Pd/Cu-free Heck and Sonogashira cross-coupling reaction by Co nanoparticles immobilized on magnetic chitosan as reusable catalyst

 

Pd/Cu-free Heck and Sonogashira cross-coupling reaction by Co nanoparticles immobilized on magnetic chitosan as reusable catalyst

Green Chem., 2017, Advance Article
DOI: 10.1039/C6GC03377F, Paper
Abdol R. Hajipour, Fatemeh Rezaei, Zahra Khorsandi
Chitosan (CS) is a porous, self-standing, nanofibrillar microsphere that can be used as a metal carrier. Amino groups on CS enable to modulate cobalt coordination using a safe organic ligand (methyl salicylate).

Pd/Cu-free Heck and Sonogashira cross-coupling reaction by Co nanoparticles immobilized on magnetic chitosan as reusable catalyst

aDepartment of Chemistry, Isfahan University of Technology, Isfahan 84156, Iran
E-mail: haji@cc.iut.ac.ir
Fax: +98 311 391 2350
Tel: +98 311 391 3262
bDepartment of Neuroscience, University of Wisconsin, Medical School, Madison, USA
Green Chem., 2017, Advance Article

DOI: 10.1039/C6GC03377F

Department of Chemistry
Office : College of Chemistry, Isfahan University of Technology, Isfahan 84156, IR IranPhone : +98 311 391xxxxFax : +98 311 391xxxxWeb Site : Prof. Abdolreza Hajipour
EDUCATION:
1970-1974               High School, Shahpour high school, Kazerun, IR, Iran
1975-1979               B.S., Chemistry, Department of Chemistry, Isfahan University, Isfahan, I.R. Iran
1981-1983               M.S., Organic Chemistry, Synthesis, Shiraz University, Shiraz, I.R. Iran
Thesis Title: “Synthesis of 2,6,7,11-Tetraphenyl Isobenzofuran B Cyclobutadiene”
Advisor: Professor Habib Firouzabadi
1990-1994               Ph.D., Organic Chemistry, Wollongong University, Australia
Dissertation Title: “Asymmetric Synthesis of Chiral Amines and Benzazepine Alkaloids from Chiral Sulfoxides”
Advisor: Professor Stephen G. Pyne

POSITIONS:
09/94-11/98            Assistant Professor, Isfahan University of Technology
12/98-02/03            Associate Professor, Isfahan University of Technology
03/03-present        Professor, Isfahan University of Technology
02/01-03/02            Visiting Scientist, University of Wisconsin Medical School, Madison, WI
04/02-09/02            Associate Researcher, University of Wisconsin Medical School, Madison, WI
10/02-1/05              Associate Scientist, University of Wisconsin Medical School, Madison, WI
1/04 to present      Senior Scientist, University of Wisconsin Medical School, Madison, WI
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Chitosan (CS) is a porous, self-standing, nanofibrillar microsphere that can be used as a metal carrier. Amino groups on CS enable to modulate cobalt coordination using a safe organic ligand (methyl salicylate). This catalyst efficiently promotes Heck cross-coupling of a large library of functional substrates under mild and sustainable conditions (polyethylene glycol as solvent at 80 °C in a short time (1 h)). The cobalt complex was also used as a heterogeneous, efficient, inexpensive, and green catalyst for Sonogashira cross-coupling reactions. The reactions of various aryl halides and phenylacetylene provided the corresponding products in moderate to good yields. More importantly, this phosphine, copper, and palladium-free catalyst was stable under the reaction conditions and could be easily reused using an external magnet for at least five successive runs without a discernible decrease in its catalytic activity.
Reaction yields were analyzed by gas chromatography (GC, BEIFEN-3420, detector type: FID, TCD equipped with Nukol™ capillary GC column, size × I.D. 30 m × 0.25 mm, df 0.25 μm). 2,3-Dimethylnaphthalene as was used as internal standard. The gas flow rate of 2 mL min-1; and oven temperature at 80 oC for 15 min and then increased to 170 oC.
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General procedure for catalyst preparation The magnetic nanoparticles (MNPs) were prepared according to the method reported in literature64 based on the precipitation of magnetite nanoparticles from a mixture of iron(III) chloride and iron(II) sulfate by ammonia (25% solution in water). Subsequently, in a round-bottom flask equipped with a mechanical stirrer and condenser, a mixture of magnetic nanoparticles and sodium sulfate (20%, w/v) was added to a solution of chitosan (1%, w/v) in acetic acid (2%, w/v) under stirring. Stirring was continued for 1 h to obtain the aqueous suspension of MNPs/CS. Then, the magnetic nanoparticles were separated from the reaction mixture by an external permanent magnet, washed with ethanol and methanol several times, and dried under vacuum at 70 °C. For the preparation of supported methyl salicylate ligands, a solution of ethanol suspension of MNPs/CS (1.5 g per 10 mL) was added to methyl salicylate (6.5 mmol), and the mixture was stirred at 60 °C for 24 h. The final Co-MS@MNPs/CS was obtained as a brown solid by the addition of CoCl2·6H2O (4.2 mmol) dissolved in 10 mL of ethanol to disperse the mixture of MNPs/CS-MS (1.01 g) in ethanol (5 mL) and stirred at 60 °C for 18 h. The resulting complex was collected by an external permanent magnet, washed with ethanol (3 × 10 mL) to remove the unreacted materials, and finally dried in air (89% yield based on the amount of Co in the catalyst determined by ICP).
General procedure for the Heck reaction In a round-bottom flask equipped with a mechanical stirrer, a mixture of K3PO4 (4 eq.), olefin (1.1 mmol), and aryl halide (1 mmol) in PEG (3 mL) was added to 5 mg of catalyst (1.1 mol% of Co) and the flask was equipped with a condenser for refluxing. The abovementioned mixture was heated at 80 °C in an oil bath. The progress of the reaction was monitored by TLC (hexane/EtOAc, 80 : 20) and gas chromatography (GC). After the completion of the reaction, the mixture was diluted with dichloromethane and water. The organic layer was washed with brine, dried over anhydrous MgSO4, and concentrated under reduced pressure. The residue was purified by column chromatography. The products were characterized by comparing their physical properties, such as m.p., IR, 1 H, and 13C NMR spectra, with those reported in literature
General procedure for Sonogashira reaction In a round-bottom flask equipped with a mechanical stirrer, phenyl acetylene (1.2 mmol), aryl halide (1.0 mmol), catalyst (10 mg), and KOH (2 eq.) in DMSO (3 mL) were stirred under an air atmosphere at 140 °C. The progress of the reaction was monitored using TLC and GC. After the completion of the reaction, the mixture was diluted with dichloromethane and water. The organic layer was washed with brine, dried over anhydrous MgSO4, and concentrated under reduced pressure. The product was isolated by column chromatography to afford the corresponding products in 55–80% yields. The products were characterized by comparing their physical properties, such as m.p, IR, 1 H, and 13C NMR spectra with those reported in literature.
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Endogenous water-triggered and ultrasound accelerated synthesis of 1,5-disubstituted tetrazoles via a solvent and catalyst-free Ugi-azide reaction

 

Endogenous water-triggered and ultrasound accelerated synthesis of 1,5-disubstituted tetrazoles via a solvent and catalyst-free Ugi-azide reaction

Green Chem., 2017, Advance Article
DOI: 10.1039/C6GC03324E, Communication
Shrikant G. Pharande, Alma Rosa Corrales Escobosa, Rocio Gamez-Montano
An ultrasound accelerated, environmentally benign Ugi-azide based method was developed for the synthesis of 1,5-disubstituted tetrazoles under solvent and catalyst-free conditions.

Endogenous water-triggered and ultrasound accelerated synthesis of 1,5-disubstituted tetrazoles via a solvent and catalyst-free Ugi-azide reaction

 *Corresponding authors
aDepartamento de Química, División de Ciencias Naturales y Exactas, Universidad de Guanajuato, Noria Alta S/N, Col. Noria Alta, Guanajuato, México
E-mail: rociogm@ugto.mx
Green Chem., 2017, Advance Article

DOI: 10.1039/C6GC03324E,  http://pubs.rsc.org/en/Content/ArticleLanding/2017/GC/C6GC03324E?utm_source=feedburner&utm_medium=feed&utm_campaign=Feed%3A+rss%2FGC+%28RSC+-+Green+Chem.+latest+articles%29#!divAbstract

A novel, sustainable, endogenous water-triggered, environmentally friendly, high substrate scope, efficient, solvent-free and catalyst-free Ugi-azide based method for the synthesis of 1,5-disubstituted tetrazoles is described.
Shrikant Pharande

Shrikant Pharande

Doctoral student

Research experience

  • Apr 2014–Jun 2014, Research chemist
    TCG Lifesciences · pune
  • Mar 2012–Dec 2013, project assistant
    CSIR – National Chemical Laboratory, Pune · Organic Chemistry Division (NCL)
N-((1-(tert-butyl)-1H-tetrazol-5-yl)(4-chlorophenyl)methyl)aniline (4a)
Based on GP, 100 mg 4-Chlorobenzaldehyde (0.71 mmol), 0.065 cm3 aniline (0.71 mmol), 0.080 cm3 ter. Butyl isocyanide (0.71 mmol), and 0.093 cm3 TMS-azide (0.71 mmol) were reacted together to afford 237 mg (97%) as a white solid.
Melting range 144-145oC,
Rf = 0.45 (Hexane-AcOEt = 7/3 V/V),
1H NMR (500 MHz, CDCl3) δ 7.34 – 7.29 (m, 4H), 7.18 – 7.13 (m, 2H), 6.79 – 6.75 (m, 1H), 6.65 (d, J = 7.6 Hz, 2H), 6.11 (d, J = 6.2 Hz, 1H), 4.78 (d, J = 5.6 Hz, 1H), 1.71 (s, 9H);
13C NMR (126 MHz, CDCl3) δ 155.03, 145.54, 136.81, 134.71, 129.62, 129.43, 129.19, 119.64, 114.42, 61.95, 53.93, 30.29;
FT-IR (ATR) νmax/cm-1 3330.5, 3052.5, 2940.9, 1603.6, 1284.1;
HRMS (ESI+): m/z calcd. for C18H20ClN5 + 342.1480, found 342.1474
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Activated nanostructured bimetallic catalysts for C-C coupling reactions: recent progress

Catal. Sci. Technol., 2016, 6,3341-3361
DOI: 10.1039/C5CY02225H, Minireview
Rohit Kumar Rai, Deepika Tyagi, Kavita Gupta, Sanjay Kumar Singh
This minireview highlights the recent progress made in the last decade towards the development of activated bimetallic alloy nanoparticle catalysts for C-C coupling reactions, including asymmetric C-C bond coupling reactions.
Minireview

Activated nanostructured bimetallic catalysts for C–C coupling reactions: recent progress

*Corresponding authors
aDiscipline of Chemistry, Indian Institute of Technology (IIT) Indore, Simrol, Indore, 452 020 India
bCentre for Material Science and Engineering, Indian Institute of Technology (IIT) Indore, Simrol, Indore, 452 020 India
E-mail: sksingh@iiti.ac.in
Fax: +91 731 2438 933
Catal. Sci. Technol., 2016,6, 3341-3361

DOI: 10.1039/C5CY02225H

Catalysts based on bimetallic nanoparticles have received tremendous scientific and industrial attention and are established as an important class of active catalysts. These catalysts displayed improved catalytic activities compared to their monometallic counterparts for several reactions, which is attributed to their highly modified surface structures (electronic and geometrical) due to the synergic cooperation between the two metals of the bimetallic nanoparticle catalyst. Moreover, such synergic interactions are more prominent in alloy nanoparticle catalysts, where the probability of metal-to-metal interactions is higher in comparison with other systems (such as core–shell nanoparticles). This minireview highlights the recent progress made in the last decade towards the development of activated bimetallic alloy nanoparticle catalysts for C–C coupling reactions, including asymmetric C–C bond coupling reactions. Herein, the influence of the modified electronic structures of the newly formed bimetallic alloy nanoparticle catalysts on their activated catalytic performance is also discussed extensively.
Dr. Sanjay Kumar Singh
Assistant Professor
Chemistry
Organometallics and Nanotech Catalysis Group
Discipline of Chemistry, School of Basic Sciences
Dr. Sanjay Kumar Singh
Assistant Professor
Chemistry
sksingh[at]iiti.ac.in
Mr. Rohit Rai
Ph.D. Student (CSIR-SRF), Since Jan. 2013
He obtained his Masters degree in Organic Chemistry from BHU Varanasi in the year 2012. He is presently engaged in the development of nanoparticle based heterogeneous catalysts for important organic reactions.
rohitrai47[at]gmail.com; phd12123108[at]iiti.ac.in

 

Ms. Deepika Tyagi
Ph.D. Student (UGC-SRF), Since Jan. 2013
She obtained her Masters degree in Organic Chemistry from C.C.S. Meerut University in the year 2011. She is presently engaged in the development of homogeneous catalysts based on organometallic and coordination complexes for important organic reactions.
tyagi.deepika30[at]gmail.com; phd12123112[at]iiti.ac.in
Deepika Tyagi Deepika Tyagi
Ph.D. Scholar
Dr. Sanjay Research Group
M-Block, IIT Indore
Email: phd12123112[at]iiti.ac.in
Research Topic: Development of homogeneous catalysts based on metal complexes for important organic reactions
Ms. Kavita Gupta
Ph.D. Student (CSIR-SRF), Since Jul., 2013
She obtained her Masters degree in Organic Chemistry from Dr. B.R.A. University, Agra in the year 2010. She is presently engaged in the development of catalytic systems for the conversion of bioderived molecules to bio-fuel components and other important products.
phd1301131005[at]iiti.ac.in
ALL AUTHORS
//////Activated nanostructured,  bimetallic catalysts,  C-C coupling reactions,  recent progress

Mechanisms and reactivity differences of proline-mediated catalysis in water and organic solvents

Catal. Sci. Technol., 2016, 6,3378-3385
DOI: 10.1039/C6CY00033A, Paper
Gang Yang, Lijun Zhou
Several key issues regarding the mechanisms of proline catalysis are unravelled by first-principles calculations that can guide future catalyst design.

Mechanisms and reactivity differences of proline-mediated catalysis in water and organic solvents

Gang Yang*a and   Lijun Zhoua  
*Corresponding authors
aCollege of Resource and Environment & Chongqing Key Laboratory of Soil Multi-scale Interfacial Process, Southwest University, Chongqing, PR China
E-mail: theobiochem@gmail.com
Fax: +86 023 68250444
Tel: +86 023 68251545
Catal. Sci. Technol., 2016,6, 3378-3385

DOI: 10.1039/C6CY00033A

Proline is an efficient and versatile catalyst for organic reactions while a number of issues remain controversial. Here, ab initio and density functional calculations were used to unravel a few key issues of catalytic mechanisms in water and organic solvents. Zwitterionic proline that predominates in water and DMSO is assumed to be the active conformation for catalysis, and reactivity differences in two solvents are revealed. Meanwhile, an abundance of experimental observations can be finely interpreted by the present computational results, including those seemingly contradictory. Although bearing lower activation barriers than that in DMSO, the production of enamines and further aldol products in water will be blocked at an early stage (J. Am. Chem. Soc., 2006, 128, 734) because the reaction in water is significantly driven towards acetyl formation that is kinetically and thermodynamically preferred. Due to significant promotion of the rate-determining proton transfer step, aldol reactions in organic solvents can be obviously initiated by the addition of some water (Angew. Chem., Int. Ed., 2004, 43, 1983). In order to show catalytic effects in water (an obviously environmentally benign solvent), proline has to be structurally modified so that canonical structures can be the principal (or sole) conformations, which is in line with the analyses of all proline-based catalysts available in water (e.g., J. Am. Chem. Soc., 2006, 128, 734, Catal. Commun., 2012, 26, 6). Thus, the present results provide insightful clues to mechanisms of proline-mediated catalysis as well as future design of more efficient catalysts.
//////Mechanisms,  reactivity,  differences,  proline-mediated catalysis, water ,  organic solvents

Intensified biocatalytic production of enantiomerically pure halophenylalanines from acrylic acids using ammonium carbamate as the ammonia source

Catal. Sci. Technol., 2016, Advance Article
DOI: 10.1039/C6CY00855K, Communication
Nicholas J. Weise, Syed T. Ahmed, Fabio Parmeggiani, Elina Siirola, Ahir Pushpanath, Ursula Schell, Nicholas J. Turner
An industrial-scale method employing a phenylalanine ammonia lyase enzyme

Intensified biocatalytic production of enantiomerically pure halophenylalanines from acrylic acids using ammonium carbamate as the ammonia source

*Corresponding authors
aManchester Institute of Biotechnology & School of Chemistry, University of Manchester, 131 Princess Street, Manchester, UK
E-mail: nicholas.turner@manchester.ac.uk
bJohnson Matthey Catalysts and Chiral Technologies, 28 Cambridge Science Park, Milton Road, Cambridge, UK
Catal. Sci. Technol., 2016, Advance Article

DOI: 10.1039/C6CY00855K

SEE

An intensified, industrially-relevant strategy for the production of enantiopure halophenylalanines has been developed using the novel combination of a cyanobacterial phenylalanine ammonia lyase (PAL) and ammonium carbamate reaction buffer. The process boasts STYs up to >200 g L−1 d−1, ees ≥ 98% and simplified catalyst/reaction buffer preparation and work up.

STR1

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///////Intensified,  biocatalytic production, enantiomerically pure,  halophenylalanines,  acrylic acids,  ammonium carbamate, ammonia source

Plastically deformed Cu-based alloys as high-performance catalysts for the reduction of 4-nitrophenol

Catal. Sci. Technol., 2016, Advance Article
DOI: 10.1039/C6CY00734A, Paper
Eredzhep Menumerov, Kyle D. Gilroy, Maryam Hajfathalian, Colin J. Murphy, Erica R. McKenzie, Robert A. Hughes, Svetlana Neretina
Plastically deformed mesoscopic structures exposed to an etching procedure are demonstrated as highly catalytic in the reduction of 4-nitrophenol.

Plastically deformed Cu-based alloys as high-performance catalysts for the reduction of 4-nitrophenol

Plastically deformed Cu-based alloys as high-performance catalysts for the reduction of 4-nitrophenol

The severe plastic deformation of metals leads to the formation of nanotextured surfaces as well as the retention of significant strain energy, characteristics which are known to promote catalytic activity. Here, we demonstrate plastically deformed surfaces of copper and copper-based alloys as being highly catalytic using the well-studied model catalytic reaction which reduces 4-nitrophenol to 4-aminophenol by borohydride. Among the materials studied, the most catalytically active is formed in a two-step process where metal chips are mechanically sheared from a Cu–Sn alloy containing precipitates and then exposed to an etchant which removes the precipitates from the exposed surface. The so-formed structures exhibit exceedingly high catalytic activity and set new benchmarks when incorporated into a fixed-bed reactor. The formation of catalytically active sites is shown to be strongly dependent on the presence of the precipitates during the deformation process, achieving an order of magnitude increase in the reaction rate constant when compared to similarly formed Cu–Sn catalysts lacking these precipitates. The work, therefore, demonstrates a new approach for generating catalytically active sites which may be applicable to other alloy combinations.

 

////Plastically deformed, Cu-based alloys,  high-performance catalysts,  reduction, 4-nitrophenol

Synthesis in mesoreactors: Ru(porphyrin)CO-catalyzed aziridination of olefins under continuous flow conditions

Catal. Sci. Technol., 2016, Advance Article
DOI: 10.1039/C6CY00207B, Communication
S. Rossi, A. Puglisi, M. Benaglia, D. M. Carminati, D. Intrieri, E. Gallo
The Ru(porphyrin)CO-catalyzed addition of aryl azides to styrenes to afford N-aryl aziridines was successfully performed for the first time in mesoreactors under continuous flow conditions.

Synthesis in mesoreactors: Ru(porphyrin)CO-catalyzed aziridination of olefins under continuous flow conditions

S. Rossi,a   A. Puglisi,*a   M. Benaglia,*a   D. M. Carminati,a  D. Intrieria and   E. Galloa  
*Corresponding authors
aDipartimento di Chimica, Università degli Studi di Milano, Via Golgi 19, Milano, Italy
E-mail: alessandra.puglisi@unimi.it, maurizio.benaglia@unimi.it
Catal. Sci. Technol., 2016, Advance Article

DOI: 10.1039/C6CY00207B

The Ru(porphyrin)CO-catalyzed addition of aryl azides to styrenes to afford N-aryl aziridines was successfully performed for the first time in mesoreactors under continuous flow conditions. Mesofluidic technology allowed for a rapid screening of different parameters and a quick identification of the optimized reaction conditions.

 

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/////Synthesis in mesoreactors, Ru(porphyrin)CO-catalyzed,  aziridination of olefins,  continuous flow conditions

Iron bis(oxazoline) complexes in asymmetric catalysis

GA

Iron bis(oxazoline) complexes in asymmetric catalysis

Asymmetric reactions catalyzed by iron complexes have attracted considerable attention because iron is a ubiquitous, inexpensive, and environmentally benign metal. Various chiral iron complexes can be prepared from bis(oxazoline) ligands and be used in asymmetric reactions. This overview charts the development and application of chiral iron bis(oxazoline) and pyridine-2,6-bis(oxazoline) catalysts through their most prominent and innovative uses in asymmetric catalysis, especially in Lewis acid and oxidation catalysis.
Catal. Sci. Technol., 2015, Advance Article
DOI: 10.1039/C5CY01357G, Minireview
Thierry Ollevier
Asymmetric reactions catalyzed by iron complexes have attracted considerable attention because iron is a ubiquitous, inexpensive, and environmentally benign metal. This overview charts the development and application of chiral iron bis(oxazoline) and pyridine-2,6-bis(oxazoline) catalysts through their most prominent and innovative uses in asymmetric catalysis, especially in Lewis acid and oxidation catalysis.

Minireview

Iron bis(oxazoline) complexes in asymmetric catalysis
Thierry Olleviera

aDépartement de chimie, Pavillon Alexandre-Vachon, Université Laval, 1045 avenue de la Médecine, Québec (Qc) G1V 0A6, Canada
E-mail: thierry.ollevier@chm.ulaval.ca
Catal. Sci. Technol., 2015, Advance Article
DOI: 10.1039/C5CY01357G

http://pubs.rsc.org/en/Content/ArticleLanding/2015/CY/C5CY01357G?utm_source=feedburner&utm_medium=feed&utm_campaign=Feed%3A+rss%2Fcy+%28RSC+-+Catalysis+Science+%26+Technology+latest+articles%29#!divAbstract

 

 

 

Basics……………

 

Bisoxazoline ligand

In chemistry, bis(oxazoline) ligands (often abbreviated BOX ligands) are a class of privileged chiral ligands containing two oxazoline rings. They are typically C2‑symmetric and exist in a wide variety of forms; with structures based around CH2 or pyridine linkers being particularly common (often generalised BOX and PyBOX respectively). The coordination complexes of bis(oxazoline) ligands are used extensively in asymmetric catalysis.

BOX and PyBOX.png

Synthesis

Further information: Synthesis of oxazoline rings

The synthesis of oxazoline rings is well established and in general proceeded via the cyclisation of a 2‑amino alcohol with any of a number of suitable functional groups. In the case of bis(oxazoline)s, synthesis is most conveniently achieved by using bi-functional starting materials; as this allows both rings to be produced at once. Of the materials suitable, dicarboxylic or dinitrile compounds are the most commonly available and hence the majority bis(oxazoline) ligands are produced from these materials.

BOX and PyBOX general synthesis.png

Part of the success of the BOX and PyBOX motifs lies in their convenient one step synthesis from malononitrile and dipicolinic acid, which are commercially available at low expense. Chirality is introduced with the amino alcohols, as these are prepared from amino acids and hence are chiral (e.g. valinol).

The advantages C2-symmetry

The left hand structure has a C2‑rotational axis whereas the right hand structure is asymmetric. Arrows indicate the theoretical attack trajectories of reagents, identical colours lead to identical transition states (and hence products) with red arrows being disfavoured due to steric repulsion.

In bis(oxazoline) complexes the metal is held close to the stereogenic centres, which will strongly influence the enantioselectivity of any process taking place there. However the C2‑symmetry of the ligand is also important in controlling this enantioselectivity.

While the presence of any symmetry element within a ligand intended for asymmetric induction might appear counterintuitive, asymmetric induction only requires that the ligand be chiral (i.e. have no improper rotation axis); it does not have to be asymmetric (i.e. devoid of any symmetry element). C2‑symmetry actually improves the enantioselectivity of the complex by reducing the number of transition states with a unique geometry. Steric/kinetic factors then usually favour the formation of a single product.[1] The benefits of C2‑symmetry in bis(oxazoline) ligands have been reviewed in depth[2]

In general, for methylene bridged BOX ligands the stereochemical outcome is consistent with a twisted square planar intermediate that was proposed based on related crystal structures.[3][4] The substituent at the oxazoline’s 4-position blocks one enantiotopic face of the substrate, leading to enantioselectivity. This is demonstrated in the following aldol-type reaction,[5] but is applicable to a wide variety of reactions such as Mannich-type reactions,[6] ene reaction,[7] Michael addition,[8] Nazarov cyclization,[9] and hetero-Diels-Alder reaction.[10]

Box Stereochemical model

On the other hand, two-point binding on a Lewis acid bearing the meridially tridentate PyBOX ligand would result in a square pyramidal complex. A study using (benzyloxy)acetaldehyde as the electrophile showed that the stereochemical outcome is consistent with the carbonyl oxygen binding equatorially and the ether oxygen binding axially.[11]

PyBox Stereochemical model

Catalytic applications

Metal complexes incorporating bis(oxazoline) ligands are effective for an wide range of asymmetric catalytic transformations and have been the subject of numerous literature reviews.[12][13][14] The neutral character of bis(oxazoline)s makes them well suited to use with noble metals, with copper complexes being particularly common.[13] Their most important and commonly used applications are in carbon–carbon bond forming reactions.

Carbon–carbon bond forming reactions

bis(oxazoline) ligands have been found to be effective for a range of asymmetric cycloaddition reactions, this began with the very first application of BOX ligands in carbenoid cyclopropanations[15] and has been expanded to include 1,3-Dipolar cycloaddition and Diels-Alder reactions. Bisoxazoline ligands have also been found to be effective for Aldol, Michael and Ene reactions, amongst many others

Evans 1997:[16] BOX assisted Aldol reaction

Aggarwal 1998:[17] BOX assisted Diels-Alder reaction resulting in verbenone synthesis. The final conversion with diphenylphosphoryl azide involves a modified Curtius rearrangement

Other reactions

The success of bis(oxazoline) ligands for carbenoid cyclopropanations led to their application for aziridination. Another common reaction is hydrosilylation, which dates back to the first use of PyBOX ligands.[18] Other niche applications include as fluorination catalysts[19] and for Wacker-type cyclisations.[20]

Nishiyama 1989:[18] Enantioselective hydrosilylation

History

The development of bis(oxazoline) ligands

Oxazoline ligands were first used for asymmetric catalysis in 1984 when Brunner et al. showed a single example, along with a number of Schiff bases, as being effective for enantioselective carbenoid cyclopropanation.[21] Schiff bases were prominent ligands at the time, having been used by Ryōji Noyori during the discovery of asymmetric catalysis in 1968[22] (for which he and William S. Knowles would later be awarded the Nobel Prize in Chemistry). Brunner’s work was influenced by that of Tadatoshi Aratani, who had worked with Noyori,[23] before publishing a number of papers on enantioselective cyclopropanation using Schiff bases.[24][25][26]

In this first usage the oxazoline ligand performed poorly, giving an ee of 4.9% compared to 65.6% from one of the Schiff base ligands. However Brunner reinvestigated oxazoline ligands during research into the monophenylation of diols, leading to the development of chiral pyridine oxazoline ligands, which achieved ee’s of 30.2% in 1986[27] and 45% in 1989.[28] In the same year Pfaltz et al. reported the use of C2‑symmetric semicorrin ligands for enantioselective carbenoid cyclopropanations, achieving impressive results with ee’s of between 92-97%.[29] Reference was made to both Brunner’s and Aratani’s work, however the design of the ligands was also largely based on his earlier work with various macrocycles.[30] A disadvantage of these ligands however, was that they required a multi-step synthesis with a low overall yield of approximately 30%.

C2-symmetric bis(oxazoline) ligands with axial chirality

Brunner’s work led to the development of very first bisoxazolines by Nishiyama et al., who synthesised the first PyBox ligands in 1989. These ligands were used in the hydrosilylation of ketones; achieving ee’s of up to 93%[18] The first BOX ligands where reported a year later by Masamune et al.[15] and were first used in copper catalysed carbenoid cyclopropanation reactions; achieving ee’s of up to 99% with 1% molar loadings. This was a remarkable result for the time and generated significant interest in the BOX motif. As the synthesis of 2-oxazoline rings was already well established at this time (literature reviews in 1949[31] and 1971[32]), research proceeded quickly, with papers from new groups being published within a year.[33][34] and review articles being published by 1996.[35] Today a considerable number of bis(oxazoline) ligands exist; structurally these are still largely based around the classic BOX and PyBOX motifs, however they also include a number of alternative structures, such as axially chiral compounds.[36][37]

 

References

 

 

  1. Ohta, Tetsuo; Ito, Junji; Hori, Kazushige; Kodama, Hidehiko; Furukawa, Isao (2000). “Lanthanide-catalyzed asymmetric 1,3-dipolar cycloaddition of nitrones to alkenes using 3,3′-bis(2-oxazolyl)-1,1′-bi-2-naphthol (BINOL-Box) ligands”. Journal of Organometallic Chemistry 603 (1): 6–12. doi:10.1016/S0022-328X(00)00024-3.

MORE…………..

Aza-bis(oxazolines) – New Chiral Ligands for Asymmetric Catalysis

M. Glos, O. Reiser, Org. Lett. 2000, 2, 2045-2048
Web edition: http://dx.doi.org/10.1021/ol005947k

graphical abstract

Aza-bis(oxazolines) are introduced as chiral ligands for asymmetric catalysis combining the advantages of easy availability of bis(oxazolines) and backbone variability of aza-semicorrins. Especially, the title ligands could be attached to a polymeric support, which allowed the development of easily recoverable copper(I)-catalysts for asymmetric cyclopropanation reactions.

 

 

 

 

 

 

 

Synthesis of Polymer Bound Azabis(oxazoline) Ligands and their Application in Asymmetric Cyclopropanations

H. Werner, C. I. Herrerí­as, M. Glos, A. Gissibl, J. M. Fraile, I. Pérez, J. A. Mayoral, O. Reiser, Adv. Synth. Catal. 2006, 348, 125-132
Web edition: http://dx.doi.org/10.1002/adsc.200505197

graphical abstract

Aza(bisoxazoline) ligands were attached to various polymeric supports and the resulting immobilized ligands were evaluated in copper(I)-catalyzed asymmetric cyclopropanations. The efficiency of these transformations depends greatly on the polymeric support, on the protocol being applied for the immobilization of the ligands, and on the preparation of the catalysts.

 

 

Cu(II)-Aza(bisoxazoline)-Catalyzed Asymmetric Benzoylations

A. Gissibl, M. G. Finn, O. Reiser, Org. Lett. 2005, 7, 2325-2328
Web edition: http://dx.doi.org/10.1021/ol0505252

graphical abstract

Racemic 1,2-diols and a-hydroxy carbonyl compounds can be asymmetrically benzoylated in a kinetic resolution in the presence of various Cu(II)-azabis(oxazoline) catalysts. A novel bisbenzyl substituted aza(bisoxazoline) ligand proved to be especially effective when immobilized on MeOPEG5000, giving 91 – ≥99% ee in 37 – 49% yield for each of five sequential reactions.

 

The role of binding constant in the efficiency of chiral catalysts immobilized by electrostatic interactions. The case of azabis(oxazoline)-copper complexes

J. M. Fraile, J. I. Garcí­a, C. I. Herrerí­as, A. Mayoral, O. Reiser, A. Socuéllamos, H. Werner, Chem. Eur. J. 2004, 10, 2997-3005
Web edition: http://dx.doi.org/10.1002/chem.200305739

graphical abstract

Azabis(oxazoline)-copper complexes are considerably more stable than the analogous bis(oxazoline)-copper complexes, as shown by theoretical calculations. The enhanced stability allows the efficient immobilization by means of electrostatic interactions with different anionic supports, such as clays and nafion-silica nanocomposites, without the loss of ligand observed with bis(oxazolines). In this way, enantioselectivities around 90% ee are obtained in the cyclopropanation reaction

 

 

Improved Synthesis of Aza-bis(oxazoline) Ligands

H. Werner, R. Vicha, A. Gissibl, O. Reiser, J. Org. Chem. 2003, 68, 10166-10168
Web edition: http://dx.doi.org/10.1021/jo0350920

graphical abstract

A straightforward synthesis of chiral aza-bis(oxazoline) (Azabox) ligands from commercial available aminoalcohols is described. The new protocol allows access to previously reported Azabox ligands in considerably improved yields but also to new derivatives, including non C2-symmetrical ones.

 

Research Group Prof. Reiser

Prof. Dr.
Oliver Reiser

 

Secretary

Phone +941/943-4630
Fax +941/943-4121

http://www-oc.chemie.uni-regensburg.de/reiser/forschung/catalysis_e.php

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Two-Step Cyanomethylation Protocol: Convenient Access to Functionalized Aryl- and Heteroarylacetonitriles

Figure

Two-Step Cyanomethylation Protocol: Convenient Access to Functionalized Aryl- and Heteroarylacetonitriles

Publication Date (Web): January 15, 2015 (Letter)
DOI: 10.1021/ol503479g

http://pubs.acs.org/doi/abs/10.1021/ol503479g

 

A two-step protocol has been developed for the introduction of cyanomethylene groups to metalated aromatics through the intermediacy of substituted isoxazoles. A palladium-mediated cross-coupling reaction was used to introduce the isoxazole unit, followed by release of the cyanomethylene function under thermal or microwave-assisted conditions. The intermediate isoxazoles were shown to be amenable to further functionalization prior to deprotection of the sensitive cyanomethylene motif, allowing access to a wide range of aryl- and heteroaryl-substituted acetonitrile building blocks.

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