ENANTIOSELECTIVE SYNTHESIS OF FULLERENES

Nazario Martín Departamento de Química Orgánica. Facultad de Ciencias Químicas

Universidad Complutense de Madrid/IMDEA-Nanociencia

[60]Fullerene

• Among the most studied molecules • Benchmark for other carbon nanoforms • Potential applications in different fields

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

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 %

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)

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

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

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Unpublished results

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

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

Submitted for publication

Submitted for publication Angew. Chem. Int. Ed. 2010, 49, 9876 –9880

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

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

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

Chiral Catalysis in Fullerene chemistry

Non-coordinating Dipolarophile

Dipolarophiles (The heteroatom coordinates to the metal)

Chiral metal complex

Dipolarophile

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

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

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

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…

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

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)

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

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

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.

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

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)

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

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

Endohedral Fullerenes Is its chemical reactivity affected?

What kind of chemical compound? It is a hydrocarbon?

H2@C60

Enantiomeric synthesis of fulleropyrrolidine-H2@C60

Unpublished results

In collaboration with Murata’s group

H2@C60 shows the same reactivity than hollow C60

1H-RMN (500MHz, 298K, CDCl3)

Enantiomeric synthesis of fulleropyrrolidine-H2@C60

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

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

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

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

• 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

*

Molecular Organic Materials Research Group Universidad Complutense/ IMDEA-Nanoscience

Madrid

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”

European Research Council Established by

The European Commission

Financial Support

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

Asymmetric Organocatalysis

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nº de publicaciones

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1,3-DIPOLAR CYCLOADICIÓN WITH AZOMETHINE YLIDES

Cicloadición (3+2) catalítica enantioselectiva

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Catalytic enantioselective [3+2] cycloaddition

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

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

Allenoate Activation by Phosphines

Aromatic phosphines do not activate efficiently!!!

8% 10 %

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

40% 60 ee (S) 48%

82 ee (S)

57% 66 ee (R)

Phosphine-catalyzed Cycloaddition of Allenoates onto [60]fullerene

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

[3+2] Cycloadition with allenoates

Assignment of the new created stereocenter

[3+2] Cycloadition with allenoates

Assignment of the new created stereocenter

[3+2] Cycloadition with allenoates

Assignment of the new created stereocenter

[3+2] Cycloadition with allenoates

Assignment of the new created stereocenter

Sector Rule

Sector Rule for the assignment of the configuration

X-Ray Chemical Structure

Chemical Structure of Cyclopenteno[4,5:1,2][60]fullerene Cycloadition with allenoates

S

Stereoconvergent cycloaddition

Stereoconvergent cycloaddition

+

De Fullerenorum

Catalyse

ad metallu , ad organicam (nucleofilicam) activationem

Usque ad metalla Usque ad organocatalysem

Münchnone

azalactone

Other Asymmetric Functionalizations in Fullerenes

• Ligandless conditions

• Stereoselective

• Only exo-adduct

S. Peddibhotla, J. J. Tepe, J. Am. Chem. Soc., 2004, 126, 12776-12777

• 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

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

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…

Enantioselective synthesis of pyrrolinefullerenes

münchnone

Enantioselective synthesis of pyrrolinefullerenes

Mechanistic pathway

soluble in organic solvent

Enantioselective synthesis of pyrrolinefullerenes

Mechanistic pathway

base

Enantioselective synthesis of pyrrolinefullerenes

Mechanistic pathway

base

Enantioselective synthesis of pyrrolinefullerenes

Mechanistic pathway

non-coordinating dipolarophile

Find the best [M]-L* pair in order to discriminate one of the dipole faces

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

Enantioselective synthesis of pyrrolinefullerenes

Further functionalization

Isolated by column chromatography

Enantioselective synthesis of pyrrolinefullerenes

Organocatalysis

Complementary methodology: with or without metal

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)

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

Stereodivergent Synthesis of Pyrrolidines

cis trans

endo exo

J. Am. Chem. Soc., 2012, 134 , 12936

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.

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

N-Metalated Azomethine Ylides

Asymmetric [3+2] Cycloadditions on C60: Mechanism

Ag

P

P

Stereodifferentiation of the two faces of the azomethine ylide

C60

C60

X Blockage of the

(si,re) face

Unpublished results

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

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

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)

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

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.

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

Asymmetric [3+2] Cycloadditions on C70: CATALYTIC CYCLE

2.242

3.007 1.944

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

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

Low yield, mixture of products.

W S

40% 60%

Thermal 1,3-dipolar cycloaddition onto C60

cis-2a trans-2a

fulleroproline

Catalytic 1,3 dipolar cycloaddition onto C60

+

cis-2a trans-2a

cis diastereoselectivity

Copper or Silver acetates

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

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

Switchable enantioselective cycloaddition onto C60

Nature Chem., 2009, 1, 578-582

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

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

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!

Stepwise or Concerted ?

N

OMe

HH

OM

PP

supra

supra

antara

cis

trans

“supra antara” not allowed [4+2] cycloadditions

HNAr CO2R

HNAr CO2R

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

Asymmetric [3+2] Cycloadditions on C60: Mechanism

Stepwise or Concerted ?

N

OMe

HH

OM

PP

supra

supra

antara

cis

trans

“supra antara” not allowed [4+2] cycloadditions

HNAr CO2R

HNAr CO2R

Stereodivergent Synthesis of Pyrrolidines

cis trans

endo exo

J. Am. Chem. Soc., 2012, 134 , 12936

[3+2] Cycloaddition with allenoates O

ptim

iza

ció

n d

e c

on

dic

ion

es