One-pot synthesis of trans-β-lactams from ferrocenylketene generated by thermal Wolff rearrangement

A series of β-lactams containing the ferrocene moiety were synthesized through the Staudinger reaction between ferrocenylketene generated by the thermal Wolff rearrangement of the corresponding diazo ketone and various imines. The stereochemical outcome has been investigated and the trans-products were isolated as the main products, opposite to the reported results by Bonini and coworkers. The absolute configuration of (±)-trans-1,4-diphenyl-3-ferrocenylazetidin-2-one (3c) was determined by X-ray analysis. The stereoselectivity is discussed from the viewpoint of the reaction mechanism.     

The Reaction of Electron-Deficient Cyclopropane Derivatives with Aromatic Amines

Abstract

N-Aryl-trans,trans-α-carboxyl-β-benzoyl-γ-aryl-γ-butyrolactams were synthesized in high yields with high stereoselectivity by the reaction of electron-deficient cyclopropane derivatives, cis-1-benzoyl-2-aryl-6,6-dimethyl-5,7-dioxo-spiro-[2 (a) Zhang , J. ; Blazecka , P. G. ; Davidson , J. G. First direct reductive amination of mucochloric acid: A simple and efficient method for preparing highly functionalized α,β-unsaturated γ-butyrolactams . Org. Lett. 2003 , 5 , 553 – 556 ; (b) Sarma, K. D.; Zhang, J.; Curran, T. T. Novel synthons from mucochloric acid: The first use of α,β-dichloro-γ-butenolides and γ-butyrolactams for direct vinylogous aldol addition. J. Org. Chem. 2007, 72, 3311–3318 . [Google Scholar] 5 (a) Chen , Y. L. ; Ding , W. Y. A simple approach to highly stereoselective synthesis of β γ-trans-γ-butyrolactones . Chem. J. Chin. Univ. 1998 , 19 , 1614 – 1616 ; (b) Chen, Y. L.; Ding, W. Y.; Cao, W. G.; Lu, C. Stereoselective synthesis of N-aryl-trans,trans-α-carboxyl-β-methoxycarbonyl-γ-aryl-γ-butyrolactones. Synth. Commun. 2002, 32, 1953–1960.  [Google Scholar]]-4,8-octadiones, with aromatic amines. The reaction mechanism was proposed.     

Highly Efficient Michael Addition Reaction of Amines Catalyzed by Silica-Supported Aluminum Chloride

Aliphatic and aromatic amines undergo smooth nucleophilic addition to α,β-unsaturated compounds in the presence of a catalytic amount of silica-supported aluminum chloride at 60 °C and under solvent-free conditions to produce the corresponding β-amino compounds in excellent yields. This method is simple and convenient and works efficiently under mild conditions. This catalyst can used again without losing its activity three times.     

One-Pot,Fluoride-Promoted Wittig Reaction

A one-pot, fluoride-promoted Wittig reaction was developed. The reactions of ethyl α-bromoacetate with aliphatic, aromatic, and heteroaromatic aldehydes in the presence of tri-n-butylphosphine and tetrabutylammonium fluoride produced α,β-unsaturated esters in good to excellent yields and E-stereoselectivity. Under the same conditions, reactions of ethyl α-bromopropionate, α-bromo acetonitrile, and α-bromoacetophenone with aliphatic and aromatic aldehydes in the presence of tri-n-butylphosphine and tetrabutylammonium fluoride produced the expected α,β-unsaturated derivatives in good E-stereoselectivity. The protocol was extended to semistabilized ylides and applied to the synthesis of some combretastatin analogs.     

Preparation of 2-azetidinones by cyclocondensation of carboxylic acids and imines via diphosphorustetraiodide

One-pot mild synthesis of 2-azetidinones was carried out by the reaction of imines and carboxylic acids in dry dichloromethane at room temperature using diphosphorus tetraiodide. It was also applied for synthesis of 3-spiro-2-azetidinones. The synthesized compounds were characterized by analytical and spectral (infrared, ¹H NMR, ¹³C NMR, and elemental analysis) data.     

Synthesis of β-lactams via Staudinger reaction using N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline as a carboxylic acid activator

N-Ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) has been used as an efficient and convenient reagent for the one-pot synthesis of β-lactams by [2+2] ketene–imine cycloaddition (Staudinger reaction). Cleanliness, simplicity of method, and good to excellent yields of products are some advantages of this method.     

Method for Regio- and Stereoselective Synthesis of (E)-β,γ-Unsaturated Acids from Aldehydes Under Solvent-Free Conditions

Synthesis of (E)-β,γ-unsaturated acids from aldehydes with malonic acid has been explored under solvent-free conditions. The modified Knoevenagel condensation reaction with N-methyl morpholine (NMM) as catalyst exhibits highly β,γ-regioselectivity and exclusively E-stereoselectivity. A mechanism accounting for both regio- and stereoselectivity has been proposed and preliminarily studied.     

Synthesis of 3-Trifluoromethyl-Substituted Benzo[f]chromene Derivatives in a One-Pot Reaction

In the presence of 1,8-diazabicycolo[5.4.0]undec-7-ene (DBU) and concentrated H₂SO₄, 2-naphthol reacted smoothly with α,β-unsaturated trifluoromethyl ketones in CH₂Cl₂ at room temperature, affording the 3-trifluoromethyl-substituted benzo[f]chromene derivatives in good to excellent yields in a one-pot reaction.

[Supplementary materials are available for this article. Go to the publisher's online edition of Synthetic Communications® for the following free supplemental resource: Full experimental and spectral details].     

BF3·OEt2: An Efficient Catalyst for Transesterification of β-Ketoesters

A facile and selective transesterification of β-ketoesters using BF₃·OEt₂ as catalyst is described. The emphasis has been placed on the reaction of methyl acetoacetate with a series of alcohols of different structures, leading in all cases to good to excellent yields.     

Synthesis of β-Lactams from Acids and Imines Using Thiocarbonyldiimidazole

Thiocarbonyldiimidazole has been found to be an efficient acid activator for the synthesis of β-lactams by ketene-imine cycloaddition at room temperature. The experimental procedure is simple and results in excellent yields of the products. All products were characterized by spectral data and elemental analyses.     

Concise Synthesis of α-(Hydroxymethyl) Alkyl and Aryl Vinyl Ketones

2,4-Diketoesters 2 have first been reported as starting materials for the synthesis of a new class of α-hydroxymethyl-α,β-unsaturated ketones 3. Thus, under heterogeneous liquid–liquid medium in the presence of concentrated aqueous potassium carbonate as a base, both aliphatic and aromatic 2,4-dioxoalkanoates 2 react with aqueous formaldehyde to afford the corresponding ketones 3 in fair to good yields.     

One-Pot Approach to the Conversion of Alcohols into α-Iodo-α,β-unsaturated Esters

(Carboethoxymethylene)triphenylphosphorane 1 can undergo the tandem reaction of iodination–oxidation–Wittig reaction with alcohol in the presence of N-iodosuccinimide (NIS) and manganese dioxide. The reaction constitutes a stereoselective one-pot procedure for the preparation of Z-configured α-iodo-α,β-unsaturated esters in good to excellent yield.     

Aza-Michael Addition of Amines to α,β-Unsaturated Compounds Using Molecular Iodine as Catalyst

Aza-Michael adducts are obtained in very good yields by the conjugate addition of aliphatic amines to α,β-unsaturated compounds using molecular iodine as catalyst in dichloromethane at room temperature. Aromatic amines were found to be reactive under reflux in toluene.     

Mild and Efficient Method for Synthesis of Eaminones Using Ytterbium Triflate as Catalyst

A mild and efficient procedure for synthesis of β-enaminones by the condensation of β-dicarbonyl compounds and amines using ytterbium triflate [Yb(OTf)₃] as catalyst is described. The catalyst can be easily recovered and reused without loss of activity.     

Synthesis of marine alkaloids leucettamines B and C by β-lactam ring rearrangement

A new method for the synthesis of marine alkaloids leucettamines B and C from Leucetta sp. sponges is described. The key step is the base-promoted rearrangement of β-lactam into imidazolone ring. Leucettamines B and C as well as their N-benzoyl derivatives were obtained in high yields. Single-crystal structures of both leucettamines B and C were determined by X-ray diffraction confirming Z-configuration of double bond at 4-position of imidazolone.     

Synthetic route for the novel pyrimidine-substituted alkanoate,acetohydrazide, and imines: Synthon for β-lactams

A simple and efficient synthesis of novel pyrimidine-substituted alkanoate, acetohydrazide, and imines is described. The synthesis of novel ethyl 2-(2,6-dimethylpyrimidin-4-yloxy)acetate (EDMPyA) 2 was performed through S_N2 O-alkylation of 2,6-dimethyl-4-hydroxypyrimidine 1 with ethyl haloacetate. The compound EDMPyA 2 was subjected to nucleophilic substitution reaction with hydrazine hydrate to afford novel 2-(2,6-dimethylpyrimidin-4-yloxy)acetohydrazide (DMPyAH) 3. This DMPyAH 3 upon condensation with differently substituted carbonyl compounds (aldehydes/ketones) furnished DMPyAH imines (DMPyAH-I) 4a–d. These imines can be used for the preparation of unique β-lactams. The structure elucidation of all the newly synthesized compounds was performed using spectroscopy (FT-IR, ¹H and ¹³C NMR) and elemental analysis (C, H, N).     

Synthesis of new α-hydroxyphosphonates and α-acetoxyphosphonates

A series of new α-hydroxyphosphonate (5–14) have been synthesized in high yields by reaction of β-chloro-α,β-unsaturated aldehydes (1–4) and trialkyl phosphite in the presence of chlorotrimethylsilane at room temperature under solvent-free conditions. In addition, compounds (5–14) were reacted with acetic anhydride in DBU to give the new α-acetoxyphosphonate derivatives (15–23). All these phosphonates (5–23) were obtained as mixtures of two (E and Z) isomers and fully characterized by multinuclear (¹H, ¹³C, and ³¹P) NMR, IR spectroscopy and HRMS.     

Overview on the phosphonation of the C=X functional groups utilizing alkyl phosphites

The main objective of this survey is to provide a comprehensive review of recent achievements related to the phosphonation processes, applying alkyl phosphites and different electrophiles (C?X, X: O, N, or C). The review discusses the important reactions of trialkyl and dialkyl phosphite reagents with a variety of aldehydes, ketones, aldimines, ketimines, hydrazones, oximes, diazo compounds, thio- and isocyanates as well as activated olefins as a convenient methodology for the synthesis of biologically important α-hydroxy- and α-aminophosphonates as well as heterocycles containing phosphorus and substituted heterocyclic phosphor esters. We are herein concentrating only on reactions that lead to phosphorylated products as they represent a vast and important research area of interest for academic, as well as for industrial, pharmaceutical and phytopharmaceutical chemists. The literature survey has been fully covered up by our group and others over the last 25 years.     

Improved Enantioselective Synthesis of Protected (3S,4S)-4-Amino-3,5-dihydroxypentanoic Acid (ADPA)

An improved enantioselective synthesis of protected (3S,4S)-4-amino-3,5-dihydroxypentanoic acid (ADPA) from L-serine has been developed. Enantioselectivity is improved by replacing the methyl ester with the tert-butyl ester and using neutral magnesium salt of esters to give β-keto ester.     

Direct Esterification of Carboxylic Acids with Alcohols Catalyzed by Iron(III) Acetylacetonate Complex

Direct condensation of carboxylic acids and alcohols with electronic, steric, and functional group variations was carried out using the environmentally benign, moisture-stable, inexpensive, and recoverable iron(III) acetylacetonate [Fe(acac)₃] as catalyst (5 mol%). This iron salt efficiently catalyzed the esterification of several primary and secondary alcohols in refluxing xylene, without the need for a dehydration reagent. The chemoselectivity of the proposed protocol was demonstrated by the selective esterification of primary alcohol functionality in racemic 1-phenylethane-1,2-diol with benzoic acid. The esterification was also applicable to unmasked α -hydroxyacid, guasiaromatic, heterocyclic, and N-protected amino acids.

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