechanism for the intermolecular hydroamination of. Finally, the lewis acid bc 6f53 is found to enable the intermolecular hydroamination of various terminal alkynes giving iminium alkynylborate complexes of the general formula. However, the combination of 5 with nab3,5c6h3cf324 denoted as nabarf4 provides a potent catalytic system for both intra and intermolecular hydroamination of alkynes. The reaction was effectively catalyzed by the ligandfree cuotf2 and afforded the intended amine derivatives in good yields after treatment of nabh3cn. Assisted catalytic intermolecular hydroamination of alkynes bytschkov, igor. However, the combination of 5 with nab3,5c 6 h 3 cf 3 2 4 denoted as nabar f 4 provides a potent catalytic system for both intra and intermolecular hydroamination of alkynes. In the ideal case, hydroamination is atom economical and green. Thus, the intermolecular hydroamination of alkynes. Intermolecular antimarkovnikov hydroamination of unactivated alkenes with sulfonamides enabled by protoncoupled electron transfer qilei zhu, david e. Intermolecular copetype hydroamination of alkenes and. Hydroamination of terminal alkynes by amines catalyzed by.
Intermolecular copetype hydroamination of alkynes using hydrazines pamela h. In the hydroamination, unsaturated molecules including alkenes, alkynes, allenes. The palladiumcatalyzed intermolecular hydroamination reaction was initially. Platinumcatalyzed intermolecular hydroamination of. For the intermolecular alkynes hydroamination synthesis of the. The most widely used chemical reaction for the functionalization of alkenes, alkynes and allenes is the addition of an ab bond across a carboncarbon. Beauchemin department of chemistry, university of ottawa, 10 marie curie, ottawa, ontario, canada, k1n 6n5 andre. Pdf heterogeneous intermolecular hydroamination of terminal. Highly enantioselective, intermolecular hydroamination of. Aqueous hydroxylamine reacts efficiently with alkynes in a markovnikov fashion to give oximes and with strained alkenes to give nalkylhydroxylamines, while unstrained alkenes are more challenging.
Goldi catalysed regio and stereoselective intermolecular. However, older results and intramolecular reactions will be. Organometallic catalysts for intramolecular 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. An ammonia equivalent for the dimethyltitanocenecatalyzed. Coppercatalyzed intermolecular hydroamination of internal. The catalytic intermolecular hydroamination of alkynes is more difficult to accomplish than the intramolecular version, thus requiring higher tempera ture. Scope and mechanistic comparison to intramolecular cyclohydroaminations.
The catalytic hydrogenation of the resulting enamines leads to substituted saturated azoles in good yields. The hydroamination of alkenes is a synthetically highly attractive transformation, for which up to now no general and efficient solution exists. Zirconium catalyzed intermolecular hydroamination of internal alkynes 1 and 4 with primary arylamine 2 affording imine 3 and enamine 5, respectively. This first report of intermolecular hydroamination of alkynes using gold catalysts was the most efficient catalyst system. 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. Hydrogenation and hydroamination reactions using boron.
The clean formation of products allowed for a facile synthesis and isolation of 23 examples of secondary amines in yields of 3399%. The direct addition of an n h bond across unsaturated c c multiple bonds hydroamination offers a promising, atom economic route to a variety of amines, enamines and imines. Our work showcases the first case of antimarkovnikov selectivity in the intermolecular coupling of amines and 1,3dienes. Intermolecular hydroamination reactions of alkynes with primary amines that are sterically less demanding than 2,6.
Dimethylaminoacrylate derivatives were also obtained with high yields. Pdf hydroamination of aromatic alkynes to imines catalyzed by. The palladium catalyzed intermolecular hydroamination reaction was initially. Rhodiumcatalyzed asymmetric intramolecular hydroamination. 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. A simple catalyst system generated in situ by combination of 5 mol. Intramolecular reaction of o 2phenylethynylanilines produces the corresponding indoles in good yields. Conspectusinter or intramolecular hydroamination reactions are a paradigmatic example. The coppercatalyzed regioselective intermolecular hydroamination of the aryl and trifluoromethyl group or electronwithdrawing group substituted internal alkynes with amines has been accomplished. Intermolecular copetype hydroamination of alkynes using.
Of these methods, the hydroamination of alkenes and alkynes, specifically the addition of an nh bond across a carboncarbon. Recently, we have shown that the cationic goldi complex a 1 figure 1, 17, 18 featuring a bulky cyclic alkylaminocarbene caac, 19 as ancillary ligand, efficiently promotes. Goldcatalyzed intermolecular hydroamination of allenes. Assisted catalytic intermolecular hydroamination of alkynes microwave. Intramolecular metalcatalyzed hydroamination of alkynes, leading to. Intermolecular, catalytic asymmetric hydroamination of bicyclic alkenes and dienes in high yield and enantioselectivity. The first intermolecular hydroamination of a 1,5diene by tsnh2 could be followed by a second intramolecular hydroamination to produce pyrrolidines in an onepot operation scheme 1. Chapter 2a basemediated hydroamination of symmetrical. Intra and intermolecular hydroamination of alkynes catalyzed by. Alkynes are hydrocarbons with carboncarbon triple bonds. Goldicatalyzed intra and intermolecular hydroamination. Intermolecular hydroamination of alkynes catalyzed by zinc. Organolathanidecatalyzed regioselective intermolecular hydroamination of alkenes, alkynes, vinylarenes, di and trivinylarenes, and methylenecyclopropanes.
Gold catalyzed intermolecular markovnikov hydroamination. Reductive deoxygenation occurs in the particular case of aryl ketones. Highly regioselective agntf 2catalyzed intermolecular hydroamination of alkynes with anilines xu zhang, bin yang, guangzhao li, xin shu, divyesh c. Ind 2 time 2 indindenyl is a highly active and general catalyst for the intermolecular hydroamination of alkynes. Chemical communications intermolecular copetype hydroamination of alkynes using hydrazines pamela h. Intramolecular hydroamination has been successfully applied in the synthesis of biologically relevant compounds, but intermolecular hydroamination is less commonly employed in synthesis, due to the possible formation of. Intermolecular hydroamination and hydroarylation reactions. Palladiumcatalyzed intermolecular hydroamination of. Pdf intermolecular copetype hydroamination of alkenes.
The primary formed imines can be hydrogenated and cleaved directly to the corresponding primary amines by catalytic hydrogenation using pdc as catalyst. The development of the copetype hydroamination as a method for the metal and acidfree intermolecular hydroamination of hydroxylamines with alkenes and alkynes is described. Copper exchanged sio2al2o3 catalyst prepared by solgel. Intermolecular hydroamination can be achieved simply upon heating alkynes and alkenes with aqueous hydroxylamine. Amines are common in finechemical, pharmaceutical, and agricultural industries. Knowles journal of the american chemical society 2018 140 2, 741747. Intra and intermolecular hydroamination of alkynes. Catalytic hydroamination of terminal alkynes with amines is the most attractive cn bond forming method. Pdf heterogeneous intermolecular hydroamination of alkynes with aromatic amines using inexpensive transition metalexchanged clay catalysts was. Intermolecular copetype hydroamination of alkynes using hydrazines. Highly enantioselective, intermolecular hydroamination of allenyl esters catalyzed by bifunctional phosphinothioureas the harvard community has made this article openly available. In the synthetic process of the derivatives, n,ndimethylformamidedmf pretreated. We further tested hydroamination of 1,5dienes with tsnh2. Catalyzed intermolecular hydroamination of alkynes with.
In this thesis, intermolecular hydroamination reactions were studied on a new type of heterogeneous catalysts in both a slurry reactor and a fixed bed reactor. 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. Your story matters citation fang, yuanqing, pamela m. Many research groups have explored inter or intramolecular hydroamination of alkynes for the synthesis of diversely. Basemediated hydroamination of alkynes accounts of chemical. Clearly general catalytic systems able to promote the intermolecular hydroamination of alkynes, especially with basic secondary amines are still missing. We report a rhcatalyzed hydroamination of 1,3dienes to generate homoallylic amines. In 2006, dake and coworkers utilized this method to synthesize a variety of pyrroles scheme 3 to understand the role of silver salts and gold complexes. Some late transition metal complexes have been investigated for enantioselective hydroamination, with good results for alkynes, 8 allenes, 9 dienes, 10 and vinylarenes. Number the chain from the end closest to the triple bond. Pdf intermolecular copetype hydroamination of alkynes.
Catalytic intermolecular hydroaminations of unactivated. Although the intermolecular hydroamination of internal alkynes with primary amines has been effectively performed using group 4based catalysts, the use of. An efficient and green approach to synthesizing enamines. Intermolecular hydroamination of 1,3dienes to generate. We report a catalytic protocol for efficient additions of cyclic and acyclic secondary alkyl amines to a wide range of alkyl olefins with complete antimarkovnikov regioselectivity. Thermodynamic considerations suggest that the hydroamination of alkynes should be easier to perform than that of alkenes. Although the catalyst has a limited lifetime up to 6 turnovers, details of the reaction mechanism have been elucidated by isolation. Highly regioselective agntf 2 catalyzed intermolecular. Hydroamination is the addition of an nh bond of an amine across a carboncarbon multiple bond of an alkene, alkyne, diene, or allene. At elevated temperatures, hydroamination is achieved with both internal and terminal alkynes as well as with sterically demanding and less demanding primary amines. The intermolecular hydroamination of unactivated alkenes with simple dialkyl amines remains an unsolved problem in organic synthesis. 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. Intermolecular hydroamination of terminal alkynes with aromatic amine has been carried out using cu exchanged sio2al2o3 as a heterogeneous catalyst.
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