Anion−π Catalysis on Fullerenes

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Article

Reference

Anion−π Catalysis on Fullerenes

LOPEZ ANDARIAS, Javier, FRONTERA, Antonio, MATILE, Stefan

Abstract

Anion−π interactions on fullerenes are about as poorly explored as the use of fullerenes in catalysis. However, strong exchange-correlation contributions and the localized π holes on their surface promise unique selectivities. To elaborate on this promise, tertiary amines are attached nearby. Dependent on their positioning, the resulting stabilization of anionic transition states on fullerenes is shown to accelerate disfavored enolate addition and exo Diels–Alder reactions enantioselectively. The found selectivities are consistent with computational simulations, particularly concerning the discrimination of differently planarized and charge-delocalized enolate tautomers by anion−π interactions. Enolate−π interactions on fullerenes are much shorter than standard π–π interactions and anion−π interactions on planar surfaces, and alternative cation−π interactions are not observed. These findings open new perspectives with regard to anion−π interactions in general and the use of carbon allotropes in catalysis.

LOPEZ ANDARIAS, Javier, FRONTERA, Antonio, MATILE, Stefan. Anion−π Catalysis on Fullerenes. Journal of the American Chemical Society , 2017, vol. 139, no. 38, p.

13296-13299

DOI : 10.1021/jacs.7b08113

Available at:

http://archive-ouverte.unige.ch/unige:97267

Disclaimer: layout of this document may differ from the published version.

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Anion- π Catalysis on Fullerenes

Javier López-Andarias,

^†

Antonio Frontera

^§

* and Stefan Matile

^†

*

†School of Chemistry and Biochemistry, University of Geneva, Quai Ernest Ansermet 30, CH-1211 Geneva, Switzerland

§Departament de Química, Universitat de les Illes Balears, Crta. de Valldemossa km 7.5, 07122, Palma de Mallorca, Baleares, Spain

ABSTRACT. Anion-π interactions on fullerenes are about as poorly explored as the use of fullerenes in catalysis. However, strong exchange-correlation contributions and the localized π holes on their surface promise unique selectivities. To elaborate on this promise, tertiary amines are attached nearby.

Dependent on their positioning, the resulting stabilization of anionic transition states on fullerenes is shown to accelerate disfavored enolate addition and exo Diels-Alder reactions enantioselectively. The found selectivities are consistent with computational simulations, particularly concerning the discrimination of differently planarized and charge-delocalized enolate tautomers by anion-π interactions. Enolate-π interactions on fullerenes are much shorter than standard π-π interactions and anion-π interactions on planar surfaces, and alternative cation-π interactions are not observed. These findings open new perspectives with regard to anion-π interactions in general and the use of carbon allotropes in catalysis.

The general concept of anion-π catalysis¹ is to stabilize anionic transition states and intermediates by anion-π interactions² on π- acidic aromatic surfaces. Introduced explicitly in 2013,¹ anion-π catalysis has since then been validated for several reactions,³ and anion-π enzymes and electric-field-assisted anion-π catalysis have been realized.⁴ So far, anion–π catalysis has been achieved on the π-acidic surface of naphthalenediimides (NDIs)^3,4 except for isolate, less convincing examples with perylenediimides.⁵ Despite much recent encouragement from theory focusing on multicenter covalency with non-classical exchange-correlation components,⁶ anion-π interactions^1-7 on fullerenes^7-16 have re- ceived little attention. The rare and recent reports deal with self- doping mechanisms in optoelectronic devices.⁷ This underrecog- nition might originate from synthetic challenges or from theoretical complications⁶ with anion-π interactions on large spherical rather than planar π surfaces. The former is less likely because fullerenes have been extensively modified and integrated into functional systems.⁸ However, as stated earlier this year, “their use in catalysis has been almost neglected.”⁹ Realized examples include fullerenes as photosensitizer for elegant Diels-Alder reactions of dienes with singlet-oxygen¹⁰ and in metal complexes for transfer hydrogenation, hydrocarboration and alkyne trimeri- zation, with contributions from the fullerene beyond scaffolding often being unclear.^9,11 The same is true for organocatalysis with perhydroxylated or -aminated, largely dearomatized fullerenes,¹² and aldol condensations with pioneering proline-fullerene conjugates were less convincing than with fullerene-free controls.¹³ The molecular electrostatic potential (MEP) surface of C60 is overall positive, i.e., compatible with anion-π interactions.¹⁴ Most interestingly, the MEP shows highly localized areas of positive potential, a bit like the dimples on a golf ball (Figure 1).¹⁴ These π holes suggested that anion-π catalysis on fullerenes could occur with unique selectivities. Consistent with an increase of the LUMO energy by +120 meV only,¹⁵ the addition of a cyclopropane in 1 was insufficient to significantly weaken these π holes (Figure 1A). A similarly poor impact of non-conjugated cyano

Figure 1. MEP surfaces of 1 (A) and 2 (B) with selected energies (0.002 a.u.) and B3LYP/6-31+G* complexes of Cl^– (C), NO3– (D) and 3-oxopropionate (E) with 1 in THF with representative distances (in Å) and interaction energies.

acceptors in 2 (–100 meV)¹⁵ gave a relatively small increase of the π holes (Figure 1B).

According to B3LYP/6-31+G* (with dispersion correction),^14,17 the formation of chloride complexes of 1 in THF (polarized con- tinuum model) was slightly unfavorable (Figure 1C). More fa- vorable edge-to-face complexes were obtained at –10 kJ mol^-1 for nitrate (Figure 1D). The alternative π-π enhanced face-to-face complex minimized at –4 kJ mol^-1 (Figure S9). For enolate-π interactions with 3-oxopropionate, face-to-face complexes with 1 were favored and with –25 kJ mol^-1 stronger than the nitrate-π complexes (Figures 1E, S11). With dicyano fullerenes 2 and beyond, interaction energies increased correspondingly (Figures S7–S11).

To explore anion-π catalysis on fullerene surfaces, the collection of conjugates 3–12 was prepared together with controls 13–

16 (Figure 2). For most variations, fullerene 17 was first cyclo- propanated with malonate 18 and then subjected to hydrolysis and decarboxylation. The activated C60-NHS ester 19¹⁶ was then reacted with the corresponding amines and alcohols (Scheme 1).¹⁷ Catalyst 11 was prepared by reacting of C60 directly with the corresponding Boc-protected cyanoacetamide. The obtained product was then deprotected with acid and methylated to afford the target molecule (Scheme S2).¹⁷

The addition of malonic acid half thioester (MAHT) 20 to acceptor 21 is attractive for anion-π catalysis because the addition product 22 allows to address stereoselectivity and chemoselectivi- ty with regard to the competing decarboxylation product 23 (Fig- ure 3).¹⁸ The reaction is significant in chemistry and biology and has some similarity with the cyclopropanation of fullerenes:

Whereas putative anion-π interactions between 17 and the pre- iodinated malonate 18 proceed to nucleophilic addition (Scheme

1: R = H 2: R = CN

R R

A B

–10 kJ mol^–1

+4 kJ mol^–1 –25 kJ mol^–1

E D

C

120

–175 kJ mol^–1

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2

Scheme 1. (a) 1) I2, DBU, toluene, 1 h, rt, 53%; 2) oDCB, 180 ºC, 6 h, quant.; 3) NHS, EDCl, dry THF, 4 h, rt, 42%;¹⁶ b) CHCl3, 0.5-2 h, rt, 73- 98% (R: See Figure 2).

Figure 2. Structure of catalysts 3–12 and their ability to selectively accelerate enolate addition (A) over decarboxylation (D, Figure 3), report- ed as ∆A/D, the A/D ratio minus that of controls 13–16 (Table 1).

1), those between malonate 20 and fullerenes 3–12 were expected to catalyze enolate addition to acceptor 21 rather than to the fullerene (Figure 3).

Among fullerene-amine conjugates with flexible, acyclic interfacers, catalyst 3 was best (Table 1, entry 2). The addition product 22 was obtained in 90% yield, accompanied by only 9% of decarboxylation. This selectivity for enolate addition, quantified as A/D = 10.0, was exceptionally high.¹⁸ Removal of the π sphere in control 13 gave A/D = 3.8 (Table 1, entry 1). The difference

∆A/D = 6.2 contains the contributions from anion-π interactions (Figure 2). Such ∆A/D values were considered convenient to generally compare the difference in selectivity of given motifs with and without fullerene (Figure 2). Longer spacers between fullerene and amine in 4 and 5 weakened ∆A/D selectivity, perhaps because of decreasing depth of the π holes with increasing distance from the cyclopropane (Figures 1, 2) or due to entropic contributions or decreasing support from the amide hydrogen- bond donor. Replacement of this donor by an oxygen acceptor in 6–8 or a methyl group in 9 gave much weaker ∆A/D selectivity (Table 1, entries 6–9 vs 5). With a bulky cyclohexyl substituent in 10, selectivity for addition compared to control 14 was sup- pressed (∆A/D = –0.4, Figure 2; Table 1, entry 10 vs 5).

With a cyano acceptor next to the amide, A/D values increased for control 15 compared to control 13 (Table 1, entry 11 vs 1) but decreased with fullerene 11 compared to fullerene 3 (Table 1, entry 12 vs 2). These complementary trends confirmed¹⁵ that the cyano group strengthens the amide hydrogen-bond donor more than the π acidity of the fullerene. In computational models, hydrogen bonding from this donor to the thioester carbonyl stabi- lized the enolate tautomer in RI1 but not in RI2 (Figures 3, S14).

Figure 3. Competing addition and decarboxylation of MAHT 20 (PMP:

p-methoxyphenyl) to acceptor 21, affording 22 and 23, and B3LYP/6- 31+G* structures of reactive intermediates RI1 without and RI2 with anion-π interactions between enolate tautomers and fullerenes (R¹ = H), with indication of interaction energies for R¹ = H (3) and R¹ = CN (11), selected bond length, α carbons (blue arrows) and present or missing hydrogen bond (red arrows), with R = Me (R = PMP and cyclohexyls as in 12 gave same trends, Figures S13–S18).

Table 1. Catalyst screening.

entry cat^a R X n S^b η1 (ee)^c η2d

η1/η2e

1 13 H NH 1 20 78 20 3.8

2 3 H NH 1 20 90 9 10.0

3 4 H NH 2 20 89 11 8.1

4 5 H NH 3 20 88 11 7.8

5 14 H NMe 1 20 77 22 3.5

6 6 H O 1 20 84 16 5.4

7 7 H O 2 20 76 17 4.5

8 8 H O 3 20 76 16 4.6

9 9 H NMe 1 20 84 15 5.5

10 10 H NCy 1 20 72 23 3.1

11 15 CN NH 1 20 83 16 5.2

12 11 CN NH 1 20 87 11 7.7

13 16 - - - 20 84 (0) 16 5.2

14 12 H - - 20 94 (21) 4 21.1

15 14 H NMe 1 24 20 80 0.25

16 6 H O 1 24 22 78 0.28

17 16 - - - 24 23 (23) 77 0.30

18 12 H - - 24 36 (55) 64 0.56

aSee Figure 2 for structures. ^bKey substrate; entries 1–14: MAHT substrate 20 (200 mM), trans-β-nitrostyrene 21 (2 M) and catalysts 3–16 (40 mM) in CDCl3/THF-d8 1:1 at 20 ºC; 15–18: substrate 24 (100 mM), 25 (110 mM) and catalyst 3–16 (20 mM) in CDCl3 at 20 ºC. ^cConversion yield of product 1, in % (entries 1–14, 22, 15–18: exo-26); in parenthesis: enanti- omeric excess, in %. ^dConversion yield of product 2, in % (entries 1–14, 23, 15–28: endo-26); ^eSelectivity: entries 1–14, A/D (addition/decarboxylation products 22/23); 15–18, exo/endo (DA products exo- 26/endo-26).

Characterized by a tetrahedral α carbon and the negative charge localized on the carboxylate, the enolate tautomer in RI1 can decarboxylate before addition. The planar tautomer in RI2 with a negative charge delocalized over both carbonyls proceeds to addition before decarboxylation. It has been previously argued that anion-π recognition of planar, charge-delocalized over bent,

OtBu O O

18

17 19

O

3–10, 12 +

tBuO

a) b)

O N

O O

RNH₂ or ROH

∆A/D

3 4 5 6 7 8 9 10 11 12 N NH O

12 3–11

n N X R O

X = NH

R = CN n

N X R O

n = 1 2 3

n = 1 2 3 N

N O

X = O

n = 1 N NH O

16

R = H N N

N

0 5 10 15

13–15

NMe NCy NH X =

–5

O SR O –O

H H SR

O O

HO SR

Ph O SR

O

O₂N O₂N Ph

20 23 (D)

21

+

catalyst

– CO₂

RI1 N⁺H NH O

R¹

R¹ = H:

R¹ = CN:

R¹ = H:

R¹ = CN:

SR O –O

OH H

22 (A) addition decarboxylation

RI2 N⁺H NH O

R¹

–118 kJ mol^-1 –136 kJ mol^-1

–122 kJ mol^-1 –132 kJ mol^-1 R = PMP

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3

Figure 4. The anionic Diels-Alder reaction of hydroxypyrone 24 and maleimide 25 with notional anionic transition state TS1 for exo products on fullerene surfaces and π-surface incompatible TS2 for endo products.

Only one arbitrary enantiomer is shown per diastereomer.

charge-localized tautomers could cause selectivity.¹⁸ Computa- tional models of RI2 with and RI1 without anion-π interactions provide unprecedented theoretical support for this speculation (Figures 3, S13–S18). With cyano fullerene 11, the interaction energies in RI1 (–136 kJ mol^–1) were stronger than in RI2 (–132 kJ mol^–1). Upon weakening of the hydrogen-bond donor in 3, the equilibrium between the tautomers shifted and RI2 (–122 kJ mol^–

1) became more stable than RI1 (–118 kJ mol^–1, Figures 3, S15, S18). These computational results were in beautiful agreement with the dramatic shift in selectivity from ∆A/D = 2.1 with 11 (vs fullerene-free control 15) to ∆A/D = 6.2 with 3 (vs 13, Figures 3 and 2). The enolate-π distances of 3.08 Å in RI2 were shorter than with standard π-π interactions (≥3.2 Å) and covalently enforced anion-π interactions on planar and smaller surfaces (3.13 Å).¹⁹ Competition from intramolecular cation-π interactions with ammonium cations was not observed.

Catalyst 12 bearing a rigidified, cyclic and chiral interfacer¹⁸ showed a great selectivity for enolate addition with an A/D value of 21.1 (Table 1, entry 14). The ∆A/D = 16.0 confirmed that enforced anion-π interactions account for this for small-molecule anion-π catalysts unprecedented selectivity for small-molecule anion-π catalysts (Figure 2, Table 1, entries 13, 14). In computational models, cyclohexyl interfacers shortened malonate- fullerene distances by 0.04 Å to 3.01 Å, and the preference for RI2 over RI1 remained (4 kJ mol^-1, Figure S16). Addition product 22 was obtained with 21% ee. Contrary to otherwise unprob- lematic asymmetric anion-π catalysis,³ similar enantioselectivity for this reaction could be observed so far only with axially chiral anion-π catalysts.²⁰ Weaker enantioselectivity with control 16 supported that anion-π interactions with the fullerene surface contribute to stereoselectivity.

The exo/endo diastereoselectivity of Diels-Alder reactions is another topic that invites for control on π-acidic surfaces.²¹ The anionic [4+2] cycloaddition of 3-hydroxy-2-pyrones 24 to dieno- phile 25 was selected as an example with strong endo selectivity (Figure 4). Fullerenes with flexible interfacers failed to change this intrinsic selectivity. The best exo/endo ratio of 0.28 obtained for fullerene 6 was not much larger than the exo/endo = 0.25 with the fullerene-free control 14 (Table 1, entries 15, 16). However, fullerene 12 with conformationally constrained interfacers gave exo/endo = 0.56 with 55% ee (Table 1, entry 18). This increase in exo production and enantioselectivity equaled the best result obtained so far on planar NDI π surfaces bearing the same rigidified, cyclic and chiral interfacer.²¹ Clearly weaker exo/endo = 0.30 obtained with 23% ee for control 16 (Table 1, entry 17) supported that anion-π interactions interactions contribute to both diastereoselectivity and enantioselectivity. They can conceivably be expected to stabilize the delocalized anion of the conjugate base of 24. Experimental support is available that this anion-π stabilization continues during the subsequent charge delocaliza-

tion in the intrinsically disfavored exo transition state TS1 of the [4+2] cycloaddition.²¹ As with above enolate addition, these anion-π interactions will naturally receive constant support from ion pairing with the covalent counterion. Further contributions from π-π interactions would be weak without the presence of the negative charge, and contrary to anion-π interactions, they would decrease, almost vanish during the cycloaddition and thus possi- bly hinder rather than support the progress of the reaction. The incompatibility of the secondary orbital interactions in the endo transition state TS2 with stabilization by similarly extended ani- on-π interactions provides a consistent explanation for the increase in exo Diels-Alder product formation on fullerene surfaces as outlined in TS1. This interpretation is in agreement with de- tailed studies of this reaction on planar π surfaces.²¹

The results with anionic Diels-Alder reactions are consistent with the selective acceleration of the disfavored enolate addition by anion-π catalysis and the theoretical insights on the underlying anion-π interactions on fullerenes. Activities that exceed results on small, quadrupolar and planar π surfaces support the potential of large, polarizable and curved surfaces for anion-π catalysis, particularly with regard to further development of the outstanding catalyst 12 by, e.g., intramolecular polarization from the opposite fullerene face, perhaps even supported by light, and with reactions that involve unusual topologies and selectivities. Taken together, our results open attractive new perspectives for the so far poorly explored use of carbon allotropes in catalysis, from the rich fullerene collection to carbon nanotubes and graphene.

ASSOCIATED CONTENT

Supporting Information. Detailed experimental procedures.

This material is available free of charge via the Internet at http://pubs.acs.org.

AUTHOR INFORMATION Corresponding Author

[email protected]

Notes

The authors declare no competing financial interest.

ACKNOWLEDGMENTS

We thank Y. Cotelle for contributions to synthesis, the NMR and the Sciences Mass Spectrometry (SMS) platforms for services, and the University of Geneva, the Swiss National Centre of Com- petence in Research (NCCR) Molecular Systems Engineering, the NCCR Chemical Biology and the Swiss NSF for financial support. J. L.-A. acknowledges a Curie fellowship (project 740288), A. F. thanks MINECO of Spain (project CTQ2014-57393-C2-1-P, FEDER funds) for financial support.

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(6)

5

SR’

O –O

OH H N⁺H X O

R

N⁺

NH O

O O

O^– N O

O

O X NMe2

addition

exo decarboxylation

endo chloride

on

X = NH O NMe NCy

R = H CN n = 1-3