Javier Iglesias-Sigüenza

Axially chiral triazoloisoquinolin-3-ylidene ligands in gold(I)-catalyzed asymmetric intermolecular (4 + 2) cycloadditions of allenamides and dienes.

The first highly enantioselective intermolecular (4 + 2) cycloaddition between allenes and dienes is reported. The reaction provides good yields of optically active cyclohexenes featuring diverse substitution patterns and up to three stereocenters. Key to the success of the process is the use of newly designed axially chiral N-heterocyclic carbene-gold catalysts.

Fullerenes as neutral carbon-based Lewis acids.

Since G. N. Lewis classified molecules into those that can donate an electron pair (bases) and those able to accept it (acids), this formally simple description has been an extremely useful tool to rationalize and also predict the reactivity of both main-group and transition-metal complexes. Thus, when a Lewis acid is combined with a base, a neutralization reaction takes place with the concomitant formation of a Lewis adduct. If we focus our attention on carbon-based Lewis bases, we find that they are very diverse in nature; typical examples are ylides, isonitriles, N-heterocyclic carbenes (NHCs), and enamines. In contrast, this notable variety is not found for carbon-based Lewis acids, which remain restricted mainly to trityl cations and some electron-poor allenes. In this regard, the recent paper by Bazan and co-workers is remarkable. Inspired by earlier experimental work with a bisfluorenyl-substituted allene, in which a related structural motif can be detected (Scheme 1a), these authors report that the archetypal fullerene molecules, C60 and C70, can behave as all-carbon Lewis acids that form the corresponding Lewis adducts by reaction with highly basic N-heterocyclic carbenes (Scheme 1b). In a typical experiment, equimolar amounts of C60 and 1,3-bis(diisopropylphenyl)imidazol-2ylidene were allowed to react at room temperature over 24 h in o-dichlorobenzene (o-DCB). After removal of the solvent under vacuum, the crude product was washed with toluene and THF. Single crystals suitable for X-ray diffraction analysis were obtained from o-DCB at 35 8C. Interestingly, the cyclopropanation reaction that often takes place when carbenes or carbene surrogates are allowed to react with fullerenes was not evident: the obtained product displayed a single junction connecting the carbene and fullerene fragments with a C1 C2 bond 1.502(16) long. To gain insight into the nature of the bonding in 2, the authors performed density functional calculations at the B3LYP/631G** level. In agreement with the experimental data, natural bond order analysis indicated that the C C bond between the carbene and the fullerene is a single bond (Wiberg bond index of 0.97) with an electron occupancy of 1.97 e. Moreover, according to natural population analysis, total charges of + 0.84 e and 0.84 e reside in the imidazole and the fullerene moieties, respectively. This overall picture of the charge distribution corresponds to a neat transfer of electron density from the carbene to the fullerene as typically occurs in Lewis acid/base adducts. In a first approximation, the stability of 2 can be attributed to the confluence of two main factors, namely: 1) the strength of the newly formed C C bond makes the adduct formation process irreversible; and 2) the LUMO of the partially formed imidazolium fragment is much higher in energy than the LUMO of less stabilized carbenium ions. This precludes formation of the cyclopropane derivative from the the primary adduct (Scheme 2a–d). The generality of the adduct formation between NHCs and fullerenes has also been confirmed by extension of this reaction to C70. Again a single-bonded adduct was obtained and interestingly, its formation occurs with complete regioselectivity. Of the five plausible regioisomeric products only the one with the carbene moiety bonded to one of the ten apical carbons of C70 is observed. Scheme 1. a) Carbene–allene adduct 1 formed by reaction between ItBu and bisfluorenyl allene. b) Reaction of C60 with IDipp to afford the IDipp–C60 adduct 2.

Synthesis of IAN-type N,N-Ligands via Dynamic Kinetic Asymmetric Buchwald-Hartwig Amination.

The Pd(0)-catalyzed coupling of racemic heterobiaryl bromides, triflates, or nonaflates with aryl/alkyl primary amines using QUINAP as the ligand provides the corresponding axially chiral heterobiaryl amines with excellent yields and enantioselectivities. Reactivity and structural studies of neutral and cationic oxidative addition intermediates support a dynamic kinetic asymmetric amination mechanism based on the labilization of the stereogenic axis in the latter and suggest that coordination of the amine to the Pd center is the stereodetermining step.

Synthesis of axially chiral heterobiaryl alkynes via dynamic kinetic asymmetric alkynylation

The dynamic kinetic Pd0-catalyzed alkynylation of racemic heterobiaryl sulfonates was used for the asymmetric synthesis of axially chiral heterobiaryl alkynes with a broad scope. The use of Pd(OAc)2/(S)-QUINAP as the precatalyst provides products in excellent yields and enantioselectivities under mild conditions (DMSO, 40 °C). Semireduction, 1,3-dipolar cycladdition or N-oxidation served to illustrate the synthetic potential of the methodology.

A Cationic Unsaturated Platinum(II) Complex that Promotes the Tautomerization of Acetylene to Vinylidene

Complex [PtMe2 (PMe2 ArDipp2 )] (1), which contains a tethered terphenyl phosphine (ArDipp2 =2,6-(2,6-i Pr2 C6 H3 )2 C6 H3 ), reacts with [H(Et2 O)2 ]BArF (BArF- =B[3,5-(CF3 )2 C6 H3 ]4- ) to give the solvent (S) complex [PtMe(S)(PMe2 ArDipp2 )]+ (2⋅S). Although the solvent molecule is easily displaced by a Lewis base (e.g., CO or C2 H4 ) to afford the corresponding adducts, treatment of 2⋅S with C2 H2 yielded instead the allyl complex [Pt(η3 -C3 H5 )(PMe2 ArDipp2 )]+ (6) via the alkyne intermediate [PtMe(η2 -C2 H2 )(PMe2 ArDipp2 )]+ (5). Deuteration experiments with C2 D2 , and kinetic and theoretical investigations demonstrated that the conversion of 5 into 6 involves a PtII -promoted HC≡CH to :C=CH2 tautomerization in preference over acetylene migratory insertion into the Pt-Me bond.

Bifunctional Squaramide Organocatalysts for the Asymmetric Addition of Formaldehyde tert-Butylhydrazone to Simple Aldehydes

The nucleophilic addition of formaldehyde tert-butylhydrazone to simple aldehydes (a formal hetero-carbonyl-ene reaction) can be performed with good reactivity and excellent enantioselectivity by virtue of the dual hydrogen-bonding activation exerted by amide-squaramide organocatalysts. The resulting hydroxydiazenes (azo alcohols) were isolated in high yields as enantiomerically enriched azoxy compounds after a regioselective azo-to-azoxy transformation. Subsequent derivatization provides an entry to relevant amino alcohols, oxazolidinones, and derivatives thereof.

Dynamic Kinetic Resolution of Heterobiaryl Ketones by Zinc-Catalyzed Asymmetric Hydrosilylation

A diastereo- and highly enantioselective dynamic kinetic resolution (DKR) of configurationally labile heterobiaryl ketones is described. The DKR proceeds by zinc-catalyzed hydrosilylation of the carbonyl group, thus leading to secondary alcohols bearing axial and central chirality. The strategy relies on the labilization of the stereogenic axis that takes place thanks to a Lewis acid-base interaction between a nitrogen atom in the heterocycle and the ketone carbonyl group. The synthetic utility of the methodology is demonstrated through stereospecific transformations into either N,N-ligands or appealing axially chiral, bifunctional thiourea organocatalysts.

Dynamic Kinetic Asymmetric Heck Reaction for the Simultaneous Generation of Central and Axial Chirality

A highly diastereo- and enantioselective, scalable Pd-catalyzed dynamic kinetic asymmetric Heck reaction of heterobiaryl sulfonates with electron-rich olefins is described. The coupling of 2,3-dihydrofuran or N-boc protected 2,3-dihydropyrrole with a variety of quinoline, quinazoline, phthalazine, and picoline derivatives takes place with simultaneous installation of central and axial chirality, reaching excellent diastereo- and enantiomeric excesses when in situ formed [Pd0/DM-BINAP] was used as the catalyst, with loadings reduced down to 2 mol % in large scale reactions. The coupling of acyclic, electron-rich alkenes can also be performed using a [Pd0/Josiphos ligand] to obtain axially chiral heterobiaryl α-substituted alkenes in high yields and enantioselectivities. Products from Boc-protected 2,3-dihydropyrrole can be easily transformed into N, N ligands or appealing axially chiral, bifunctional proline-type organocatalysts. Computational studies suggest that a β-hydride elimination is the stereocontrolling step, in agreement with the observed stereochemical outcome of the reaction.

N-Heterotricyclic cationic carbene ligands. Synthesis, reactivity and coordination chemistry

The direct dialkylation of triazolo[4,3-b]isoquinolin-3-ylidene structures readily affords dicationic N-heterotricyclic azolium salts. These are suitable starting materials for the synthesis of transition metal complexes containing N-heterotricyclic, cationic ligands characterized by extended charge delocalization. Silver and gold complexes as well as mono- and dicationic rhodium(i) complexes have been prepared and characterized, and the electronic properties of the ligand have been evaluated by using the TEP parameter and by comparison with a non-cationic analogue. X-Ray diffraction analysis of several carbene-metal complexes shows a negligible effect of the charge on the structures of the complexes. The catalytic activity of a tricationic gold complex has been evaluated in the intramolecular hydroarylation of a terminal alkyne.

Fingerprinting the Nature of Anions in Pyrylium Complexes: Dual Binding Mode for Anion-π Interactions

The interplay between noncovalent interactions that involve oxygenated heteroaromatic rings have been studied for the first time in this work. In particular, we report an advance in knowledge-based anion-π interactions together with (C-H)+ ⋅⋅⋅anion contacts. To understand how the anion modulates these interactions, the synthesis of pyrylium salts with a variety of anions was performed by using an anionic metathesis methodology. The synthesized pyrylium complexes were classified in series, for example, anions derived from halogens, from oxoacids, from p-block elements, and from transition metals. Crystallographic data, DFT calculations, and NMR spectroscopy methods provided access to an overall insight into the noncovalent behavior of the anion in this kind of system. Based on the DFT calculations and 1 H NMR spectroscopy, pyrylium protons can be used as chemical tags to detect noncovalent interactions in this type of compound.