Hydroxy Amides Research Articles

Chemoselective Lipase-Catalyzed Synthesis of Amido Derivatives from 5-Hydroxymethylfurfurylamine.

The acylations of furfurylamine and 5-hydroxymethylfurfurylamine (HMFA) have been studied finding immobilized Candida antarctica lipase B (CALB) as an ideal biocatalyst. CALB was used immobilized on two different supports (Novozyme 435 and EziG-CALB), with the polymer-coated controlled porosity glass carrier material from EnginZyme being an excellent carrier to yield an active and stable enzymatic preparation for the acylation of the primary amine group. The amount of the acyl donor in the reaction was a key factor to achieve the mono- and chemoselective N-protection of HMFA with large excess of ethyl acetate leading to the formation of the N,O-diacetylated product. Thus, a series of 16 nonactivated esters were used to selectively modify the amine group of HMFA, obtaining 9 hydroxy amides under mild reaction conditions and with quantitative yields through chromatography-free transformations. The influence of substrate concentration was studied, resulting in complete conversions in all cases after 22 h (100-1000 mM). Excellent results were observed at 100 and 200 mM of HMFA, while higher concentrations led to longer reaction times and, to some extent, the formation of the diacetylated product (up to 7% after 22 h at 1 M). After this optimization, a metric analysis was performed to confirm the high sustainability of the presented process (E-factor of 1.1 excluding solvents) upon intensification of the biotransformation to 1 g at 200 mM HMFA concentration. The possibility of obtaining orthogonally protected HMFA-derived amido esters has been achieved through a clean and sequential one-pot process using EziG-CALB, which involved the use of ethyl methoxy acetate as the nonactivated ester for N-acylation and the activated vinyl acetate for O-protection.

Passerini Reaction to Access α‐Hydroxy Amides by Facile Decarbonylation/Decarboxylation of Oxalic Acid

Abstractα‐Hydroxy amides are an essential class of compounds found in natural products and bioactive molecules of drug candidates. Herein we report a facile and direct approach to these compounds through oxalic acid decarbonylation/decarboxylation during the Passerini three‐component reaction (P‐3CR) under solvent‐free conditions with microwave heating. This very convenient methodology provides the title compounds through a possible concerted intramolecular decarbonylation/decarboxylation from the α‐acyloxy amide intermediate.

Highly Heat-Resistant Poly(Amido Hydroxy Amides) with Increased Elongation at Break and Photosensitive Formulations Based on Them

Highly Heat-Resistant Poly(Amido Hydroxy Amides) with Increased Elongation at Break and Photosensitive Formulations Based on Them

γ-Hydroxy Amides from Tartaric Acid: Versatile Chiral Building Blocks for the Total Synthesis of Natural Products.

"Chiral pool" compounds possessing well defined stereocenters and suitable functionality serve as excellent building blocks for the synthesis of natural products and therapeutically important compounds. Tartaric acid is a C2 -symmetric molecule available in both enantiomeric forms. It was extensively utilized in the synthesis of privileged chiral ligands/catalysts such as TADDOLs, and as a start point in the synthesis of plethora of compounds. The advent of several new C-C bond forming reactions offers opportunity for the development of novel synthetic strategies based on chiral pool compounds. We found that the desymmetrization of the bis-dimethyl amide/Weinreb amide derived from tartaric acid can be accomplished by controlled addition of Grignard /organolithium reagents leading to the mono keto amides, the reduction of which affords the γ-hydroxy amides. This account describes our research efforts of more than a decade on the synthesis and application of diverse γ-hydroxy amides derived from tartaric acid in the total synthesis of structurally simple to complex bio-active natural products.

Quantum chemical calculation based investigation of synergistic chelating between multiple hydroxyamide ligands and La3+ ion

In this paper, Density Functional Method at B3LYP/SDD level has been implemented in order to study enhanced interaction with lanthanum ion (La3+) in presence of multiple molecules of chelating ligand hydroxyamide (HA) for efficient extraction of lanthanides. Geometrical analysis of optimized structure, thermochemical analysis, potential energy surface study, electron density profile determination and localized orbital locator analysis, molecular orbital analysis, density of states analysis and vibrational spectral (IR spectra) analysis of the complex consisting of one, two, three, and four hydroxyamide ligands with lanthanum have been performed. Calculated geometrical parameters, interaction energies, change in Gibb’s free energy, change in enthalpy, change in entropy, and HOMO-LUMO study indicate the formation feasibility, as well as stability of the complexes, is enhanced while a higher number of hydroxyamide ligand interact with La(III). Structural analysis and vibrational analysis exhibit the formation of hydrogen bond-like non-bonded interaction between hydroxyamide and lanthanum. The orbital analysis provides the underlying reason for the bond formation between lanthanum and doubly bonded oxygen atom with carbon in the hydroxyamide ligand. The above study helps to analyse the interaction of lanthanum with hydroxyamide in order to design chelating extractant for efficient extraction of this rare earth element.

Highly enantioselective Ir/f-amphox-catalyzed hydrogenation of ketoamides: efficient access to chiral hydroxy amides

Asymmetric synthesis of chiral hydroxy amides has been successfully accomplished by asymmetric hydrogenation of prochiral α-, β-, γ-, δ-keto amides catalyzed by Ir/f-amphox with up to >99% conversion and >99% ee.

Microwave-Assisted Aminolysis of Lactones Under Solvent- and Catalyst- Free Conditions

Background: Aminolysis of lactones is an important reaction for the synthesis of hydroxy amides. This reaction generally requires rather harsh conditions, such as high pressure and temperature or strong alkali metal catalysts. Microwave-assisted reactions have provided a great impetus to organic synthesis, especially for accelerating the reactions. The combination of microwave heating and solventfree conditions is a particularly attractive methodology in modern organic synthesis because it leads to enhanced conversion rates, easier work-up, higher yields and in general cleaner reactions. Keywords: Aminolysis, lactones, microwave irradiation, hydroxy amides.

Selective Reduction of β-Keto Amides to α,β-Unsaturated Olefinic Amides and β-Hydroxy Amides by Using Sodium Borohydride as the Reductant

Selective Reduction of <i>β</i>-Keto Amides to <i>α</i>,<i>β</i>-Unsaturated Olefinic Amides and <i>β</i>-Hydroxy Amides by Using Sodium Borohydride as the Reductant

ChemInform Abstract: Tandem α‐Alkylation/Asymmetric Transfer Hydrogenation of Acetophenones with Primary Alcohols.

AbstractAn interesting direct α‐alkylation/asymmetric transfer hydrogenation of acetophenones is achieved with simple primary aliphatic alcohols using an in situ generated Ru‐catalyst having an amino acid hydroxy amide ligand.

Amide-transforming activity of Streptomyces: possible application to the formation of hydroxy amides and aminoalcohols

To develop an efficient bioconversion process for amides, we screened our collection of Streptomyces strains, mostly obtained from soil, for effective transformers. Five strains, including the SY007 (NBRC 109343) and SY435 (NBRC 109344) of Streptomyces sp., exhibited marked conversion activities from the approximately 700 strains analyzed. These strains transformed diverse amide compounds such as N-acetyltetrahydroquinoline, N-benzoylpyrrolidine, and N-benzoylpiperidine into alcohols or N,O-acetals with high activity and regioselectivity. N,O-acetal was transformed into alcohol by serial tautomerization and reduction reactions. As such, Streptomyces spp. can potentially be used for the efficient preparation of hydroxy amides and aminoalcohols.

Functionalized N‐Heterocyclic Carbene Ligands for Dual Enantioselective Control in the Cu‐Catalyzed Conjugate Addition of Dialkylzinc Compounds to Acyclic Enones

AbstractA series of highly tunable, functionalized azolium compounds have been synthesized from chiral α‐amino acid derivatives such as β‐amino alcohols or α‐amino esters. The combination of a Cu salt and a chiral azolium efficiently facilitated the asymmetric conjugate addition (ACA) reactions of acyclic enones with dialkylzinc under ambient conditions without temperature control. Of the (hydroxy amide)‐functionalized azolium ligand precursors, which were derived from β‐amino alcohols, an azolium salt containing a tert‐butyl group as the stereodirecting group was found to be the best choice of ligand. Ligand screening revealed that the use of an azolium salt containing a sterically bulky alkyl substituent such as N‐CHRR′ on the azolium ring led to a marked increase in the enantioselectivity of the ACA reaction. Thus, a new efficient (hydroxy amide)‐functionalized azolium ligand precursor such as 26, which was prepared from 1‐(diphenylmethyl)benzimidazole and (S)‐tert‐leucinol, has been developed. The treatment of benzalacetone (30) with Et2Zn in the presence of catalytic amounts of [Cu(OTf)]2(C6H6) and 26 at room temperature gave the corresponding 1,4‐adduct 31 with excellent enantioselectivity (92 % ee). On the other hand, the enantioselectivity of the ACA reactions of acyclic enones with dialkylzinc was successfully reversed by the use of (ester amide)‐functionalized azolium salts, which were obtained from α‐amino esters. Several functionalized azolium ligand precursors from readily available serine esters have been designed and synthesized. Finally, it was found that 30 could react with Et2Zn under the influence of a bis(hexafluoroacetylacetonato)copper(II) salt and C2‐symmetric azolium salt 36 to afford ent‐31 in almost quantitative yield with 89 % ee. A plausible reaction mechanism for the switching of the stereoselectivity in the ACA reaction by these two functionalized azolium compounds is described.

High Throughput Screening of a Catalyst Library for the Asymmetric Transfer Hydrogenation of Heteroaromatic Ketones: Formal Syntheses of (R)‐Fluoxetine and (S)‐Duloxetine

AbstractA total of 21 amino acid based ligands including hydroxy amide, thioamide, and hydroxamic acid functionalities, respectively, were combined with [Ru(p‐cymene)Cl2]2 and [RhCp*Cl2]2, and used as catalysts for the asymmetric transfer hydrogenation of four different heteroaromatic ketones in 2‐propanol. The reactions were performed on a Chemspeed automated high‐throughput screening robotic platform. Optimal catalysts were identified for the individual heterocyclic substrate classes. Based on these results, the formal syntheses of the antidepressant drugs (R)‐fluoxetine and (S)‐duloxetine were conducted by using the found catalysts in the key reaction step, which results in high isolated yields (94 %) and excellent product enantioselectivities (&gt;99 % ee) of the formed 1,3‐amino alcohols.

Recent Advance of Amino-acids and Their Derivatives as Chiral Ligands in Asymmetric Transfer Hydrogenation of Ketones

The asymmetric transfer hydrogenation (ATH) reaction of prochiral ketones is an important method to produce chiral alcohols. Recently, the application of chiral amino acids and their derivatives as ligands in ATH of prochiral ketones promoted by the ruthenium, rhodium or iridium complexes have been attracted more attentions. Herein the catalytic properties of amino acids, amino acid based amides, thioamides, hydroxamic acids, hydrazides, amino alcohols and hydroxy amides as ligands in the ruthenium, rhodium or iridium catalyzed ATH of prochiral ketones have been overviewed.

ChemInform Abstract: The Lactonization of 2′-Hydroxyhydrocinnamic Acid Amides: A Potential Prodrug for Amines.

The lactonization of two hydroxy amides ― 4-methoxyaniline 3-(2'-hydroxyphenyl)-3,3-dimethylpropionic acid amide (2b) and 4-methoxyaniline 3-(2'-hydroxy-4',6'-dimethylphenyl)-3,3-dimethylpropionic acid amide (3b) ― was studied over a pH range of 1-8. Due to the slowness of its reaction, a third hydroxy amide ― 4-methoxyaniline 3-(2'-hydroxyphenyl) propionic acid amide (1b) ― was investigated only at pH values of 7.5 and 10. The lactonization of 2b and 3b, which was found to be subject to general catalysis by buffer components, was observed to be catalyzed concurrently but not concertedly by both the acidic and basic forms of the buffer

ChemInform Abstract: Rearrangement of 2-Azabicyclo(2.2.1)hept-5-en-3-ones: Synthesis of cis- 3-Aminocyclopentane Carboxylic Acid Derivatives.

The γ-lactam 4 was converted into the bromo ester 6 and the latter compound was transformed in five steps into the diester 10. Similarly the lactam 4 was converted into the hydroxy amide 17via the intermediacy of the dihalogeno compound 11. Compounds 10 and 17 are potential precursors of deoxycarbocyclic nucleosides. Unexpectedly, the lactam 4 furnished the addition product 25 on reaction with benzeneselenenyl bromide and a tentative rationale for the preferred reaction pathway is proposed.

ChemInform Abstract: Ketopinic Acid Derived Bis(hydroxy amides) as Cheap, Chiral Ligands for the Enantioselective Ethylation of Aromatic Aldehydes.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Tandem 6π-Electrocyclization and Cycloaddition of Nitrodienes to Yield Multicyclic Nitroso Acetals

Upon heating, nitrodienes rearrange through 6pi-electrocyclization to form nitronate intermediates, which can be captured through tandem [3 + 2] dipolar cycloadditions to form highly functionalized nitroso acetals. The one-pot, two-step domino process is highly efficient, proceeding with good facial selectivity and exoselectivity. Dipolarophiles featuring electron-rich, -neutral, and -deficient carbon-carbon double bonds are viable substrates for [3 + 2] cycloadditions with the in situ generated nitronates. In addition, the highly functionalized nitroso acetal products can be hydrogenolyzed selectively to form densely functionalized spirocyclic hydroxy amides or hydroxy gamma-amino acids.

ChemInform Abstract: New Amidophosphine-phosphinites (tLANOPs) as Chiral Ligands for Asymmetric Hydrogenation Reactions.

Abstract The new amidophosphine-phosphinite (AMPP) ligands 4a–g (called tLANOP ligands) derived from the chiral hydroxy amide (R)- or (S)-2-hydroxy-3,3,N-trimethylbutyramide have been prepared in 48–83% yield. The crystal structures of the square planar complexes [(SP-4-3)-Pd((R)-dmphea)((S)-4a)]BF4 and [Rh((R)-4a)(COD)]BF4 have allowed the absolute configurations of the ligands to be assigned. In both complexes the 7-membered chelating ring of 4a has virtually the same twist-boat conformation. With this class of ligands the rhodium catalyzed asymmetric hydrogenation of 4-oxoisophorone enol acetate gave (S)-phorenol acetate in up to 71% ee. The iridium catalyzed asymmetric hydrogenation of the cyclic iminium salts 16a and 16b afforded after work-up the corresponding cyclic secondary amine (S)-17 in up to 86% ee, when bulky groups were present on the phenyl substituents on the two phosphorus atoms.

Pyroglutamate-derived hydroxyamide ligands: synthesis and application to asymmetric catalysis

The synthesis of a series of chiral hydroxy amide ligands is described. These ligands were used in a ruthenium-catalysed transfer hydrogenation reaction where one ligand gave the product in 72% ee. The ligands were also used in two titanium-catalysed reactions, an alkylation where ee’s of up to 74% were achieved and a phenyl acetylene addition where more modest selectivities were observed.

Ketopinic Acid Derived Bis(hydroxy amides) as Cheap, Chiral Ligands for the Enantioselective Ethylation of Aromatic Aldehydes

AbstractReadily accessible, C2‐ and pseudo‐C2‐symmetric bis(hydroxy amides), derived from commercially available (+)‐ketopinic acid and protic diamines, are promising, cheap, chiral ligands for the synthetically valuable, enantioselective addition of organozinc reagents to carbon electrophiles. A series of ligands of this type, having key structural differences, has been synthesized and tested in the enantioselective ethylation of benzaldehydes and (E)‐cinnamaldehyde, in order to gain information on the origin of ligand efficiency. The results obtained allow for the definition of a privileged structural pattern for the design of improved cheap ligands and support interesting models proposed for both the acting catalytic species and the controlling transition states. The most efficient ligands proved to be less efficient than commercially available (–)‐MIB; nevertheless, an impressive efficiency level was obtained, which should sustain interest in this cheap type of ligands.