The applications of Schiff bases in Ti-catalyzed asymmetric alkynylation of aldehydes

Sciff bases 1 and 2, which were derived from chiral aminoalcohols, were used as ligands in Ti-catalyzed asymmetric alkynylation of aldehydes. Good enantioselectivities (up to 88% ee) and high chemical yields (80-90%) were obtained.     

Determination of the rates of formation and hydrolysis of the Schiff bases formed by pyridoxal 5′-phosphate and copolypeptides containing l-lysine

We determined the apparent rate constants of formation (k₁) and hydrolysis (k₂) of the Schiff bases formed between pyridoxal 5′-phosphate (PLP) and l-lysine and l-alanine copolymers of different compositions, as well as those formed between PLP and l-lysine and l-glutamic acid copolymers, at various pH values, a temperature of 25 °C and an ionic strength of 0.1 M. The k₁ values obtained in neutral and acidic media were independent of the copolymer composition. The efficiency of the intramolecular acid catalysis for the formation of the Schiff bases was found to be somewhat higher than that of PLP—primary amine systems (the slope of the Brøwted plot was α=0.77). The most stable of the Schiff bases studied was that with a protonated imine nitrogen and phosphate group and a unprotonated pyridine nitrogen.     

Asymmetric alkyne addition to aldehydes catalyzed by Schiff bases made from 1,1′-bi-2-naphthol and chiral benzylic amines

Several 1,1′-bi-2-naphthol (BINOL)-based Schiff bases were prepared from the condensation of (R)-3,3′-diformyl BINOL with chiral benzylic amine derivatives. These compounds were used to catalyze the reaction of phenylacetylene with aldehydes in the presence of ZnEt₂ with up to 85% ee and 83% yield.     

DMAP-catalyzed cyclization of Schiff bases with α-halo ketones: Synthesis of 1,4-benzoxazines

We demonstrate that 1,4-benzoxazines can be efficiently synthesized using 4-dimethylaminopyridine (DMAP) as a catalyst. We found that the DMAP catalyst can successfully promote the incorporation of the activated carbon atoms of α-halo ketones into the Schiff bases. The 1,4-benzoxazines can be synthesized through the formation of C–O and C–C bonds in high yield, using DMAP as the catalyst, α-halo ketones and phenolic Schiff bases as the reactants. Furthermore, a possible mechanism is proposed. This work provides a simple and efficient route to prepare the 1,4-benzoxazines.     

Three-component and nonclassical reaction of phosphines with enynes and aldehydes: formation of γ-lactones featuring α-phosphorus ylides

Inverted carbenoid species, generated from attack of phosphines at the α(δ')-carbon of hex-2-en-4-ynedioic acid dialkyl esters, react with aldehydes to give γ-lactones possessing an α-phosphorus ylide moiety.     

Exogenous bridge and tautomer effects on magnetic interaction of binuclear copper(II) complexes of μ-phenolato Schiff bases

Four enol-form binuclear copper complexes with different exogenous bridges, [Cu2(L)(μ-Cl)] (1), [Cu(L)(μ-N3)]· DMF (2), [Cu2(L)(μ-OCH3)] (3) and [Cu2(L)(μ-C3H3N2)]· 1/2C2H5OH (4), where L is the trivalence anion of binucleating ligand 2,6-diformyl-4-methylphenol di(tenzoylhydrazone), have been synthesized and characterized. Crystal data for complex (3) are as follows: space group P1- , a=0.8294(1), 6=0.9333(3), c= 1.473 6(6) nm, α=79.51(3)°, β=80.93(2)°,γ=81.32(2)°, Z=1. The magnetic measurements indicated that the effect of exogenous bridging ligands on magnetic interaction is corresponding to that in spectrochemical series. The effect of enol- and keto-form tautomer on magnetic interaction was explained from the point of view of structural factors and electron effects by using molecular mechanks and quantum chemistry calculations.     

Two-carbon homologation of aldehydes and ketones to α,β-unsaturated aldehydes

Phosphonate reagents were developed for the two-carbon homologation of aldehydes or ketones to unbranched- or methyl-branched α,β-unsaturated aldehydes. The phosphonate reagents, diethyl methylformyl-2-phosphonate dimethylhydrazone and diethyl ethylformyl-2-phosphonate dimethylhydrazone, contained a protected aldehyde group instead of the usual ester group. A homologation cycle entailed condensation of the reagent with the starting aldehyde, followed by removal of the dimethylhydrazone protective group with a biphasic mixture of 1 M HCl and petroleum ether. This robust two-step process worked with a variety of aldehydes and ketones. Overall isolated yields of unsaturated aldehyde products ranged from 71% to 86% after the condensation and deprotection steps.     

Enantioselective α-vinylation of aldehydes via the synergistic combination of copper and amine catalysis

The enantioselective α-vinylation of aldehydes using vinyl iodonium triflate salts has been accomplished via the synergistic combination of copper and chiral amine catalysis. These mild catalytic conditions provide a direct route for the enantioselective construction of enolizable α-formyl vinylic stereocenters without racemization or olefin transposition. These high-value coupling adducts are readily converted into a variety of useful olefin synthons.     

Enantioselective α-arylation of aldehydes via the productive merger of iodonium salts and organocatalysis

The enantioselective α-arylation of aldehydes has been accomplished using diaryliodonium salts and a combination of copper and organic catalysts. These mild catalytic conditions provide a new strategy for the enantioselective construction and retention of enolizable α-formyl benzylic stereocenters, a valuable synthon for the production of medicinal agents. As one example, this new asymmetric protocol has been applied to the rapid synthesis of (S)-ketoprofen, a commercially successful oral and topical analgesic.     

Unexpected C-C bond cleavage of α-nitroketone in the presence of TsNBr2: A new pathway for C-N bond formation

A new catalyst-free protocol for C-N bond formation via the cleavage of α-nitroketone has been developed. When α -nitroketones are treated with TsNBr₂ in the presence of potassium carbonate, unexpected cleavage of C(O)-CHNO₂ bond of α -nitroketone was observed followed by the formation of corresponding amide. Various nitroketones could be converted to corresponding amide using this procedure.     

Antioxidant properties of phenolic Schiff bases: structure–activity relationship and mechanism of action

Phenolic Schiff bases are known for their diverse biological activities and ability to scavenge free radicals. To elucidate (1) the structure–antioxidant activity relationship of a series of thirty synthetic derivatives of 2-methoxybezohydrazide phenolic Schiff bases and (2) to determine the major mechanism involved in free radical scavenging, we used density functional theory calculations (B3P86/6-31+(d,p)) within polarizable continuum model. The results showed the importance of the bond dissociation enthalpies (BDEs) related to the first and second (BDE_d) hydrogen atom transfer (intrinsic parameters) for rationalizing the antioxidant activity. In addition to the number of OH groups, the presence of a bromine substituent plays an interesting role in modulating the antioxidant activity. Theoretical thermodynamic and kinetic studies demonstrated that the free radical scavenging by these Schiff bases mainly proceeds through proton-coupled electron transfer rather than sequential proton loss electron transfer, the latter mechanism being only feasible at relatively high pH.     

Reaction of Schiff bases anions with α,ω-dihaloalkanes: Synthetic route to cyclic α-aminoacid derivatives.

Addition-elimination versus substitution reactions.     

Oxazolidinone/enamine ratios in the reactions of α-silyloxy and α-alkoxy aldehydes with proline

α-Silyloxy and α-alkoxy aldehydes (propanal derivatives 1–4), when treated with proline in DMSO-d₆, give oxazolidinones rather than enamines. In fact, the relative trend is much stronger than that of all other carbonyl compounds examined, including simple aldehydes, α-branched aldehydes, α-(alkylthio)aldehydes, and standard ketones. For 1–4, the high prevalence of oxazolidinones prevents or delays the partial racemization of the α-stereocenters.     

Reaction of Schiff bases anions with 4-halo-2-butenoates: Selective synthesis of α-cyclopropyl and γ,δ unsaturated α-amino acid derivatives.

Copper-catalyzed substitution reactions.     

Synthesis and reaction of tricyclic tetrathiins and pentathiepins: novel formation of α-disulfines

Cyclic polysulfanes containing a norbornane skeleton (tetrathiins and pentathiepins) were synthesized by two methods. One is the sulfurization of camphor hydrazone with disulfur dichloride, and the other is the reaction of thiocamphor with disulfur dichloride. The reduction of tetrathiin with LiEt₃BH gave the corresponding dithiol that further reacted with methyl iodide to afford the corresponding methyl sulfide. Reaction of tetrathiin with (Ph₃P)₂PdCl₂ or NiBr₂ resulted in the formation of the corresponding dithiolene metal complexes. Tetrathiins were stereoselectively oxidized by m-CPBA to afford the corresponding α-disulfines.     

Aryl-oxadiazole Schiff bases: Synthesis, α-glucosidase in vitro inhibitory activity and their in silico studies

α-Glucosidase enzyme is a therapeutic target for diabetes mellitus and its inhibitors play a vital role in the treatment of this disease. A new series of aryl-oxadiazole Schiff bases (1–18) were synthesized and evaluated for α-glucosidase inhibitory potential. Fifteen compounds 1–8, 11–13, and 15–18 showed excellent inhibition with IC₅₀ values ranging from 0.30 ± 0.2 to 35.1 ± 0.80 µM as compared to the standard inhibitor acarbose (IC₅₀ = 38.45 ± 0.80 µM), nonetheless, the remaining compounds were found to have moderate activity. Among the series, compounds 7 (IC₅₀ = 0.30 ± 0.2 μM) with hydroxy groups at phenyl rings on either side of the oxadiazole ring was identified as the most potent inhibitor of α-glucosidase. The molecular docking studies were conducted to understand the binding mode of active inhibitors with the active site of enzyme and results supported the experimental data.     

Photoreaction of α-phenylcrotononitrile derivatives: the facile cyclopropane ring formation

Irradiation of 4-methyl, 4,4-dimethyl, and 4,4,4-trimethyl derivatives of 2-phenylcrotononitrile gives the corresponding 1-cyano-1-phenylcyclopropanes in high yields.     

Unexpected formation of fluorine-containing tetrahydrocarbazole during the reaction of indole, paraformaldehyde, and fluorine-containing β-ketoesters

A surprise and mild method to prepare fluorine-containing indole derivatives through a one-pot three-component condensation reaction sequence is presented. To our surprise, during the reaction of preparation of fluorine-containing indole derivatives, unexpected formation of fluorine-containing tetrahydrocarbazole was found. Moreover, this method has been demonstrated in the preparation of functionalized polycyclic indole derivatives in a straightforward and atom-economical manner.