Highly chemoselective and efficient Strecker reaction of aldehydes with TMSCN catalyzed by MgI2 etherate under solvent-free conditions

Abstract

Strecker reaction of various substituted aromatic aldehydes, heteroaromatic aldehydes, aliphatic aldehydes and α,β-unsaturated aldehydes with trimethylsilyl cyanide (TMSCN) was realized in the presence of 5?mol % of MgI₂ etherate in a mild, efficient and highly chemoselective manner under solvent-free conditions.     

Unique chemoselective Clauson-Kass reaction of substituted aniline catalyzed by MgI2 etherate

Clauson-Kass reaction of various substituted aniline, primary aryl amide, and sufonyl amide with 2,5-dimethoxytetrahydrofuran was realized in the presence of 10 mol % of MgI₂ etherate in a mild, efficient, and highly chemoselective manner. Iodide counterion and solvents (i.e., MeCN) played the critical roles for the unique reactivity of this catalytic system.     

A Facile and Efficient Synthesis of 3-Aryloxazolidin-2-ones from Isocyanates and Epoxides Promoted by MgI2 Etherate

We described a mild and efficient procedure for the synthesis of 3-aryloxazolidin-2-ones via the cycloaddition of isocyanates with epoxides in the presence of MgI₂ etherate (MgI₂ ? (OEt₂)_n) in good yields.     

Highly efficient three-component Strecker-type reaction catalyzed by MgI2 etherate under solvent-free conditions

A concise, straightforward and efficient method has been developed for the synthesis of α-aminonitriles by an one-pot three-component condensation of aldehydes or ketones, amines and trimethylsilyl cyanide catalyzed by MgI₂ etherate under solvent-free conditions. This protocol has some advantages such as mild reaction condition, simple work-up, short reaction time and high product yields.     

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.     

Efficient Preparation of Biologically Important 1,2-Amino Alcohols

An efficient three-step methodology developed for the preparation of 1,2-amino alcohols. In the first step a rapid coupling between bromoketones and potassium phthalimide in ionic liquid produced α-phthalimido ketones in quantitative yields, which is followed by a facile reduction using NaCNBH₃ in acetic acid to give corresponding phthalimido alcohols and finally effecting hydrazinolysis in water at 60 °C to yield biologically important 1,2-amino alcohols.     

Efficient Protocol for Stereoselective Epoxidation of Cinnamic Esters Using TsNBr2

An efficient method has been developed for the synthesis of epoxide from cinnamic esters without any catalyst. The reaction was performed in CH₃CN–water (4:1) using N,N-dibromo-p-toluenesulfonamide (TsNBr₂) in alkaline conditions. This procedure can be utilized for stereoselective synthesis of epoxides from cinnamic esters in excellent yield in a shorter reaction time with exclusive formation of the trans-isomer. The method was further extended successfully for styrenes.     

Water-Mediated Strecker Reaction: An Efficient and Environmentally Friendly Approach for the Synthesis of α-Aminonitriles via a Three-Component Condensation

The synthesis of α-aminonitriles by a direct three component Strecker reaction has been achieved in water, which is found to be an inexpensive, non-toxic and eco-friendly reaction medium for the nucleophilic addition. This protocol is effective to a wide variety of substrates with different functional groups and does not require the use any other catalyst.     

Synthesis of Enantiomerically Enriched α-Bromonitriles from Amino Acids

Two methods were investigated for the preparation of six chiral α-bromonitriles with different optic purities. The nitrous deamination of amino acids gives α-bromoacids, which react with chlorosulfonyl isocyanate followed by triethylamine to afford α-bromonitriles with moderate enantiomeric excess. However, the dehydration of corresponding α-bromoamids using thionyl chloride gives α-bromonitriles with good enantiomeric excess up to 94%. The use of phosphoryl chloride instead of thionyl chloride results in more than 30% racemization as determined by high-performance liquid chromatograpic analysis.     

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.     

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.     

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.     

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.     

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.     

Direct access to α,α′-diarylated ketones through N-heterocyclic carbene-catalyzed 1,6-addition of aromatic aldehydes to para-quinone methides

N-Heterocyclic carbene-catalyzed 1,6-addition of aromatic aldehydes to para-quinone methides has been developed. This method could efficiently furnish α,α′-diarylated ketones with good to high yields, which contain various functional groups.     

Synthesis of Substituted Isoxazoles and Pyrazoles from α-α-Dioxoketen Dithioacetals Under Solvothermal Conditions

Some new 3,4,5-substituted isoxazoles, 3,4,5 and 1,3,4,5-substituted pyrazoles were prepared by reaction of α,α-oxoketen dithioacetals with hydroxylamine hydrochloride; phenyl hydrazine and hydrazine hydrate respectively under solvothermal conditions involving an ecofriendly method without any environmental pollution. The yields are in the range of 71–91%. The structure of the new compounds were established upon their elemental analysis, IR, ¹H NMR, and ¹³C NMR.     

Iodobenzene-catalyzed synthesis of α,α′-dihydroxy ketones: In situ generation of [bis(trifluoroacetoxy)iodo]benzene

Exposure of ethynyl carbinols to oxone/(CF₃CO)₂O in the presence of a catalytic amount of iodobenzene afforded α,α′-dihydroxy ketones in good yield, which are common structural motifs in natural products and biologically active compounds. Compared with traditional methods, this method is more convenient and avoids using stoichiometric amounts of hypervalent iodine reagents.     

Synthesis of Bis(phosphonatomethyl)-, Bis(phosphinatomethyl)-, and Bis(phosphinoxidomethyl)amines,as Well as Related Ring Bis(phosphine) Platinum Complexes

The double Kabachnik–Fields condensation of primary amines with 2 equivalents of the other reagents (formaldehyde and a >P(O)H species, such as dialkyl phosphites, diphenylphosphine oxide, as well as the related dioxaphosphorine and oxaphosphorine derivatives) carried out under microwave conditions afforded the title products in 79–94% yields. The bis(phosphinoxidomethyl)amines were converted, after double deoxygenation, to the corresponding ring platinum complexes.