Vicinal Diamines Research Articles

Interactions of 3‐Acylisocoumarins with Ethane‐1,2‐diamines: A Simple Route to 3,4‐Dihydro‐6H‐pyrazino[1,2‐b]isoquinolin‐6‐ones and Their Hydrogenated Derivatives

AbstractThe recyclization of isocoumarins under the N‐nucleophile action is a well‐known route to different isoquinolones. But addition of functional groups in such substrates can provide more complicated nitrogen‐containing heterocycles. In this study, the easy formation of 3,4‐dihydro‐6H‐pyrazino[1,2‐b]isoquinolin‐6‐one system via the interaction of 3‐acylisocoumarins and ethane‐1,2‐diamines is demonstrated. As the acyl component of reaction, 3‐acetyl‐ and 3‐benzoylisocoumarins, 2,3‐dihydro‐1H‐benzo[c]chromene‐4,6‐dione, and heteroanalogs of 3‐acetylisocoumarin were successfully used; and the amino component was represented by ethane‐1,2‐diamine, some cyclic vicinal diamines, methyl 2,3‐diaminopropanoate, and N1‐methylethane‐1,2‐diamine. The variation of substrates gave different structures with 3,4‐dihydro‐6H‐pyrazino[1,2‐b]isoquinolin‐6‐one core; and the number of products can grow extremely because of this core's aptitude to reduction. Thus, 1,2,3,4‐tetrahydro‐6H‐pyrazino[1,2‐b]isoquinolin‐6‐ones, 1,2,3,4,11,11a‐hexahydro‐6H‐pyrazino[1,2‐b]isoquinolin‐6‐ones and 1,3,4,6,11,11a‐hexahydro‐2H‐pyrazino[1,2‐b]isoquinolines were synthetized by using various reduction methods for separate 3,4‐dihydro‐6H‐pyrazino[1,2‐b]isoquinolin‐6‐ones.

Crystal structures of two unexpected products of vicinal diamines left to crystallize in acetone.

Herein we report the crystal structures of two benzodiazepines obtained by reacting N,N'-(4,5-diamino-1,2-phenylene)bis(4-methylbenzenesulfonamide) (1) or 4,5-(4-methylbenzenesulfonamido)benzene-1,2-diaminium dichloride (1·2HCl) with acetone, giving 2,2,4-trimethyl-8,9-bis(4-methylbenzenesulfonamido)-2,3-dihydro-5H-1,5-benzodiazepine, C26H30N4O4S2 (2), and 2,2,4-trimethyl-8,9-bis(4-methylbenzenesulfonamido)-2,3-dihydro-5H-1,5-benzodiazepin-1-ium chloride 0.3-hydrate, C26H31N4O4S2+·Cl-·0.3H2O (3). Compounds 2 and 3 were first obtained in attempts to recrystallize 1 and 1·2HCl using acetone as solvent. This solvent reacted with the vicinal diamines present in the molecular structures, forming a 5H-1,5-benzodiazepine ring. In the crystal structure of 2, the seven-membered ring of benzodiazepine adopts a boat-like conformation, while upon protonation, observed in the crystal structure of 3, it adopts an envelope-like conformation. In both crystalline compounds, the tosylamide N atoms are not in resonance with the arene ring, mainly due to hydrogen bonds and steric hindrance caused by the large vicinal groups in the aromatic ring. At a supramolecular level, the crystal structure is maintained by a combination of hydrogen bonds and hydrophobic interactions. In 2, amine-to-tosyl N-H...O and amide-to-imine N-H...N hydrogen bonds can be observed. In contrast, in 3, the chloride counter-ion and water molecule result in most of the hydrogen bonds being of the amide-to-chloride and ammonium-to-chloride N-H...Cl types, while the amine interacts with the tosyl group, as seen in 2. In conclusion, we report the synthesis of 1, 1·2HCl and 2, as well as their chemical characterization. For 2, two synthetic methods are described, i.e. solvent-mediated crystallization and synthesis via a more efficient and cleaner route as a polycrystalline material. Salt 3 was only obtained as presented, with only a few crystals being formed.

Iron(II)-Catalyzed 1,2-Diamination of Styrenes Installing a Terminal NH2 Group Alongside Unprotected Amines.

1,2-Diamination of alkenes represents an attractive way to generate differentiated vicinal diamines, which are prevalent motifs in biologically active compounds and catalysts. However, existing methods are usually limited in scope and produce diamines where one or both nitrogens are protected, adding synthetic steps for deprotection and further N-functionalization to reach a desired target. Furthermore, the range of amino groups that can be introduced at the internal position is fairly limited. Here we describe a 1,2-diamination of styrenes that directly installs a free amino group at the terminal position and a wide variety of unprotected nitrogen nucleophiles (primary or secondary alkyl or aromatic amines, sulfoximines, N-heterocycles, and ammonia surrogate) at the internal position. Two complementary sets of conditions encompass electronically activated and deactivated styrenes with diverse substitution patterns and functional groups. Moreover, this strategy can be extended to the 1,2-aminothiolation of styrenes.

Iron(II)‐Catalyzed 1,2‐Diamination of Styrenes Installing a Terminal NH2 Group Alongside Unprotected Amines

1,2‐Diamination of alkenes represents an attractive way to generate differentiated vicinal diamines, which are prevalent motifs in biologically active compounds and catalysts. However, existing methods are usually limited in scope and produce diamines where one or both nitrogens are protected, adding synthetic steps for deprotection and further N‐functionalization to reach a desired target. Furthermore, the range of amino groups that can be introduced at the internal position is fairly limited. Here we describe a 1,2‐diamination of styrenes that directly installs a free amino group at the terminal position and a wide variety of unprotected nitrogen nucleophiles (primary or secondary alkyl or aromatic amines, sulfoximines, N‐heterocycles, and ammonia surrogate) at the internal position. Two complementary sets of conditions encompass electronically activated and deactivated styrenes with diverse substitution patterns and functional groups. Moreover, this strategy can be extended to the 1,2‐aminothiolation of styrenes.

B2(OH)4-Mediated Reductive Ring-Opening of N-Tosyl Aziridines by Nitroarenes: A Green and Regioselective Access to Vicinal Diamines.

The nucleophilic ring-opening of aziridine derivatives provides an important synthetic tool for the preparation of various β-functionalized amines. Amines as nucleophiles are employed to prepare synthetically useful 1,2-diamines in the presence of various catalysts or activators. Herein, the B2(OH)4-mediated reductive ring-opening transformation of N-tosyl aziridines by nitroarenes was developed. This aqueous protocol employed nitroarenes as cheap and readily available amino sources and proceeds under external catalyst-free conditions. Control experiments and DFT calculations pointed to the in situ reduction of nitroarenes to aryl amines via N-aryl boramidic acid (E) and an SN1-type ring-opening of N-tosylaziridines by the resultant aryl amines with high regioselectivity.

Electrochemical study of the reactivity of furfural and 5-hydroxymethylfurfural with aliphatic primary (di)amines

Furfural (FF) and 5-hydroxymethylfurfural (HMF) are important and prospective renewable sources for chemical, fuel, material or pharmaceutical industry, the furfurylamines being the desired precursors. In this contribution new effects related to the reactivity of FF and HMF with various aliphatic primary (di)amines were observed using an electrochemical approach in water solutions. Following an initial investigation of electroreduction, the course of condensation reactions in basic buffers under various stoichiometric conditions was electrochemically monitored. Using five aliphatic amines and two (α,β- and α,ω-) diamines, a variety of products (mainly Schiff-bases) was identified. As a pilot study for “one-pot” reductive amination, the mixture of FF and n-PrNH2 was electrochemically reduced in basic buffers. The vicinal diamine (analogue of a pinacol) was the main product, together with the expected furfurylamine.

Enantioselective Transformations by "1 + x" Synergistic Catalysis with Chiral Primary Amines.

ConspectusSynergistic catalysis is a powerful tool that involves two or more distinctive catalytic systems to activate reaction partners simultaneously, thereby expanding the reactivity space of individual catalysis. As an established catalytic strategy, organocatalysis has found numerous applications in enantioselective transformations under rather mild conditions. Recently, the introduction of other catalytic systems has significantly expanded the reaction space of typical organocatalysis. In this regard, aminocatalysis is a prototypical example of synergistic catalysis. The combination of aminocatalyst and transition metal could be traced back to the early days of organocatalysis and has now been well explored as an enabling catalytic strategy. Particularly, the acid-base properties of aminocatalysis can be significantly expanded to include usually electrophiles generated in situ via metal-catalyzed cycles. Later on, aminocatalyst has also been exploited in synergistically combining with photochemical and electrochemical processes to facilitate redox transformations. However, synergistically combining one type of aminocatalyst with many different catalytic systems remains a great challenge. One of the most daunting challenges is the compatibility of aminocatalysts in coexistence with other catalytic species. As nucleophilic species, aminocatalysts may also bind with metal, which leads to mutual inhibition or even quenching of the individual catalytic activity. In addition, oxidative stability of aminocatalyst is also a non-neglectable issue, which causes difficulties in exploring oxidative enamine transformations.In 2007, we developed a vicinal diamine type of chiral primary aminocatalysts. This class of primary aminocatalysts was developed and evolved as functional and mechanistic mimics to the natural aldolase and has been widely applied in a number of enamine/iminium ion-based transformations. By following a "1 + x" synergistic strategy, the chiral primary amine catalysts were found to work synergistically or cooperatively with a number of transition metal catalysts, such as Pd, Rh, Ag, Co, and Cu, or other organocatalysts, such as B(C6F5)3, ketone, selenium, and iodide. Photocatalysis and electrochemical processes can also be incorporated to work together with the chiral primary amine catalysts. The 1 + x catalytic strategy enabled us to execute unexploited transformations by fine-tuning the acid-base and redox properties of the enamine intermediates and to achieve effective reaction and stereocontrol beyond the reach individually. During these efforts, an unprecedented excited-state chemistry of enamine was uncovered to make possible an effective deracemization process. In this Account, we describe our recent efforts since 2015 in exploring synergistic chiral primary amine catalysis, and the content is categorized according to the type of synergistic partner such that in each section the developed synergistic catalysis, reaction scopes, and mechanistic features are presented and discussed.

Chiral vicinal diamines as promising ligands in Pd-catalyzed reductive Heck type cyclizations

Palladium complexes with inexpensive and available vicinal diamines can serve as catalysts for the reductive Heck-type cyclization. o-Bromo-N-(2-phenylallyl)anilides are converted into the corresponding 3-methyl-3-phenylindolines, the analogous cyclization occurred for 2-bromo-4-methylphenyl 2-phenylallyl ether and N-(2-bromophenyl)-2-phenylacrylamides. The use of (1R,2R)-N,N’-dibenzylcyclohexane-1,2-diamine provides up to 35% ee of the indolines; this is the first case of asymmetric induction during the reductive Heck reaction involving diamine complexes.

Cobalt-Promoted Photoredox 1,2-Amidoamination of Alkenes with N-Sulfonamidopyridin-1-ium Salts and Free Amines.

A cobalt-promoted photoredox 1,2-amidoamination of alkenes with N-sulfonamidopyridin-1-ium salts and free amines for the synthesis of unsymmetrical vicinal diamines has been developed. The reaction handles N-(sulfonamido)pyridin-1-ium salts as the sulfonamidyl radical precursors and free amines as the nucleophilic terminating reagents to enable the formation of two new C(sp3)-N bonds in a single reaction step and offers a route to selectively producing unsymmetrical vicinal diamines with an exquisite selectivity and a good compatibility of functional groups.

Photoredox-catalyzed unsymmetrical diamination of alkenes for access to vicinal diamines.

A photoredox-catalyzed unsymmetrical diamination of alkenes by using N-aminopyridinium salts and nitriles as the amination reagents has been developed. Various vicinal diamines were obtained in moderate to excellent yields under mild reaction conditions. Furthermore, this protocol could be applied in the late-stage modification of pharmaceuticals and natural products. Preliminary mechanistic studies suggested that this methodology may undergo a radical pathway followed by a Ritter-type reaction.

Telescoped synthesis of vicinal diamines via ring-opening of electrochemically generated aziridines in flow

Telescoped synthesis of vicinal diamines via ring-opening of electrochemically generated aziridines in flow

Regioselective Synthesis of Unsymmetrical Vicinal Diamines via Azidoimination of Alkenes with TMSN3 and Ketimines.

2-Azidoimines are versatile precursors to value-added vicinal unsymmetrical diamines, which are among the most common motifs in biologically active compounds. Herein, we report their operationally simple synthesis through a highly regioselective intermolecular azidoamination of olefins under metal-free conditions. The approach proceeded through azide and iminyl, two differentiated N-centered radicals. The synthetic potential of the protocols was further established via the condensation/amination sequential cascade and chemoselective, orthogonal transformations to access vicinal primary diamines.

Ring Opening of Aziridines by Pendant Sulfamates Allows for Regioselective and Stereospecific Preparation of Vicinal Diamines.

The ring opening of aziridines by pendant sulfamates is a viable strategy for the rapid preparation of vicinal diamines. Our reaction is compatible with both disubstituted cis- and trans-aziridines; unsubstituted, N-alkyl, and N-aryl sulfamates engage effectively. In all cases examined, the cyclization reaction is perfectly regioselective and stereospecific. Once activated, the product oxathiazinane heterocycles can be ring opened with a diverse range of nucleophiles.

Synthesis of 2,3‐Diaminoindolesvia a Copper‐Iodine Co‐catalytic Strategy

Comprehensive SummaryA one‐pot synthesis of vicinal diamines using indoles, azoles and phenothiazines in a tandem multi‐component reaction is developed. The utilization of a copper‐iodine co‐catalytic system enables the generation of a diverse range of vicinal diaminoindoles with good selectivity and moderate to good yields. An attractive aspect of this method is that it can be conducted under mild and environmentally friendly conditions, showcasing its potential as an alternative approach for synthesizing vicinal diamines. Moreover, the use of a multicomponent tandem reaction highlights the power and versatility of such strategies in synthetic chemistry.

An efficient triethyl phosphite-promoted one-pot synthesis of vicinal diamines from arylglyoxals and aniline derivatives

An effective protocol for synthesis of some new vicinal diamine derivatives is reported through a one-pot reaction between arylglyoxals and aniline derivatives promoted by triethyl phosphite as a reductive coupling reagent. All reactions were conducted in ethanol as solvent at room temperature and the stable solid products were obtained by simple filtering off the precipitated solids in high yields. The structures of all products were proved by 1H and 13C NMR and IR spectral and elemental analysis data.

Enantioselective and Enantioconvergent Iron‐Catalyzed C(sp3)‐H Aminations to Chiral 2‐Imidazolidinones

Comprehensive SummaryEnantioselective or enantioconvergent iron‐catalyzed ring‐closing C(sp3)‐H aminations of N‐aroyloxyurea through intermediate iron nitrene species provide chiral 2‐imidazolidinones in up to 99% yield and with up to 95% ee (40 examples). This is a rare example in which sustainable iron catalysis is combined with C(sp3)‐H amination and asymmetric catalysis. Chiral 2‐imidazolidinones are prevalent structural motifs in bioactive molecules and can also be hydrolyzed to valuable chiral vicinal diamines in a single step.

Kinetic Resolution of trans-2,3-Aziridinyl Alcohols via Hydroxyl Directed Regio- and Enantioselective Ring Opening Reactions

An efficient kinetic resolution of racemic trans-2,3-aziridinyl alcohols is established via zinc catalyzed ring opening reactions with various amines as the nucleophiles. The directing effect of the hydroxyl group and the precise enantiodiscrimination by dinuclear zinc cooperative catalyst are the keys to success of high regioselectivity and enantioselectivity. A range of enantioenriched vicinal diamines and trans-2,3-aziridinyl alcohols were obtained in good yields with excellent ee values. To the best of our knowledge, this is the first example of directed enantioselective nucleophilic ring opening reactions of 2,3-aziridinyl alcohols.

Modular and practical diamination of allenes

Vicinal diamines are privileged scaffolds in medicine, agrochemicals, catalysis, and other fields. While significant advancements have been made in diamination of olefins, diamination of allenes is only sporadically explored. Furthermore, direct incorporation of acyclic and cyclic alkyl amines onto unsaturated π systems is highly desirable and important, but problematic for many previously reported amination reactions including the diamination of olefins. Herein, we report a modular and practical diamination of allenes, which offers efficient syntheses of β,γ-diamino carboxylates and sulfones. This reaction features broad substrate scope, excellent functional group tolerability, and scalability. Experimental and computational studies support an ionic reaction pathway initiated with a nucleophilic addition of the in situ formed iodoamine to the electron deficient allene substrate. An iodoamine activation mode via a halogen bond with a chloride ion was revealed to substantially increase the nucleophilicity of the iodoamine and lower the activation energy barrier for the nucleophilic addition step.

Asymmetric Synthesis of Vicinal Tetrasubstituted Diamines via Reductive Coupling of Ketimines Templated by Chiral Diborons.

We herein describe the chiral diboron-templated asymmetric homocoupling of aryl alkyl ketimines, providing for the first time a series of chiral vicinal tetrasubstituted diamines with excellent ee values and good to high yields. The powerful and efficient diboron-participated [3,3]-sigmatropic rearrangement is successfully demonstrated by the homocoupling of a variety of ketimines thanks to the rational design and engineering of chiral diborons. Systematic DFT studies suggest that two chiral diborons adopt different conformational assembling strategies to couple the diboron template with ketimine substrates in their tight concerted transition states to ensure the excellent enantioselectivities. The synthetic value of chiral vicinal tetrasubstituted diamines is demonstrated by the asymmetric α-bromination of aliphatic aldehydes by employing a chiral vicinal tetrasubstituted diamine-based organocatalyst.

Asymmetric Synthesis of Vicinal Tetrasubstituted Diamines via Reductive Coupling of Ketimines Templated by Chiral Diborons

AbstractWe herein describe the chiral diboron‐templated asymmetric homocoupling of aryl alkyl ketimines, providing for the first time a series of chiral vicinal tetrasubstituted diamines with excellent ee values and good to high yields. The powerful and efficient diboron‐participated [3,3]‐sigmatropic rearrangement is successfully demonstrated by the homocoupling of a variety of ketimines thanks to the rational design and engineering of chiral diborons. Systematic DFT studies suggest that two chiral diborons adopt different conformational assembling strategies to couple the diboron template with ketimine substrates in their tight concerted transition states to ensure the excellent enantioselectivities. The synthetic value of chiral vicinal tetrasubstituted diamines is demonstrated by the asymmetric α‐bromination of aliphatic aldehydes by employing a chiral vicinal tetrasubstituted diamine‐based organocatalyst.