Light-Induced Access to Carbazole-1,3-dicarbonitrile: A Thermally Activated Delayed Fluorescent (TADF) Photocatalyst for Cobalt-Mediated Allylations.

The stability of a photocatalyst under irradiation is important in photoredox applications. In this work, we investigated the stability of a thermally activated delayed fluorescence (TADF) photocatalyst {3DPAFIPN [2,4,6-tris(diphenylamino)-5-fluoroisophthalonitrile]}, recently employed in photoredox-mediated processes, discovering that in the absence of quenchers the chromophore is unstable and is efficiently converted by irradiation with visible light into another species based on the carbazole-1,3-dicarbonitrile moiety. The new species obtained is itself a TADF emitter and finds useful applications in photoredox transformations. At the excited state, it is a strong reductant and was efficiently applied to cobalt-mediated allylation of aldehydes, whereas other TADFs (4CzIPN and 3DPAFIPN) failed to promote efficient photocatalytic cycles.

Diastereoselective and enantioselective photoredox pinacol coupling promoted by titanium complexes with a red-absorbing organic dye.

The pinacol coupling reaction, a reductive coupling of carbonyl compounds that proceeds through the formation of ketyl radicals in the presence of an electron donor, affords the corresponding 1,2-diols in one single step. The photoredox version of this transformation has been accomplished using different organic dyes or photoactive metal complexes in the presence of sacrificial donors such as tertiary amines or Hantzsch's ester. Normally, the homo-coupling of such reactive ketyl radicals is neither diastereo- nor enantio-selective. Herein, we report a highly diastereoselective pinacol coupling reaction of aromatic aldehydes promoted by 5 mol% of the non-toxic, inexpensive and available Cp2TiCl2 complex. The key feature that allows the complete control of diastereoselectivity is the employment of a red-absorbing organic dye in the presence of a redox-active titanium complex. Taking advantage of the well-tailored photoredox potential of this organic dye, the selective reduction of Ti(iv) to Ti(iii) is achieved. These conditions enable the formation of the d,l (syn) diastereoisomer as the favored product of the pinacol coupling (d.r. > 20 : 1 in most of the cases). Moreover, employing a simply prepared chiral SalenTi complex, the new photoredox reaction gave a complete diastereoselection for the d,l diastereoisomer, and high enantiocontrol (up to 92% of enantiomeric excess).

Nickel-Mediated Enantioselective Photoredox Allylation of Aldehydes with Visible Light.

Here we report a practical, highly enantioselective photoredox allylation of aldehydes mediated by chiral nickel complexes with commercially available allyl acetate as the allylating agent. The methodology allows the clean stereoselective allylation of aldehydes in good to excellent yields and up to 93 % e.e. using a catalytic amount of NiCl2 (glyme) in the presence of the chiral aminoindanol-derived bis(oxazoline) as the chiral ligand. The photoredox system is constituted by the organic dye 3DPAFIPN and a Hantzsch's ester as the sacrificial reductant. The reaction proceeds under visible-light irradiation (blue LEDs, 456 nm) at 8-12 °C. Compared to other published procedures, no metal reductants (such as Zn or Mn), additives (e.g. CuI) or air-sensitive Ni(COD)2 are necessary for this reaction. Accurate DFT calculations and photophysical experiments have clarified the mechanistic picture of this stereoselective allylation reaction.

4-Fluoro-Threonine: From Diastereoselective Synthesis to pH-Dependent Conformational Equilibrium in Aqueous Solution.

4-Fluoro-threonine, the only fluoro amino acid of natural origin discovered so far, is an interesting target for both synthetic and theoretical investigations. In this work, we lay the foundation for spectroscopic characterization of 4-fluoro-threonine. First, we report a diastereoselective synthetic route, which is suitable to produce synthetic material for experimental characterization. The addition of the commercially available ethyl isocyanoacetate to benzyloxyacetaldehyde led to the corresponding benzyloxy-oxazoline, which was hydrolyzed and transformed into ethyl (4S*,5S*)-5-hydroxymethyl-2-oxo-4-oxazolidinecarboxylate in a few steps. Fluorination with diethylamino sulfur trifluoride (DAST) afforded ethyl (4S*,5S*)-5-fluoromethyl-2-oxo-4-oxazolidinecarboxylate, which was deprotected to give the desired diastereomerically pure 4-fluoro-threonine, in 8-10% overall yield. With the synthetic material in our hands, acid-base titrations have been carried out to determine acid dissociation constants and the isoelectric point, which is the testing ground for the theoretical analysis. We have used machine learning coupled with quantum chemistry at the state-of-the-art to analyze the conformational space of 4-fluoro-threonine, with the aim of gaining insights from the comparison of computational and experimental results. Indeed, we have demonstrated that our approach, which couples a last-generation double-hybrid density functional including empirical dispersion contributions with a model combining explicit first-shell molecules and a polarizable continuum for describing solvent effects, provides results and trends in remarkable agreement with experiments. Finally, the conformational analysis applied to fluoro amino acids represents an interesting study for the effect of fluorine on the stability and population of conformers.

Photoredox Propargylation of Aldehydes Catalytic in Titanium.

A practical and effective photoredox propargylation of aldehydes promoted by 10 mol % of [Cp2TiCl2] is presented. No stoichiometric metals or scavengers are used for the process. A catalytic amount of the cheap and simply prepared organic dye 3DPAFIPN is used as the reductant for titanium. The reaction displayed a broad scope, and no traces of allenyl isomers were detected for simple propargyl bromide, whereas mixtures of propargyl and allenyl isomers were observed for substituted propargyl bromides.

Metallaphotoredox catalysis with organic dyes.

The use of organic dyes to promote organic reactions by photoredox catalysis is continuously expanding and was recently reviewed by Nicewicz. The synthesis of new dyes, their application in flow photoredox reactions, and their use in stereoselective and multicomponent transformations have considerably expanded the repertoire of application of organic dyes in photoredox mediated reactions. The low costs of these dyes, their tailored synthesis and availability in combination with the development of new concepts and careful catalytic cycle design (made possible by the application of fine theoretical investigations and deep understanding) are guiding the widespread application of organic dyes in the metallaphotoredox catalysis area. Developments and recent applications of different metal catalyzed processes mediated by organic dyes are covered by this review.

A Journey from Thermally Tunable Synthesis to Spectroscopy of Phenylmethanimine in Gas Phase and Solution.

Phenylmethanimine is an aromatic imine with a twofold relevance in chemistry: organic synthesis and astrochemistry. To tackle both aspects, a multidisciplinary strategy has been exploited and a new, easily accessible synthetic approach to generate stable imine-intermediates in the gas phase and in solution has been introduced. The combination of this formation pathway, based on the thermal decomposition of hydrobenzamide, with a state-of-the-art computational characterization of phenylmethanimine laid the foundation for its first laboratory observation by means of rotational electric resonance spectroscopy. Both E and Z isomers have been accurately characterized, thus providing a reliable basis to guide future astronomical observations. A further characterization has been carried out by nuclear magnetic resonance spectroscopy, showing the feasibility of this synthetic approach in solution. The temperature dependence as well as possible mechanisms of the thermolysis process have been examined.

Chemical bonding in cuprous complexes with simple nitriles: octet rule and resonance concepts versus quantitative charge-redistribution analysis.

Chemical bonding in a set of six cuprous complexes with simple nitriles (CN-, HNC, HCN, CH3NC, and CH3CN) is investigated by means of a recently devised analysis scheme framed in density-functional theory and quantitatively singling out concurrent charge flows such as σ donation and π backdonation. The results of our analysis are comparatively assessed against qualitative models for charge redistribution based on the popular concepts of octet rule and resonance structures, and the relative importance of different charge-flow channels relating to σ donation, π back-donation, polarization, and hyperconjugation is discussed on a quantitative basis.

Asymmetric Reactions Enabled by Cooperative Enantioselective Amino- and Lewis Acid Catalysis.

Organocatalysis-the branch of catalysis featuring small organic molecules as the catalysts-has, in the last decade, become of central importance in the field of asymmetric catalysis, so much that it is now comparable to metal catalysis and biocatalysis. Organocatalysis is rationalized and classified by a number of so-called activation modes, based on the formation of a covalent or not-covalent intermediate between the organocatalyst and the organic substrate. Among all the organocatalytic activation modes, enamine and iminium catalysis are widely used for the practical preparation of valuable products and intermediates, both in academic and industrial contexts. In both cases, chiral amines are employed as catalysts. Enamine activation mode is generally employed in the reaction with electrophiles, while nucleophiles require the iminium activation mode. Commonly, in both modes, the reaction occurs through well-organized transitions states. A large variety of partners can react with enamines and iminium ions, due to their sufficient nucleophilicity and electrophilicity, respectively. However, despite the success, organocatalysis still suffers from narrow scopes and applications. Multicatalysis is a possible solution for these drawbacks because the two different catalysts can synergistically activate the substrates, with a simultaneous activation of the two different reaction partners. In particular, in this review we will summarize the reported processes featuring Lewis acid catalysis and organocatalytic activation modes synergically acting and not interfering with each other. We will focus our attention on the description of processes in which good results cannot be achieved independently by organocatalysis or Lewis acid catalysis. In these examples of cooperative dual catalysis, a number of new organic transformations have been developed. The review will focus on the possible strategies, the choice of the Lewis acid and the catalytic cycles involved in the effective reported combination. Additionally, some important key points regarding the rationale for the effective combinations will be also included. π-Activation of organic substrates by Lewis acids, via formation of electrophilic intermediates, and their reaction with enamines will be also discussed in this review.

Al(Salen) Metal Complexes in Stereoselective Catalysis.

Salen ligands are a class of Schiff bases simply obtained through condensation of two molecules of a hydroxyl-substituted aryl aldehyde with an achiral or chiral diamine. The prototype salen, or N,N'-bis(salicylidene)ethylenediamine has a long history, as it was first reported in 1889, and immediately, some of its metal complexes were also described. Now, the salen ligands are a class of N,N,O,O tetradentate Schiff bases capable of coordinating many metal ions. The geometry and the stereogenic group inserted in the diamine backbone or aryl aldehyde backbone have been utilized in the past to efficiently transmit chiral information in a variety of different reactions. In this review we will summarize the important and recent achievements obtained in stereocontrolled reactions in which Al(salen) metal complexes are employed. Several other reviews devoted to the general applications and synthesis of chromium and other metal salens have already been published.