Copper Chloride‐Catalyzed Aerobic Oxidative Annulation of N‐Furfuryl‐β‐Enaminones:Access to Polysubstituted Pyrroles and Indoles

Copper chloride‐catalyzed aerobic oxidative annulation of N‐furfuryl‐β‐enaminones provides access to polysubstituted pyrroles and indoles. This protocol involves an unprecedented copper chloride‐catalyzed oxidative chlorination of furan and pyrrole rings with oxygen as the terminal oxidant.

     

Michael Reaction of Nitroalkanes with β‐Nitroacrylates under a Solid Promoter: Advanced Regio‐ and Diastereoselective Synthesis of Nitro‐Functionalized α,β‐Unsaturated Esters and 1,3‐Butadiene‐2‐carboxylates

A new class of nitro‐functionalized α,β‐unsaturated esters has been prepared by a regio‐ and diastereoselective Michael addition of nitroalkanes to β‐nitroacrylates, performed at room temperature, under carbonate on polymer as promoter, and in the presence of ethyl acetate as eco‐friendly solvent. Moreover, by the modular choice of the reaction conditions the method allows the synthesis of 1,3‐butadiene‐2‐carboxylates.     

The One‐Pot Wittig Reaction: A Facile Synthesis of α,β‐Unsaturated Esters and Nitriles by Using Nanocrystalline Magnesium Oxide

Nanocrystalline magnesium oxide was found to be an effective heterogeneous, solid base catalyst for the one‐pot Wittig reaction to afford α,β‐unsaturated esters and nitriles in excellent yields with high E‐stereoselectivity in the presence of triphenylphosphine under mild conditions.     

Synthesis of Furans and Pyrroles from 2‐Alkoxy‐2,3‐dihydrofurans Through a Nucleophilic Substitution‐Triggered Heteroaromatization

An effective method to synthesize α‐functionalized furan and pyrrole derivatives was developed using 2‐alkoxy‐2,3‐dihydrofurans as modular precursors. This protocol featured a previously unreported tandem nucleophilic substitution/heteroaromatization reaction. Nucleophiles such as indole, α‐oxoketene dithioacetal, trimethoxybenzene, and dimethoxynaphthalene can react readily with 2‐alkoxy‐2,3‐dihydrofurans to afford α‐functionalized five‐membered ring heterocycles in the presence of acid catalysts, such as copper bromide and iron chloride. The mechanism of the reaction was also discussed, in which the first step, nucleophilic substitution, is the key in triggering the succeeding heteroaromatization. This method can also be extended to the synthesis of dihydrothiophenes.

     

Ruthenium(II)‐Catalyzed Protocol for Preparation of Diverse α,β‐ and β,β‐Dihaloenones from Diazodicarbonyls

Efficient one‐step syntheses of α,β‐ and β,β‐dihaloenones were achieved by ruthenium(II)‐catalyzed reactions between cyclic or acyclic diazodicarbonyl compounds and oxalyl chloride or oxalyl bromide in moderate to good yields. This methodology offers several significant advantages, which include ease of handling, mild reaction conditions, one‐step reaction, and the use of an effective and non‐toxic catalyst. The synthesized compounds were further transformed into highly functionalized novel molecules bearing aromatic rings on the enone moiety using the Suzuki reaction.

     

One‐Pot/Four‐Step/Palladium‐Catalyzed Synthesis of Indole Derivatives: The Combination of Heterogeneous and Homogeneous Systems

One‐pot, four‐step syntheses of indoles using both solid‐supported heterogeneous and homogeneous palladium catalysts and reagents were carried out. Such a combination of these two‐phase catalysts and reagents causes a dramatic increase in yield, and it is a simple process. The presented methodology is effective for four‐step reactions to provide various functionalized indoles.     

One‐Pot Synthesis of Fluorovinyl Acetates and β,β‐Difluoro Carboxylates from a Hypervalent Iodine and Hydrogen Fluoride‐Based Fluorination Reagent

A new strategy for the synthesis of fluorovinyl acetates and β,β‐difluoro carboxylates using a hypervalent iodine and hydrogen fluoride‐based fluorination reagent is established through a silver‐catalyzed one‐pot reaction involving formation of carbon‐oxygen and carbon‐nitrogen bonds. The generated fluoroalkenes substituted with the carbon‐oxygen and carbon‐nitrogen bond on the β‐position have the potential to be transformed into various products which would be difficult to obtain via direct fluorination.

     

Preparation of 2H‐1,4‐Benzoxazin‐2‐one Derivatives under Heterogeneous Conditions via Domino Process

Carbonate on polymer is a valuable solid supported reagent (SSR) to promote, under eco‐friendly conditions, the preparation of 2H‐1,4‐benzoxazin‐2‐one derivatives starting from β‐nitroacrylates and aminophenols via a domino process.     

Cationic copolymers of α,β‐poly‐(N‐2‐hydroxyethyl)‐DL‐aspartamide (PHEA) and α,β‐polyasparthylhydrazide (PAHy): synthesis and characterization

In the present study the derivatization of two water‐soluble synthetic polymers, α,β‐poly(N‐2‐hydroxyethyl)‐DL ‐aspartamide (PHEA) and α,β‐polyasparthylhydrazide (PAHy), with glycidyltrimethylammonium chloride (GTA) is described. This reaction permits the introduction of positive charges in the macromolecular chains of PHEA and PAHy in order to make easier the electrostatic interaction with DNA. Different parameters affect the reaction of derivatization, such as GTA concentration and reaction time. PHEA reacts partially and slowly with GTA; on the contrary the reaction of PAHy with GTA is more rapid and extensive. The derivatization of PHEA and PAHy with GTA is a convenient method to introduce positive groups in their chains and it permits the preparation of interpolyelectrolyte complexes with DNA. © 2000 Society of Chemical Industry     

Three‐Component One‐Pot Synthesis of α‐Hydroxylamino Phosphonates using Ionic Liquids

α‐Hydroxylamino phosphonates are synthesised in a one‐pot operation by three‐component coupling reactions of aldehydes, hydroxylamines and diethyl phosphite using 1‐butyl‐3‐methylimidazolium tetrafluoroborate ([bmim]BF₄) or 1‐butyl‐3‐methylimidazolium hexafluorophosphate ([bmim]PF₆) ionic liquids under mild and neutral conditions. The recovered ionic liquids can be recycled for four to five runs without loss of activity.     

Multi‐Enzymatic Synthesis of Optically Pure β‐Hydroxy α‐Amino Acids

A novel enzymatic production system of optically pure β‐hydroxy α‐amino acids was developed. Two enzymes were used for the system: an N‐succinyl L ‐amino acid β‐hydroxylase (SadA) belonging to the iron(II)/α‐ketoglutarate‐dependent dioxygenase superfamily and an N‐succinyl L ‐amino acid desuccinylase (LasA). The genes encoding the two enzymes are part of a gene set responsible for the biosynthesis of peptidyl compounds found in the Burkholderia ambifaria AMMD genome. SadA stereoselectively hydroxylated several N‐succinyl aliphatic L ‐amino acids and produced N‐succinyl β‐hydroxy L ‐amino acids, such as N‐succinyl‐L ‐β‐hydroxyvaline, N‐succinyl‐L ‐threonine, (2S,3R)‐N‐succinyl‐L ‐β‐hydroxyisoleucine, and N‐succinyl‐L ‐threo‐β‐hydroxyleucine. LasA catalyzed the desuccinylation of various N‐succinyl‐L ‐amino acids. Surprisingly, LasA is the first amide bond‐forming enzyme belonging to the amidohydrolase superfamily, and has succinylation activity towards the amino group of L ‐leucine. By combining SadA and LasA in a preparative scale production using N‐succinyl‐L ‐leucine as substrate, 2.3 mmol of L ‐threo‐β‐hydroxyleucine were successfully produced with 93% conversion and over 99% of diastereomeric excess. Consequently, the new production system described in this study has advantages in optical purity and reaction efficiency for application in the mass production of several β‐hydroxy α‐amino acids.

     

Chiral Imidodiphosphoric Acids‐Catalyzed Friedel–Crafts Reactions of Indoles/Pyrroles with 3‐Hydroxy‐indolyloxindoles: Enantioselective Synthesis of 3,3‐Diaryloxindoles

The first enantioselective Friedel–Crafts alkylation of indoles and pyrroles with 3‐hydroxy‐3‐indolyloxindoles to access two novel types of 3,3‐diaryloxindoles catalyzed by chiral imidodiphosphoric acids has been reported. A range of quaternary carbon centered 3,3‐diaryloxindoles were synthesized in high yield (up to >99%) with excellent enantioselectivity (up to 98% ee) at low catalyst loadings (as low as 0.5 mol%). The Friedel–Crafts reaction between indoles and 3‐hydroxy‐3‐indolyloxindoles is amenable to gram scale syntheses.

     

Efficient Synthesis of β,γ‐Alkynyl α‐Amino Acid Derivatives by Ag(I)‐Catalyzed Alkynylation of α‐Imino Esters

The first catalytic synthesis of β,γ‐alkynyl α‐amino acid derivatives was achieved by direct addition of terminal alkynes to α‐imino esters in the presence of an Ag(I) salt under mild reaction conditions.     

Iterative One‐Pot α‐Glycosylation Strategy: Application to Oligosaccharide Synthesis

Based on the combined use of dimethylformamide (DMF) modulation and neighboring group participation, three iterative one‐pot α‐glycosylation methods, i.e., one‐pot (α,α)‐, one‐pot (β,α)‐, and one‐pot (α,β)‐glycosylations, were developed. These methods are applicable to a range of thioglycosyl donors, confer stereocontrol in α‐/β‐glycosidic bond formation, and thus provide for rapid access to oligosaccharides with various permutations of anomeric configurations. The utility of these one‐pot glycosylation methods is demonstrated in the synthesis of eight non‐natural and natural oligosaccharide targets, including the core 1 serine conjugate, core 8 serine conjugate, the D ‐Gal‐α(1→3)‐D ‐Glc‐α(1→3)‐L ‐Rha trisaccharide unit of the cell wall component in Streptococcus pneumoniae, and the D ‐Glc‐α(1→2)‐D ‐Glc‐α(1→3)‐D ‐Glc trisaccharide terminus of the N‐linked glycan precursor. Confirmation of the anomeric configurations of these oligosaccharides is evidenced by ¹H, ¹³C, ¹³C‐non‐proton decoupling, and heteronuclear correlation 2D NMR experiments. Global deprotection of selected oligosaccharide targets is illustrated.     

[3+2] Cycloaddition of Propargylamines and α‐Acylketene Dithioacetals: A Synthetic Strategy for Highly Substituted Pyrroles

A new [3+2] cycloaddition strategy for the direct synthesis of highly substituted pyrroles from the readily available α‐acylketene dithioacetals (or related substrates) and commercially available propargylamines under mild metal‐free conditions has been developed. In this reaction, the acyl group plays a critical role in driving the conjugate addition of propargylamine and further cyclization to give pyrroles. Furthermore, the wide scope was confirmed by the preparation of 1,2,3,4‐tetrasubstituted pyrroles (60–70% yields) via a formal 1,2‐acyl migrating [3+2] cycloaddition pathway with N‐methylprop‐2‐yn‐1‐amine as the secondary amine component.     

Poly‐α,β‐(3‐hydroxypropyl)‐DL‐aspartamide: A new drug carrier

Poly‐α,β‐(3‐hydroxypropyl)‐DL ‐aspartamide (PHPA) was synthesized by the ring‐open reaction of polysuccinimide (PSI) and 3‐hydroxypropylamine. The polymer was characterized by ¹H‐NMR, ¹³C‐NMR, FTIR, and GPC. Mark–Houwink coefficients were obtained from viscometry and GPC measurements, K = 5.53 × 10⁻³ and α = 0.78 in water. The acute toxicity of PHPA was examined and it revealed no death in ICR mice up to the dose treated of 15.3 kg/kg, and hematological parameters showed no significant difference between treated and control animals. The potential use of PHPA as a drug carrier was also investigated. In a typical case, a contraceptive drug, norethindrone (NET), was bonded to PHPA, and the drug sustained released as long as 120 days an in vitro test. © 2000 John Wiley & Sons, Inc. J Appl Polym Sci 77: 2411–2417, 2000     

Friedel–Crafts Reaction of Indoles with Isatin‐Derived β,γ‐Unsaturated α‐Keto Esters Using a BINOL‐Derived Bisoxazoline (BOX)/Copper(II) Complex as Catalyst

Several chiral BINOL‐derived bisoxazoline (BOX)/copper(II) complexes were synthesized and evaluated as catalysts for the Friedel–Crafts reaction of indoles with isatin‐derived β,γ‐unsaturated α‐keto esters. The resulting bis‐indole products bearing a quaternary stereocenter were obtained in excellent yields and enantioselectivities. Additionally, the desired products were practically transformed to α‐amino esters, α‐hydroxy esters and α‐keto amides. It is noteworthy that this catalytic procedure was conducted with a catalyst loading of 0.5 mol% without any discernible decrease in the reactivity or enantioselectivity.

     

Synthesis of a novel linear water‐soluble β‐cyclodextrin polymer

A novel linear water‐soluble β‐cyclodextrin polymer has been prepared by grafting β‐cyclodextrin on poly[(methyl vinyl ether)‐alt‐(maleic anhydride)]. First, lithium hydride was used to obtain the mono‐alkoxide β‐CD. Grafting of β‐CD derivatives to the polymer backbone was then carried out by an esterification method. Using this method, polymers containing various amounts of β‐CD were synthesized. The resulting grafted polymers were characterized by two complementary methods, ¹H NMR and IR spectroscopy. The first was used to calculate the degree of substitution for the low amounts of β‐CD. The second method was very useful to evaluate the degree of substitution and the molar ratio of CD especially for high amounts of grafting. Our results indicate good agreement between both methods for intermediate rates. Copyright © 2004 Society of Chemical Industry     

Palladium‐Catalyzed Divergent Arylation with Triazolopyridines: One‐Pot Synthesis of 6‐Aryl‐2‐α‐styrylpyridines

We have developed a new strategy for palladium‐catalyzed arylation reactions with triazolopyridines, wherein two different chemical transformations (C‐3 vs. C‐7) are observed by differentiating the substrates using different bases. The reactive palladium carbenoids were directly generated from triazolopyridines and underwent denitrogenative arylations with aryl bromides. Intriguingly, when potassium carbonate was replaced with potassium tert‐butoxide, direct C H arylation occurred at the most acidic position (C‐7). Moreover, two different catalytic arylation events were successfully performed in a one‐pot sequence, providing a convenient access to 6‐aryl‐2‐α‐styrylpyridines.