Dehydrative Reaction Research Articles

Polycyclic N‐Heterocyclic Compounds. Part 81: Synthesis and Evaluation of Pentacyclic 1,2,4,5‐Tetrahydro[1]benzothieno[2′,3′:6,7]thiepino[4,5‐e]imidazo[1,2‐c]pyrimidine and Related Compounds as Potential Antiplatelet Aggregators

Dehydrative ring closure reactions were carried out on fused 4‐(2‐hydroxyethylamino) (or 2‐hydroxyethoxy or 2‐hydroxyethylthio)pyrimidines (2a, 2b, 2c) to give fused 2,3‐dihydroimidazo[1,2‐c] (or 2,3‐dihydrooxazolo[3,2‐c] or 2,3‐dihydrothiazolo[3,2‐c])pyrimidines. This reaction produced the pentacyclic 1,2,4,5‐tetrahydro[1]benzothieno[2′,3′:6,7]thiepino[4,5‐e]imidazo[1,2‐c]pyrimidine (3a) and 1,2,4,5‐tetrahydro[1]benzothieno[2′,3′:6,7]thiepino[4,5‐e]thiazolo[3,2‐c]pyrimidinium chloride (3c) from the 2‐hydroxyethylamino‐derivative and 2‐hydroxyethylthio‐derivative, respectively. In contrast, 2‐hydroxyethoxy‐derivative (2b) gave the rearrangement product, 3‐(2‐chloroethyl)‐5,6‐dihydro[1]benzothieno[3′,2′:2,3]thiepino[4,5‐d]pyrimidin‐4(3H)‐one (4). Effects of the synthesized compounds on collagen‐induced platelet aggregation were also evaluated.

Nanoporous Aluminosilicate-Mediated Synthesis of Ethers by a Dehydrative Etherification Approach

High aluminum containing nanoporous aluminosilicate materials, produced by an evaporation-induced self-assembly process, efficiently catalyze the formation of unsymmetrical ethers by a dehydrative etherification reaction in high isolated yields. By carrying out the reaction under dilute conditions, the quantities of reagents can be reduced to near stoichiometric quantities.

ChemInform Abstract: Reagent Controlled β‐Specific Dehydrative Glycosylation Reactions with 2‐Deoxy‐sugars.

AbstractIt is demonstrated that 2‐deoxysugar hemiacetals react with 1‐tosyl‐4‐nitroimidazol to generate intermediates which react with S‐ or O‐nucleophiles to give β‐glycosides exclusively.

A procedure for Appel halogenations and dehydrations using a polystyrene supported phosphine oxide

The conversion of a commercially available polystyrene supported phosphine oxide into synthetically useful polymeric halophosphonium salts using oxalyl chloride/bromide takes place at room temperature in 5min and generates only CO and CO2 as by-products. The polymeric halophosphonium salts so obtained are useful reagents for Appel halogenations and other dehydrative coupling reactions. This gives rise to a simple three-step synthesis cycle for Appel and related reactions using a commercially available polymeric phosphine oxide with very simple purification and no phosphorus waste.

Catalyst‐Free Dehydrative α‐Alkylation of Ketones with Alcohols: Green and Selective Autocatalyzed Synthesis of Alcohols and Ketones

Direct dehydrative α-alkylation reactions of ketones with alcohols are now realized under simple, practical, and green conditions without using external catalysts. These catalyst-free autocatalyzed alkylation methods can efficiently afford useful alkylated ketone or alcohol products in a one-pot manner and on a large scale by CC bond formation of the in situ generated intermediates with subsequent controllable and selective Meerwein-Pondorf-Verley-Oppenauer-type redox processes.

Homogeneous Gold Catalysis – A Hot Spot of Innovation

Lower energy consumption, faster reactions and higher selectivities are some of the intrinsic properties of catalysis. These are important aspects of green chemistry and have made catalysis research one of the key technologies of the 21st century, a very important subject not only for chemists in research and production but also for the whole society. Over the last decade homogeneous gold catalysis has become one of the major innovative areas in catalysis research, continuously providing new catalysis reactions. We have witnessed an initial dominance of methodology development, followed by strong interests in mechanistic studies and catalyst development. In the recent past many new applications in synthesis have been developed, for both natural product synthesis and synthesis of compounds for material science. The catalyst structure is well defined and the manifold of analytical tools of molecular chemistry allows a safe structural assignment of the pre-catalysts, sometimes even of the active catalyst or intermediates of moderate reactivity. Computational chemistry allows a quite precise analysis of the electronic structure of the catalyst, intermediates of the reaction and otherwise inaccessible transition states. Such insights are much more difficult to obtain in the related field of heterogeneous catalysis. In this special issue a collection of publications from leading scientists is presented, covering current hot topics in the field: gold-catalyzed synthesis of heterocycles and polycycles, ligands for gold catalysis, cascade reactions, oxidative CC bond formation and dehydrative reactions.1 A. Stephen K. Hashmi Ruprecht-Karls-Universität Heidelberg Guest Editor

Biology-Orientated Synthesis of Putrescine Bisamides Gigantamide A, Dasyclamide, and Cucullamide

Starting from putrescine and the requisite carboxylic acids­, first syntheses of bioactive natural products gigantamide A, dasyclamide, and cucullamide were accomplished in very good overall yields using an appropriate sequence of dehydrative coupling reactions. The syntheses of the corresponding dehomo analogues of these natural products are also described. Regioselective diisobutylaluminum hydride reduction of an unhindered carbonyl group in citraconimide is the key step.

Reagent Controlled β-Specific Dehydrative Glycosylation Reactions with 2-Deoxy-Sugars

N-Sulfonyl imidazoles activate 2-deoxy-sugar hemiacetals for glycosylation presumably by converting them into glycosyl sulfonates in situ. By matching the leaving group ability of the sulfonate with the reactivity of the donor, it is possible to obtain β-specific glycosylation reactions. The reaction serves as proof of the principle that, by choosing promoters that can modulate the reactivity of active intermediates, it is possible to place glycosylation reactions entirely under reagent control.

PdII‐Catalyzed Spiroketalization of Ketoallylic Diols

A high-yielding stereoselective method for forming spiroketals from simple ketoallylic diols is reported. Employing catalytic [PdCl2(MeCN)2] in THF at 0 °C, these dehydrative cyclization reactions require only mild conditions to produce vinyl-substituted spiroketals in high yields after brief reaction times with water as the only byproduct. Using this method, the stereochemical information embedded at the nucleophile is transmitted "down-the-chain" and efficiently sets the stereochemistry at both the anomeric carbon atom and the newly formed allylic stereocenter.

A highly efficient thiourea catalyzed dehydrative nucleophilic substitution reaction of 3-substituted oxindoles with xanthydrols

We report a highly efficient thiourea catalyzed dehydrative nucleophilic substitution reaction. The Schreiner's thiourea catalyst A1 catalyzed the alkylation of 3-substituted oxindoles with xanthydrols well, to furnish quaternary oxindoles in high yield. The ESI-MS analysis confirms the interaction of 3-substituted oxindole 1 with the thiourea, which might facilitate the oxindole–hydroxindole tautomerization for the alkylation.

Collective synthesis of several 2,7′-cyclolignans and their correlation by chemical transformations

Collective synthesis of anti-malarial 2,7'-cyclolignans has been stereoselectively achieved employing (±)-cyclogalgravin (2) as a linchpin through a series of functional group conversions, including redox reactions. Interestingly, 2 can be correlated with the neolignan (±)-kadangustin J (1) isolated from a different plant source, through a highly efficient dehydrative cyclization reaction with excellent diastereotopic differentiation of the veratryl group and concomitant construction of the C1–C7 bond. It is noteworthy that the first total synthesis of stereodivergent (±)-8,8'-epi-aristoligone (5), (±)-8'-epi-aristoligone (7), (±)-8'-epi-8-OH-aristoligone (8) and (±)-8'-epi-aristoligol (9) was demonstrated.

Recent Advances of Transition Metal-Catalyzed Aerobic Dehydrative Reactions of Alcohols and Amines and Related Researches

Recent Advances of Transition Metal-Catalyzed Aerobic Dehydrative Reactions of Alcohols and Amines and Related Researches

A Practical One‐Step Synthesis of 1,2‐Oxazoline Derivatives from Unprotected Sugars and Its Application to Chemoenzymatic β‐N‐Acetylglucosaminidation of Disialo‐oligosaccharide

AbstractA facile and practical method for synthesis of sugar oxazolines (=dihydrooxazoles) from the corresponding N‐acetyl‐2‐amino sugars has been developed by using 2‐chloro‐1,3‐dimethyl‐1H‐benzimidazol‐3‐ium chloride (CDMBI) as a dehydrative condensing agent. The intramolecular dehydrative reaction between the 2‐acetamido group and the anomeric OH group of unprotected N‐acetyl‐2‐amino sugars took place smoothly in H2O, leading to the formation of a 1,2‐oxazoline (=4,5‐dihydrooxazole) moiety in good yield. Since the reaction proceeds in H2O without using any protecting groups, the resulting oxazolines can be utilized as effective glycosyl donors for the subsequent enzymatic glycosylation. We have successfully demonstrated a highly efficient chemoenzymatic transglycosylation of a disialo‐oligosaccharide moiety to p‐nitrophenyl N‐acetylglucosaminide catalyzed by a mutant endo‐N‐acetylglucosaminidase without isolating disialo‐oligosaccharide oxazoline as synthetic intermediate.

Palladium‐Catalyzed N‐Alkylation of Amides and Amines with Alcohols Employing the Aerobic Relay Race Methodology

AbstractPossibly because homogeneous palladium catalysts are not typical borrowing hydrogen catalysts and ligands are thus ineffective in catalyst activation under conventional anaerobic conditions, they had not been used in the N‐alkylation reactions of amines/amides with alcohols in the past. By employing the aerobic relay race methodology with Pd‐catalyzed aerobic alcohol oxidation being a more effective protocol for alcohol activation, ligand‐free homogeneous palladiums are successfully used as active catalysts in the dehydrative N‐alkylation reactions, giving high yields and selectivities of the alkylated amides and amines. Mechanistic studies implied that the reaction most probably proceeds via the novel relay race mechanism we recently discovered and proposed.

ChemInform Abstract: FeCl3‐ and GaCl3‐Catalyzed Dehydrative Coupling Reaction of Chromone‐Derived Morita—Baylis—Hillman Alcohols with Terminal Alkynes.

FeCl3- and GaCl3-catalyzed dehydrative coupling reactions of chromone-derived Morita-Baylis-Hillman (MBH) alcohols with terminal alkynes were developed. The reactions provided exclusively α-regioselective and acetylene-substituted products in good yields.

FeCl3‐ and GaCl3‐Catalyzed Dehydrative Coupling Reaction of Chromone‐Derived Morita‐Baylis‐Hillman Alcohols with Terminal Alkynes

AbstractFeCl3‐ and GaCl3‐catalyzed dehydrative coupling reactions of chromone‐derived Morita‐Baylis‐Hillman (MBH) alcohols with terminal alkynes were developed. The reactions provided exclusively α‐regioselective and acetylene‐substituted products in good yields.

A simple and efficient approach to the synthesis of 2-substituted benzimidazole via sp3 C–H functionalization

A facile and novel approach to the synthesis of 2-substituted benzimidazole was developed via a tandem reaction following sp3 C–H functionalization. Here we report a simple, efficient and tandem oxidative dehydrative coupling reaction of N-benzylbezene-1,2-diamine in the presence of oxidant tert-butyl hydroperoxide (TBHP) in solvent acetonitrile to give substituted benzimidazole.

Cyclopropenium Cation Promoted Dehydrative Glycosylations Using 2-Deoxy- and 2,6-Dideoxy-Sugar Donors

Dehydrative glycosylation reactions using 2-deoxy- and 2,6-dideoxy-sugar donors promoted by a combination of 3,3-dichloro-1,2-diphenylcyclopropene and tetrabutylammonium iodide (TBAI) are described. The reactions are α-selective and proceed under mild conditions at room temperature without the need for special dehydrating agents. The reaction is shown to be effective with a number of glycosyl acceptors, including those possessing acid and base sensitive functionality.

Synthesis of (E)-3′-Phosphonoalkenyl Modified Nucleoside Phosphonates via a Highly Stereoselective Olefin Cross-Metathesis Reaction

The synthesis of (E)-3'-phosphonoalkenyl and 3'-phosphonoalkyl modified nucleoside analogues with a β-D-erythrofuranose moiety is reported. The highly stereoselective olefin cross-metathesis reaction was applied to introduce the phosphonoalkenyl group at the 3'-position of the sugar moiety with absolute (E)-selectivity. The 3',6'-cyclomonophosphonic acids of 3'-phosphonoethyl-β-D-erythrofuranosyl nucleosides were synthesized via a dehydrative intramolecular cyclization reaction. None of the synthesized compounds shows significant in vitro activity against HIV, HCV, and RSV.

O-Benzenedisulfonimide: An Organic Reagent and Organocatalyst of Renewed Interest

Synthesized nearly one century ago as a saccharine-like sweetener compound, the o-benzenedisulfonimide has received a discontinuous attention in the past. In the last century, various synthetic procedures have been reported, in confirmation of the interest in this intriguing compound. In recent years, it has been used as a leaving group in reactions of nucleophilic substitution of amines with alcohols or phenols to give the corresponding ethers. Its N-fluoroderivative is a stable and efficient fluorinating agent, which has found applications in several asymmetric syntheses. In previous studies, its conjugated base has been extensively used as stabilizing counter-ion of arenediazonium salts; safely isolated and stored in a dry state, ready to use, they have been applied successfully in many dediazoniation reactions, with interesting mechanistic insights. More recently, due to its high acidity, the o-benzenedisulfonimide has been used in catalytic amounts in some common acid-catalyzed organic reactions. Valuable aspects of this catalyst are its easy recovery from the reaction mixture and its reuse in other reactions, with clear economic and ecological advantages. Finally, the disulfonimide functional group has been proposed as a powerful chiral motif for strong Brønsted acids in asymmetric organocatalysis. Keywords: o-benzenedisulfonimide, organic synthesis, stabilizing anion, organocatalysis, recoverable catalyst, recyclable catalyst, anthranilic acid, o-aminobenzenesulfonic acid, o-bis(methylsulfanyl)benzene, N-Hydroxy-o-benzenedisulfonimide, N-Halogen-o-benzenedisulfonimides, N-Aryl, N-Alkyl, N-dialkylaminoalkyl-o-benzenedisulfonimides, N-Dialkylcarbamoyl-o-benzenedisulfonimides, N-Trialkylsilyl and N-trialkylstannyl-o-benzenedisulfonimides, trialkyl chlorosilane, chlorostannane, Baeyer-Villiger reagent, N-Fluoro-o-benzenedisulfonimide, enolates, azaenolates, 1,3-dicarbonyl compounds, ortho-methalated, silyl enol ethers, Grignard reagent, phenyllithium, ortho-lithiated aromatic, NFSI, DMG, arenediazonium, arenediazonium tetra-fluoroborates, sulfonates, trifluoroacetates, fluorinated disulfonimides, Diaryldiazenes and aryl(tert-butyl)diazenes, Aryl methanesulfonates, N-Alkylanilines, S-Aryl thiol esters, Hydrodediazoniation with Hydrogen Peroxide, Heck-type Arylation Reactions, DEHYDRATIVE REACTIONS, RITTER-TYPE REACTIONS, NAZAROV ELECTROCYCLIZATION, Asymmetric Organocatalysis