Recent developments in the utility of Zn(L-proline)2 as benign and recyclable metallo-organocatalyst in organic synthesis

The coordination of Zn (II) with L - proline as a choral ligand makes the initiated complex Zn(L-proline)₂ a moderately soft Lewis acid. Recently Zn(L-proline)₂ has emerged as a promising reusable chiral catalyst which could be utilized in a diversity of transformations. The present short review article focuses mainly on recent developments in utility of Zn(L-proline)₂ in organic synthesis. This includes Aldol condensation, synthesis of heterocyclic compounds with five, six and fused rings.     

Effect of the Nature of the Substituent in N‐Alkylimidazole Ligands on the Outcome of Deprotonation: Ring Opening versus the Formation of N‐Heterocyclic Carbene Complexes

Complexes [Re(CO)₃(N‐RIm)₃]OTf (N‐RIm=N‐alkylimidazole, OTf=trifluoromethanesulfonate; 1 a – d ) have been straightforwardly synthesised from [Re(OTf)(CO)₅] and the appropriate N‐alkylimidazole. The reaction of compounds 1 a – d with the strong base KN(SiMe₃)₂ led to deprotonation of a central C? H group of an imidazole ligand, thus affording very highly reactive derivatives. The latter can evolve through two different pathways, depending on the nature of the substituents of the imidazole ligands. Compound 1 a contains three N‐MeIm ligands, and its product 2 a features a C‐bound imidazol‐2‐yl ligand. When 2 a is treated with HOTf or MeOTf, rhenium N‐heterocyclic carbenes (NHCs) 3 a or 4 a are afforded as a result of the protonation or methylation, respectively, of the non‐coordinated N atom. The reaction of 2 a with [AuCl(PPh₃)] led to the heterobimetallic compound 5 , in which the N‐heterocyclic ligand is once again N‐bound to the Re atom and C‐coordinated to the gold fragment. For compounds 1 b – d , with at least one N‐arylimidazole ligand, deprotonation led to an unprecedented reactivity pattern: the carbanion generated by the deprotonation of the C2? H group of an imidazole ligand attacks a central C? H group of a neighbouring N‐RIm ligand, thus affording the product of C? C coupling and ring‐opening of the imidazole moiety that has been attacked ( 2 c , d ). The new complexes featured an amido‐type N atom that can be protonated or methylated, thus obtaining compounds 3 c , d or 4 c , d , respectively. The latter reaction forces a change in the disposition of the olefinic unit generated by the ring‐opening of the N‐RIm ligand from a cisoid to a transoid geometry. Theoretical calculations help to rationalise the experimental observation of ring‐opening (when at least one of the substituents of the imidazole ligands is an aryl group) or tautomerisation of the N‐heterocyclic ligand to afford the imidazol‐2‐yl product.     

Micellar structure of an oligopeptide surfactant “trimeric N -dodecanoyl-L-proline potassium salt” in aqueous solution – small-angle neutron scattering study

Structures of the micelles which are formed by the chiral oligopeptide surfactant N-dodecanoyl-L-proline tripeptide anions have been examined using small-angle neutron scattering spectral analysis. Results show that the chiral N-dodecanoyl-L-proline trimeric anions may form a spherical micelle with an aggregation number of 36 and that the oligopeptide portions with a poly-L-proline I-type helical structure are saturated with water. Received: 21 March 2001 Accepted: 5 April 2001     

Palladium acetate assisted synthesis of five-membered N-polyheterocycles

Abstract

The metal-assisted synthesis of heterocyclic compounds is known to be one of the extremely developing as well as significant concepts of organic chemistry. Because of their expensive, complex working of the instrument and difficult procedures, the methodologies used earlier for the heterocycle synthesis were less amicable to the researchers. The Pd(OAc)₂-mediated cyclic reactions have been recognized to be very effective for both the stereoselective as well as regioselective formation of the 5-membered N-bearing heterocyclic compounds. The different uses of palladium acetate, as a catalyst in the formation of 5-membered N-containing polyheterocycles, are covered in this review article.     

Transition Metal Acetate Promoted Syntheses of Some New N‐Heterocycles by Multicomponent Reactions

The intermolecular cyclization reactions of N‐tosyl‐ethylenediamine with glyoxal promoted by transition metal acetate at different ratios gave three N‐heterocyclic compounds. The ligand in compound 1 contains one N‐heterocycle, which is formed by a one‐pot three‐component reaction. In compound 2 , two imidazolidine rings and one piperazine ring are fused together to form a tricyclic skeleton by a one‐pot five‐component reaction. Two 1,3,6‐triazabicyclo[3.3.0]octanes are connected by one C–C bond to form the skeleton of 3 , which is constructed from a one‐pot nine‐component reaction. It revealed that the key factor for the preparation of these compounds is the ratio of starting materials, as well as the presence of corresponding transition metal acetates.     

Poly(β-Amino acids). VI. Synthesis and conformational properties of poly[(r)-3-pyrrolidinecarboxylic acid]

Racemic and optically active 3-pyrrolidinecarboxylic acids (β-proline) were synthesized, and their polymers, poly[(RS)-β-proline] and poly[(R)-β-proline], were prepared by the polycondensation reaction of the p-nitrophenyl esters. Model compounds, N-cyclopentylcarboxylic acid pyrrolidide and N-cyclopentylcarbonyl-(R)-3-pyrrolidinecarboxylic acid pyrrolidide, were synthesized to elucidate the conformation of the polymer. The solution properties of poly[(R)-β-proline] and the model compounds were investigated by means of circular dichroism (CD) and NMR spectroscopy. The spectral patterns of the polymer and model compounds were similar in various solvents. Poly[(R)-β-proline] and poly[(RS)-β-proline] showed identical NMR spectra. These results suggest that poly[(R)-β-proline] may exist in a random conformation consisting of mixtures of cis and trans amide bonds. The conformational study of cyclopentanecarboxylic acid pyrrolidide by NMR spectroscopy with a shift reagent, Eu(fod)₃, in CDCl₃ implied that the plane containing the amide group bisects the cyclopentane ring. This suggests that each amide plane in the polymer in chloroform may also bisect the pyrrolidine ring.     

Binuclear meta‐xylyl‐linked Ag(I)‐N‐heterocyclic carbene complexes of N‐alkyl/aryl‐alkyl‐substituted bis‐benzimidazolium salts: synthesis,crystal structures and in vitro anticancer studies

Salts of meta‐xylyl‐linked N‐ethyl/n‐butyl/benzyl‐substituted bis‐benzimidazolium having hexafluorophosphate counterions have been synthesized. The corresponding binuclear Ag(I)‐N‐heterocyclic carbene complexes were prepared by the reaction of Ag₂O. The N‐heterocyclic carbene (NHC) ligand precursor 7 and Ag(I)–NHC complexes 10 and 11 have been structurally characterized by single‐crystal X‐ray diffraction technique. All of the reported compounds have been tested for their anticancer activity using human colorectal (HCT 116) cancer cell lines. Sterically varied benzimidazolium salts displayed significant activity against HCT 116 cell line, yielding IC₅₀ values in the range 0.1–19.4 µ m , while Ag(I)–carbene complexes showed exceptionally good activity (0.2–1.3 µ m ) against tested cancer cell lines. Copyright © 2013 John Wiley & Sons, Ltd.     

Effect of the Composition of the Aqueous Organic Solvent on the Kinetics of N-Acylation of α-Amino Acids with 4-Nitrophenyl 4-Nitrobenzoate

Equations relating the N-acylation rate constants of glycine, L--alanine, DL-threonine, and L-proline with 4-nitrophenyl 4-nitrobenzoate in water-acetonitrile, water-2-propanol, and water-2-methyl-2-propanol solvents to the composition of the medium were obtained, and reaction rate constants in water were calculated.     

Cationic Heterocycles as Ligands: Synthesis and Reactivity with Anionic Nucleophiles of Cationic Triruthenium Clusters Containing C‐Metalated N‐Methylquinoxalinium or N‐Methylpyrazinium Ligands

The cationic cluster complexes [Ru₃(CO)₁₀(μ‐H)(μ‐κ²N,C‐L¹Me)]⁺ ( 3 ⁺; HL¹=quinoxaline) and [Ru₃(CO)₁₀(μ‐H)(μ‐κ²N,C‐L²Me)]⁺ ( 5 ⁺; HL²=pyrazine) have been prepared as triflate salts by treatment of their neutral precursors [Ru₃(CO)₁₀(μ‐H)(μ‐κ²N,C‐Lⁿ)] with methyl triflate. The cationic character of their heterocyclic ligands is responsible for their enhanced tendency to react with anionic nucleophiles relative to that of hydrido triruthenium carbonyl clusters that have neutral N‐heterocyclic ligands. These clusters react instantaneously with methyl lithium and potassium tris‐sec‐butylborohydride (K‐selectride) to give neutral products that contain novel nonaromatic N‐heterocyclic ligands. The following are the products that have been isolated: [Ru₃(CO)₉(μ‐H)(μ₃‐κ²N,C‐L¹Me₂)] ( 6 ; from 3 ⁺ and methyl lithium), [Ru₃(CO)₉(μ‐H)(μ₃‐κ²N,C‐L¹HMe)] ( 7 ; from 3 ⁺ and K‐selectride), [Ru₃(CO)₉(μ‐H)(μ₃‐κ²N,C‐L²Me₂)] ( 8 ; from 5 ⁺ and methyl lithium), and [Ru₃(CO)₉(μ‐H)(μ₃‐κ²N,C‐L²HMe)] ( 11 ; from 5 ⁺ and K‐selectride). Whereas the reactions of 3 ⁺ lead to products that arise from the attack of the corresponding nucleophile at the C atom of the only CH group adjacent to the N‐methyl group, the reactions of 5 ⁺ give mixtures of two products that arise from the attack of the nucleophile at one of the C atoms located on either side of the N‐methyl group. The LUMOs and the atomic charges of 3 ⁺ and 5 ⁺ confirm that the reactions of these clusters with anionic nucleophiles are orbital‐controlled rather than charge‐controlled processes. The N‐heterocyclic ligands of all of these neutral products are attached to the metal atoms in nonconventional face‐capping modes. Those of compounds 6 – 8 have the atoms of a ligand C?N fragment σ‐bonded to two Ru atoms and π‐bonded to the other Ru atom, whereas the ligand of compound 11 has a C? N fragment attached to a Ru atom through the N atom and to the remaining two Ru atoms through the C atom. A variable‐temperature ¹H NMR spectroscopic study showed that the ligand of compound 7 is involved in a fluxional process at temperatures above ?93 °C, the mechanism of which has been satisfactorily modeled with the help of DFT calculations and involves the interconversion of the two enantiomers of this cluster through a conformational change of the ligand CH₂ group, which moves from one side of the plane of the heterocyclic ligand to the other, and a 180° rotation of the entire organic ligand over a face of the metal triangle.     

Facile One‐Pot Synthesis of N‐Alkylated Benzimidazole and Benzotriazole from Carbonyl Compounds

An efficient one‐pot N‐alkylation of benzimidazole and benzotriazole from carbonyl compounds and tosylhydrazide has been accomplished via copper powder‐catalyzed N—H bond insertion affording N‐alkylated products in good yields. The reaction can tolerate a wide range of carbonyl compounds, such as aryl, alkyl, heterocyclic and α,β‐unsaturated ketones, and aldehydes.     

A Proton-Responsive Pyridyl(benzamide)-Functionalized NHC Ligand on Ir Complex for Alkylation of Ketones and Secondary Alcohols

A Cp*Ir(III) complex ( 1 ) of a newly designed ligand L¹ featuring a proton-responsive pyridyl(benzamide) appended on N - heterocyclic carbene (NHC) has been synthesized. The molecular structure of 1 reveals a dearomatized form of the ligand. The protonation of 1 with HBF₄ in tetrahydrofuran gives the corresponding aromatized complex [Cp*Ir(L¹H)Cl]BF₄ ( 2 ). Both compounds are characterized spectroscopically and by X-ray crystallography. The protonation of 1 with acid is examined by ¹H NMR and UV-vis spectra. The proton-responsive character of 1 is exploited for catalyzing α-alkylation of ketones and β-alkylation of secondary alcohols using primary alcohols as alkylating agents through hydrogen-borrowing methodology. Compound 1 is an effective catalyst for these reactions and exhibits a superior activity in comparison to a structurally similar iridium complex [Cp*Ir(L²)Cl]PF₆ ( 3 ) lacking a proton-responsive pendant amide moiety. The catalytic alkylation is characterized by a wide substrate scope, low catalyst and base loadings, and a short reaction time. The catalytic efficacy of 1 is also demonstrated for the syntheses of quinoline and lactone derivatives via acceptorless dehydrogenation, and selective alkylation of two steroids, pregnenolone and testosterone. Detailed mechanistic investigations and DFT calculations substantiate the role of the proton-responsive ligand in the hydrogen-borrowing process.     

NHC copper complexes functionalized with sulfoxide and sulfone moieties

A series of N‐heterocyclic copper carbene complexes bearing sulfoxide and sulfone moieties have been prepared. In case of new copper compounds with sulfone ligand, the solid‐state structures were determined using X‐Ray crystallography. Obtained complexes were investigated as catalysts in such transformations as: 1,3‐dipolar cycloaddition of alkynes and azides (CuAAC), A³ coupling reaction and β‐hydroboration and compared with standard copper catalytic systems.     

<Emphasis Type="Italic">N</Emphasis>-Bromoacetyl-β-<Emphasis Type="SmallCaps">D</Emphasis>-glycopyranosylamines in the synthesis of glycoconjugates of nitrogen-containing physiologically active compounds

A series of nitrogen-containing physiologically active compounds underwent smooth N-monoalkylation with N-bromoacetyl-β-glycopyranosylamines derived from N-acetyl-D-glucosamine and lactose. This reaction was demonstrated to be promising for the introduction of carbohydrate residues into heterocyclic compounds, viz., pyridine, imidazole, pyrimidinetrione, carboline, and piperazine derivatives, and into an amino acid, 5-hydroxy-L-tryptophan, which is unstable in alkaline media. Dedicated to Academician N. K. Kochetkov on the occasion of his 90th birthday. __________ Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 5, pp. 1256–1259, May, 2005.     

Reductive Dimerization of Triruthenium Clusters Containing Cationic Aromatic N‐Heterocyclic Ligands

The cationic cluster complexes [Ru₃(μ‐H)(μ‐κ²N,C‐L¹ Me)(CO)₁₀]⁺ ( 1 ⁺; HL¹ Me=N‐methylpyrazinium), [Ru₃(μ‐H)(μ‐κ²N,C‐L² Me)(CO)₁₀]⁺ ( 2 ⁺; HL² Me=N‐methylquinoxalinium), and [Ru₃(μ‐H)(μ‐κ²‐N,C‐L³ Me)(CO)₁₀]⁺ ( 3 ⁺; HL³ Me=N‐methyl‐1,5‐naphthyridinium), which contain cationic N‐heterocyclic ligands, undergo one‐electron reduction processes to become short lived, ligand‐centered, trinuclear, radical species ( 1 – 3 ) that end in the formation of an intermolecular C? C bond between the ligands of two such radicals, thus leading to neutral hexanuclear derivatives. These dimerization processes are selective, in the sense that they only occur through the exo face of the bridging ligands of trinuclear enantiomers of the same configuration, as they only afford hexanuclear dimers with rac structures (C₂ symmetry). The following are the dimeric products that have been isolated by using cobaltocene as reducing agent: [Ru₆(μ‐H)₂{μ₆‐κ⁴N₂,C₂‐(L¹ Me)₂}(CO)₁₈] ( 5 ; from 1 ⁺), [Ru₆(μ‐H)₂{μ₆‐κ⁴N₂,C₂‐(L² Me)₂}(CO)₁₈] ( 6 ; from 2 ⁺), and [Ru₆(μ‐H)₂{μ₄‐κ⁸N₂,C₆‐(L³ Me)₂}(CO)₁₈] ( 7 ; from 3 ⁺). The structures of the final hexanuclear products depend on the N‐heterocyclic ligand attached to the starting materials. Thus, although both trinuclear subunits of 5 and 6 are face‐capped by their bridging ligands, the coordination mode of the ligand of 5 is different from that of the ligand of 6 . The trinuclear subunits of 7 are edge‐bridged by its bridging ligand. In the presence of moisture, the reduction of 3 ⁺ with cobaltocene also affords a trinuclear derivative, [Ru₃(μ‐H)(μ‐κ²N,C‐L^3′ Me)(CO)₁₀] ( 8 ), whose bridging ligand (L^3′ Me) results from the formal substitution of an oxygen atom for the hydrogen atom (as a proton) that in 3 ⁺ is attached to the C⁶ carbon atom of its heterocyclic ligand. The results have been rationalized with the help of electrochemical measurements and DFT calculations, which have also shed light on the nature of the odd‐electron species, 1 – 3 , and on the regioselectivity of their dimerization processes. It seems that the sort of coupling reactions described herein requires cationic complexes with ligand‐based LUMOs.     

High-yielding method for preparation of carbocyclic or N-containing heterocyclic β-keto esters using in situ activated sodium hydride in dimethyl sulphoxide

It was found that NaH suspension in DMSO was highly activated when reacted with an alcohol. The in situ generated NaH/alkoxide mixture permitted very rapid and complete deprotonation and acylation of various cyclic ketones with alkyl carbonates at ambient temperature. Activated NaH/alkoxide in DMSO is particularly effective in Dieckmann condensations, where it affords 5- and 6-membered carbocyclic or N-containing heterocyclic β-keto esters in high yields. A heterocyclic Dieckmann condensation was performed on a molar scale, demonstrating the scalability of the procedure. Besides, DMSO is non-toxic, relatively inexpensive and environmentally benign solvent.     

Utility and Synthetic Uses of Mannich Reaction: An Efficient Route for Synthesis of Thiadiazino‐[1,3,5][3,2‐a]benzimidazoles

The utilities of the Mannich reaction in synthetic organic chemistry are reviewed. The behaviors of Mannich reactions on several bifunctional heterocyclic compounds have been reported. A new class of heterocyclic compounds, thiadiazino[1,3,5][3,2‐a]benzimidazoles 12a–g, were obtained by reaction of 2‐mercaptobenzimidazole with primary aliphatic amines in a one‐step synthesis. An attempt to apply this reaction using primary aromatic amines lead to the formation of the well‐known Mannich bases 11a–g rather than the N‐substituted thiadiazines 13.     

Heterocyclic o-Chloroaldehydes as Synthons in Organic and Inorganic Sulfur Chemistry

Abstract

Many heterocyclic o-chloroaldehydes are easy to prepare, for example via the Vilsmeier chloroformylation reaction. Due to the electron withdrawing effect of the formyl group, the halogen atom is normally a nucleofuge. This can be used to prepare a range of o-substituted heterocyclic aldehydes showing interesting rearrangement reactions. Such types of compounds are also useful as starting materials for the preparation of annelated heterocyclic systems.

We have demonstrated that heterocyclic mercapto groups can be protected as t-butylthioethers. Furthermore, we have found that thiolation of heterocyclic systems containing reactive halogen substituents can conveniently be carried out via the easily prepared t-butylsulfides.

This method has been used in the preparation of a number of N₂S₂-ligands. The resulting transition metal N₂S₂-complexes have been used in the study of model systems for one of the active sites in cytochrome c oxidase. The method also gives access to polymeric heterocyclic multisulfur transition metal complexes with high electrical conductivity.     

Synthesis of 4‐substituted styrene compounds via palladium catalyzed Suzuki–Miyaura reaction using bidentate Schiff base ligands

Air‐stable symmetric Schiff base have been synthesized and proved to be efficient ligands for Suzuki–Miyaura reaction between aryl bromides and arylboronic acids using PdCl₂(CH₃CN)₂ as palladium source under aerobic conditions. The coupling reaction proceeded smoothly using N,N‐bis(anthracen‐9‐ylmethylene)benzene‐1,2‐diamine (L₇) as ligand to provide 4‐substituted styrene compounds in good yields. Copyright © 2009 John Wiley & Sons, Ltd.     

The Bismuth (III) Chloride Mediated N-Derivatization of L-Proline and Pipecolinic Esters in Aqueous Media

An efficient method for the N-derivatization, in aqueous media, of L-proline and pipecolinic esters is reported, using benzotriazole as a synthetic auxiliary.