nazario martín - jst
TRANSCRIPT
![Page 1: Nazario Martín - JST](https://reader031.vdocuments.co/reader031/viewer/2022012105/61dbf60c44f3dd3b68626795/html5/thumbnails/1.jpg)
ENANTIOSELECTIVE SYNTHESIS OF FULLERENES
Nazario Martín Departamento de Química Orgánica. Facultad de Ciencias Químicas
Universidad Complutense de Madrid/IMDEA-Nanociencia
![Page 2: Nazario Martín - JST](https://reader031.vdocuments.co/reader031/viewer/2022012105/61dbf60c44f3dd3b68626795/html5/thumbnails/2.jpg)
[60]Fullerene
• Among the most studied molecules • Benchmark for other carbon nanoforms • Potential applications in different fields
![Page 3: Nazario Martín - JST](https://reader031.vdocuments.co/reader031/viewer/2022012105/61dbf60c44f3dd3b68626795/html5/thumbnails/3.jpg)
Fullerenes for Mimiking Photosynthesis
e-
1a 2: M = H2
1b 2: M = Zn
hn
Angew. Chem. Int. Ed. 2006, 45, 4637
Chem. Sci., 2011, 2, 1677
Chem. Rev. 1998, 98, 2527-2547
Energy Environ. Sci., 2011, 4, 604
![Page 4: Nazario Martín - JST](https://reader031.vdocuments.co/reader031/viewer/2022012105/61dbf60c44f3dd3b68626795/html5/thumbnails/4.jpg)
Fullerenes for Organic Photovoltaics
With V. Dyakonov et al., Adv. Funct. Mater. 2005, 15, 1979 With E. Palomares et al., Adv. Funct. Mater. 2010, 16, 2695
With J. Bisquert et al., J. Phys. Chem. Lett. 2010, 1, 2566
With D. Vanderzande et al., J. Phys. Chem. C 2011, 115, 10873
P3HT
DPM-12
C12H25O OC12H25
S
R
n
e
Energy Conversion Efficiency of ~3 %
![Page 5: Nazario Martín - JST](https://reader031.vdocuments.co/reader031/viewer/2022012105/61dbf60c44f3dd3b68626795/html5/thumbnails/5.jpg)
Fullerenes for Nanoscience
Angew. Chem. Int. Ed., 2007, 46, 7874 Chem. Rev. 2009, 109, 2081–2091 Nature Chem. 2010, 2, 374
STM images (taken at 170 K) in UHV with the surface held at 300 K.
Preferential nucleation at the elbow of the “herringbone” reconstruction
This supramolecular ordering is the result of two combined effects: 1) The interaction of the molecular tail with the surface 2) The ,-interactions among the C60 cages
FCC
HCP
HCP
DW
DW
20 25 30 35 40 45 50 55 60 65 70
0
20
40
Hei
ght (
Å)
Distance (Å)
![Page 6: Nazario Martín - JST](https://reader031.vdocuments.co/reader031/viewer/2022012105/61dbf60c44f3dd3b68626795/html5/thumbnails/6.jpg)
STM image of a single molecule of C60-Fl2-C60 (1.0 V and I = 0.5 nA)
With N. Agraït et al. Nano Lett. 2011,11, 2236–2241 J. Phys. Chem. C 2011, 115, 17973–17978
Unambiguous One-Molecule Conductance Measurements under Ambient Conditions
Fullerenes for Organic Electronics
![Page 7: Nazario Martín - JST](https://reader031.vdocuments.co/reader031/viewer/2022012105/61dbf60c44f3dd3b68626795/html5/thumbnails/7.jpg)
Hexaaducts of C60: a highly versatile multivalent scaffold
With J. Rojo, Chem. Commun. 2010, 46, 3860 – 3862 Chem. Eur. J. 2011, 17, 766 – 769
Fullerenes for Biomedical Applications
Biomacromolecules 2013, 14, 431−437
![Page 8: Nazario Martín - JST](https://reader031.vdocuments.co/reader031/viewer/2022012105/61dbf60c44f3dd3b68626795/html5/thumbnails/8.jpg)
Representative examples of covalently connected exTTFs
J. Am. Chem. Soc. 2010, 132, 8048-8055 J. Am. Chem. Soc. 2012, 134, 16103−16106
J. Am. Chem. Soc. 2004, 126, 5340-5341 Chem. Eur. J. 2005, 11, 4819-4834 Chem. Commun. 2006, 30, 3202
Chem. Eur. J. 2008, 14, 6379-6390
J. Am. Chem. Soc. 2009, 131, 12218-12229
Energy Environ. Sci. 2011, 4, 765 Angew. Chem. Int. Ed. 2006, 45, 4478-4482
Nano Lett. 2007, 7, 2602
Unpublished results
![Page 9: Nazario Martín - JST](https://reader031.vdocuments.co/reader031/viewer/2022012105/61dbf60c44f3dd3b68626795/html5/thumbnails/9.jpg)
3.495 3.558 3.599
a) b) c)
Angew. Chem. Int. Ed. 2007, 46, 1847
Strategies for Concave-Convex Supramolecular Ensembles
J. Am. Chem. Soc. 2006, 128, 7172 Angew. Chem. Int. Ed. 2009, 48, 815
J. Am. Chem. Soc., 2008, 130, 10674
J. Am. Chem. Soc. 2010, 132, 1772 J. Am. Chem. Soc. 2011, 133, 3184 J. Am. Chem. Soc. 2010, 132, 5351
Angew. Chem. Int. Ed. 2008, 47, 1094
J. Am. Chem. Soc., 2010, 132, 17387
Chem. Commun., 2008, 5993.
Chem. Sci., 2011, 2, 1384
exTTF
![Page 10: Nazario Martín - JST](https://reader031.vdocuments.co/reader031/viewer/2022012105/61dbf60c44f3dd3b68626795/html5/thumbnails/10.jpg)
hn
e- e-
hn
J. Am. Chem. Soc. 2012, 134, 16103
J. Am. Chem. Soc. 2012, 134, 9183 Submitted for publication
J. Am. Chem. Soc. 2012, 134, 19401
e- e-
hn hn
![Page 11: Nazario Martín - JST](https://reader031.vdocuments.co/reader031/viewer/2022012105/61dbf60c44f3dd3b68626795/html5/thumbnails/11.jpg)
Submitted for publication
Submitted for publication Angew. Chem. Int. Ed. 2010, 49, 9876 –9880
![Page 12: Nazario Martín - JST](https://reader031.vdocuments.co/reader031/viewer/2022012105/61dbf60c44f3dd3b68626795/html5/thumbnails/12.jpg)
Chirality in Fullerenes: • Is an important but undeveloped issue of interest in fields such as materials science and medicinal chemistry (racemic mixtures are typically used). • Enantiopure fullerenes have been made from chiral starting materials or by separating racemic mixtures. • The lack of a general enantioselective synthetic methodology has limited the use of enantiopure fullerene derivatives. • Well-defined chiral carbon atoms linked to the fullerene sphere are able to perturb the
inherent symmetry of the fullerene π-system. • It would be highly desirable to have an enantioselective catalytic synthesis of chiral fullerene derivatives.
Nature Chem., 2009, 1, 578-582
![Page 13: Nazario Martín - JST](https://reader031.vdocuments.co/reader031/viewer/2022012105/61dbf60c44f3dd3b68626795/html5/thumbnails/13.jpg)
Catalytic asymmetric 1,3-dipolar cycloadditions: α-Iminoesters as dipole precursors
• Most of the catalytic asymmetric versions are based on α-iminoesters as dipoles. • The great effectiveness of this ylide precursor is due: a) to the acidity of the enolizable Cα position b) to the formation of a rigid five membered N,O-bidentate metalated azomethine ylide Both aspects facilitate the asymmetric induction from the chiral ligand.
J. Adrio, J. C. Carretero, Chem. Commun., 2011, 47, 6784-6794
![Page 14: Nazario Martín - JST](https://reader031.vdocuments.co/reader031/viewer/2022012105/61dbf60c44f3dd3b68626795/html5/thumbnails/14.jpg)
X
X
Chiral Ligand (Differentiate the two faces
of the dipole)
Metal (AgI, ZnII, CuI/II, NiII, CaII)
1,3-Dipole
Generation of the chiral metal complex
![Page 15: Nazario Martín - JST](https://reader031.vdocuments.co/reader031/viewer/2022012105/61dbf60c44f3dd3b68626795/html5/thumbnails/15.jpg)
Chiral Catalysis in Fullerene chemistry
Non-coordinating Dipolarophile
Dipolarophiles (The heteroatom coordinates to the metal)
Chiral metal complex
Dipolarophile
![Page 16: Nazario Martín - JST](https://reader031.vdocuments.co/reader031/viewer/2022012105/61dbf60c44f3dd3b68626795/html5/thumbnails/16.jpg)
ab metallis
Nature Chem., 2009, 1, 578-582
HNRO2C Ar
(2S,5R)-trans
(2R,5S)-trans
HNAr CO2R
O
O
O
O
P
P
tBuOMe
tButBu
OMetButBu
OMetBu
OMetButBu
(R)-DTBM SegPhos
(S)-DTBM SegPhos
up to 99% of er up to 96% of er
Et3NCu(OTf)2
J. Am. Chem. Soc., 2012, 134 , 12936
Fully Stereodivergent Synthesis of Fullerenes
![Page 17: Nazario Martín - JST](https://reader031.vdocuments.co/reader031/viewer/2022012105/61dbf60c44f3dd3b68626795/html5/thumbnails/17.jpg)
Ag
P
P
Stereodifferentiation of the two faces of the azomethine ylide
C60
C60
X Blockage of the
(si,re) face
Unpublished results
N
OMe
NC
H
HO
AgP
P Ph
PhPh
Ph
![Page 18: Nazario Martín - JST](https://reader031.vdocuments.co/reader031/viewer/2022012105/61dbf60c44f3dd3b68626795/html5/thumbnails/18.jpg)
Stereodivergent Synthesis of Pyrrolidines
J. Am. Chem. Soc., 2012, 134 , 12936
cis/ trans diasteroselectivity in fullerene endo/exo diasteroselectivity in conventional olefins C-2 Carbon configuration is always mantained
![Page 19: Nazario Martín - JST](https://reader031.vdocuments.co/reader031/viewer/2022012105/61dbf60c44f3dd3b68626795/html5/thumbnails/19.jpg)
Hierarchical Selectivity in Fullerenes: Site-, Regio-, Diastereo-, and Enantiocontrol of the 1,3-Dipolar Cycloaddition to C70
Selectivity is still a major challenge in fullerene research. The careful choice of the experimental conditions affords chiral [70]fullerene derivatives with unusually high site- and regioselectivity.
Angew. Chem. Int. Ed. 2011, 50, 6060 –6064
vs
C60 C70
Double bonds closer to the polar region are the most reactive ones in C70…
![Page 20: Nazario Martín - JST](https://reader031.vdocuments.co/reader031/viewer/2022012105/61dbf60c44f3dd3b68626795/html5/thumbnails/20.jpg)
Selectivity Levels in the Asymmetric [3+2] Cycloaddition to C70
94-99%
from 80:20 to 90:10
NArO
OR+
Angew. Chem. Int. Ed. 2011, 50, 6060 –6064
![Page 21: Nazario Martín - JST](https://reader031.vdocuments.co/reader031/viewer/2022012105/61dbf60c44f3dd3b68626795/html5/thumbnails/21.jpg)
2.242
3.007 2.186
2.886
ONIOM(B3LYP/LANL2DZ:PM6) Ball&stick:tube
TSeq1 (0.0)
TSax1 (+2.1)
Asymmetric [3+2] Cycloadditions on C70: REGIOSELECTIVITY
Two aproximations depending upon the thienyl group is oriented in eq or ax on the C70
Equatorial
Axial
Equatorial aproximation is favoured
Theoretical study carried out using dppe/ Ag(I)
![Page 22: Nazario Martín - JST](https://reader031.vdocuments.co/reader031/viewer/2022012105/61dbf60c44f3dd3b68626795/html5/thumbnails/22.jpg)
Site- and Regioselectivity. Fukui indexes at the α-γ sites (The different values for the atoms predict an asynchronous reaction and a regioselectivity)
Angew. Chem. Int. Ed. 2011, 50, 6060 –6064
Fukui nucleophilic function on the carbon atoms of the dipole show an enolate-like nucleophilicity of the azomethine
![Page 23: Nazario Martín - JST](https://reader031.vdocuments.co/reader031/viewer/2022012105/61dbf60c44f3dd3b68626795/html5/thumbnails/23.jpg)
Figure. Chemical shifts of the regioisomers formed for the cis products a-f. The assignment has been made taking into account the strong deshielding effect characteristic for the polar region of C70. Meier, M. S.; Poplawska, M. P.; Compton, A. L.; Shaw, J. P.; Selegue, J. P.; Guarr, T.F., J. Am. Chem. Soc. 116, 7044-7048 (1994).
1H NMR spectra
![Page 24: Nazario Martín - JST](https://reader031.vdocuments.co/reader031/viewer/2022012105/61dbf60c44f3dd3b68626795/html5/thumbnails/24.jpg)
2.242
3.007 3.173
2.212
ONIOM(B3LYP/LANL2DZ:PM6) Ball&stick:tube
TSeq1 (0.0)
TSeq1-trans (+6.7)
Asymmetric [3+2] Cycloadditions on C70: DIASTEREOSELECTIVITY
IN OUT
Cis azomethine ylides cycloadd preferentially to trans. We supose that cis-trans equilibrium in the initial azomethine ylide is a low energy process. Thus, according to Curtin-Hammet, we only need to compare the high of both processes.
![Page 25: Nazario Martín - JST](https://reader031.vdocuments.co/reader031/viewer/2022012105/61dbf60c44f3dd3b68626795/html5/thumbnails/25.jpg)
2.242
3.007 2.909
2.223
ONIOM(B3LYP/LANL2DZ:PM6) Ball&stick:tube
TSeq1 (0.0)
TSeq2 (+1.9)
Asymmetric [3+2] Cycloadditions on C70: ENANTIOSELECTIVITY
The attack on the si,re face is not favoured. Therefore, Peq1 is the final product
![Page 26: Nazario Martín - JST](https://reader031.vdocuments.co/reader031/viewer/2022012105/61dbf60c44f3dd3b68626795/html5/thumbnails/26.jpg)
Angew. Chem. Int. Ed. 2011, 50, 6060 –6064 J. Am. Chem. Soc., 2012, 134 , 12936
de= 94-99% de= 80-94% ee= 90-99% ee= 86-99%
Diastereo and Enantioselectivity (similar to C60)
![Page 27: Nazario Martín - JST](https://reader031.vdocuments.co/reader031/viewer/2022012105/61dbf60c44f3dd3b68626795/html5/thumbnails/27.jpg)
Chaur, Melin, Ortiz, Echegoyen, Angew. Chem. Int. Ed. 2009, 48, 7514 Lu, Akasaka, Nagase, Chem. Commun. 2011, 47, 5942 Rodríguez-Fortea, Balch, Poblet, Chem. Soc. Rev. 2011, 40, 3551
Are cages of Fullerenes able to encapsulate atoms, clusters or small molecules
Endohedral Fullerenes
La@C82
![Page 28: Nazario Martín - JST](https://reader031.vdocuments.co/reader031/viewer/2022012105/61dbf60c44f3dd3b68626795/html5/thumbnails/28.jpg)
Endohedral fullerenes
- Is the reactivity of the fullerene affected by the entrapped species? -What kind of atom(s)/molecule(s) are placed inside the fullerene cage?
- Is the fullerene actually a cage or there is an interaction between the atom(s)/molecule(s) and the carbon sphere?
- The atom(s)/molecule(s) inside the sphere are static, in motion?
Gd3N-Ih@C80
![Page 29: Nazario Martín - JST](https://reader031.vdocuments.co/reader031/viewer/2022012105/61dbf60c44f3dd3b68626795/html5/thumbnails/29.jpg)
Endohedral Fullerenes Is its chemical reactivity affected?
What kind of chemical compound? It is a hydrocarbon?
H2@C60
![Page 30: Nazario Martín - JST](https://reader031.vdocuments.co/reader031/viewer/2022012105/61dbf60c44f3dd3b68626795/html5/thumbnails/30.jpg)
Enantiomeric synthesis of fulleropyrrolidine-H2@C60
Unpublished results
In collaboration with Murata’s group
H2@C60 shows the same reactivity than hollow C60
![Page 31: Nazario Martín - JST](https://reader031.vdocuments.co/reader031/viewer/2022012105/61dbf60c44f3dd3b68626795/html5/thumbnails/31.jpg)
1H-RMN (500MHz, 298K, CDCl3)
Enantiomeric synthesis of fulleropyrrolidine-H2@C60
![Page 32: Nazario Martín - JST](https://reader031.vdocuments.co/reader031/viewer/2022012105/61dbf60c44f3dd3b68626795/html5/thumbnails/32.jpg)
0
3
1
2
372.979 795.175500 600 700
Abs
Wavelength [nm]
-12.8788
14.5455
0
10
CD [mdeg]
430nm
CD
solvent: CS2/CDCl3 (1:3)
face (Re,Si)
face (Si,Re)
Circular Dichroism spectra
![Page 33: Nazario Martín - JST](https://reader031.vdocuments.co/reader031/viewer/2022012105/61dbf60c44f3dd3b68626795/html5/thumbnails/33.jpg)
The H2 molecule is not active in the IR since the dipolar moment is not modified during the vibration. On the contrary it is active in Raman spectroscopy. The asymmetry of the fullerene sphere should be responsible for this experimental finding under routine conditions.
IR Spectrum of fulleropyrrolidine-H2@C60
![Page 34: Nazario Martín - JST](https://reader031.vdocuments.co/reader031/viewer/2022012105/61dbf60c44f3dd3b68626795/html5/thumbnails/34.jpg)
100011001200130014001500160017001800
IR-MI-503-Cu IR-H2atC60 IR-MI-503-Ag
0
0,05
0,1
0,15
0,2
Frequency / cm -1
410041504200425043004350440044504500
IR-MI-503-Cu IR-H2atC60 IR-MI-503-Ag
0
0,0005
0,001
0,0015
0,002
0,0025
0,003
Frequency / cm -1
The strength vibration of the H2 molecule is active in IR !!!
Unpublished results In collaboration with Navarrete group
IR Spectrum of fulleropyrrolidine-H2@C60
The translation–rotation coupling is measured as a splitting of absorption lines in the IR spectrum
![Page 35: Nazario Martín - JST](https://reader031.vdocuments.co/reader031/viewer/2022012105/61dbf60c44f3dd3b68626795/html5/thumbnails/35.jpg)
Non-activated Dipolarophile
HOMO Activation or nucleophilic activation
Organocatalysis in Fullerenes Chemistry: Phosphine-catalyzed Cycloaddition of Allenoates onto [60]fullerene
Angew. Chem. Int. Ed. 2013, DOI: 10.1002/anie.201301292, in press
![Page 36: Nazario Martín - JST](https://reader031.vdocuments.co/reader031/viewer/2022012105/61dbf60c44f3dd3b68626795/html5/thumbnails/36.jpg)
• We have described the first enantiomeric synthesis of fullerenes by using asymmetric catalysis.
• The use of a suitable chiral catalyst controls the addition of fullerenes to both faces of a 1,3-dipole, thus determining the stereochemical outcome.
• Organocatalysis has been successfully used in fullerene chemistry affording cyclopentenofullerenes with high ee values.
• This methodology is currently being extended to other systems, namely endohedral fullerenes, other dipoles (münchnones).
Conclusions
*
![Page 37: Nazario Martín - JST](https://reader031.vdocuments.co/reader031/viewer/2022012105/61dbf60c44f3dd3b68626795/html5/thumbnails/37.jpg)
Molecular Organic Materials Research Group Universidad Complutense/ IMDEA-Nanoscience
Madrid
![Page 38: Nazario Martín - JST](https://reader031.vdocuments.co/reader031/viewer/2022012105/61dbf60c44f3dd3b68626795/html5/thumbnails/38.jpg)
Molecular Organic Materials Research Group (M2O-UCM) Dra. Beatriz Illescas Dra. Mª Angeles Herranz Dr. Angel Martín Dr. Andreas Gouloumis Dr. Salvatore Filippone Dr. Emilio Pérez Dr. Juan Luis Delgado Dr. Juan Luis López Dra. Carmen Atienza Dr. Juan Marco Dr. Damien Joly Dr. Laura Rodriguez Dr. Vanesa Marcos Dr. Silvia Reboredo PhD Raúl García PhD Enrique Maroto PhD Andrea Larosa PhD Helena Isla PhD Antonio Muñoz PhD Carmen Villegas PhD María Gallego PhD Javier López PhD Alberto Insuasti PhD Jaime Mateos PhD Luis Moreira PhD Sonia Vela PhD Sara Vidal Theoretical Groups Enrique Ortí University of Valencia (Spain)
Miquel Solá University of Girona (Spain)
Collaborations Prof. Dirk M. Guldi University of Erlangen (Germany)
Prof. Takeshi Akasaka University of Tsukuba (Japan)
Prof. Maurizio Prato University of Trieste (Italy)
Prof. Martin Bryce University of Durham (UK)
Prof. Luis Echegoyen Univeristy of Clemson (USA)
Prof. James Durrant Imperial College (UK)
Prof. Serdar Sariciftci Univeristy of Linz (Austria)
Prof. Vladimir Dyakonov University of Würsburg (Germany)
Prof. Rodolfo Miranda University Autonoma of Madrid, Spain
Prof. Nicolás Agrait University Autonoma of Madrid, Spain
Prof. Emilio Palomares ICIQ, Tarragona, Spain
Prof. Jean Françoise Nierengarten University of Strasbourg (France)
Financial support MINECO of Spain (CTQ2011-24652/BTQ) CAM MadriSolar (PPQ-000225-0505) Spanish-Japanese Project MINECO 2010 European Commission (EUROMAP) Proyecto Singular Estratégico (MICINN) Marie Curie (FUNMOLS) CONSOLIDER “Nanociencia molecular”
![Page 39: Nazario Martín - JST](https://reader031.vdocuments.co/reader031/viewer/2022012105/61dbf60c44f3dd3b68626795/html5/thumbnails/39.jpg)
European Research Council Established by
The European Commission
Financial Support
![Page 40: Nazario Martín - JST](https://reader031.vdocuments.co/reader031/viewer/2022012105/61dbf60c44f3dd3b68626795/html5/thumbnails/40.jpg)
Metal catalysis vs Organocatalysis
Organocatalysis
• Commercial availability and price • Robustness
• Work up simplicity
• Production of metallic residues
• Compatibility to H2O-air
• Scale up
• Field of application
Metal Catalysis
![Page 41: Nazario Martín - JST](https://reader031.vdocuments.co/reader031/viewer/2022012105/61dbf60c44f3dd3b68626795/html5/thumbnails/41.jpg)
Asymmetric Organocatalysis
0 100 200 300 400 500 600
nº de publicaciones
2000
2001
2002
2003
2004
2005
2006
2007
2008
2009
añ
o Catálisis metálicaCatálisis enzimáticaOrganocatálisis
![Page 42: Nazario Martín - JST](https://reader031.vdocuments.co/reader031/viewer/2022012105/61dbf60c44f3dd3b68626795/html5/thumbnails/42.jpg)
Intr
od
uc
ció
n
1,3-DIPOLAR CYCLOADICIÓN WITH AZOMETHINE YLIDES
Cicloadición (3+2) catalítica enantioselectiva
0
2
4
6
8
10
12
14
16
18
20
2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011
Año
nº d
e pu
blic
acio
nes
Organocatálisis
Catálisis metálica
Catalytic enantioselective [3+2] cycloaddition
![Page 43: Nazario Martín - JST](https://reader031.vdocuments.co/reader031/viewer/2022012105/61dbf60c44f3dd3b68626795/html5/thumbnails/43.jpg)
Non-coordinating Dipolarophile
Chiral N-metallated AMY
HOMO Activation vs nucleophilic activation
ab metallis ad organicam, catalysem
(Transition metal and base)
Chiral metal free nucleophile
(Chiral phosphine)
Angew. Chem. Int. Ed. 2013, DOI: 10.1002/anie.201301292, in press
![Page 44: Nazario Martín - JST](https://reader031.vdocuments.co/reader031/viewer/2022012105/61dbf60c44f3dd3b68626795/html5/thumbnails/44.jpg)
Phosphine-catalyzed Cycloaddition of Allenoates onto [60]fullerene
Op
tim
iza
ció
n d
e c
on
dic
ion
es
Angew. Chem. Int. Ed. 2013, DOI: 10.1002/anie.201301292, in press
![Page 45: Nazario Martín - JST](https://reader031.vdocuments.co/reader031/viewer/2022012105/61dbf60c44f3dd3b68626795/html5/thumbnails/45.jpg)
Allenoate Activation by Phosphines
Aromatic phosphines do not activate efficiently!!!
8% 10 %
![Page 46: Nazario Martín - JST](https://reader031.vdocuments.co/reader031/viewer/2022012105/61dbf60c44f3dd3b68626795/html5/thumbnails/46.jpg)
60% 22 ee (R)
49% 16 ee (S)
43% 56 ee (R) 67%
16 ee (R) P-containing heterocycles
Aliphatic phosphines do activate but are not always selective
Allenoate Activation by Phosphines
![Page 47: Nazario Martín - JST](https://reader031.vdocuments.co/reader031/viewer/2022012105/61dbf60c44f3dd3b68626795/html5/thumbnails/47.jpg)
40% 60 ee (S) 48%
82 ee (S)
57% 66 ee (R)
Phosphine-catalyzed Cycloaddition of Allenoates onto [60]fullerene
![Page 48: Nazario Martín - JST](https://reader031.vdocuments.co/reader031/viewer/2022012105/61dbf60c44f3dd3b68626795/html5/thumbnails/48.jpg)
Extension of methodology
Conversion: 49% ee: 88%
Conversion: 36% ee: 92%
Conversion: 19% ee: >99%
Conversion: 28% ee: 80%
Conversion: 57% ee: 74%
Phosphine-catalyzed Cycloaddition of Allenoates onto [60]fullerene
![Page 49: Nazario Martín - JST](https://reader031.vdocuments.co/reader031/viewer/2022012105/61dbf60c44f3dd3b68626795/html5/thumbnails/49.jpg)
[3+2] Cycloadition with allenoates
Assignment of the new created stereocenter
![Page 50: Nazario Martín - JST](https://reader031.vdocuments.co/reader031/viewer/2022012105/61dbf60c44f3dd3b68626795/html5/thumbnails/50.jpg)
[3+2] Cycloadition with allenoates
Assignment of the new created stereocenter
![Page 51: Nazario Martín - JST](https://reader031.vdocuments.co/reader031/viewer/2022012105/61dbf60c44f3dd3b68626795/html5/thumbnails/51.jpg)
[3+2] Cycloadition with allenoates
Assignment of the new created stereocenter
![Page 52: Nazario Martín - JST](https://reader031.vdocuments.co/reader031/viewer/2022012105/61dbf60c44f3dd3b68626795/html5/thumbnails/52.jpg)
[3+2] Cycloadition with allenoates
Assignment of the new created stereocenter
![Page 53: Nazario Martín - JST](https://reader031.vdocuments.co/reader031/viewer/2022012105/61dbf60c44f3dd3b68626795/html5/thumbnails/53.jpg)
Sector Rule
Sector Rule for the assignment of the configuration
![Page 54: Nazario Martín - JST](https://reader031.vdocuments.co/reader031/viewer/2022012105/61dbf60c44f3dd3b68626795/html5/thumbnails/54.jpg)
X-Ray Chemical Structure
Chemical Structure of Cyclopenteno[4,5:1,2][60]fullerene Cycloadition with allenoates
S
![Page 55: Nazario Martín - JST](https://reader031.vdocuments.co/reader031/viewer/2022012105/61dbf60c44f3dd3b68626795/html5/thumbnails/55.jpg)
Stereoconvergent cycloaddition
![Page 56: Nazario Martín - JST](https://reader031.vdocuments.co/reader031/viewer/2022012105/61dbf60c44f3dd3b68626795/html5/thumbnails/56.jpg)
Stereoconvergent cycloaddition
+
![Page 57: Nazario Martín - JST](https://reader031.vdocuments.co/reader031/viewer/2022012105/61dbf60c44f3dd3b68626795/html5/thumbnails/57.jpg)
De Fullerenorum
Catalyse
ad metallu , ad organicam (nucleofilicam) activationem
Usque ad metalla Usque ad organocatalysem
![Page 58: Nazario Martín - JST](https://reader031.vdocuments.co/reader031/viewer/2022012105/61dbf60c44f3dd3b68626795/html5/thumbnails/58.jpg)
Münchnone
azalactone
Other Asymmetric Functionalizations in Fullerenes
![Page 59: Nazario Martín - JST](https://reader031.vdocuments.co/reader031/viewer/2022012105/61dbf60c44f3dd3b68626795/html5/thumbnails/59.jpg)
• Ligandless conditions
• Stereoselective
• Only exo-adduct
S. Peddibhotla, J. J. Tepe, J. Am. Chem. Soc., 2004, 126, 12776-12777
![Page 60: Nazario Martín - JST](https://reader031.vdocuments.co/reader031/viewer/2022012105/61dbf60c44f3dd3b68626795/html5/thumbnails/60.jpg)
• Chiral ligands
• Preformed chiral catalyst
• Enantioselective
• Only exo-adduct
A. D. Melhado, M. Luparia, F. D. Toste, J. Am. Chem. Soc., 2007, 129, 12638-12639
![Page 61: Nazario Martín - JST](https://reader031.vdocuments.co/reader031/viewer/2022012105/61dbf60c44f3dd3b68626795/html5/thumbnails/61.jpg)
Enantioselective synthesis of pyrrolinefullerenes
Pyrrolino[3,4:1,2][60]fullerenes
• More stable at high temperatures • Potential further functionalization
Alternative to the pyrrolidinefullerenes
Metal-catalysis
![Page 62: Nazario Martín - JST](https://reader031.vdocuments.co/reader031/viewer/2022012105/61dbf60c44f3dd3b68626795/html5/thumbnails/62.jpg)
Enantioselective synthesis of pyrrolinefullerenes
• Development of new chiral catalytic systems • Based on non-precious metals (Cu) • Apply novel systems outside of the fullerene chemistry • Δ1-Pyrrolines allow accessing to biologically active molecules
Use of C60 as benchmark for…
![Page 63: Nazario Martín - JST](https://reader031.vdocuments.co/reader031/viewer/2022012105/61dbf60c44f3dd3b68626795/html5/thumbnails/63.jpg)
Enantioselective synthesis of pyrrolinefullerenes
münchnone
![Page 64: Nazario Martín - JST](https://reader031.vdocuments.co/reader031/viewer/2022012105/61dbf60c44f3dd3b68626795/html5/thumbnails/64.jpg)
Enantioselective synthesis of pyrrolinefullerenes
Mechanistic pathway
soluble in organic solvent
![Page 65: Nazario Martín - JST](https://reader031.vdocuments.co/reader031/viewer/2022012105/61dbf60c44f3dd3b68626795/html5/thumbnails/65.jpg)
Enantioselective synthesis of pyrrolinefullerenes
Mechanistic pathway
base
![Page 66: Nazario Martín - JST](https://reader031.vdocuments.co/reader031/viewer/2022012105/61dbf60c44f3dd3b68626795/html5/thumbnails/66.jpg)
Enantioselective synthesis of pyrrolinefullerenes
Mechanistic pathway
base
![Page 67: Nazario Martín - JST](https://reader031.vdocuments.co/reader031/viewer/2022012105/61dbf60c44f3dd3b68626795/html5/thumbnails/67.jpg)
Enantioselective synthesis of pyrrolinefullerenes
Mechanistic pathway
non-coordinating dipolarophile
Find the best [M]-L* pair in order to discriminate one of the dipole faces
![Page 68: Nazario Martín - JST](https://reader031.vdocuments.co/reader031/viewer/2022012105/61dbf60c44f3dd3b68626795/html5/thumbnails/68.jpg)
CuI(OTf)complex /NEt3
PhCl 61% 88 94 6
+ +
AgSbF6 /NEt3
PhF 33% 86 93 7
(-)-1,2-BPE(RR)
(S)-Me-f-KetalPhos
YIELD ee
1,3 dipolar cycloaddition of Munchnones: FulleroPyrrolines
CuI(OTf)complex /NEt3 RT , o-DCB
25% 70 15 85
FESULPHOS
![Page 69: Nazario Martín - JST](https://reader031.vdocuments.co/reader031/viewer/2022012105/61dbf60c44f3dd3b68626795/html5/thumbnails/69.jpg)
Enantioselective synthesis of pyrrolinefullerenes
Further functionalization
Isolated by column chromatography
![Page 70: Nazario Martín - JST](https://reader031.vdocuments.co/reader031/viewer/2022012105/61dbf60c44f3dd3b68626795/html5/thumbnails/70.jpg)
Enantioselective synthesis of pyrrolinefullerenes
Organocatalysis
![Page 71: Nazario Martín - JST](https://reader031.vdocuments.co/reader031/viewer/2022012105/61dbf60c44f3dd3b68626795/html5/thumbnails/71.jpg)
Complementary methodology: with or without metal
![Page 72: Nazario Martín - JST](https://reader031.vdocuments.co/reader031/viewer/2022012105/61dbf60c44f3dd3b68626795/html5/thumbnails/72.jpg)
S. R. Wilson, Q. Lu, J. Cao, Y. Wu, C. J. Welch D. Schuster, Tetrahedron, 1996, 52, 5131-5142
Enantioselective synthesis of pyrrolinefullerenes
Sector rule: stereocenter assignment by CD
(S) (R)
(R)
(S)
![Page 73: Nazario Martín - JST](https://reader031.vdocuments.co/reader031/viewer/2022012105/61dbf60c44f3dd3b68626795/html5/thumbnails/73.jpg)
Stereodivergent Synthesis of Pyrrolidines
J. Am. Chem. Soc., 2012, 134 , 12936
cis/ trans diasteroselectivity in fullerene endo/exo diasteroselectivity in conventional olefins C-2 Carbon configuration is always mantained
![Page 74: Nazario Martín - JST](https://reader031.vdocuments.co/reader031/viewer/2022012105/61dbf60c44f3dd3b68626795/html5/thumbnails/74.jpg)
Stereodivergent Synthesis of Pyrrolidines
cis trans
endo exo
J. Am. Chem. Soc., 2012, 134 , 12936
![Page 75: Nazario Martín - JST](https://reader031.vdocuments.co/reader031/viewer/2022012105/61dbf60c44f3dd3b68626795/html5/thumbnails/75.jpg)
Plausible mechanism of the AMY cycloaddition onto different double bonds
J. Am. Chem. Soc., 2012, 134 , 12936
Intermediate stabilized by a benzylic cation and a fullerene anion, where the stereochemistry (R) of the C-2 is yet defined.
![Page 76: Nazario Martín - JST](https://reader031.vdocuments.co/reader031/viewer/2022012105/61dbf60c44f3dd3b68626795/html5/thumbnails/76.jpg)
acknowledgment
Enrique Maroto Dr. A. Martín-Domenech Prof. M. Suarez
Prof. N. Martín Dr. Marta Izquierdo Prof. T. Akasaka and his group
Calculations Prof. F. P. Cossío Dr. Abel de Cózar
Dr. Juan Marco
![Page 77: Nazario Martín - JST](https://reader031.vdocuments.co/reader031/viewer/2022012105/61dbf60c44f3dd3b68626795/html5/thumbnails/77.jpg)
N-Metalated Azomethine Ylides
![Page 78: Nazario Martín - JST](https://reader031.vdocuments.co/reader031/viewer/2022012105/61dbf60c44f3dd3b68626795/html5/thumbnails/78.jpg)
Asymmetric [3+2] Cycloadditions on C60: Mechanism
![Page 79: Nazario Martín - JST](https://reader031.vdocuments.co/reader031/viewer/2022012105/61dbf60c44f3dd3b68626795/html5/thumbnails/79.jpg)
Ag
P
P
Stereodifferentiation of the two faces of the azomethine ylide
C60
C60
X Blockage of the
(si,re) face
Unpublished results
![Page 80: Nazario Martín - JST](https://reader031.vdocuments.co/reader031/viewer/2022012105/61dbf60c44f3dd3b68626795/html5/thumbnails/80.jpg)
Geometries for the TSs in the first step for the [3+2] cycloaddition. In both cases is a non-concerted reaction
TS1(major)
(re,si) attack
(0.0) (+2.8 kcal/mol)
2.031 2.823
TS1(minor)
2.055 2.813
(si,re) attack
![Page 81: Nazario Martín - JST](https://reader031.vdocuments.co/reader031/viewer/2022012105/61dbf60c44f3dd3b68626795/html5/thumbnails/81.jpg)
Energy Profile for the formation of the final product (Pcis)
Unpublished results
INT2 rapidly form the final cycloadduct INT3 through TS2. Therefore, Ptrans cannot be the result of rotation of INT2 It results from the ylide isomerization previous to the cycloaddition process
The endothermic process ensures the cycle regeneration and the recovery of the catalyst
The stereochemistry of all new centres is defined in the first
step !!!
2.031 2.823
![Page 82: Nazario Martín - JST](https://reader031.vdocuments.co/reader031/viewer/2022012105/61dbf60c44f3dd3b68626795/html5/thumbnails/82.jpg)
2.242
3.007 2.186
2.886
ONIOM(B3LYP/LANL2DZ:PM6) Ball&stick:tube
TSeq1 (0.0)
TSax1 (+2.1)
Asymmetric [3+2] Cycloadditions on C70: REGIOSELECTIVITY
Two aproximations depending upon the thienyl group is oriented in eq or ax on the C70
Equatorial
Axial
Equatorial aproximation is favoured
Theoretical study carried out using dppe/ Ag(I)
![Page 83: Nazario Martín - JST](https://reader031.vdocuments.co/reader031/viewer/2022012105/61dbf60c44f3dd3b68626795/html5/thumbnails/83.jpg)
Regioselectivity. Fukui indexes at the α-γ sites (The different values for the atoms predict an asynchronous reaction and a regioselectivity)
Angew. Chem. Int. Ed. 2011, 50, 6060 –6064
Fukui nucleophilic function on the carbon atoms of the dipole show an enolate-like nucleophilicity of the azomethine
![Page 84: Nazario Martín - JST](https://reader031.vdocuments.co/reader031/viewer/2022012105/61dbf60c44f3dd3b68626795/html5/thumbnails/84.jpg)
2.242
3.007 3.173
2.212
ONIOM(B3LYP/LANL2DZ:PM6) Ball&stick:tube
TSeq1 (0.0)
TSeq1-trans (+6.7)
Asymmetric [3+2] Cycloadditions on C70: DIASTEREOSELECTIVITY
IN OUT
Cis azomethine ylides cycloadd preferentially to trans. We supose that cis-trans equilibrium in the initial azomethine ylide is a low energy process. Thus, according to Curtin-Hammet, we only need to compare the high of both processes.
![Page 85: Nazario Martín - JST](https://reader031.vdocuments.co/reader031/viewer/2022012105/61dbf60c44f3dd3b68626795/html5/thumbnails/85.jpg)
2.242
3.007 2.909
2.223
ONIOM(B3LYP/LANL2DZ:PM6) Ball&stick:tube
TSeq1 (0.0)
TSeq2 (+1.9)
Asymmetric [3+2] Cycloadditions on C70: ENANTIOSELECTIVITY
The attack on the si,re face is not favoured. Therefore, Peq1 is the final product
![Page 86: Nazario Martín - JST](https://reader031.vdocuments.co/reader031/viewer/2022012105/61dbf60c44f3dd3b68626795/html5/thumbnails/86.jpg)
Asymmetric [3+2] Cycloadditions on C70: CATALYTIC CYCLE
2.242
3.007 1.944
![Page 87: Nazario Martín - JST](https://reader031.vdocuments.co/reader031/viewer/2022012105/61dbf60c44f3dd3b68626795/html5/thumbnails/87.jpg)
Figure. Chemical shifts of the regioisomers formed for the cis products a-f. The assignment has been made taking into account the strong deshielding effect characteristic for the polar region of C70. Meier, M. S.; Poplawska, M. P.; Compton, A. L.; Shaw, J. P.; Selegue, J. P.; Guarr, T.F., J. Am. Chem. Soc. 116, 7044-7048 (1994).
1H NMR spectra
![Page 88: Nazario Martín - JST](https://reader031.vdocuments.co/reader031/viewer/2022012105/61dbf60c44f3dd3b68626795/html5/thumbnails/88.jpg)
Catalytic 1,3 dipolar cycloaddition onto C60
+
Cu(ACN)4ClO4 / (Et3N)
Yield d.e
45% 94% 82%
(2S,5S)-2a
18%
(2R,5R)-2a
Nature Chem., 2009, 1, 578-582
Carretero et al., JACS, 2005, 127, 16394
![Page 89: Nazario Martín - JST](https://reader031.vdocuments.co/reader031/viewer/2022012105/61dbf60c44f3dd3b68626795/html5/thumbnails/89.jpg)
Low yield, mixture of products.
W S
40% 60%
Thermal 1,3-dipolar cycloaddition onto C60
cis-2a trans-2a
fulleroproline
![Page 90: Nazario Martín - JST](https://reader031.vdocuments.co/reader031/viewer/2022012105/61dbf60c44f3dd3b68626795/html5/thumbnails/90.jpg)
Catalytic 1,3 dipolar cycloaddition onto C60
+
cis-2a trans-2a
cis diastereoselectivity
Copper or Silver acetates
![Page 91: Nazario Martín - JST](https://reader031.vdocuments.co/reader031/viewer/2022012105/61dbf60c44f3dd3b68626795/html5/thumbnails/91.jpg)
Catalytic 1,3 dipolar cycloaddition onto C60
+
(2S,5S)-2a (2R,5R)-2a
Nature Chem., 2009, 1, 578-582
(si,re) face
(re,si) face
![Page 92: Nazario Martín - JST](https://reader031.vdocuments.co/reader031/viewer/2022012105/61dbf60c44f3dd3b68626795/html5/thumbnails/92.jpg)
Catalytic 1,3 dipolar cycloaddition onto C60
+
Cu(ACN)4ClO4 / (Et3N)
Yield d.e
45% 94% 82%
(2S,5S)-2a
18%
(2R,5R)-2a
Cu(ACN)4PF6 / (Bu4NAcO) 60% >99% 96% 4%
Cu(AcO)2 88% >99% 95% 5%
AgAcO 60% >99% 5% 95%
Nature Chem., 2009, 1, 578-582
Fesulphos
dppe
![Page 93: Nazario Martín - JST](https://reader031.vdocuments.co/reader031/viewer/2022012105/61dbf60c44f3dd3b68626795/html5/thumbnails/93.jpg)
Switchable enantioselective cycloaddition onto C60
Nature Chem., 2009, 1, 578-582
![Page 94: Nazario Martín - JST](https://reader031.vdocuments.co/reader031/viewer/2022012105/61dbf60c44f3dd3b68626795/html5/thumbnails/94.jpg)
Ag
P
P
Stereodifferentiation of the two faces of the azomethine ylide
C60
C60
X Blockage of the
(si,re) face
Unpublished results
N
OMe
NC
H
HO
AgP
P Ph
PhPh
Ph
![Page 95: Nazario Martín - JST](https://reader031.vdocuments.co/reader031/viewer/2022012105/61dbf60c44f3dd3b68626795/html5/thumbnails/95.jpg)
Geometries for the TSs in the first step for the [3+2] cycloaddition. In both cases is a non-concerted reaction
TS1(major)
(re,si) attack
(0.0) (+2.8 kcal/mol)
2.031 2.823
TS1(minor)
2.055 2.813
(si,re) attack
![Page 96: Nazario Martín - JST](https://reader031.vdocuments.co/reader031/viewer/2022012105/61dbf60c44f3dd3b68626795/html5/thumbnails/96.jpg)
Nature Chem., 2009, 1, 578-582 up to 96% of er
first experimental evidence of a stepwise mechanism
The scope of our methodology has been expanded to enable a complete switch in the diastereoselectivity!
![Page 97: Nazario Martín - JST](https://reader031.vdocuments.co/reader031/viewer/2022012105/61dbf60c44f3dd3b68626795/html5/thumbnails/97.jpg)
Stepwise or Concerted ?
N
OMe
HH
OM
PP
supra
supra
antara
cis
trans
“supra antara” not allowed [4+2] cycloadditions
HNAr CO2R
HNAr CO2R
![Page 98: Nazario Martín - JST](https://reader031.vdocuments.co/reader031/viewer/2022012105/61dbf60c44f3dd3b68626795/html5/thumbnails/98.jpg)
Switching the Stereoselectivity: Fulleropyrrolidines “a la Carte”
Nature Chem., 2009, 1, 578-582
HNRO2C Ar
(2S,5R)-trans
(2R,5S)-trans
HNAr CO2R
O
O
O
O
P
P
tBuOMe
tButBu
OMetButBu
OMetBu
OMetButBu
(R)-DTBM SegPhos
(S)-DTBM SegPhos
J. Am. Chem. Soc., 2012, 134 , 12936
up to 99% of er up to 96% of er
Et3NCu(OTf)2
Et3NCu(OTf)2
![Page 99: Nazario Martín - JST](https://reader031.vdocuments.co/reader031/viewer/2022012105/61dbf60c44f3dd3b68626795/html5/thumbnails/99.jpg)
Asymmetric [3+2] Cycloadditions on C60: Mechanism
![Page 100: Nazario Martín - JST](https://reader031.vdocuments.co/reader031/viewer/2022012105/61dbf60c44f3dd3b68626795/html5/thumbnails/100.jpg)
Stepwise or Concerted ?
N
OMe
HH
OM
PP
supra
supra
antara
cis
trans
“supra antara” not allowed [4+2] cycloadditions
HNAr CO2R
HNAr CO2R
![Page 101: Nazario Martín - JST](https://reader031.vdocuments.co/reader031/viewer/2022012105/61dbf60c44f3dd3b68626795/html5/thumbnails/101.jpg)
Stereodivergent Synthesis of Pyrrolidines
cis trans
endo exo
J. Am. Chem. Soc., 2012, 134 , 12936
![Page 102: Nazario Martín - JST](https://reader031.vdocuments.co/reader031/viewer/2022012105/61dbf60c44f3dd3b68626795/html5/thumbnails/102.jpg)
[3+2] Cycloaddition with allenoates O
ptim
iza
ció
n d
e c
on
dic
ion
es