Stereoselective catalytic in-flow synthesis of chiral molecules

Continuous-flow systems have emerged as a powerful technology for performing chemical transformations and have recently attracted attention also for the preparation of chiral APIs (active pharmaceutical ingredients). Recently developed stereoselective transformations performed in chiral organocatalytic reactors under continuous flow conditions will be presented. Both packed-bed and monolithic reactors, either made by silica and/or organic polymers, have been successfully used in metal-free reactions promoted by immobilized enantiopure primary or secondary amines. The possibility to perform organocatalytic reactions in (micro)-mesoreactors and to synthesize in flow-mode chiral intermediates of pharmaceutical interest will be also discussed. On the other hand, 3D-printing technology allows chemists to build devices with high precision and well-defined architecture. Stereoselective catalytic in-flow reactions in 3D-printed reactors will be also briefly highlighted. The combination of these two only partially explored technologies in stereoselective organic synthesis opens new and intriguing possibilities; the fabrication of ad hoc designed reactors and other devices, to perform at best different reactions becomes now feasible and gives new impulse to the use of enabling technologies in the synthesis of complex molecules

Flow chemistry, organocatalysis and 3D-printing : valuable tools in the synthesis of chiral compounds

Recently developed organocatalytic stereoselective transformations using polymer-based packed bed and catalytic reactors will be presented. Furthermore, the use of different bifunctional chiral metal-free catalysts in micro- and mesofluidic devices will be described. Metal-free stereoselective additions of activated nucleophiles to\uf020\uf062\uf02dnitrostyrenes were investigated under continuous-flow conditions in microreactors. The potential of this flow chemistry approach was demonstrated by the successful synthesis of an advanced intermediate for the preparation of the GABAB receptor agonist Baclofen and other Active Pharmaceutical Ingredients (APIs) such as (S)-Pregabalin and (S)-Warfarin

X-ray study of bow shocks in runaway stars

Massive runaway stars produce bow shocks through the interaction of their winds with the interstellar medium, with the prospect for particle acceleration by the shocks. These objects are consequently candidates for non-thermal emission. Our aim is to investigate the X-ray emission from these sources. We observed with XMM-Newton a sample of five bow shock runaways, which constitutes a significant improvement of the sample of bow shock runaways studied in X-rays so far. A careful analysis of the data did not reveal any X-ray emission related to the bow shocks. However, X-ray emission from the stars is detected, in agreement with the expected thermal emission from stellar winds. On the basis of background measurements we derive conservative upper limits between 0.3 and 10 keV on the bow shocks emission. Using a simple radiation model, these limits together with radio upper limits allow us to constrain some of the main physical quantities involved in the non-thermal emission processes, such as the magnetic field strength and the amount of incident infrared photons. The reasons likely responsible for the non-detection of non-thermal radiation are discussed. Finally, using energy budget arguments, we investigate the detectability of inverse Compton X-rays in a more extended sample of catalogued runaway star bow shocks. From our analysis we conclude that a clear identification of non-thermal X-rays from massive runaway bow shocks requires one order of magnitude (or higher) sensitivity improvement with respect to present observatories.Fil: del Valle, Maria Victoria. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Argentino de Radioastronomía. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Argentino de Radioastronomía; ArgentinaFil: Romero, Gustavo Esteban. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Argentino de Radioastronomía. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Argentino de Radioastronomía; ArgentinaFil: Peri, Cintia Soledad. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Argentino de Radioastronomía. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Argentino de Radioastronomía; ArgentinaFil: Benaglia, Paula. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Argentino de Radioastronomía. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Argentino de Radioastronomía; ArgentinaFil: De Becker, M.. Université de Liège; Bélgic

A radio-map of the colliding winds in the very massive binary system HD 93129A

Radio observations are an effective tool to discover particle acceleration regions in colliding-wind binaries, through detection of synchrotron radiation; these regions are natural laboratories for the study of relativistic particles. Wind-collision region (WCR) models can reproduce the radio continuum spectra of massive binaries that contain both thermal and non-thermal radio emission; however, key constraints for models come from high-resolution imaging. Only five WCRs have been resolved to date at radio frequencies at milliarcsec (mas) angular scales. The source HD 93129A, prototype of the very few known O2 I stars, is a promising target for study: recently, a second massive, early-type star about 50 mas away was discovered, and a non-thermal radio source detected in the region. Preliminary long-baseline array data suggest that a significant fraction of the radio emission from the system comes from a putative WCR. We sought evidence that HD 93129A is a massive binary system with colliding stellar winds that produce non-thermal radiation, through spatially resolved images of the radio emitting regions. We completed observations with the Australian Long Baseline Array (LBA) to resolve the system at mas angular resolutions and reduced archival Australia Telescope Compact Array (ATCA) data to derive the total radio emission. We also compiled optical astrometric data of the system in a homogeneous way. We reduced historical Hubble Space Telescope data and obtained absolute and relative astrometry with milliarcsec accuracy. The astrometric analysis leads us to conclude that the two stars in HD 93129A form a gravitationally bound system. The LBA data reveal an extended arc-shaped non-thermal source between the two stars, indicative of a WCR. The wind momentum-rate ratio of the two stellar winds is estimated. The ATCA data show a point source with a change in flux level ...Comment: Accepted in Astronomy and Astrophysic

Additive manufacturing technologies : 3D printing in organic synthesis

The manufacturing of a three-dimensional product from a computer-driven digital model (3D printing) has found extensive applications in several fields. Additive manufacturing technologies offer the possibility to fabricate ad hoc tailored products on demand, at affordable prices, and have been employed to make customized and complex items for actual sale. However, despite the great progress and the countless opportunities offered by the 3D printing technology, surprisingly a relatively limited number of applications have been documented in organic chemistry. This review will focus specifically on the exploitation of additive manufacturing technologies in the synthesis of organic compounds, and, in particular, on the use of 3D-printed catalysts and 3D printed reactors, and on the fabrication and use of 3D printed flow reactors

Evidence of non-thermal X-ray emission from HH 80

Protostellar jets appear at all stages of star formation when the accretion process is still at work. Jets travel at velocities of hundreds of km/s, creating strong shocks when interacting with interstellar medium. Several cases of jets have been detected in X-rays, typically showing soft emission. For the first time, we report evidence of hard X-ray emission possibly related to non-thermal processes not explained by previous models of the post-shock emission predicted in the jet/ambient interaction scenario. HH 80 is located at the south head of the jet associated to the massive protostar IRAS 18162-2048. It shows soft and hard X-ray emission in regions that are spatially separated, with the soft X-ray emission region situated behind the region of hard X-ray emission. We propose a scenario for HH 80 where soft X-ray emission is associated to thermal processes from the interaction of the jet with denser ambient matter and the hard X-ray emission is produced by synchrotron radiation at the front shock.Comment: Accepted for publication in ApJ

Stereolithography 3D-Printed Catalytically Active Devices in Organic Synthesis

This article describes the synthesis of stereolithography (SLA) 3D-printed catalyst-impregnated devices and their evaluation in the organocatalyzed Friedel\u2013Crafts alkylation of N\u2013Me\u2013indole with trans--nitrostyrene. Using a low-cost SLA 3D printer and freeware design software, dierent devices were designed and 3D-printed using a photopolymerizable resin containing a thiourea-based organocatalyst. The architectural control oered by the 3D-printing process allows a straightforward production of devices endowed with dierent shapes and surface areas, with high reproducibility. The 3D-printed organocatalytic materials promoted the formation of the desired product up to a 79% yield, although with longer reaction times compared to reactions under homogeneous conditions

DBS-Based Eutectogels: Organized Vessels to Perform the Michael Addition Reaction**

Supramolecular eutectogels were obtained from the gelation of 1,3 : 2,4-dibenzylidene-D-sorbitol (DBS) in cholinium chloride-based deep eutectic solvents (DES), differing for the nature of the hydrogen bond donor. Ethylene glycol, diethylene glycol, triethylene glycol, glycerol and urea were tested. Soft materials were fully characterized, determining critical gelation concentration, gel-sol transition temperatures and mechanical properties. Furthermore, to have information about the organization of the gelator in the tridimensional network, resonance light scattering, circular dichroism and microscopy investigations were performed. Eutectogels were used as organized “vessels” to perform the L-proline catalyzed Michael addition reaction. The probe reaction was carried out in gel phase and in DES solution. Data collected shed light on the effect that gel microenvironment exerts on the outcome of the reaction. In general, gel phases allowed having comparable or even better results than the ones collected in DES solution, with better results obtained in soft materials with the highest organization, as accounted for by the presence of larger aggregates and the occurrence of stronger intermolecular interactions. In turn, this accounts also for the effect of substrates structure that indicates that better yields could be obtained in the presence of more flexible nucleophile and dienones, having more extended π-surface

Evaluation of In-Batch and In-Flow Synthetic Strategies towards the Stereoselective Synthesis of a Fluorinated Analogue of Retro-Thiorphan

A stereoselective synthetic strategy for the preparation of trifluoromethylamine mimics of retro-thiorphan, involving a diastereoselective, metal-free catalytic step, has been studied in batch and afforded the target molecule in good yields and high diastereoselectivity. A crucial point of the synthetic sequence was the catalytic reduction of a fluorinated enamine with trichlorosilane as reducing agent in the presence of a chiral Lewis base. The absolute configuration of the key intermediate was unambiguously assigned by X-ray analysis. The synthesis was also investigated exploiting continuous flow reactions; that is, an advanced intermediate of the target molecule was synthesized in only two in-flow synthetic modules, avoiding isolation and purifications of intermediates, leading to the isolation of the target chiral fluorinated amine in up to an 87:13 diastereoisomeric ratio

Organocatalytic Michael addition to (D)-mannitol-derived enantiopure nitroalkenes: A valuable strategy for the synthesis of densely functionalized chiral molecules

Carbohydrates are abundant renewable resources and are a feedstock for green chemistry and sustainable synthesis of the future. Among the hexoses and the pentoses present in biomass, mannitol was selected in the present project as a valuable platform, directly available from the chiral pool, to build highly functionalized molecules. Starting from (R)-2,3-O-cyclohexylidene glyceraldehyde, which is easily prepared in a large scale from D-mannitol, an enantiopure chiral nitro alkene was prepared by reaction with nitromethane, and its reactivity studied. Organocatalytic Michael addition of dimethyl malonate, \u3b2-keto esters, and other nucleophiles on the nitro alkene afforded high stereoselectivity and densely functionalized chiral molecules, which were further synthetically developed, leading to five-membered lactones and bicyclic lactams. Preliminary studies showed that the metal-free catalytic reaction on the chiral nitro alkene can be performed under continuous flow conditions, thus enabling the use of (micro)mesofluidic systems for the preparation of enantiomerically pure organic molecules from the chiral pool