Angel Martín-Domenech

Hierarchical Selectivity in Fullerenes: Site‐, Regio‐, Diastereo‐, and Enantiocontrol of the 1,3‐Dipolar Cycloaddition to C70

Since the discovery of fullerenes and their further preparation on a multigram scale, these molecular carbon allotropes have been thoroughly investigated from the chemical viewpoint in the search for new modified fullerenes that are able to exhibit unconventional properties for practical applications. Furthermore, this knowledge has allowed a faster and better understanding of the chemical reactivity of the related carbon nanostructures, in particular of the promising carbon nanotubes, endohedral fullerenes, and the most recent graphenes. However, the number of studies on the reactivity of higher fullerenes is comparatively scarce and the use of asymmetric catalysis in these systems has been neglected so far. Higher fullerenes include a great diversity of molecules with different structures and chemical behavior that, because of the minor degree of symmetry, give rise to a complex covalent chemistry, in which chirality is an important and fascinating aspect. The preparation of chiral fullerenes has been based on chiral starting materials or, alternatively, on the most common racemic syntheses followed by complex, expensive, and highly time-consuming chromatographic isolation and purification processes. However, even when the isolation of the different isomers is feasible, the high costs and low abundance of higher fullerenes make necessary the availability of an efficient synthetic methodology to limit a broad distribution of products. Recently, we reported a straightforward procedure catalyzed by silver or copper acetate to efficiently obtain pyrrolidino[60]fullerenes with stereochemical control by enantioselective cycloaddition of azomethine ylides to the C60 molecule. [8] However, the extension of the scope of such a methodology to higher fullerenes, namely C70, is not a trivial process because C70 has to face many distinct levels of selectivity. Unlike C60, C70 lacks a spherical symmetry and has four different types of double bonds on the cage. The most common additions to [70]fullerene proceed in a 1,2 manner with a regioselectivity driven by the release of the strain of the double bond. Accordingly, additions occur preferentially at the most strained fullerene double bonds, namely those located at the polar zone (a site followed by b and g sites). The flatter equatorial region is less reactive and the addition only rarely takes place at the double bond of the d site. Particularly, cycloadditions of azomethine ylides typically give rise to the a, followed by the b, and a small amount of the g regioisomers (C(8) C(25), C(7) C(22), C(1) C(2) according to the systematic numbering; Figure 1). We propose to refer to these isomers (a, b, etc.) and to this form of selectivity as “site isomers” and site selectivity, respectively, to distinguish them from the regioisomers that result from the addition of nonsymmetric 1,3-dipoles to a double bond of the fullerene sphere. Indeed, depending on the orientation of the asymmetric azomethine ylide addition to the fullerene double bond, two regioisomers are, in turn, possible for each of the formed cycloadducts (see Figure 1). Furthermore, each of these regioisomeric pyrrolidines could be formed in a cis or trans configuration (diastereomers) and, in turn, in both of the enantiomeric forms. Herein we describe an efficient catalytic site-, regio-, diastereo-, and enantioselective cycloaddition of N-metalated azomethine ylides to C70 at low temperatures and while maintaining the atom economy principle. This methodology [*] E. E. Maroto, Dr. S. Filippone, Dr. . Mart n-Domenech, Prof. Dr. N. Mart n Departamento de Qu mica Org nica I Facultad de Ciencias Qu micas Ciudad Universitaria s/n, 28040 Madrid (Spain) Fax: (+ 34)91-394-4103 E-mail: nazmar@quim.ucm.es Homepage: http://www.ucm.es/info/fullerene

On the Mechanism of the Thermal Retrocycloaddition of Pyrrolidinofullerenes (Retro-Prato Reaction)

In contrast to N-methyl or N-unsubstituted pyrrolidinofullerenes, which efficiently undergo the retrocycloaddition reaction to quantitatively afford pristine fullerene, N-benzoyl derivatives do not give this reaction under the same experimental conditions. To unravel the mechanism of the retrocycloaddition process, trapping experiments of the in-situ thermally generated azomethine ylides, with an efficient dipolarophile were conducted. These experiments afforded the respective cycloadducts as an endo/exo isomeric mixture. Theoretical calculations carried out at the DFT level and by using the two-layered ONIOM (our own n-layered integrated molecular orbital and molecular mechanics) approach underpin the experimental findings and predict that the presence of the dienophile is not a basic requirement for the azomethine ylide to be able to leave the fullerene surface under thermal conditions. Once the 1,3-dipole is generated in the reaction medium, it is efficiently trapped by the dipolarophile (maleic anhydride or N-phenylmaleimide). However, for N-unsubstituted pyrrolidinofullerenes, the participation of the dipolarophile in assisting the 1,3-dipole to leave the fullerene surface throughout the whole reaction pathway is also a plausible mechanism that cannot be ruled out.

Switching the Stereoselectivity: (Fullero)Pyrrolidines “a la Carte”

Stereodivergent syntheses of cis/trans pyrrolidino[3,4:1,2]fullerenes and endo/exo pyrrolidines are reported with high enantioselectivity levels. Fullerenes are revealed as a useful benchmark to develop suitable catalysts to control the stereochemical outcome and to shed light on the mechanism involved in the related 1,3-dipolar cycloaddition.

H-bond-assisted regioselective (cis-1) intramolecular nucleophilic addition of the hydroxyl group to [60]fullerene.

The one-step reaction of 2,6-dihydroxyphenylmethyl ketone and sarcosine with [60]fullerene in refluxing chlorobenzene affords, in a totally regioselective process, the cis-1 bicyclic-fused organofullerene through a new intramolecular nucleophilic addition of one hydroxy group to the fullerene double bond. Experimental findings reveal the presence of a methyl group on C-2 of the pyrrolidine ring as an essential requirement for the cyclization process, whereas the existence of a H-bond between a second hydroxylic group and the nitrogen atom of the pyrrolidine ring seems to favor the approaching geometry without determining the reaction outcome. Theoretical calculations using the two-layered ONIOM approach and density functional theory support the experimental findings, predicting the strong impact that the presence of the methyl substituent on the C-2 of the pyrrolidine ring has on the molecular geometry and, hence, on the intramolecular cyclization process.

Regio- and stereospecific synthesis of substituted cyclohexenediols from 7-oxabicyclo[2.2.1]hept-5-en-2-ols and organolithium reagents

Abstract The bridge opening reactions of 7-oxabicyclo[2.2.1]hept-5-en-2-ols,4 and6 with organolithium reagents proceed with complete regio- and stereoselectivity to produce highly functionalized cyclohexene derivatives5 and7, respectively.

Regioselective intramolecular nucleophilic addition of alcohols to C60: one-step formation of a cis-1 bicyclic-fused fullerene.

The first example of intramolecular nucleophilic addition of an alcohol to a fullerene double bond is described. In particular, the straightforward one-step reaction of commercially available sarcosine, hydroxyacetaldehyde, and [60]fullerene, in refluxing chlorobenzene, affords a structurally complex novel pyrrolidinofullerene endowed with a furan ring simultaneously fused to both the pyrrolidine and fullerene moieties, which has been spectroscopically and electrochemically characterized. The 2-fold cyclization reaction occurs in a totally regioselective stepwise process leading exclusively to the cis-1 isomer. Theoretical calculations (DFT and ONIOM approach) predict that, in contrast to the previous examples with phenols, which require the existence of an intramolecular H-bond and the presence of a methyl group on C-2 of the pyrrolidine ring to afford the cyclized pyran-fused pyrrolidinofullerenes, the formation of the oxygen pentagonal ring is highly favored and does not present such structural constrains. Actually, the 5-exo-trig cyclization reaction involving the nucleophilic attack of the hydroxyl group to the fullerene surface is moderately exothermic although it has a substantially high energy barrier in accordance with the fact that high temperatures have to be reached to obtain the final product.

Mass Spectrometry Studies of the Retro-Cycloaddition Reaction of Pyrrolidino and 2-Pyrazolinofullerene Derivatives Under Negative ESI Conditions

Substituted pyrrolidino- and 3-alkyl-2-pyrazolinofullerenes ionize under ESI and MALDI mass spectrometry conditions and negative mode of detection undergoing mass spectral fragmentations, which can be easily correlated with the reported results for the thermal and electrochemical retro-cycloaddition reactions of these compounds. 2-Pyrazolinofullerenes lead directly to a [60]fullerene product ion formed through a retro-cycloaddition process regardless of the substituents attached at the carbon and nitrogen atoms of the heterocyclic ring. These results are different from whose reported for the thermal and electrochemical processes. In contrast, pyrrolidinofullerenes undergo different fragmentative reactions depending upon the substituents (hydrogen, alkyl, or acyl) attached at the nitrogen atom of the heterocyclic ring leading eventually to the pristine C60 in the last step of the fragmentation pathway.

Adduct removal from methanofullerenes viareductive electrochemistry

Electrochemical reduction of different spiromethanofullerenes leads to adduct removal, opening the way to new protecting–deprotecting groups in fullerene chemistry.

Reductive electrolysis of [60]fullerene mono-methanoadducts in THF leads to the formation of bis-adducts in high yields

A new reaction, electrolytically induced adduct transfer between [60]fullerene mono-adducts, leads to bis-adducts with a unique regioisomer distribution.