| 1. |
- Cele, Zamani E. D., et al.
(författare)
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Catalytic asymmetric carbon-carbon bond forming reactions catalyzed by tetrahydroisoquinoline (TIQ) N,N '-dioxide ligands
- 2013
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Ingår i: Tetrahedron. - : Elsevier BV. - 0957-4166 .- 1362-511X. ; 24:4, s. 191-195
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Tidskriftsartikel (refereegranskat)abstract
- The use of TIQ-N,N'-dioxide ligands in asymmetric C-C bond forming reactions is described. In the Michael addition of cyclohexane-1,3-dione and malonates to beta,gamma-unsaturated alpha-ketoesters, excellent yields (up to 93%) and moderate to good enantioselectivities (70-89% ee) were obtained. The catalytic hetero-ene reaction of 2-methoxypropene with phenylglyoxal gave the ene product in excellent yield (95%) with moderate enantioselectivity (77% ee). The catalyst system performed well at temperatures ranging from 0 to 30 degrees C and relatively low catalyst loading (0.2-5 mol %) with dichloromethane being the preferred solvent for all reactions.
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| 2. |
- Chakka, Sai Kumar, et al.
(författare)
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Iridium-catalyzed asymmetric hydrogenation of olefins using TIQ phosphine-oxazoline ligands
- 2010
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Ingår i: Tetrahedron. - : Elsevier BV. - 0957-4166 .- 1362-511X. ; 21:18, s. 2295-2301
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Tidskriftsartikel (refereegranskat)abstract
- A novel family of tetrahydroisoquinoline (TIQ) phosphine-oxazoline ligands and four corresponding iridium complexes have been developed and applied to the asymmetric hydrogenation of unfunctionalized olefins. The results showed that the best conversion rates were observed in up to 99% with an enantiomeric excess of 91%.
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| 3. |
- Chakka, Sai Kumar, et al.
(författare)
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Synthesis and Screening of C-1-Substituted Tetrahydroisoquinoline Derivatives for Asymmetric Transfer Hydrogenation Reactions
- 2010
-
Ingår i: European Journal of Organic Chemistry. - : Wiley. - 1434-193X .- 1099-0690. ; :5, s. 972-980
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Tidskriftsartikel (refereegranskat)abstract
- Tetrahydroisoquinoline (TIQ) derivatives exhibit good biological activity. However, utilization of TIQ compounds in asymmetric catalysis is limited. This paper presents a series of TIQ derivatives in asymmetric transfer hydrogenation (ATH) reactions. Chiral TIQ amino alcohol ligands were synthesized and screened for the ATH reaction of aromatic ketones. The effect of a cis- and trans-phenyl substitution at the C-1 position on the ligand backbone was investigated both experimentally and computationally. The results showed that the trans orientation on the TIQ scaffold yields higher turnover rates with a selectivity of 94% ee obtained at room temperature with an Ru complex. The cis isomer results in a high turnover rate with no selectivity. The trans isomer gave 99% ee at lower temperatures. Furthermore, it was observed that substitution at the C-3-alpha position results in a drop of the enantioselectivity and the reactivity of the catalyst.
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| 4. |
- Kawthekar, Rahul B., et al.
(författare)
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Synthesis of tetrahydroisoquinoline (TIQ)-oxazoline ligands and their application in enantioselective Henry reactions
- 2010
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Ingår i: Tetrahedron. - : Elsevier BV. - 0957-4166 .- 1362-511X. ; 21:7, s. 846-852
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Tidskriftsartikel (refereegranskat)abstract
- A novel family of eleven new tetrahydroisoquinoline (TIQ)-oxazoline intermediates and five corresponding copper(II) catalysts has been developed and applied to the catalytic asymmetric Henry reaction of various aldehydes with nitromethane to provide beta-hydroxy nitroalkanes in high conversion (>99%) This paper describes the synthesis of the TIQ compounds from L-dihydroxyphenylalanine (L-DOPA) as the starting material The chiral ligands were complexed in situ with various transition metals such as Cu, Sc, Co, Zn, Ni and Mn and tested as a chiral catalyst for the Henry reaction The reaction was optimized in terms of the metal, counter ion, solvent, temperature and over a range of substrates The corresponding catalyst with copper(II) acetate and 2-propanol as the solvent provides the best enantioselectivities (up to 77% ee) of the corresponding nitroalcohol for 4-chlorobenzaldehyde.
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| 5. |
- Pawar, Sunayna S., et al.
(författare)
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Comparison of Tetrahydroisoquinoline (TIQ) Thiazole and Oxazoline Ligands for Asymmetric Henry Reactions
- 2012
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Ingår i: South African Journal of Chemistry. - 0379-4350 .- 1996-840X. ; 65, s. 23-29
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Tidskriftsartikel (refereegranskat)abstract
- A series of novel C-1 symmetric thiazole ligands with a tetrahydroisoquinoline (TIQ) backbone were synthesized. Their application in the catalytic asymmetric Henry reaction was investigated with comparison to a corresponding TIQ oxazoline ligand. The Cu(II)-oxazoline complex was more reactive and furnished moderate enantioselectivities up to 61:36 (syn:anti) with 75:25 diastereomeric excess, while the Cu(II)-thiazole complexes had lower selectivity. This is the first example where a direct comparison between an N, N-type thiazole and oxazoline ligands has been studied.
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| 6. |
- Peters, Byron K., et al.
(författare)
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Synthesis of tetrahydroisoquinoline-diamine ligands and their application in asymmetric transfer hydrogenation
- 2010
-
Ingår i: Tetrahedron. - : Elsevier BV. - 0957-4166 .- 1362-511X. ; 21:6, s. 679-687
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Tidskriftsartikel (refereegranskat)abstract
- The use of the tetrahydroisoquinoline scaffold is well documented in biologically active compounds. However, reports of the utilisation of tetrahydroisoquinoline compounds in asymmetric catalysis are limited. The synthesis of novel diamine ligands possessing the tetrahydroisoquinoline (tetrahydroisoquinoline) backbone and evaluation of their activity in the asymmetric transfer hydrogenation of acetophenone are presented. The diamine ligands in conjunction with i-PrOH as the hydrogen source and [RhCl2(Cp*)](2) as the metal precursor proved to be the most effective of the tetrahydroisoquinoline derivatives for this catalytic system. Water was found to have a profound influence on the enantioselectivity of the reaction. Optimisation of the amount water, i-PrOH and catalytic loading content rendered the best result of 70% enantioselectivity for the (S)-1-phenylethanol isomer product.
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| 7. |
- Wu, Haibo, et al.
(författare)
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Site- and Enantioselective Iridium-Catalyzed Desymmetric Mono-Hydrogenation of 1,4-Dienes
- 2021
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Ingår i: Angewandte Chemie International Edition. - : Wiley. - 1433-7851 .- 1521-3773. ; 60:35, s. 19428-19434
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Tidskriftsartikel (refereegranskat)abstract
- The control of site selectivity in asymmetric mono-hydrogenation of dienes or polyenes remains largely underdeveloped. Herein, we present a highly efficient desymmetrization of 1,4-dienes via iridium-catalyzed site- and enantioselective hydrogenation. This methodology demonstrates the first iridium-catalyzed hydrogenative desymmetriation of meso dienes and provides a concise approach to the installation of two vicinal stereogenic centers adjacent to an alkene. High isolated yields (up to 96%) and excellent diastereo- and enantioselectivities (up to 99:1 d.r. and 99% ee) were obtained for a series of divinyl carbinol and divinyl carbinamide substrates. DFT calculations reveal that an interaction between the hydroxy oxygen and the reacting hydride is responsible for the stereoselectivity of the desymmetrization of the divinyl carbinol. Based on the calculated energy profiles, a model that simulates product distribution over time was applied to show an intuitive kinetics of this process. The usefulness of the methodology was demonstrated by the synthesis of the key intermediates of natural products zaragozic acid A and (+)-invictolide.
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| 8. |
- Yang, Jianping, et al.
(författare)
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Combined Theoretical and Experimental Studies Unravel Multiple Pathways to Convergent Asymmetric Hydrogenation of Enamides
- 2021
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Ingår i: Journal of the American Chemical Society. - : American Chemical Society (ACS). - 0002-7863 .- 1520-5126. ; 143:51, s. 21594-21603
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Tidskriftsartikel (refereegranskat)abstract
- We present a highly efficient convergent asymmetric hydrogenation of E/Z mixtures of enamides catalyzed by N,P–iridium complexes supported by mechanistic studies. It was found that reduction of the olefinic isomers (E and Z geometries) produces chiral amides with the same absolute configuration (enantioconvergent hydrogenation). This allowed the hydrogenation of a wide range of E/Z mixtures of trisubstituted enamides with excellent enantioselectivity (up to 99% ee). A detailed mechanistic study using deuterium labeling and kinetic experiments revealed two different pathways for the observed enantioconvergence. For α-aryl enamides, fast isomerization of the double bond takes place, and the overall process results in kinetic resolution of the two isomers. For α-alkyl enamides, no double bond isomerization is detected, and competition experiments suggested that substrate chelation is responsible for the enantioconvergent stereochemical outcome. DFT calculations were performed to predict the correct absolute configuration of the products and strengthen the proposed mechanism of the iridium-catalyzed isomerization pathway.
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| 9. |
- Zheng, Jia, et al.
(författare)
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Iridium-catalysed enantioselective formal deoxygenation of racemic alcohols via asymmetric hydrogenation
- 2019
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Ingår i: NATURE CATALYSIS. - : NATURE PUBLISHING GROUP. - 2520-1158. ; 2:12, s. 1093-1100
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Tidskriftsartikel (refereegranskat)abstract
- Asymmetric hydrogenation of alkenes is one of the most powerful tools for the preparation of optically active compounds. However, to achieve high enantioselectivity, the starting olefin in most cases needs to be isomerically pure in either the cis or the trans form. Generally, most olefination protocols provide olefins as isomeric mixtures that are difficult to separate, and in many cases also generate lots of waste. In contrast, the synthesis of racemic alcohols is straightforward and highly atom-efficient, with products that are easier to purify. Here, we describe a strategy that enables rapid access to chiral alkanes via enantioconvergent formal deoxygenation of racemic alcohols. Mechanistic studies indicate an Ir-mediated elimination of water and subsequent in situ hydrogenation. This approach allows rapid and efficient assembly of chiral intermediates and is exemplified in the total synthesis of antidepressant sertraline and sigma(2) receptor PB 28.
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| 10. |
- Zheng, Jia, et al.
(författare)
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The Effect of Conformational Freedom vs Restriction on the Rate in Asymmetric Hydrogenation : Iridium-Catalyzed Regio- and Enantioselective Monohydrogenation of Dienones
- 2024
-
Ingår i: Chemistry - A European Journal. - 0947-6539 .- 1521-3765. ; 30:13
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Tidskriftsartikel (refereegranskat)abstract
- Transition metal-catalyzed asymmetric hydrogenation constitutes an efficient strategy for the preparation of chiral molecules. When dienes are subjected to hydrogenation, control over regioselectivity still presents a large challenge and the fully saturated alkane is often yielded. A few successful monohydrogenations of dienes have been reported, but hitherto these are only efficient for dienes comprised of two distinctly different olefins. Herein, the reactivity of a conjugated carbonyl compound as a function of their conformational freedom is studied, based on a combined experimental and theoretical approach. It was found that alkenes in the (s)-cis conformation experience a large rate acceleration while (s)-trans restrained alkenes undergo hydrogenation slowly. Ultimately, this reactivity aspect was exploited in a novel method for the monohydrogenation of dienes based on conformational restriction ((s)-cis vs (s)-trans). This mode of discrimination conceptually differs from existing monohydrogenations and dienones constructed of two olefins similar in nature could efficiently be hydrogenated to the chiral alkene (up to 99 % ee). The extent of regioselection is even powerful enough to overcome the conventional reactivity order of substituted olefins (di>tri>tetra). This high yielding and atom-economical protocol provides an interesting opportunity to instal a stereogenic center on a carbocycle, while leaving a synthetically useful alkene untouched.
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| 11. |
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| 12. |
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| 13. |
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| 14. |
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| 15. |
- Betterley, Nolan M., et al.
(författare)
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Bi(OTf)(3) Enabled C-F Bond Cleavage in HFIP : Electrophilic Aromatic Formylation with Difluoro(phenylsulfanyl)methane
- 2018
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Ingår i: Asian Journal of Organic Chemistry. - : Wiley. - 2193-5807 .- 2193-5815. ; 7:8, s. 1642-1647
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Tidskriftsartikel (refereegranskat)abstract
- Bismuth(III) trifluoromethanesulfonate [Bi(OTf)(3)] mediated mild electrophilic aromatic formylation utilizing difluoro(phenylsulfanyl)methane (PhSCF2H) as a formylating agent in hexafluoro-2-propanol (HFIP) as a recyclable ionizing solvent has been developed. The active formylating species was generated via C-F bond cleavage and was characterized to be a bis(phenylsulfanyl)methyl cation by experimental and computational H-1 and C-13 NMR.
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| 16. |
- Biosca, Maria, et al.
(författare)
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Extending the Substrate Scope of Bicyclic P-Oxazoline/Thiazole Ligands for Ir-Catalyzed Hydrogenation of Unfunctionalized Olefins by Introducing a Biaryl Phosphoroamidite Group
- 2015
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Ingår i: Chemistry - A European Journal. - : Wiley. - 0947-6539 .- 1521-3765. ; 21:8, s. 3455-3464
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Tidskriftsartikel (refereegranskat)abstract
- This study identifies a series of Ir-bicyclic phosphoroamidite-oxazoline/thiazole catalytic systems that can hydrogenate a wide range of minimally functionalized olefins (including E-and Z-tri- and disubstituted substrates, vinylsilanes, enol phosphinates, tri- and disubstituted alkenylboronic esters, and alpha,beta-unsaturated enones) in high enantioselectivities (ee values up to 99%) and conversions. The design of the new phosphoroamidite-oxazoline/thiazole ligands derives from a previous successful generation of bicyclic N-phosphane-oxazoline/thiazole ligands, by replacing the N-phosphane group with a pi-acceptor biaryl phosphoroamidite moiety. A small but structurally important family of Ir-phosphoroamidite-oxazoline/thiazole precatalysts has thus been synthesized by changing the nature of the N-donor group (either oxazoline or thiazole) and the configuration at the biaryl phosphoroamidite moiety. The substitution of the N-phosphane by a phosphoroamidite group in the bicyclic N-phosphane-oxazoline/thiazole ligands extended the range of olefins that can be successfully hydrogenated.
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| 17. |
- Cadu, Alban, et al.
(författare)
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Birch Reaction Followed by Asymmetric Iridium-Catalysed Hydrogenation
- 2011
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Ingår i: Synthesis (Stuttgart). - : Georg Thieme Verlag KG. - 0039-7881 .- 1437-210X. ; :23, s. 3796-3800
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Tidskriftsartikel (refereegranskat)abstract
- Birch reaction products are asymmetrically hydrogenated with high enantio- and diastereoselectivity via iridium catalysts. This new method of producing chiral compounds was explored for a variety of 1,3-di- and 1,2,4-tri-substituted cyclohexadienes.
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| 18. |
- Cadu, Alban, et al.
(författare)
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Development of iridium-catalyzed asymmetric hydrogenation : New catalysts, new substrate scope
- 2012
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Ingår i: Journal of Organometallic Chemistry. - : Elsevier BV. - 0022-328X .- 1872-8561. ; 714, s. 3-11
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Forskningsöversikt (refereegranskat)abstract
- A review. The asym. hydrogenation of olefins is a tremendously powerful tool used to synthesize chiral mols. The field was pioneered using rhodium- and ruthenium- based catalysts; however, catalysts based on both of these metals suffer from limitations, such as the need for directing substituents near or even adjacent to the olefin. Iridium-based catalysts do not suffer from this flaw and can thus hydrogenate a wide variety of olefins, including some tetra substituted ones. It is also possible for iridium-based catalysts to hydrogenate hetero-π bonds such as those found in heteroarom. rings. This review summarizes the contributions made to this field by the authors in the past few years. [on SciFinder(R)]
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| 19. |
- Cadu, Alban, 1987-
(författare)
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Iridium Catalysed Asymmetric Hydrogenation of Pyridines
- 2013
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis presents the hydrogenation of substituted pyridines using N,P-ligated iridium catalystsin homogeneous media. These iridium catalysts were developed within this research group in thepast decade. This method of hydrogenation is highly stereoselective, and in several cases good to excellent ees were obtained.The hydrogenation of substituted pyridines was studied: by screening for the catalyst giving thehighest conversion and ee, by optimising the reaction conditions and by attempting to improve existingcatalysts. New substrates were synthesised for this process, in particular alkyl substituted Nprotectedpyridines. Their reduction provided chiral piperidines, which could be used as chiralbuilding blocks once deprotected.
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| 20. |
- Cadu, Alban, 1987-, et al.
(författare)
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Iridium catalysis : Application of asymmetric reductive hydrogenation
- 2013
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Ingår i: Dalton Transactions. - : Royal Society of Chemistry (RSC). - 1477-9226 .- 1477-9234. ; 42:40, s. 14345-14356
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Tidskriftsartikel (refereegranskat)abstract
- Iridium, despite being one of the least abundant transition metals, has found several uses. N,P-ligated iridium catalysts are used to perform many highly selective reactions. These methodologies have been developed extensively over the past 15 years. More recently, the application of iridium N,P catalysts in asymmetric hydrogenation has been a focus of research to find novel applications and to expand on their current synthetic utility. The aim of this perspective is to highlight the advances made by the Andersson group.
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| 21. |
- Cadu, Alban, 1987-, et al.
(författare)
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Iridium-Catalyzed Asymmetric Hydrogenation of Substituted Pyridines
- 2013
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Ingår i: Asian Journal of Organic Chemistry. - : Wiley. - 2193-5807. ; 2:12, s. 1061-1065
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Tidskriftsartikel (refereegranskat)abstract
- Asymmetric hydrogenation of ortho-substituted pyridines catalyzed by N,P-ligated iridium is demonstrated. To facilitate this reaction, the aromaticity of the pyridines was weakened by forming N-iminopyridium ylides. The reactions give very high conversions, and after a single recrystallization, excellent ee of up to 98 % was obtained. This method lends itself to the synthesis of chiral piperidine building blocks.
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| 22. |
- Cheruku, Pradeep, et al.
(författare)
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Access to chiral tertiary amines via the iridium-catalyzed asymmetric hydrogenation of enamines
- 2008
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Ingår i: Tetrahedron Letters. - : Elsevier BV. - 0040-4039 .- 1359-8562. ; 49:51, s. 7290-7293
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Tidskriftsartikel (refereegranskat)abstract
- The asymmetric hydrogenation of N,N-dialkyl and N-alkyl-N-aryl enamines to chiral tertiary amines was studied. All the N,P-ligated iridium complexes investigated were active catalysts for the reaction, but only those with bicycle-supported oxazoline-phosphine ligands gave reasonable stereoinduction. The best catalyst produced a range of chiral tertiary amines in up to 87% ee.
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| 23. |
- Cheruku, Pradeep, et al.
(författare)
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Iridium-N,P-ligand-catalyzed enantioselective hydrogenation of diphenylvinylphosphine oxides and vinylphosphonates
- 2009
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Ingår i: Journal of the American Chemical Society. - : American Chemical Society (ACS). - 0002-7863 .- 1520-5126. ; 131:23, s. 8285-8289
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Tidskriftsartikel (refereegranskat)abstract
- Diphenylvinylphosphine oxides and di- and trisubstituted vinylphosphonates have been employed as substrates in iridium-catalyzed asymmetric hydrogenations. Complete conversions and excellent enantioselectivities (up to and above 99% ee) were observed for a range of substrates with both aromatic and aliphatic groups at the prochiral carbon. We have also hydrogenated electron-deficient carboxyethylvinylphosphonates with excellent stereoselectivity (up to and above 99% ee). The hydrogenated products of both classes of substrates are synthetically useful intermediates.
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| 24. |
- Church, Tamara L, et al.
(författare)
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Enantioselectivity in the Iridium-Catalyzed Hydrogenation of Unfunctionalized Olefins
- 2010
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Ingår i: ORGANOMETALLICS. - : ACS American Chemical Society. - 0276-7333 .- 1520-6041. ; 29:24, s. 6769-6781
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Tidskriftsartikel (refereegranskat)abstract
- The iridium catalyzed asymmetric hydrogenation of largely unfunctionalized olefins has been studied by DFT calculations using a full experimentally tested combination of ligand and substrate All possible diastereomeric pathways were considered within four different hydrogenation mechanisms The effect of a solvent continuum was also considered and both the gas phase and solvent continuum calculations favored the same mechanism This mechanism passed through Ir-III and Ir-V intermediates and was consistent with the sense of stereoselection observed experimentally Comparing the calculations to those performed on a model system permitted an evaluation of the model system s utility in representing the full one A simple general method for predicting the sense of stereoselection in iridium-catalyzed olefin hydrogenation was developed and tested against published data
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| 25. |
- Church, Tamara L., et al.
(författare)
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Iridium catalysts for the asymmetric hydrogenation of olefins with nontraditional functional substituents
- 2008
-
Ingår i: Coordination chemistry reviews. - : Elsevier BV. - 0010-8545 .- 1873-3840. ; 252:5-7, s. 513-531
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Forskningsöversikt (refereegranskat)abstract
- Chiral iridium catalysts have now been used in the asymmetric hydrogenation of largely unfunctionallized olefins for a decade. Recently, they have also been applied to substrates with more exotic functional groups, including non-coordinating ones. These, unlike coordinating substituents, cannot direct asymmetric hydrogenation by rhodium- or ruthenium-based catalysts. This review discusses several classes of these less familiar substrates, outlines the progress that has been made toward their stereoselective hydrogenation, and highlights the role of iridium complexes in this emerging field. We hope this will inspire researchers to consider iridium-catalyzed asymmetric hydrogenation as a potential route to a broad range of chiral compounds.
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| 26. |
- Diesen, Jarle Sidney, 1968-
(författare)
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Asymmetric Hydrogenations of Imines, Vinyl Fluorides, Enol Phosphinates and Other Alkenes Using N,P-Ligated Iridium Complexes
- 2008
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The research described in this thesis is directed toward the efficient, enantioselective synthesis of chiral products that have useful functionality. This goal was pursued through catalytic asymmetric hydrogenation, a reaction class that selectively introduces one or two stereocenters into a molecule in an atom-efficient step. This reaction uses a small amount (often <1 mol%) of a chiral catalyst to impart stereoselectivity to the product formed. Though catalytic asymmetric hydrogenation is not a new reaction type, there remain many substrate classes for which it is ineffective. The present thesis describes efforts to extend the reaction to some of these substrates classes. Some of the products synthesized in these studies may eventually find use as building blocks for the production of chiral pharmaceuticals, agrochemicals, or flavouring or colouring agents. However, the primary and immediate aim of this thesis was to develop and demonstrate new catalysts that are rapid and effective in the asymmetric hydrogenation of a broad range of compounds. Paper I describes the design and construction of two new, related chiral iridium compounds that are catalysts for asymmetric hydrogenation. They each contain an N,P-donating phosphinooxazoline ligand that is held together by a rigid bicyclic unit. One of these iridium compounds catalyzed the asymmetric hydrogenation of acyclic aryl imines, often with very good enantioselectivities. This is particularly notable because acyclic imines are difficult to reduce with useful enantioselectivity. The second catalyst was useful for the asymmetric hydrogenation of two aryl olefins. In Paper II, the class of catalysts introduced into Paper I is expanded to include many more related compounds, and these are also applied to the asymmetric hydrogenation of prochiral imines and olefins. By studying a range of related catalysts that differ in a single attribute, we were able to probe how different parts of the catalyst affect the yield and selectivity of the hydrogenation reactions. Whereas iridium catalysts had been applied to the asymmetric hydrogenation of imines and largely unfunctionalized olefins prior to this work (with varied degrees of success), they had not been used to reduce fluoroolefins. Their hydrogenation, which is discussed in Paper III, was complicated by concomitant defluorination to yield non-halogenated alkanes. To combat this problem, several iridium-based hydrogenation catalysts were applied to the reaction. Two catalysts stood out for their ability to produce chiral fluoroalkanes in good enantioselectivity while minimizing the defluorination reaction, and one of these bore a phosphinooxazoline ligand of the type described in Papers I and II. Enol phosphinates are another class of olefins that had not previously been subjected to iridium-catalyzed asymmetric hydrogenation. They do, however, constitute an attractive substrate class, because the product chiral alkyl phosphinates can be transformed into chiral alcohols or chiral phosphines with no erosion of enantiopurity. Iridium complexes of the phosphinooxazoline ligands described in Papers I and II were extremely effective catalysts for the asymmetric hydrogenation of enol phosphinates. They produced alkyl phosphinates from di- and trisubstituted enol phosphinate, β-ketoester-derived enol phosphinates, and even purely alkyl-substituted enol phopshinates, in very high yields and enantioselectivities.
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| 27. |
- Engman, Mattias, 1979-
(författare)
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Chemo- and Enantioselective Hydrogenations : The Struggle of Expanding the Substrate Scope of Iridium Catalyzed Asymmetric Hydrogenations of Olefins
- 2009
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The asymmetric hydrogenation of olefins is a facile and popular method of reaching chiral products. Whereas ruthenium- and rhodium-catalyzed asymmetric hydrogenations have a long history, the use of iridium in this area is new but fast-growing. Since the first chiral N,P-ligated iridium catalyst was created in the late 1990s, the growing pool of N,P ligands has filled up rapidly, but most have been tested with a limited range of standard olefins. To extract the full potential of these complexes, new methods using substrates having many possible applications must be developed. This thesis focuses on the iridium-catalyzed asymmetric hydrogenation of three different new substrate classes to yield very high conversions and enantiomeric excesses (ee's). As the use of fluorine has recently become common in many different fields of chemistry, the asymmetric reduction of fluoroolefins to reach chiral products having fluorine at the stereogenic centers is highly interesting. We studied this reaction and eventually obtained very high ee values and lower degree of defluorination (Paper I and Paper II). The hydrogenations of trifluoromethylated olefins to reach products useful in applications reaching from pharmaceuticals to additives in liquid crystal displays (LCDs) were also challenging, but fruitful (Paper III). As asymmetric hydrogenation usually demands differences in the substituents of the double bond, the highly selective reduction of 1,1-diaryl olefins having similar aryls give a new perspective on the broad scope of substrates that N,P-ligated iridium complexes can reduce selectively (paper IV).
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| 28. |
- Engman, Mattias, et al.
(författare)
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Highly Selective Iridium-Catalyzed Asymmetric Hydrogenation of Trifluoromethyl Olefins : A New Route to Trifluoromethyl-Bearing Stereocenters
- 2009
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Ingår i: Advanced Synthesis and Catalysis. - : Wiley. - 1615-4150 .- 1615-4169. ; 351:3, s. 375-378
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Tidskriftsartikel (refereegranskat)abstract
- Fluorine-containing compounds are useful in many applications ranging from pharmaceuticals to ferroelectric crystals. We have developed a new, highly enantioselective synthetic route to trifluoromethyl-bearing stereocenters in up to 96% ee via asymmetric hydrogenation using N,P-ligated iridium catalysts. We also hydrogenated an isomeric mixture of olefins; this reaction gave the hydrogenation product highly enantioselectively (87% ee), and only the E isomer was present after the reaction had reached 56% conversion.
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| 29. |
- Engman, Mattias, et al.
(författare)
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Iridium-Catalyzed Asymmetric Hydrogenation of Fluorinated Olefins Using N,P-Ligands : A struggle with hydrogenolysis and selectivity
- 2007
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Ingår i: Journal of the American Chemical Society. - : American Chemical Society (ACS). - 0002-7863 .- 1520-5126. ; 129:15, s. 4536-4537
-
Tidskriftsartikel (refereegranskat)abstract
- To broaden the substrate scope of asymmetric iridium-catalyzed hydrogenation, fluorine-functionalized olefins were synthesized and hydrogenated with iridium complexes. Preliminary results showed high levels of fluorine elimination together with low selectivity. The loss of vinylic fluorine at first seemed difficult to handle, but further studies revealed that a catalyst with an azanorbornyl scaffold in the ligand gave more promising results. With this in mind, a new ligand was developed. This gave among the best results published to date for fluorine asymmetric hydrogenation, yielding high conversion and very high ee's with very little fluorine elimination. Further increasing the selectivity, the trials also revealed that tetrasubstituted fluorine-containing olefins can be hydrogenated with high ee's, despite that this class of compounds has usually shown low reactivity in this reaction type.
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| 30. |
- Gayet, Arnaud, 1977-
(författare)
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Development of New Chiral Bicyclic Ligands : Applications in Catalytic Asymmetric Transfer Hydrogenation, Epoxidations, and Epoxide Rearrangements
- 2005
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis describes the synthesis and application of new chiral bicyclic ligands and their application in asymmetric catalysis. The studies involved: [i] The development of novel chiral bicyclic amino sulfur ligands and their use in transfer hydrogenation. [ii] The development of the kinetic resolution of racemic epoxide through the use of chiral lithium amides. [iii] The synthesis and application of chiral bicyclic amine in the organocatalysed epoxidation of alkenes. [iv] Development and application of new chiral diamine ligands in the rearrangement of epoxides into allylic alcohols.[i] The preparation of two-series of amino thiol ligands based on the structure of camphor is described, together with their application in the iridium-catalysed asymmetric transfer hydrogenation of acetophenone using isopropanol as the hydrogen source. Excellent activity and good enantioselectivity have been achieved using 2 mol% of chiral ligand in combination with [IrCl(COD)]2.[ii] The chiral diamines (1S,3R,4R)-3-(pyrrolidine-1-ylmethyl)-2-aza-bicyclo[2.2.1]heptane and its (2R,5R)-dimethylpyrrolidine derivative were applied to the kinetic resolution of a variety of racemic 5-7 membered cycloalkene oxides with lithium diisopropylamide (LDA) as the bulk base. Using 5 mol% of the chiral diamines, both unreacted epoxides and allylic alcohols could be produced in enantiomeric excess up to 99%.[iii] The synthesis of chiral bicyclic amines and their use in the organocatalysed epoxidation of alkene has been described. Using a substoichiometric amount of the chiral amines and aldehydes as ligands precursors, with Oxone® as oxidant, a good activity but moderate enantioselectivity was observed for the epoxidation of trans-stilbene. [iv] The preparation of 6-substituted-7-bromo-aza-bicyclo[2.2.1]heptanes via nucleophilic addition of organocopper reagents to 3-bromo-1-azoniatricyclo[2.2.1.0]heptyle bromide has been described. These compounds have been utilised as chiral building blocks in the preparation of novel chiral diamine ligands, which have been successfully applied to the catalysed asymmetric rearrangement of epoxide into the corresponding allylic alcohol.
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| 31. |
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| 32. |
- He, Lei, et al.
(författare)
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Asymmetric Hydrogenation of Imines Using NHC-Phosphine Iridium Complexes
- 2023
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Ingår i: Asian Journal of Organic Chemistry. - 2193-5807 .- 2193-5815. ; 12:6
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Tidskriftsartikel (refereegranskat)abstract
- α-Chiral amines represent a frequently observed functional group in pharmaceuticals. Here, the synthesis of such motifs (up to 91% ee) is described by asymmetric hydrogenation of imines catalyzed by NHC,P-iridium complexes. The hydrogenation proceeded smoothly, even under balloon pressure of hydrogen atmosphere. Mechanistic experiments indicated that the reduction most likely advances by a combination of direct hydrogenation and a hydrogen transfer process using either H2 or iPrOH as the reductant, respectively.
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| 33. |
- Hedberg, Christian, et al.
(författare)
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Catalytic Asymmetric Total Synthesis of Muscarinic Receptor Antagonist (R)-Tolterodine
- 2005
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Ingår i: Advanced Synthesis and Catalysis. - : Wiley. - 1615-4150 .- 1615-4169. ; 347:5, s. 662-666
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Tidskriftsartikel (refereegranskat)abstract
- A convenient and high yielding method for the preparation of (R)-tolterodine, utilizing a catalytic asymmetric Me-CBS reduction was developed. Highly enantioenriched (R)-6-methyl-4-phenyl-3,4-dihydrochromen-2-one (94% ee) was recrystallized to yield practically enantiopure material (ee >99%) and converted to (R)-tolterodine in a four-step procedure. The configuration of the crucial stereocenter was preserved during the synthesis and the obtained product was identified by chiral HPLC to be the (R)-tolterodine enantiomer.
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| 34. |
- Hedberg, Christian, 1975-
(författare)
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Design, Synthesis, Mechanistic Rationalization and Application of Asymmetric Transition-Metal Catalysts
- 2005
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis describes mechanistic studies, rational ligand design, and synthesis of asymmetric transition metal catalysts. The topics addressed concerned [Papers I-VII]:[I] The asymmetric addition of diethyl zinc to N-(diphenylphosphinoyl)benzalimine catalyzed by bicyclic 2-azanorbornyl-3-methanols was studied. An efficient route to both diastereomers of new bicyclic 2-azanorbornyl-3-methanols with an additional chiral center was developed, in the best case 97% ee was obtained with these ligands. The experimental results were rationalized by a computational DFT-study.[II] An aza-Diels-Alder reaction of cyclopentadiene with chiral heterocyclic imines derived from (S)-1-phenylethylamine and different heteroaromatic aldehydes was developed. The cycloaddition proved to be highly diastereoselective and offers a very rapid access to possible biologically active compounds and interesting precursors for chiral (P,N)-ligands. [III] A convenient and high-yielding method for the preparation of (R)-tolterodine, utilizing a catalytic asymmetric Me-CBS reduction was developed. Highly enantio-enriched (R)-6-methyl-4-phenyl-3,4-dihydrochromen-2-one (94% ee) was recrystallized to yield practically enantiopure material (ee >99%) and converted to (R)-tolterodine in a four-step procedure. [IV] The reaction mechanism of the iridium-phosphanooxazoline-catalyzed hydrogenation of unfunctionalized olefins has been studied by means of DFT-calculations (B3LYP) and kinetic experiments. The calculations suggest that the reaction involves an unexpected IrIII-IrV catalytic cycle facilitated by coordination of a second equivalent of dihydrogen. On the basis of the proposed catalytic cycle, calculations were performed on a full system with 88 atoms. These calculations were also used to explain the enantioselectivity displayed by the catalyst.[V and VI] A new class of chiral (P,N)-ligands for the Ir-catalyzed asymmetric hydrogenation of aryl alkenes was developed. These new ligands proved to be highly efficient and tolerate a broad range of substrates. The enantiomeric excesses are, so far, the best reported and can be rationalized using the proposed selectivity model.[VII] The complex formed between the quincorine-amine, containing both a primary and a quinuclidine amino function, and [Cp*RuCl]4 catalyzes the hydrogenation of aromatic and aliphatic ketones in up to 90% ee approx. 24-times faster than previously reported Ru-diamine complexes. The reason for the lower but opposite stereoselectivity seen with the quincoridine-amine, as compared to the quincorine-amine, was rationalized by a kinetic and computational study of the mechanism. The theoretical calculations also revealed a significantly lower activation barrier for the alcohol mediated split of dihydrogen, as compared to the non-alchol mediated process. A finding of importance also for the diphosphine/diamine mediated enantioselective hydrogenation of ketones.
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| 35. |
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| 36. |
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| 37. |
- Jiang, Tuo, et al.
(författare)
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Palladium-Catalyzed Oxidative Synthesis of a-Acetoxylated Enones from Alkynes
- 2016
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Ingår i: Angewandte Chemie International Edition. - : Wiley-VCH Verlagsgesellschaft. - 1433-7851 .- 1521-3773. ; 55:19, s. 5824-5828
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Tidskriftsartikel (refereegranskat)abstract
- We report a palladium-catalyzed oxidative functionalization of alkynes to generate -acetoxylated enones in one step. A range of functional groups are well-tolerated in this reaction. Mechanistic studies, including the use of O-18-labeled DMSO, revealed that the ketone oxygen atom in the product originates from DMSO.
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| 38. |
- Kaukoranta, Päivi, et al.
(författare)
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Iridium Catalysts with Chiral Imidazole-Phosphine Ligands for Asymmetric Hydrogenation of Vinyl Fluorides and other Olefins
- 2008
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Ingår i: Advanced Synthesis and Catalysis. - : Wiley. - 1615-4150 .- 1615-4169. ; 350:7-8, s. 1168-1176
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Tidskriftsartikel (refereegranskat)abstract
- New chiral bidentate imidazole-phosphine ligands have been prepared and evaluated for the iridium-catalysed asymmetric hydrogenation of olefins. The imidazole-phosphine-ligated iridium catalysts hydrogenated trisubstituted olefins with the same sense of enantiodiscrimination as known iridium catalysts possessing oxazole and thiazole as N-donors. The imidazole-based catalysts were shown to hydrogenate vinyl fluorides, in some cases with the highest ee values published to date.
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| 39. |
- Kerdphon, Sutthichat, et al.
(författare)
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C-N Coupling of Amides with Alcohols Catalyzed by N-Heterocyclic Carbene-Phosphine Iridium Complexes
- 2015
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Ingår i: Journal of Organic Chemistry. - : American Chemical Society (ACS). - 0022-3263 .- 1520-6904. ; 80:22, s. 11529-11537
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Tidskriftsartikel (refereegranskat)abstract
- N-heterocyclic carbene-phosphine iridium complexes (NHC-Ir) were developed/found to be a highly reactive catalyst for N-monoalkylation of amides with alcohols via hydrogen transfer. The reaction produced the desired product in high isolated yields using a wide range of substrates with low catalyst loading and short reaction times.
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| 40. |
- Kerdphon, Sutthichat, et al.
(författare)
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Diastereo- and Enantioselective Synthesis of Structurally Diverse Succinate, Butyrolactone, and Trifluoromethyl Derivatives by Iridium-Catalyzed Hydrogenation of Tetrasubstituted Olefins
- 2019
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Ingår i: ACS Catalysis. - : American Chemical Society (ACS). - 2155-5435. ; 9:7, s. 6169-6176
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Tidskriftsartikel (refereegranskat)abstract
- A highly efficient iridium N,P-ligand-catalyzed asymmetric hydrogenation of functionalized tetrasubstituted olefins lacking a directing group has been developed. Various structural diverse chiral succinate derivatives were obtained in high yields and excellent enantio- and diastereoselectivities (up to 99% ee) using 0.5-1.0 mol % catalyst loadings. This stereoselective reaction is applicable for the synthesis of chiral acyclic molecules (up to >99% ee) having two contiguous stereogenic centers and is compatible with various aromatic, aliphatic, and heterocyclic systems, a variety of functional groups of different electronic nature. Furthermore, this asymmetric protocol allows a short enantioselective route to the butyrolactone building block, an intermediate in the synthesis of anticancer agent BMS-871 and pharmaceuticals (2S)-(-)-Verapamil and (2S)-(-)-Gallopamil.
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| 41. |
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| 42. |
- Krajangsri, Suppachai, et al.
(författare)
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Tandem Peterson olefination and chemoselective asymmetric hydrogenation of β-hydroxy silanes
- 2019
-
Ingår i: Chemical Science. - : Royal Society of Chemistry. - 2041-6520 .- 2041-6539. ; 10:12, s. 3649-3653
-
Tidskriftsartikel (refereegranskat)abstract
- Here, we report the first Ir-N,P complex catalyzed tandem Peterson olefination and asymmetric hydrogenation of -hydroxy silanes. This reaction resulted in the formation of chiral alkanes in high isolated yields (up to 99%) and excellent enantioselectivity (up to 99% ee) under mild conditions. Modification of the reaction conditions provides a choice to transform either an olefin or the -hydroxy silane in a chemoselective manner. Additionally, based on this method, an expedient enantioselective synthesis of (S)-(+)--curcumene, from a simple ketone, was accomplished in two steps with 75% overall yield and 95% ee.
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| 43. |
- Li, Jia-Qi, et al.
(författare)
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Asymmetric Hydrogenation of Allylic Alcohols Using Ir-N,P-Complexes
- 2016
-
Ingår i: ACS Catalysis. - : American Chemical Society (ACS). - 2155-5435. ; 6:12, s. 8342-8349
-
Tidskriftsartikel (refereegranskat)abstract
- In this study, a series of gamma,gamma-disubstituted and beta,gamma-disubstituted allylic alcohols were prepared and successfully hydrogenated using suitable N,P-based Ir complexes. High yields and excellent enantioselectivities were obtained for most of the substrates studied. This investigation also revealed the effect of the acidity of the N,P-Ir-complexes on the acid sensitive allylic alcohols. DFT Delta pK(a) calculations were used to explain the effect of the N,P-ligand on the acidity of the corresponding Ir-complex. The selectivity model of the reaction was used to accurately predict the absolute configuration of the hydrogenated alcohols.
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| 44. |
- Li, Jia-Qi, et al.
(författare)
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Bicyclic phosphine-thiazole ligands for the asymmetric hydrogenation of olefins
- 2010
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Ingår i: Tetrahedron. - : Elsevier BV. - 0957-4166 .- 1362-511X. ; 21:11-12, s. 1328-1333
-
Tidskriftsartikel (refereegranskat)abstract
- New bicyclic thiazole-based chiral N,P-chelating ligands were developed. High activities and enantioselectivities were achieved in the iridium-catalyzed asymmetric hydrogenation of olefins with the new ligands.
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| 45. |
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| 46. |
- Li, Jia-Qi, et al.
(författare)
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Highly Enantioselective Iridium Catalyzed Hydrogenation of α, β-Unsaturated Esters
- 2012
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Ingår i: Chemistry - A European Journal. - : Wiley. - 0947-6539 .- 1521-3765. ; 18:34, s. 10609-10616
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Forskningsöversikt (refereegranskat)abstract
- α,β-Unsaturated esters have been employed as substrates in iridium-catalyzed asymmetric hydrogenation. Full conversions and good to excellent enantioselectivities (up to 99 % ee) were obtained for a broad range of substrates with both aromatic- and aliphatic substituents on the prochiral carbon. The hydrogenated products are highly useful as building blocks in the synthesis of a variety of natural products and pharmaceuticals.
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| 47. |
- Li, Jia-Qi, et al.
(författare)
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Room temperature and solvent-free iridium-catalyzed selective alkylation of anilines with alcohols
- 2013
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Ingår i: Chemical Communications. - : Royal Society of Chemistry (RSC). - 1359-7345 .- 1364-548X. ; 49:55, s. 6131-6133
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Tidskriftsartikel (refereegranskat)abstract
- A bidentate iridium NHC-phosphine complex has been developed and applied to the N-monoalkylation of aromatic amines with a wide range of primary alcohols and to the N-heterocyclization of amino alcohols. This reaction resulted in high isolated product yields, even at room temperature and under solvent-free conditions.
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| 48. |
- Li, Xingzhen, et al.
(författare)
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Mono-N-Alkylation of Sulfonamides with Alcohols Catalyzed by Iridium N-Heterocyclic Carbene-Phosphine Complexes
- 2022
-
Ingår i: Asian Journal of Organic Chemistry. - : Wiley. - 2193-5807 .- 2193-5815. ; 11:7
-
Tidskriftsartikel (refereegranskat)abstract
- A N-heterocyclic carbene-phosphine iridium complex is presented for the efficient and selective mono-N-alkylation of sulfonamides with alcohols based on a borrowing hydrogenation strategy. Herein, water is the only by-product and this methodology thus offers a more environmentally benign and interesting alternative to the use of traditional alkylating reagents. This facile protocol tolerates a large number of (hetero) aromatic and aliphatic sulfonamides as well as (hetero) aromatic and aliphatic alcohols to obtain the desired product is high isolated yield (up to 98%). The alkylation completely retards after the formation of the secondary sulfonamide and no over-alkylation was observed in all cases. The option to run the reaction under solvent-free conditions as well as the scalability of this borrowing hydrogenation are key features of this protocol.
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| 49. |
- Liu, Jianguo, et al.
(författare)
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Iridium-catalysed asymmetric hydrogenation of allylic alcohols via dynamic kinetic resolution
- 2018
-
Ingår i: Nature Catalysis. - : Springer Science and Business Media LLC. - 2520-1158. ; 1:6, s. 438-443
-
Tidskriftsartikel (refereegranskat)abstract
- Dynamic kinetic resolutions (DKRs) allow for the conversion of both enantiomers of starting material into a single enantiomer of product, hence avoiding the 50% yield limit observed in traditional kinetic resolutions. Transition-metal-catalysed variants have become an important and useful method in asymmetric synthesis. Here we report an asymmetric hydrogenation of allylic alcohols using an Ir–N,P-ligand complex via DKR. In contrast to the many DKRs involving carbonyl reduction, this methodology allows for DKR during alkene reduction. Mechanistic studies support the hypothesis that racemization of the substrate is achieved by cleavage and reforming of the oxygen–carbon bond. Under the cooperative dynamic kinetic asymmetric hydrogenation, a broad range of chiral alcohols containing two stereogenic centres were produced with excellent diastereoselectivities (up to 95:5) and enantioselectivities (up to 99%).
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| 50. |
- Liu, Jianguo, 1985-
(författare)
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Iridium Catalysed Asymmetric Hydrogenation of Olefins and Dynamic Kinetic Resolution in the Asymmetric Hydrogenation of Allylic Alcohols
- 2017
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The work described in this thesis is focused on exploring the efficacy of iridium-catalysed asymmetric hydrogenation of precursors to chiral alcohols and chiral cyclohexanes. A range of allylic alcohols including γ,γ-dialkyl allylic alcohols and (Z)-allylic alcohols were prepared and evaluated in the asymmetric hydrogenation using iridium catalysts resulting in chiral alcohols in high yields and excellent enantioselectivity. This methodology was applied in the formal synthesis of Aliskiren, an efficient renin inhibitor drug, using the asymmetric hydrogenation of an allylic alcohol as a key-step. Another project concerned the dynamic kinetic resolution of racemic secondary allylic alcohols using Ir-N,P catalysts under hydrogenation conditions. A range of secondary allylic alcohols and protected alcohols were evaluated in the asymmetric hydrogenation via dynamic kinetic resolution using Ir-N,P catalysts. The corresponding chiral saturated alcohols were formed in good yield with excellent diastereoselectivites (up to 95/5) and enantioselectivities (>99% ee). The last part of this thesis is directed towards the development of highly regio- and enantioselective asymmetric hydrogenation of 1,4-cyclohexadienes and its application in the preparation of useful chiral cyclohexenone intermediates. Non-functionalised, functionalised and heterocycle-containing cyclohexadienes were evaluated. Good yield of regioselectively mono-hydrogenated silyl protected enol ethers were obtained in most cases with excellent enantioselectivity.
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