Straightforward α‐Amino Nitrile Synthesis Through Mo(CO)6‐Catalyzed Reductive Functionalization of Carboxamides

The selective reduction of amides into an intermediate hemiaminal catalyzed by Mo(CO)₆ together with the inexpensive and easy to handle TMDS (1,1,3,3‐tetramethyldisiloxane) as reducing agent, followed by subsequent trapping of the hemiaminal with a cyanide source, allows for the straightforward synthesis of α‐amino nitriles. The methodology presented here, displays high levels of chemoselectivity allowing for the reduction of amides in the presence of functional groups such as ketones, imines, aldehydes, and acids, which affords a simple route for the synthesis of α‐amino nitriles with a broad scope of functionalities in high yields. Furthermore, the applicability of this methodology is demonstrated by scale up experiments and by derivatization of the target compounds into synthetically interesting products. The selective cyanation is successfully applied in late stage functionalizations of amide containing drugs and prolinol derivatives.     

催化还原胺类衍生物N-单烷基化反应一锅法合成4,6-二(异丙基氨基)-1,3-苯二酚

以 2-氯-4,6-二硝基-1,3-苯二酚为原料,丙酮为烷基源,氢气为还原剂,研究了在10%Pd/C催化剂上一锅法合成N-单烷基氨基苯酚化合物 4,6-二(异丙基氨基)-1,3-苯二酚的反应工艺. 考察了反应条件如醋酸量、丙酮浓度、氢气压力、催化剂量和反应时间对反应的影响,开发出一条高收率、高选择性制备N-单烷基氨基苯酚化合物的合成路线.     

Unprecedented SnCl2·2H2O-mediated intramolecular cyclization of nitroarenes via C-N bond formation: a new entry to the synthesis of cryptotackieine and related skeletons

A mild, efficient, and one-pot protocol for the intramolecular cyclization of 2-substituted nitroarenes via C-N bond formation using SnCl₂·2H₂O is described. The versatility of the method has been demonstrated by synthesizing two sets of polycyclic structures based on privileged structures of indole and pyrrole, and of the alkaloid cryptotackieine associated with antimalarial activity. Our new approach provides a powerful entry into polycyclic structures related to an alkaloid.     

On-capillary fluorescent labeling of saccharides for capillary electrophoresis

The feasibility of on-capillary derivatization of saccharides by aromatic amine-based fluorescent labeling agents was tested. To avoid the problematic evolution of gaseous hydrogen cyanide, the Schiff base reduction by sodium cyanoborohydride, as the second step of the standard reductive amination protocol, was omitted. Glucose was used as a model analyte and 7-amino-1,3-naphthalenedisulfonic acid as the labeling agent. Our experiments showed that the direct reaction of the saccharide with the labeling agent in 2.5-M acetic acid yields a labeled product that is sufficiently stable to be separated from the labeling agent in 20-mM phosphate buffer, pH 3.5, and detected using UV detection. The glucose and label zones were introduced separately into the capillary and mixed using a negative voltage. Mixing voltage, its duration, the concentration of acetic acid in the reaction zone, and the waiting time between mixing and separation were optimized. To show the applicability of the procedure to a broader range of analytes, a mixture of different types of saccharides, that is, xylose (pentose), fucose (hexose), glucose (hexose), N-acetylglucosamine (N-acetylaminosaccharide), and lactose (disaccharide), was subjected to derivatization and analysis under the optimal conditions. The linearity and repeatability of the process were evaluated as critical parameters for its analytical applications. Six-point calibration dependences in the 1–50 mM range showed excellent determination coefficients of 0.9992 or higher for all five saccharides tested. The repeatability of the labeled saccharide peak areas was between 2.2% and 4.3%.     

Reductive activation of arenecarbonitriles for the reactions with some carbon-centered electrophiles: the reaction mechanisms and synthetic applications

Synthetic and mechanistic aspects of the developed approach to the activation of aromatic nitriles are considered. The approach is based on the transformation of aromatic nitriles into stable anionic reduced forms. The latter, as shown for the reactions with alkyl halides and cyanoarenes, are promising reactants for the reactions with carbon-centered electrophiles. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 4, pp. 754–765, April, 2008.     

Ruthenium-Catalyzed Direct Reductive Amination of Carbonyl Compounds for the Synthesis of Amines: An Overview

Reductive amination is a valuable method for amine synthesis that has been the topic of a century‘s worth of in-depth study in both academia and industry. Amines and their derivatives serve as incredibly adaptable building blocks for a broad array of organic substrates and are significant precursors for a myriad of advanced chemicals, physiologically active compounds, agrochemicals, biomolecules, pharmaceuticals, and polymers. The creation of innovative catalytic processes for the long-term and selective synthesis of amines from readily accessible and environmentally benign reagents remains a top priority in chemical research. Both heterogeneous and homogeneous catalysts have been designed with success to enable these reactions to explore new amines. Ruthenium catalysts are employed in reductive amination owing to their stability, selectivity, versatility, low toxicity, and high efficiency. This review comprehensively overviews the Ru-catalyzed reductive amination processes and includes the literature from 2009 to 2022.     

CO2 Hydroboration: Impact of the Boryl Moieties on the Reactivity of Four Bis(boryl)acetal Compounds toward 2,6-Diisopropylaniline

The hydroboration of CO₂ into bis(boryl)acetal (BBA) compounds is an important transformation, since it enabled to selectively reduce CO₂ by 4e^- and to subsequently use the BBA compounds as C₁ and C_n sources. However, the influence of the nature of the boryl moieties on the reactivity of BBA compounds has not been evaluated so far. In the present study, four BBA compounds – including two new ones – were reacted with 2,6-diisopropylaniline to afford the expected imine. Significant differences in the rate of the reaction from minutes to weeks have been observed depending on the BBA used, showing the importance of the nature of the boryl moieties. Theoretical investigations enabled to propose a mechanism involving the addition of the aniline to the BBA as the rate-determining step and to determine that the steric hindrance of the BBA compounds is the main factor driving the rate of this condensation reaction.     

Reductive Cyclopropanations Catalyzed by Dinuclear Nickel Complexes

Dinuclear Ni complexes supported by naphthyridine‐diimine (NDI) ligands catalyze the reductive cyclopropanation of alkenes with CH₂Cl₂ as the methylene source. The use of mild terminal reductants (Zn or Et₂Zn) confers significant functional‐group tolerance, and the catalyst accommodates structurally and electronically diverse alkenes. Mononickel catalysts bearing related N chelates afford comparatively low cyclopropane yields (≤20 %). These results constitute an entry into catalytic carbene transformations from oxidized methylene precursors.     

Nickel‐Catalyzed Carboxylation of Benzylic C−N Bonds with CO2

A user‐friendly Ni‐catalyzed reductive carboxylation of benzylic C?N bonds with CO₂ is described. This procedure outperforms state‐of‐the‐art techniques for the carboxylation of benzyl electrophiles by avoiding commonly observed parasitic pathways, such as homodimerization or β‐hydride elimination, thus leading to new knowledge in cross‐electrophile reactions.     

Total synthesis of lasofoxifene and nafoxidine

An intramolecular reductive coupling process of diketone with low-valent titanium species to form a dihydronapthalene skeleton was an important step in the synthesis of nafoxidine (1) and lasofoxifene (2). Diketone 6 was prepared in a convenient, three-step sequence starting from 3-methoxy benzaldehyde in good yields.