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We have studied the impact of achiral substituents on the chiral supramolecular architectures of diketopyrrolo[3,4-c]pyrrole-1,2,3-1H-triazole (DPP) dyes. We decorated the same chiral DPP motif with substituent groups on the nitrogen atoms of the lactam moiety: the hydrophobic n-octyl alkyl chain, the hydrophilic tri(ethyleneglycol) (TEG) chain and the thermo-cleavable tert-butoxycarbonyl (t-Boc) carbamate group. In spite of having identical conjugated chromophore and chiral appendages, in aggregated form the three dyes displayed profoundly different optical,chiroptical,electrochemical and thermal features. ECD measurements revealed differences in the aggregation modes, which would be in accessible by most other techniques. We found strong chiroptical features, which would have major implications in the context of chiral organic opto-electronics and in the development of other highly innovative technological applications.

The increasing attention towards environmentally friendly synthetic protocols has boosted studies directed to the development of green and sustainable methods for direct C−H bond arylation of (hetero)arenes. In this context, here the infrared (IR) irradiation‐assisted solvent‐free Pd‐catalyzed direct C−H bond arylation of (hetero)arenes was achieved. Several heteroaryl‐aryl coupling reactions were described, also involving heterocycles commonly used as building blocks for the synthesis of organic semiconductors. The reaction tolerated many functional groups on the aromatic nuclei. The IR‐irradiation as the energy source compared favorably with thermal heating and, in combination with solvent‐free conditions, provided an important contribution to the development of protocols fitting with the principles of green chemistry., No solvent needed: Pd‐catalyzed (hetero)aryl–aryl coupling via C−H bond activation is proven in solvent‐free conditions under IR irradiation as effective and convenient energy source. The reaction efficiently works on several conjugated cores and tolerates several functional groups on aryl iodides used as coupling partners. The protocol opens the way to energy‐effective solvent‐free methods in organic synthesis.

The chiroptical features of chiral diketopyrrolo[3,4-c]pyrrole (DPP) derivatives have been only marginally investigated to date. In this regard, we have synthesized ad hoc four chiral DPP dyes, functionalized with enantiopure alkyl groups from natural sources either on the lactam moieties or on the terminal positions of the π-conjugated backbone, to promote an efficient self-assembly into chiral supramolecular structures. For each of them, the aggregation modes has been investigated by absorbance and ECD spectroscopies in conditions of solution aggregation and on thin films, considering the effects of deposition technique (drop casting vs. spin coating) and post-deposition operations (solvent and thermal annealing). The effect of the structure of lateral π-conjugated units attached to the central DPP scaffold, as well as that of the position of the alkyl chiral group, has been assessed. ECD revealed superior capability, compared to absorbance spectroscopy, to provide information on the aggregation modes and to detect the possible co-existence of multiple aggregation pathways.

A fruitful switch from tert-butyl to cumene hydroperoxide was able to overcome a difficulty arose in the enantioselective oxidation of fluorinated aryl benzyl sulfide with hydroperoxides in the presence of a titanium/(S, S)-hydrobenzoin catalyst. New experiments show the complementarity of the old and the new protocols and indicate unequivocally the right choice leading to the corresponding highly enantioenriched sulfoxides. Moreover, in a totally unexpected way, the new protocol was able to overcome another difficulty arose in another field of research, that is the enantioselective oxidation of a fluorinated aryl phenacyl sulfide. Also in this case, the complementarity of behavior is acting. Finally, this investigation gives new support to the attribution of configuration of sulfoxides with ECD techniques, but only if the protocol outlined in our past research was followed thoroughly.

Two crystalline benzyl phenyl sulfides, bearing at the same time both a pentafluorophenyl and a nitrophenyl moiety in two different assemblies, were investigated by means of single crystal X-ray diffraction. The main assembly interactions were recognized and compared with the different behaviors of analogous sulfides bearing only one of these two functional groups. Since short contacts involving fluorine atoms have been a source of controversy, their contribution to the stability of the crystal was analyzed both with the help of Hirshfeld surface analysis, and with a comparison with items in the Cambridge Structural Database. The situation of a gauche-conformed sulfide having two contemporary interactions involving electron poor aryl groups is of particular interest.

The multi-component Betti reaction of 2-naphthol, benzaldehyde and (S)-amines, that usually provides highly valuable aminobenzylnaphthol bearing two stereogenic centers, yielded a completely racemic product, when (S)-valine methyl ester was employed as the amine in the usual reaction protocol. The cause of this drawback, that appears to be overlooked in the literature, was investigated. As a result, new reaction conditions were set up, that were able to yield the expected useful product, having two fully resolved stereogenic centers. Furthermore, when the effect of substituents on the phenyl ring was preliminarily studied, we found that 4-fluoro- and 4-chlorobenzaldeyde gave stereoisomerically pure compounds also in the original reaction protocol.

Direct arylation of 5-octylthieno[3,4-c]pyrrole-4,6-dione with a series of functionalized aryl iodides via C-H bond activation is demonstrated in a deep eutectic solvent made of choline chloride and urea in non-anhydrous conditions and without exclusion of air. This is the first demonstration of a thiophene-aryl coupling via direct arylation in deep eutectic solvents.

Direct arylation of thienopyrrolodione, diketopyrrolopyrroles, benzodithiophene derivatives, and fluorinated heteroarenes with functionalized aryl iodides is proven in solvent-free and non-anhydrous conditions. The reaction is performed in the presence of air and tolerates several functional groups on both the coupling partners, enabling a convenient synthesis of extended heteroaromatic conjugated molecules.

Three beta-keto sulfoxides (1-3) were synthesized in enantiopure form and investigated by means of circular dichroism (CD) spectroscopy, both in electronic and vibrational range (ECD, VCD), in combination with quantum chemical calculations. For compound 2, the X-ray structure was available; thus, the ECD in the solid state was also considered to reveal the differences between the molecular species in both states. Despite the simplicity of all ?-keto sulfoxides under investigation (29 atoms), reproducing even the major spectral VCD features failed for two compounds, making the use of VCD not ideal to assign their absolute configuration in a reliable way. We demonstrated, however, that the use of ECD spectroscopy, both in solution and solid state, can easily, unambiguously, and without any complication simulate all bands by applying the standard protocol for calculations. This study may stimulate the debate on the need of the use of two chiroptical methods simultaneously in the determination of absolute configurations.

A series of 13 enantiopure aryl benzyl sulfoxides (1a, 1b, 1c, 1d, 1e, 1f, 1g, 1h, 1i, 1j, 1k, 1l, 1m) with different substituents on the two aromatic rings has been previously analyzed by means of electronic circular dichroism (CD) spectroscopy. Most of these compounds are crystalline and their X-ray structure is established. For almost one-half of the series, CD spectra measured in the solid state were quite different from those in acetonitrile solution. We demonstrate that the difference is due to strong exciton couplings between molecules packed closely together in the crystal. The computational approach consists of time-dependent density functional theory (TDDFT) calculations run on “dimers” composed of nearest neighbors found in the lattice. Solid-state CD spectra are well reproduced by the average of all possible pairwise terms. The relation between the crystal space group and conformation, and the appearance of solid-state CD spectra, is also discussed. Chirality 26:462–470, 2013. © 2013 Wiley Periodicals, Inc.

The multicomponent reaction between 2-naphthol, aryl aldehydes and ammonia or amines yields aminobenzylnaphthols in a process known as the Betti reaction, which was first uncovered at the beginning of the 20th century. The aminobenzylnaphthols could be easily resolved into their enantiomers. After a long silence, the results of our research a decade ago on this useful reaction and on the chiral materials produced has stimulated further work in a number of other laboratories. As a result, novel applications of the Betti reaction to produce new chiral aminobenzylnaphthols were reported together with the evaluation of these chiral bases in asymmetric synthesis. Herein, we present a selection of the relevant studies on this topic.

The title reaction generally proceeds with high yields and provides the products with high stereoselectivity.

High ee values (up to 94–96% ee) and moderate isolated yields (48–50%) were achieved in the preparation of Sulindac alkyl esters. These molecules are simple and straightforward precursors of Sulindac, an anti-inflammatory drug that has also been recently investigated in anti-cancer therapy. The key step of the overall procedure was the enantioselective hydroperoxide oxidation of the Sulindac sulfide alkyl esters in the presence of chiral complexes of titanium with either ( S , S )- or ( R , R )-hydrobenzoin. Various reaction conditions were investigated in order to obtain the best balance between yield and enantioselectivity.

Single crystal X-ray structure determination of four crystals of alkyl or aryl p-haloaryl sulfoxides is reported. Intramolecular short contacts between the ortho-hydrogen of the aryl ring and the oxygen of the sulfinyl group were found to determine the conformations of the sulfoxides. On the other hand, in the absence of classical hydrogen bond donors, crystal packing arrangements are the results of intermolecular aryl hydrogen-oxygen short contacts and of interactions involving halogen atoms. From a comparison of the structures of the investigated sulfoxides with other literature data, the crystal packings of these types of compound appear to derive from a complex balance among different interactions.

The results of a combined computational-experimental study of the oxidation of various fluorinated aryl benzyl sulfides using tert-butyl hydroperoxide (TBHP) in the presence of a complex of titanium and (S,S)-hydrobenzoin are presented. As observed in previous studies for other aryl benzyl sulfides, the reaction leads to enantiopure sulfoxides (ee>98 %) in good isolated yields (81–96 %) except the case of pentafluorobenzyl pentafluorophenyl sulfide for which a lower ee (61 %) is observed. DFT computations on a model-system formed by the substrate, the oxidant TBHP and the [(S,S)-hydrobenzoin]2-Ti complex satisfactorily explain this unexpected item. The enantioselectivity is governed by the relative energy of the two diastereomeric octahedral complexes that form if TBHP approaches the initial complex between substrate and [(S,S)-hydrobenzoin]2-Ti before the oxygen transfer. For pentafluorobenzyl pentafluorophenyl sulfide, the two octahedral complexes are almost degenerate and, thus, they form in similar amounts. As the two corresponding diastereomeric transition states are similar in energy, the probability to follow one or the other diastereomeric reaction channel becomes comparable, which leads to the lower enantiomeric excess experimentally observed. Our computations indicate that the particular “folded conformation”, adopted by the substrate only if both phenyl rings are fluorinated, is the key factor that determines the near degeneracy of the two diastereomeric octahedral complexes.

Benzyl p-bromophenyl sulfoxide 1 was obtained on a multigram scale and in an enantiomerically pure form by an enantioselective catalytic oxidation, using tert-butyl hydroperoxide in the presence of chiral titanium complexes. Some mechanistic and stereochemical features of interest were studied in this process. Compound 1 was then subjected to two different substitution reactions with Grignard reagents, which caused two sequentially stereocontrolled carbon-for-carbon displacements, leading to chiral nonracemic dialkyl sulfoxides.

An experimental investigation of the enantioselective oxidation of aryl benzyl sulfides by tert-butyl hydroperoxide in the presence of a titanium/hydrobenzoin catalyst has shown that these sulfides are ideal substrates for this catalytic system, with negligible interference by the substituents on the aryl groups. A reaction mechanism based on DFT computations has been proposed. The DFT MPWB1K functional was used in the theoretical investigation to account for weak hydrogen-bonding and pi interactions. The computed reaction profile explains the experimentally observed enantioselectivity, which is determined by the thermodynamics of the first phase of the reaction. A detailed discussion of the hydrogen-bonding and pi interactions that drive the reaction along the observed stereochemical path is given.

A series of experiments was performed to test a theoretical model that we have recently proposed to explain the highly enantioselective oxidation of aryl benzyl sulfides with tert-butyl hydroperoxide in the presence of a complex between titanium and (S,S)- or (R,R)-hydrobenzoin. The studied variations involved the sulfides, the ligands, and the order of addition of reactants. The reaction path predicted by our model was confirmed in every experiment. In particular, aryl benzyl sulfides behaved as the ideal substrate for this type of asymmetric oxidation, which yields synthetically useful, enantiopure aryl benzyl sulfoxides in a straightforward manner. The theoretical model of the enantioselective oxidation of aryl benzyl sulfides in the presence of chiral titanium catalysts was tested with a series of experiments in which the reagents and conditions were varied. It was confirmed that aryl benzyl sulfides are an ideal substrate for this oxidation protocol, which yields the synthetically useful chiral non-racemic aryl benzyl sulfoxides. © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.