A Chiral Titanocene Complex as Regiodivergent Photoredox Catalyst: Synthetic Scope and Mechanism of Catalyst Generation.

We describe a combined synthetic, spectroscopic, and computational study of a chiral titanocene complex as a regiodivergent photoredox catalyst (PRC). With Kagan's complex catCl2 either monoprotected 1,3-diols or 1,4-diols can be obtained in high selectivity from a common epoxide substrate in a regiodivergent epoxide opening depending on which enantiomer of the catalyst is employed. Due to the catalyst-controlled regioselectivity of ring opening and the broader substrate scope, the PRC with catCl2 is also a highly attractive branching point for diversity-oriented synthesis. The photochemical processes of cat(NCS)2, a suitable model for catCl2, were probed by time-correlated single-photon counting. The photoexcited complex displays a thermally activated delayed fluorescence as a result of a singlet-triplet equilibration, S1 ⇄ T1, via intersystem crossing and recrossing. Its triplet state is quenched by electron transfer to the T1 state. Computational and cyclic voltammetry studies highlight the importance of our sulfonamide additive. By bonding to sulfonamide additives, chloride abstraction from [catCl2]- is facilitated, and catalyst deactivation by coordination of the sulfonamide group is circumvented.

Reductive Amination in the Synthesis of Pharmaceuticals.

Reductive amination plays a paramount role in pharmaceutical and medicinal chemistry owing to its synthetic merits and the ubiquitous presence of amines among biologically active compounds. It is one of the key approaches to C-N bond construction due to its operational easiness and a wide toolbox of protocols. Recent studies show that at least a quarter of C-N bond-forming reactions in the pharmaceutical industry are performed via reductive amination. This Review concisely compiles information on 71 medical substances that are synthesized by reductive amination. Compounds are grouped according to the principle of action, which includes drugs affecting the central nervous system, drugs affecting the cardiovascular system, anticancer drugs, antibiotics, antiviral and antifungal medicines, drugs affecting the urinary system, drugs affecting the respiratory system, antidiabetic medications, drugs affecting the gastrointestinal tract, and drugs regulating metabolic processes. A general synthetic scheme is provided for each compound, and the description is focused on reductive amination steps. The green chemistry metric of reaction mass efficiency was calculated for all reactions.

Anthracene-rhodium complexes with metal coordination at the central ring - a new class of catalysts for reductive amination.

A new class of anthracene complexes with a metal coordinated at the central ring was applied in catalysis for the first time. As a result, a simple and efficient protocol for reductive amination that involves CO as a reducing agent has been developed. The rhodium complex [(cyclooctadiene)Rh(C10H4Me2(OMe)4)]+ (1 mol%) catalyses such reactions under mild conditions (40-130 °C) and produces a variety of amines in good yields (74-95%) without affecting the functional groups. The protocol is acceptable for all combinations of aldehydes (aromatic and aliphatic), ketones (aromatic and aliphatic) and amines (aromatic and aliphatic; primary and secondary).

Formal reductive addition of acetonitrile to aldehydes and ketones.

An efficient and highly productive rhodium-catalyzed method for the synthesis of nitriles employing aldehydes or ketones, methyl cyanoacetate, water and carbon monoxide as starting materials has been developed. Simple rhodium chloride without any ligands can be used. The fine tuning of the substrate can lead to the activity higher than 5000 TON.

{2,2'-[Ethane-1,2-diylbis(nitrilo-methan-yl-yl-idene)]diphenolato}(iso-propano-lato)aluminium di-chloro-methane hemisolvate.

In the title compound, [Al(C16H14N2O2)(C3H7O)]·0.5CH2Cl2, the salen complex is monomeric and the dichlormethane solvent mol-ecule lies on a crystallographic twofold axis. The central Al atom is fivefold coordinated and possesses a square-based pyramidal environment. The Al-OAlk( (i) prop-yl) bond [1.7404 (14) Å] is much shorter than the Al-OAr(salen) bond lengths [1.7974 (15) and 1.8094 (14) Å]. The iso-propyl-oxo group forms an intra-molecular C-H⋯N hydrogen bond. In the crystal, the complex mol-ecules are linked by weak C-H⋯O inter-actions.

Catalytic utilization of converter gas - an industrial waste for the synthesis of pharmaceuticals.

Converter gas is a large scale waste product that is usually burned to carbon dioxide and contributes to the world emission of greenhouse gases. Herein we demonstrate that instead of burning the converter gas can be used as a reducing agent in organic reactions to produce valuable pharmaceuticals and agrochemicals. In particular, amide-based selected drug molecules have been synthesized by a reaction of aromatic nitro compounds and carboxylic acids in the presence of converter gas. In addition, we showed that this gas can also be conveniently utilized to carryout classical reductive amination reaction.

Sodium Hypophosphite as a Bulk and Environmentally Friendly Reducing Agent in the Reductive Amination.

NaH2PO2 was found to promote reductive amination. Being nontoxic, stable, environmentally benign, and available in bulk amounts, this reducing agent showed a powerful potential to compete with classical reductants applied in the target process. An E factor of 1 was achieved for the substrate scope. Different carbonyl compounds reacted with amines under the developed conditions. The reaction demonstrated a great compatibility with a wide range of functional groups. Reaction conditions were scaled up to 200-fold.

Crystal structure of 4,8-di-tert-butyl-6,6-di-chloro-13-ethyl-2,10-dimethyl-13,14-di-hydro-12H-dibenzo[d,i][1,3,7,2]dioxaza-silecine toluene 0.25-solvate.

The coordination polyhedron at the silicon atom in the title compound, C26H37Cl2NO2Si·0.25C7H8, is typical for penta-coordinated silicon derivatives and represents a slightly distorted trigonal bipyramid with an N atom and a Cl atom in the apical positions and the two O atoms and the other Cl atom occupying the equatorial sites. There are two independent mol-ecules in the asymmetric unit. The N-Si-Cl fragment in each is close to linear [178.24 (5) and 178.71 (5)°], in good agreement with 4e-3c theory, as is the elongation of the apical bond lengths [Si-Cl = 2.1663 (7) and 2.1797 (7) Å] in comparison with the equatorial bonds [Si-Cl = 2.0784 (7) and 2.0748 (7) Å]. Orthogonal least-squares fitting of the two independent mol-ecules resulted in r.m.s. deviation of 0.017 Å. The conformations of the two mol-ecules are almost the same, with corresponding torsion angles differing by less than 5.5°. The toluene solvent mol-ecule is disordered about an inversion centre.

Aluminum complexes based on pyridine substituted alcohols: synthesis, structure, and catalytic application in ROP.

A series of substituted pyridine dialcohols (2,6-bis(hydroxyalkyl)pyridines), 1-4, was used for the synthesis of various types of aluminum complexes. Aluminum methyl derivatives, 2-4a, were obtained by the reaction of AlMe3 with the corresponding ligand or transmetallation reactions of germylenes. Aluminum chloride complexes, 3-4b, were obtained by substitution of the Me group under the action of chlorinating agents. Methoxy-, 2-4c, or benzyloxy-, 2d, aluminum complexes were synthesized in transalkoxylation reaction of Me2Al(OX) (X = Me, Bn) by the corresponding ligand. All complexes obtained were thoroughly investigated by multinuclear NMR and X-ray analysis. It has been established that the structure of the ligand (number of carbon atoms) determines the nature of the complexes formed. Compounds were used as initiators of ring-opening polymerization of l-lactide and ε-caprolactone and showed moderate activity with controlled or immortal character.