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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.

A comprehensive and critical overview of the sustainable strategies for direct C–H bond arylation of (hetero)arenes, based on the use of recoverable catalysts, sustainable solvents and non-conventional energy sources, has been performed.

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.

Production of added value compounds from waste materials is of utmost importance for the development of a sustainable society especially regarding their use as catalysts in industrially relevant synthetic reactions. Herein, we show the production of laccases from four white-rot fungi, which were grown on agricultural residues, specifically Trametes versicolor 11269, Pleurotus ostreatus 1020, Panus tigrinus 707 and Lentinula edodes SC-495. The produced laccases were tested on biphasic laccase-mediator system (LMS) for the biocatalytic oxidation of the model substrate benzyl alcohol into benzaldehyde. The biphasic LMS was carried out in the presence both of tetrahydrofuran as co-solvent and of the mediator 2,2,6,6-tetramethyl-1-piperidinyloxyl (TEMPO) due to its high redox potential and its ability to perform the oxidation. Tolerance studies showed that the dialyzed solutions were able to tolerate 1% of co-solvent, while a concentration of 10% v/v negatively affected their activity. Performances in the biocatalytic oxidation of laccase solutions from different purification steps were compared. Similar conversion was observed for laccase in dialysis and gel filtration product versus commercial T. versicolor laccase. The latter oxidized almost 99% of substrate while the other laccase solutions were able to reach a conversion from 91% for the laccase solution from P. tigrinus 707 after dialysis, to 50% for the laccase solution from P. ostreatus 1020 after gel filtration. This work highlights the potential of unpurified laccase solutions to be used as catalysts in synthetic reactions.

The solvent-free Betti reaction of 2-naphthol, 4-nitrobenzaldehyde and (S)-valine methyl ester gave the corresponding aminobenzylnaphthol of the (S,S)-2-(((hydroxynaphth-1-yl)(4′-nitrophenyl)methyl)amino)-3-methylbutanoic acid methyl ester in good yield (59%). This product was fully characterized. We observed that the racemization that occurs in some Betti reactions with (S)-valine methyl ester was absent in this reaction, and thus the predominant (S,S)-product was obtained.

The Betti reaction of 2-naphthol, benzaldehyde and (S)-1-(4-nitrophenyl)ethylamine without any solvent gave the corresponding aminobenzylnaphthol, that is the (S,S)-1-(phenyl((1′-4-nitrophenyl-ethyl)amino)methyl)-2-naphthol, in good yield (56%). The absolute configuration of the title compound was attributed by NMR analysis, a procedure that is reliable if compared with the data obtained by X-ray diffraction experiments.

ObjectivesOur aim was to investigate the durability of different initial regimens in patients starting ART with CD4+ counts 5 log10 copies/mL.MethodsThis was a retrospective study of HIV-infected patients prospectively followed in the ICONA cohort. Those who started ART with boosted protease inhibitors (bPIs), NNRTIs or integrase strand transfer inhibitors (InSTIs), with CD4+ 5 log10 copies/mL, were included. The primary endpoint was treatment failure (TF), a composite endpoint defined as virological failure (VF, first of two consecutive HIV-RNA >50 copies/mL after 6 months of treatment), discontinuation of class of the anchor drug or death. Independent associations were investigated by Poisson regression analysis in a model including age, gender, mode of HIV transmission, CDC stage, HCV and HBV co-infection, pre-treatment HIV-RNA, CD4+ count and CD4+/CD8+ ratio, ongoing opportunistic disease, fibrosis FIB-4 index, estimated glomerular filtration rate, haemoglobin, platelets, neutrophils, calendar year of ART initiation, anchor drug class (treatment group) and nucleos(t)ide backbone.ResultsA total of 1195 patients fulfilled the inclusion criteria: 696 started ART with a bPI, 315 with an InSTI and 184 with an NNRTI. During 2759 person-years of follow up, 642 patients experienced TF. Starting ART with bPIs [adjusted incidence rate ratio (aIRR) (95% CI) 1.62 (1.29–2.03) versus starting with NNRTIs; P ConclusionsIn patients starting ART with 5 log10 HIV-RNA copies/mL, the durability of regimens based on InSTIs was longer than that of NNRTI- and bPI-based regimens.

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.

Along the lines of a systematic investigation of conformational constraints promoted by weak interactions, the aryl-stacked structures of some chiral cyclic phosphonamides synthesised with the aid of Betti bases as chirality inducers were investigated by X-ray diffraction analysis and NMR spectroscopy. The synthesised systems showed the stacked conformation between two of their aryl groups, leading to pre-organized structures. The pi-pi stacking motif between the aromatic rings was observed in solid state and in solution, suggesting that this supramolecular synthon could be used as a conformational constraining tool in the development of drug molecule candidates based on chiral cyclic phosphonamides. The disabling of the pi-pi stacking motif was pursued by adding an ortho-substituent on one aromatic ring.

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.

Croconaine dyes are appealing molecules synthesized via the condensation of croconic acid and reactive electron-donating aromatic or heterocyclic systems. Here, matrix-assisted laser desorption/ionization (MALDI) mass spectrometry (MS) investigation of indolenine-based croconaines is presented for the first time. Archetype proton-transfer matrices, such as 2,5-dihydroxybenzoic acid (DHB) and α-cyano-4-hydroxycinnamic acid (CHCA), 9-aminoacridine (9AA) as the protonating/deprotonating matrix, and electron-transfer (ET) secondary-reaction matrices, such as 1,5-diaminonapthalene (DAN) and trans-2-[3-(4-t-butyl-phenyl)-2-methyl-2-propenylidene]malononitrile (DCTB), were investigated. DHB, CHCA, and 9AA generate a mix of odd-electron molecular ions and protonated, sodiated, and potassiated adducts. Among the ET matrices, DAN was found to be capable of directing the ionization process toward the exclusive formation of odd-electron molecular ions M+• without fragmentation. MALDI tandem MS provides useful structural characterization of croconaine dyes, thus making identification very straightforward for all investigated compounds. Interestingly the fragmentation of bromo-containing croconaines revealed, for the first time, the gas-phase formation of a bromime cation [Br]+.

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.

NH-sulfoximines are emerging as useful and important targets in drug discovery and synthetic organic chemistry. We report herein the development of an efficient, convenient, and sustainable continuous-flow strategy, for the direct, straightforward preparation of NH-sulfoximines by using sulfides or sulfoxides as suitable starting material. The flow process uses PhI(OAc)2 as the oxidant and aqueous solutions of ammonia as the N source. The scope of the reaction has been demonstrated by using several substituted sulfides and sulfoxides including enantioenriched and biologically relevant starting materials. The flow strategy was found to be more convenient with respect to conventional batch processing.

Aminobenzylnaphthols are a class of compounds containing a large aromatic molecular surface which makes them suitable candidates to study the role of C—H...π interactions. We have investigated the effect of methyl or methoxy substituents on the assembling of aromatic units by preparing and determining the crystal structures of (S,S)-1-{(4-methylphenyl)[(1-phenylethyl)amino]methyl}naphthalen-2-ol, C26H25NO, and (S,S)-1-{(4-methoxyphenyl)[(1-phenylethyl)amino]methyl}naphthalen-2-ol, C26H25NO2. The methyl group influenced the overall crystal packing even if the H atoms of the methyl group did not participate directly either in hydrogen bonding or C—H...π interactions. The introduction of the methoxy moiety caused the formation of new hydrogen bonds, in which the O atom of the methoxy group was directly involved. Moreover, the methoxy group promoted the formation of an interesting C—H...π interaction which altered the orientation of an aromatic unit.

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.

International audience; A series of indolenine-based croconaines has been synthesized and their molecular structure has been investigated together with their solid state organization. Ambipolar semiconducting properties have been demonstrated in thin-film transistors, suggesting croconaines as a new class of molecular materials for organic electronics.

A series of ten chiral aryl benzyl sulfoxides with perfluorinated aryl or benzyl rings, obtained by enantioselective oxidation of sulfides, has been investigated by means of electronic circular dichroism (ECD) spectroscopy and time-dependent DFT (TDDFT) calculations. The (per)fluorination of the aromatic rings has a large impact on the conformer population, the molecular orbitals shape, and the character of electronic transitions. In this series, the transition responsible for the “sulfoxide primary” CD band has a large charge transfer (CT) character, as demonstrated by the CT metric index ΓNTO. As a consequence, global DFT hybrids such as B3LYP are largely inaccurate in the prediction of excited states; nevertheless, a correct simulation of CD spectra may be achieved by using range-separated functionals such as CAM-B3LYP. The use of the empirical Mislow's rule for assigning the absolute configuration is strongly discouraged for this class of compounds.

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.

Pentafluorobenzyl pentafluorophenyl sulfide is oxidised with moderate e.e. value and a low yield by the usually highly successful oxidation protocol based upon tert-butyl hydroperoxide (TBHP) in the presence of a titanium/hydrobenzoin complex. This disappointing result resisted until the present work, in which the switch of the oxidation agent (from TBHP to cumene hydroperoxide), suggested by our previous computations, yielded the enantiopure sulfoxide. This valuable chiral compound was obtained in good yields (76%) without resorting to a chromatographic separation. DFT computations uncovered that this favourable reactivity was originated by a stabilizing π−π−stacking between the phenyl group of the oxidant and the pentafluorophenyl moiety of the substrate.

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.

Some aminophenyl benzyl sulfides or benzyl pyridyl sulfides were asymmetrically oxidized with tert-butyl hydroperoxide in the presence of a complex between titanium i-propoxide and (S, S)-hydrobenzoin, an oxidation system that works particularly well with a vast set of aryl benzyl sulfides. Notwithstanding the presence of nitrogen-containing moieties that, in principle, could interfere with the correct co-ordination of the sulfide to the metal center, satisfactory levels of enantioselectivity (up to 78%) were measured for this oxidation process. © 2013 Taylor & Francis.

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.

A number of studies investigating trace eyeblink conditioning have found impaired, but not eliminated, acquisition of conditioned responses (CRs) in both animals and humans with hippocampal removal or damage. The underlying mechanism of this residual learning is unclear. The present study investigated whether the impaired level of learning is the product of residual hippocampal function or whether it is mediated by another memory system that has been shown to function normally in delay eyeblink conditioning. Performance of bilateral medial temporal lobe amnesic patients who had a prior history of participating in eyeblink conditioning studies was compared to a control group with a similar training history and to an untrained control group in a series of single cue trace conditioning tasks with 500 ms, 250 ms, and 0 ms trace intervals. Overall, patients acquired CRs to a level similar to the untrained controls, but were significantly impaired compared to the trained controls. The pattern of acquisition suggests that amnesic patients may be relying on the expression of previously acquired, likely cerebellar based, procedural memory representations in trace conditioning.

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.

Chronic misuse of alcohol affects an integrated neural circuit supporting the formation of associative memories acquired during eyeblink classical conditioning (R. McGlinchey-Berroth et al., 1995). The authors of this study investigated single-cue trace conditioning in amnesic and nonamnesic abstinent alcoholic individuals who either were or were not trained in a single-cue delay conditioning task. Overall, untrained alcoholic participants were severely impaired in acquisition, and alcoholic participants previously trained in single-cue delay conditioning performed similarly to untrained control participants. Individual performance in acquisition varied significantly within task but was relatively stable between the trace and delay tasks; there were nonamnesic and amnesic alcoholic participants who acquired responses at a normal rate in both delay and trace conditioning. The similarity of performances in delay and trace conditioning suggests a common source of impairment across both tasks.

Cisplatin is the most important metal-based drug used in tumor therapy; however, it suffers from severe side effects and a limited spectrum of activity. Since phosphonates are known to have a selective tropism for bones and calcified tissues, we have carried on the synthesis of different platinum complexes with a phosphonate ligand. The ligand used is diethyl [(methylsulfinyl)methyl]phosphonate (SMP), which can act as an O,S-donor towards Pt. Moreover, since the sulfur atom is a stable stereogenic center, the ligand is obtained in two enantiomeric forms. The synthesised complexes have the general formula [PtL2(SMP)], in which L2 stands for a bidentate (dimethylmalonate, 1,2-diaminocyclohexane, ethylenediamine) or two monodentate (chloride) ligands. The formation of a five-membered chelate ring contributes to the chemical stability of complexes with SMP, and 2D NMR experiments have allowed determination of the ring puckering, which is dependent upon the chirality of the sulfur stereocenter. For the (S) configuration at the sulfur center (free ligand), the δ puckering of the chelate ring is favoured. Preliminary studies have shown that these compounds are stable under physiological conditions. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)

Several carbanionic leaving groups can be easily displaced from the sulfinyl group by organometallic reagents. The reaction follows a highly stereoselective course of inversion of configuration. Provided that a ready route to the precursor sulfinyl compound is available (e.g. an enantioselective oxidation of the corresponding sulfide), the process can be transformed into an easy and versatile procedure for the stereoselective synthesis of sulfoxides. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)

The ability of bilateral medial temporal lobe amnesic patients (MT; n = 8) and normal participants (NC; n = 8) to acquire a conditional discrimination in trace and delay eyeblink conditioning paradigms was investigated. Experiment 1 assessed trace conditional discrimination learning by using a light conditional stimulus (S+/S−) and tone conditioned stimulus (CS) separated by a 1-s trace. NCs responded differentially on S+ trials (mean percent conditioned responses = 66) versus S− trials (30), whereas MTs were impaired in their acquisition of the conditional discrimination (S+ = 51, S− = 43). In Experiment 2, the temporal separation was eliminated. NCs acquired the conditional discrimination (S+ = 70, S− = 29). MTs were unable to respond differentially (S+ = 42, S− = 37). The findings indicate that the hippocampal system is essential in acquiring a conditional discrimination, even in a delay paradigm.

After the discovery of a few cases of lower enantioselectivity in the oxidation of aryl benzyl sulfides with hydroperoxides in the presence of a complex between titanium isopropoxide and (S, S)-hydrobenzoin, a screening of the oxidation of new substrates that are related to the structures that gave low ee values, was performed. From this screening, we confirmed that only a few sulfides remain as exceptions within a framework of exceptionally high stereoselectivity of the oxidation reaction. Moreover, the exceptions are clearly identified and are connected to particular coordinating moieties present on the aryl groups. (C) 2015 Elsevier Ltd. All rights reserved

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.