Acid-promoted Condensation Research Articles

Domino Sequences Involving Stereoselective Hydrazone-Type Heck Reaction and Denitrogenative [1,5]-Sigmatropic Rearrangement

Although the Heck reactions of alkene partners with various electrophiles have achieved great success, the variant focused on carbon═heteroatom counterparts still remains elusive. Herein, we report a Pd(0)-catalyzed asymmetric intramolecular hydrazone-type Heck reaction of N-[(Z)-3-iodoallyl]-aminoacetaldehyde and hydrazine hydrate (NH2NH2-H2O), wherein the required hydrazone is in situ generated via an acid-promoted condensation. A key strategic advantage of this Heck paradigm is that the resultant Heck product allylic diazene rapidly undergoes stereospecific denitrogenative [1,5]-sigmatropic rearrangement, eventually furnishing a domino sequence toward 3-substituted tetrahydropyridine (THP) with high enantioselectivity. The substrate-induced diastereoselective version has also been realized, exclusively giving cis-2,5-disubstituted THPs. The utility of this sequence is demonstrated by the formal synthesis of multiple valuable bioactive targets, including 3-ethylindoloquinolizine, preclamol, and niraparib.

Access to ortho-Hydroxyphenyl Ketimines via Imine Anion-Mediated Smiles Rearrangement.

We have achieved a facile access to N-(2-halophenyl)-2-hydroxyphenylimine derivatives via imine anion-mediated Smiles rearrangement. When 2-(2-halophenoxy)benzonitriles were treated with 1.2-1.4 equiv of organolithium reagents, nucleophilic addition to the nitrile group followed by Smiles rearrangement occurred to give various N-(2-halophenyl)-2-hydroxyphenylimine derivatives, which are sometimes difficult to synthesize by the conventional acid-promoted condensation reaction between carbonyl compounds and aniline derivatives, in good to excellent chemical yields (up to 91%).

Chemical switching in reaction behavior of azine: Synthesis of a novel thienodiazepine derivative

We previously have reported that an acid-promoted condensation of a hydrazonoester derived from phenylalanine afforded an azine which was converted to a pyrrole through 3 steps: isomerization to dienamine, [3,3]-sigmatropic rearrangement, and cyclization. In this study, reaction behavior of the intermediate proved to be switched depending on the type of the aromatic ring. Hydrazonoesters derived from thienylalanines afforded various thienodiazepine derivatives under thermal acidic conditions. A more reactive thiophene ring is likely to undergo Friedel-Crafts reaction prior to isomerization to dienamine.

Quaternized Tröger’s base polymer with crown ether unit for alkaline stable anion exchange membranes

Anion exchange membrane fuel cells (AEMFCs) have drawn great attention since the alkaline condition enables the use of non-platinum catalysts. Nevertheless, the lack of alkali-stable and highly conductive anion exchange membranes (AEMs) impedes the development of AEMFCs. Herein, a series of novel quaternized Tröger’s base polymer AEMs are prepared via acid-promoted condensation reaction and Menshutkin reaction. It is found that QTBPCE-2.5 AEM demonstrates the highest hydroxide conductivity of 39.0 mS cm−1 at 30 °C, and this value is higher than that of commercialized Tokuyama AHA. The introduction of intrinsic microporosity into the polymer matrix, which is favorable to the rapid ion conduction, may account for the high conductivity. Furthermore, the loss of ionic exchange capacity and conductivity of QTBPCE-2.5 are both less than 10% after the stability test (1 M KOH, 80 °C, 192 h). The introduction of electron-donating crown ether is responsible for good alkaline stability. The present result shows that the as-designed AEMs have the potential for the applications in AEMFCs.

Two N-{[4-(3-aryl-4-sydnonyl-idene-amino)-5-sulfan-yl-idene-1H-1,2,4-triazol-3-yl]meth-yl}benzamides as disordered ethanol monosolvates.

Two new N-{[4-(3-aryl-4-sydnonyl-idene-amino)-5-sulfanyl-idene-1H-1,2,4-triazol-3-yl]meth-yl}benzamides have been prepared by acid-promoted condensation reactions between 3-aryl-4-formyl-sydnones and N-[(4-amino-5-sulfanyl-idene-1H-1,2,4-triazol-3-yl)meth-yl]benzamide, and both have been crystallized as ethanol monosolvates. N-{[4-(3-Phenyl-4-sydnonyl-idene-amino)-5-sulfanyl-idene-1H-1,2,4-triazol-3-yl]meth-yl}benzamide ethanol monosolvate, C19H15N7O3S·C2H6O (I), and N-({4-[3-(4-methyl-phen-yl)-4-sydnonyl-idene-amino]-5-sulfanyl-idene-1H-1,2,4-triazol-3-yl}meth-yl)benzamide ethanol monosolvate, C20H17N7O3S·C2H6O (II), differ only in the presence of a methyl group for (II) instead of a hydrogen atom for (I), and in both of them the ethanol component is disordered over two sets of atomic sites having occupancies of 0.836 (6) and 0.164 (6) in (I), and 0.906 (6) and 0.094 (6) in (II). Combinations of O-H⋯O and N-H⋯O hydrogen bonds link the mol-ecules into cyclic, centrosymmetric four-mol-ecule aggregates. Comparisons are made with the structures of some related compounds.

Synthesis of secondary and tertiary amides without coupling agents from amines and potassium acyltrifluoroborates (KATs).

Although highly effective for most amide syntheses, the activation of carboxylic acids requires the use of problematic coupling reagents and is often poorly suited for challenging cases such as N-methyl amino acids. As an alternative to both secondary and tertiary amides, we report their convenient synthesis by the rapid oxidation of trifluoroborate iminiums (TIMs). TIMs are easily prepared by acid-promoted condensation of potassium acyltrifluoroborates (KATs) and amines and are cleanly and rapidly oxidized to amides with hydrogen peroxide. The overall transformation can be conducted either as a one-pot procedure or via isolation of the TIM. The unique nature of the neutral, zwitterionic TIMs makes possible the preparation of tertiary amides via an iminium species that would not be accessible from other carbonyl derivatives and can be conducted in the presence of unprotected functional groups including acids, alcohols and thioethers. In preliminary studies, this approach was applied to the late-stage modifications of long peptides and the iterative synthesis of short, N-methylated peptides without the need for coupling agents.

Synthesis of a novel π-extended hybrid rhodamine dye with far-red fluorescence emission and its application in bioimaging

A new π-extended fluorescent dye, a hybrid of naphthocoumarin and rhodamine (NCR), has been developed by the acid-promoted condensation of 2-(4-diethylamino-2-hydroxy) benzoylbenzoic acid with naphthocoumarin. Compared with those of traditional rhodamine fluorophores, the maximum absorption and emission wavelengths of the π-extended NCR are obviously red-shifted. Based on this dye, we constructed the novel Cu2+-selective fluorescent probe NCR-Cu, demonstrating the value of this functional dye. Via a specific Cu2+-promoted ring-opening and hydrolysis processes, it shows high selectivity and sensitivity for Cu2+ detection with the detection limit down to the 10−8 M range. At the same time, the probe NCR-Cu is living cell membrane permeable and can be utilized as a practical vehicle for visualizing Cu2+ in living cells by fluorescence microscopy.

ChemInform Abstract: An Efficient Synthesis of Coumarin‐ and Quinolone‐Annulated Thiazole Derivatives via Ligand‐Free Iron (III)‐Catalyzed Coupling Followed by Acid‐Promoted Condensation.

Abstract An efficient strategy for the synthesis of coumarin- and quinolone-annulated thiazole derivatives using sodium sulfide as a sulfur source has been achieved via ligand-free iron (III)-catalyzed coupling followed by acid-promoted condensation. This synthetic protocol is one-pot, less expensive, and affords the products in good yields.

An efficient synthesis of coumarin- and quinolone-annulated thiazole derivatives via ligand-free iron (III)-catalyzed coupling followed by acid-promoted condensation

Abstract An efficient strategy for the synthesis of coumarin- and quinolone-annulated thiazole derivatives using sodium sulfide as a sulfur source has been achieved via ligand-free iron (III)-catalyzed coupling followed by acid-promoted condensation. This synthetic protocol is one-pot, less expensive, and affords the products in good yields.

One-step synthesis of a fluorescein derivative and mechanistic studies

We report a convenient method for the one-step synthesis of a fluorescein derivative under acidic conditions. Mechanistic studies indicate that the acid-promoted condensation of o-tolualdehyde and 4-chlororesorcinol to form the fluorescein derivative proceeds through a cyclization-oxidation pathway while an alternative oxidation–cyclization pathway remains possible.

ChemInform Abstract: Facile Synthesis and Nitration of cis-syn-cis-2,6-Dioxodecahydro-1H,5H- diimidazo(4,5-b:4′,5′-e)pyrazine.

The title ring system was synthesized for the first time by acid-promoted condensation of ureas with 1,4-diformyl-2,3,5,6-tetrahydroxypiperazine. Nitrosation and nitration of the polycycle occurs first at the piperazine nitrogens. Successive further nitration leads to tetra-, penta-, and hexanitro derivatives. X-ray crystallographic analysis of the tetra- and hexanitro derivatives established the cis-syn-cis configuration and an all-axial conformation for this ring system. Possible reasons for the stereoselectivity of the condensation reaction are discussed

Acetic acid-promoted condensation of o-phenylenediamine with aldehydes into 2-aryl-1-(arylmethyl)-1H-benzimidazoles under microwave irradiation

An efficient and simple procedure was developed for the green synthesis of various 2-aryl-1-(arylmethyl)-1H-benzimidazoles in high yields by acetic acid-promoted condensation of o-phenylenediamine with aldehydes in air under microwave irradiation and transition metal catalystfree conditions.

A unified strategy for enantioselective total synthesis of cladiellin and briarellin diterpenes: total synthesis of briarellins E and F and the putative structure of alcyonin and revision of its structure assignment.

Enantioselective total syntheses of briarellin E (12) and briarellin F (13), as well as the structure originally proposed for the cladiellin diterpene alcyonin (10), have been realized. Comparison of the spectral data for synthetic 10, natural alcyonin, cladiellisin (33), and cladiellaperoxide (34), as well as chemical transformations of 10 and natural alcyonin, suggest that the structure of this coral metabolite is allylic peroxide 11. The unified approach detailed herein can be used to access both C4-deoxygenated and C4-oxygenated cladiellins and briarellins. The central step in these syntheses is acid-promoted condensation of (Z)-alpha,beta-unsaturated aldehydes 17 with cyclohexadienyl diols 18 to form intermediates 16 incorporating the hexahydroisobenzofuran core and five stereocenters of these marine diterpenes (Scheme 1 ).

Synthesis, Structures, and Coordinating Properties of Phosphole-Containing Hybrid Calixpyrroles

Symmetric and asymmetric hybrid calixpyrroles containing a σ4-phosphole or σ4-2,3-dihydrophosphole unit (symmetric and asymmetric σ4-P,N2,X-hybrids: X = S, O) were prepared by using acid-promoted condensation reactions of the corresponding σ4-phosphatripyrranes with 2,5-bis(1-hydroxy-1-methylethyl)heteroles. The X-ray crystallographic analyses of the symmetric and asymmetric σ4-P,N2,X-hybrids show that the cavity sizes of the σ4-P,N2,S-hybrids are larger than those of the σ4-P,N2,O-hybrids, mainly reflecting the difference in edge-to-edge distances of the thiophene and furan rings. The symmetric σ4-P,N2,X-hybrids and the asymmetric σ4-P,N2,S-hybrid were successfully converted to the corresponding σ3 forms by reductive desulfurization at the phosphorus center. Each of the symmetric σ3-P,N2,X-hybrids was obtained as a mixture of two conformers, where the lone pair of the phosphorus atom is located inside (in) and outside (out) the cavity. The interconversion between the in and out type conformers of the asy...

Monophosphaporphyrins: Oxidative π-Extension at the Peripherally Fused Carbocycle of the Phosphaporphyrin Ring

The 18pi-sigma3- and 22pi-sigma4-phosphaporphyrins were successfully prepared by an acid-promoted condensation between a phosphatripyrrane and a 2,5-bis[hydroxy(phenyl)methyl]pyrrole, and their structures, aromaticity, and optical and electrochemical properties were disclosed. Notably, a sigma4-phosphaporphyrinogen and the 18pi-sigma3-phosphaporphyrin undergo oxidative pi-extension at the peripherally fused carbocycle to afford the 22pi-sigma4-phosphaporphyrin.

Phosphole-Containing Hybrid Calixpyrroles: New Multifunctional Macrocyclic Ligands for Platinum(II) Ions

Phosphole-containing hybrid calixpyrroles have been prepared by acid-promoted condensation reactions. σ3-Calix[1]phosphole[1]thiophene[2]pyrrole reacts with PtCl2(COD) to afford an unusual type of macrocyclic Pt(II)−monophosphine complex bearing a η3-cyclooctadienyl ligand, in which the phosphole and pyrrole units bind the Pt−Cl moiety through cooperative, noncovalent bonding interactions.

Enantioselective Total Synthesis of Briarellins E and F: The First Total Syntheses of Briarellin Diterpenes

Enantioselective total syntheses of briarellin E (4) and briarellin F (5) have been achieved starting with (S)-(+)-carvone and (S)-(-)-glycidol. These total syntheses are the first of briarellin diterpenes. The central step in these syntheses is acid-promoted condensation of cyclohexadienyl diol 15 and (Z)-alpha,beta-unsaturated aldehyde 16 to form, with complete stereocontrol, the hexahydroisobenzofuran core and six stereocenters of these coral metabolites. These syntheses also feature stereospecific photolytic deformylation of beta,gamma-unsaturated aldehyde 17 to remove the extraneous carbon introduced in the Prins-pinacol step, chemo- and stereoselective hydroxyl-directed epoxidation of dienyl alcohol 18 to incorporate the C3 oxygen stereocenter, regio- and stereoselective rearrangement of epoxy ester 19 to install the C4 oxygen substituent, efficient dehydrative cyclization of a 1,6-diol intermediate to form the oxepane ring, and diastereoselective Nozaki-Hiyama-Kishi cyclization of vinyl iodide aldehyde 25 to forge the oxacyclononane ring and the C6 hydroxyl stereocenter. These total syntheses establish the absolute configurations of 4 and 5, define a concise strategy for the total synthesis of briarellin diterpenes, and provide additional illustrations of the uncommon utility of pinacol-terminated cationic cyclizations for stereocontrolled synthesis of complex oxacyclic natural products.

Condensations of N-arylhydroxylamines for the preparation of 5,5′-di- tert-butyl-2,2′-dihydroxydiphenylamine

Acid-promoted condensation of 4- tert-butyl-2-hydroxylaminoanisole with p- tert-butylphenol resulted in the formation of 5,5′-di- tert-butyl-2,2′-dihydroxydiphenylamine upon demethylation with BBr 3. Protection of the acidic phenol unit was required to isolate the acid labile N-arylhydroxylamine intermediate.

A General Strategy for the Synthesis of Cladiellin Diterpenes: Enantioselective Total Syntheses of 6-Acetoxycladiell-7(16),11-dien-3-ol (Deacetoxyalcyonin Acetate), Cladiell-11-ene-3,6,7-triol, Sclerophytin A, and the Initially Purported Structure of Sclerophytin A

Enantioselective total syntheses of the cladiellin diterpenes, 6-acetoxycladiell-7(16),11-dien-3-ol (deacetoxyalcyonin acetate, 6), cladiell-11-ene-3,6,7-triol (1), sclerophytin A (8), and tetracyclic diether 7, have been achieved by differential elaboration of tricyclic allylic alcohol 57. The central step in these syntheses is acid-promoted condensation of alpha,beta-unsaturated aldehydes 45, 69 or 87, and cyclohexadienyl diol 44 to form, with complete stereocontrol, the hexahydroisobenzofuran core and five stereocenters of these cladiellin diterpenes. These syntheses also feature stereospecific photolytic deformylation of beta,gamma-unsaturated aldehydes 46, 70, and 71 to remove the extraneous carbon introduced in the Prins-pinacol step; chemo- and stereoselective hydroxyl-directed epoxidation of 49, 72, and 90 followed by regioselective reductive opening with hydride to install the C3 tertiary hydroxyl group; and a diastereoselective Nozaki-Hiyama-Kishi cyclization of iodoaldehyde 56 to forge the oxacyclononane ring and the C6 hydroxyl stereocenter. Other key transformations include chemo- and stereoselective hydroxyl-directed epoxidation of tricyclic allylic alcohol 57 followed by regioselective reductive opening with hydride to install the C7 tertiary hydroxyl center of 1 and 8; chemo-, regio-, and stereoselective intramolecular oxymercuration-reductive demercuration of dienyl diol 62 to form the bridging tetrahydropyran ring of tetracyclic diether 7; and photochemical isomerization of the endocyclic double bond of 92 and 1 to give exocyclic congeners 7 and 8. The absolute stereochemistry of the synthetic products originates from two chiral nonracemic starting materials, (S)-(+)-carvone and (S)-(-)-glycidol. These syntheses define a versatile and concise strategy for the total synthesis of cladiellin diterpenes and provide additional illustrations of the uncommon utility of pinacol-terminated cationic cyclizations for the stereocontrolled synthesis of complex oxacyclic products.

A New Method for Stereocontrolled Synthesis of Substituted Tetrahydrothiophenes

A variety of substituted 3-acyltetrahydrothiophenes can be prepared with high stereoselectivity in 50−70% yield by acid-promoted condensation of mercapto allylic alcohols 1 (X = S) with aldehydes and ketones. The mercapto allylic alcohol must be substituted at the internal alkene carbon and the terminal alkene carbon must be unsubstituted. This new synthesis of tetrahydrothiophenes will be most useful for preparing 3-acyltetrahydrothiophenes having cis side chains at C2 and C5. The complete preservation of enantiomeric purity in the conversion of (4R)-9 to tetrahydrothiophene 22 is consistent with a cyclization-pinacol pathway (24 → 25 → 26 → 27, Scheme 8).