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The possible combinations and connections of microwave (MW) and catalysts are discussed. MW-assisted reactions, such as the direct esterification or the alkylating esterification of phosphinic acid...

The reaction of 1H-imidazol-1-ylacetic acid and two equivalents of phosphorus trichloride/phosphorous acid at 75 °C in sulfolane, or in the presence of catalytic amounts of [bmim][BF4] afforded zoledronic acid in yields up to 75%. The joint use of the ionic liquid additive and sulfolane as the solvent was synergetic affording highly valuable zoledronic acid in a record yield of 93%.

Several new trans-dihydronarciclasine analogues were stereo­selectively synthesised by applying our feasible and efficient process developed recently. These new phenanthridone alkaloid derivatives were obtained in both racemic and optically active forms. During their enantioselective syntheses, high selectivities (up to 99% ee) were achieved by using (8S,9S)-9-amino(9-deoxy)epiquinine as an organocatalyst. The modifications, the introduction of ethoxy or methoxy groups, were made in ring A of the phenanthridone scaffold.

The microwave (MW) technique has become an important tool also in the organophosphorus field of organic chemistry. On the one hand, otherwise reluctant reactions, such as the esterification of P-acids, may be enhanced by the effect of MW, while on the other hand, catalysts may be omitted, or catalyst systems may be simplified on MW irradiation. This later group includes the Kabachnik–Fields reactions, alkylation of active methylene-containing compounds, O-alkylations, deoxygenations, as well as the Hirao reaction. It is also the purpose of this review to elucidate the scope and limitations of the MW tool, to interpret the MW effects, and to model the distribution of local overheatings and their beneficial effect.1 Introduction2 The Esterification of Phosphinic Acids2.1 Synthetic Results2.2 Scope and Limitation of the Application of MWs2.3 Modelling the Distribution of the Local Overheatings and Predicting­ Their Effect3 The Simplification of Catalytic Systems3.1 Replacement of the Catalyst by MW Irradiation3.1.1 The Kabachnik–Fields Reaction3.1.2 Solid–Liquid Phase Alkylation of Active Methylene-Containing Compounds3.1.3 Solid–Liquid Phase Alkylation of Phosphinic Acids3.1.4 The Deoxygenation of Phosphine Oxides3.2 The Hirao Reaction without Added P-Ligands4 Conclusions

A monoaza-15-crown-5 lariat ether derived from d -glucose 1 has been applied as a chiral phase-transfer catalyst in the Michael addition of diethyl, dimethyl, diisopropyl and dibenzyl malonates to enones under mild conditions to afford the adducts with good to excellent enantioselectivities. In the reaction of diethyl malonate with substituted trans-chalcone, the adducts with in enantioselectivities up to 89% ee. Among the reactions of substituted diethyl malonates, those of diethyl acetoxymalonate gave the best results (96% ee). The effect of the substituents of the chalcone was also investigated in reactions with diethyl acetoxymalonate. Among the chalcones substituted on the β-aryl, the para-substituted compounds resulted in the highest enantioselectivities (88–97% ee). The substituents on the benzoyl aryl of chalcone caused a decrease in the enantioselectivity compared to the unsubstituted case. The adducts with furyl or thiophenyl substituents were formed with >99% ee. The glucose-based catalyst also proved to be effective in the cases of diisopropyl and dibenzyl acetoxymalonates (including ees up to 99% ee). The reactions of diethyl acetoxymalonate with cyclic enones gave the corresponding Michael adducts with enantioselectivities up to 83%. The absolute configuration of one of the new Michael adducts was determined by CD spectroscopy.

Application of the microwave (MW) technique offers many advantages in organophosphorus syntheses. Reluctant reactions may take place on MW irradiation. In most cases, MWs make the reactions more efficient in respect of rate, selectivity and yield. The benefits are shown via representative examples. MW irradiation may replace a catalyst, or simplify catalytic systems. The synthesis of catalysts incorporating heterocyclic P-ligands is also discussed. Where it was relevant, structural chemical details were also provided.

New chiral monoaza-15-crown-5 type macrocycles annelated to methyl 4,6-O-benzylidene-α-D-galactopyranoside have been synthesized. These crown ethers proved to be efficient catalysts in a few asymmetric reactions under mild phase transfer catalytic conditions. Michael adducts were formed with good to excellent enantioselectivities, so the addition of diethyl acetamidomalonate to β-nitrostyrene took place with up to 92% ee, while the reaction of diethyl acetoxymalonate with chalcones proceeded with up to 99% ee. Using diethyl bromomalonate as the nucleophile, the chiral cyclopropane derivatives were formed in up to 99% ee with the addition to chalcone, in up to 78% ee in the reaction with benzylidene malononitrile, and in up to 76% ee in the reaction with 2-benzylidene-1,3-diphenyl-1,3-propanedione applying α-D-galactoside-based crown ethers as the catalysts. In the Michael addition, the substituents of the chalcone had a considerable impact on the outcome of the reactions. Quantum chemical calculations have also been employed to evaluate the origin of the stereoselectivities.

The solid–liquid phase C-alkylation of active methylene containing compounds with C=O or P=O functions under phase transfer catalysis or microwave conditions has been summarized in this minireview. The mono- and dialkylation of the methylene containing derivatives was investigated under microwave (MW) conditions. It was found that in many cases, there was no need to use phase transfer catalyst under MW conditions. Moreover, most of the reactions were carried out without any solvent. These results mean a serious green chemical advantage.

The use of the microwave (MW) technique has many advan­tages in organophosphorus chemistry. MW irradiation may replace a catalyst, or simplify a catalytic system. New reactions may also become possible under MW irradiation. In most cases, microwaves just make the reactions more efficient in respect of rate, selectivity and yield. The benefits are shown via representative examples. In another field, our methods developed for the resolution of cyclic phosphine oxides and phosphinates are summarized. After deoxygenation, the racemic or optically active P-heterocycles were used as P-ligands in platinum complexes that together with other derivatives are potential catalysts. The third topic embraces the optimization of the synthesis of dronic acids/dronates. Starting from the cor­responding carboxylic acids and using methanesulfonic acid as the solvent, 3 equivalents of phosphorus trichloride is enough as the P-reactant. Applying sulfolane as the solvent, the opti­mum set of reactants comprises 2 equivalents of phosphorus trichloride and phosphorous acid.

A few new d-mannitol-based monoaza-15-crown-5 type chiral lariat ethers and 18-crown-6 type macrocycles were synthesized. These crown compounds were used as phase transfer catalysts in asymmetric Michael addititons and in a Darzens condensation under mild conditions to afford the corresponding products in a few cases in good to excellent enantioselectivities. In the Michael addition of diethyl acetoxymalonate to trans-chalcone, in the addition of diethyl acetamidomalonate to s-nitrostyrene, in the reaction of diethyl bromomalonate with benzylidene malononitriles, in the cyclopropanation reaction of diethyl bromomalonate and 2-benzylidene-1,3-indandione, and in the Darzens condensation of α-chloroacetophenone with benzaldehyde, maximum enantioselectivities of 39%, 65%, 99%, 56%, and 62%, respectively, were obtained in the presence of the d-mannitol-based macrocycles as the catalysts.

A feasible and enantioselective total synthesis of (−)-trans-dihydronarciclasine [(−)-1], a highly biologically active alkaloid, was devised starting from vanillin (8). The key step of this new synthesis was an asymmetric, organocatalytic Michael addition, in which an optically active nitropentanone [(−)-13] was obtained from a butenone derivative (12). Excellent enantioselectivity (>99% ee) was achieved using the (8S,9S)-9-amino(9-deoxy)epiquinine (16) organocatalyst. The target molecule can be prepared in 13 steps from compound (−)-13. The total synthesis has provided a facile and first access to the ent-form of naturally occurring (+)-trans-dihydronarciclasine, a highly potent cytostatic alkaloid.

According to literature, the synthesis of dronic acid derivatives from the corresponding carboxylic acids using phosphorus trichloride and phosphorous acid as the P-reactants is controversial, due to the wide range of molar ratios and diverse conditions. In this minireview, we summarize our results on the clarification of these problems. For example, with zoledronic acid and risedronic acid, we found that, using methanesulfonic acid (MSA) as the solvent, 3.2 equivalents of phosphorus trichloride was enough. Generalizing this optimized method, etidronate, fenidronate, ibandronate and alendronate were obtained in yields of 38%–57%, which is reasonable for valuable dronates, and in most cases, with high purities. Mechanistic aspects are also discussed.

To further broaden the methods for the heterogeneous phase alkylation of CH acidic compounds, the dialkylation of diethyl ethoxycarbonylmethylphosphonate was studied in the presence of Cs2CO3 under microwave and solvent-free conditions. It was found that after repeating the alkylations by the addition of newer portions of the alkylating agent and the base on a few occasions, the dialkylation was quite efficient. Even dialkyl derivatives with different alkyl groups could be synthesized. The presence of a phase-transfer catalyst was harmful, as prevented the formation of the dialkyl products.

The spread of microwave (MW) equipment has brought about a tremendous development in synthetic organic chemistry. This environmentally friendly methodology, associated often with solventless conditions, has also had a positive impact on organophosphorus chemistry, allowing new reactions to be carried out, or increasing the rate, selectivity and yield. In special cases, MW irradiation may replace phase transfer or other kinds of catalysts. Reactions, such as the derivatization of phosphinic acids, the inverse Wittig protocol, Diels– Alder cycloadditions, fragmentation-related phosphorylations, phospha-Michael additions, Kabachnik–Fields condensations, the addition of >P(O)H species to carbonyl compounds, substitution of

A few new l-threitol-based lariat ethers incorporating a monoaza-15-crown-5 unit were synthesized starting from diethyl l-tartrate. These macrocycles were used as phase transfer catalysts in asymmetric Michael addition reactions under mild conditions to afford the adducts in a few cases in good to excellent enantioselectivities. The addition of 2-nitropropane to trans-chalcone, and the reaction of diethyl acetamidomalonate with β-nitrostyrene resulted in the chiral Michael adducts in good enantioselectivities (90% and 95%, respectively). The substituents of chalcone had a significant impact on the yield and enantioselectivity in the reaction of diethyl acetoxymalonate. The highest enantiomeric excess (ee) values (99% ee) were measured in the case of 4-chloro- and 4-methoxychalcone. The phase transfer catalyzed cyclopropanation reaction of chalcone and benzylidene-malononitriles using diethyl bromomalonate as the nucleophile (MIRC reaction) was also developed. The corresponding chiral cyclopropane diesters were obtained in moderate to good (up to 99%) enantioselectivities in the presence of the threitol-based crown ethers.

A series of substituted diethyl arylphosphonates was synthesized by the microwave-assisted Arbuzov reaction of triethyl phosphite and aryl bromides in the presence of NiCl2 as the catalyst under solvent-free conditions in good yields. The resulting phosphonates were hydrolyzed to the corresponding arylphosphonic acids whose acidity was evaluated by physicochemical methods.

A variety of reactions including esterifications, alkylations, additions, cycloadditions, fragmentations, and condensations were carried out under microwave MW-assisted and solventless conditions, occasionally in ionic liquids (ILs). In a few cases, MW was synergic with phase transfer catalysis or could substitute it. A variety of P(III) ligands were developed and converted to Pt(II) complexes that can be used as catalysts. Finally, phosphorylations and the Kabachnik–Fields reaction were monitored and optimized by an on-line method, in situ Fourier transform IR spectroscopy.

Optimum conditions for the solid–liquid phase alkylation of methylenebis(diphenylphosphine oxide) (MBDPPO) and ethyl cyanomethylphosphonate (ECMP) were explored studying the role of phase transfer catalysis and microwave (MW) irradiation, as well as the effect of the cation of the alkali carbonate. It was found that the alkylation of MBDPPO may be best accomplished in acetonitrile, in the presence of a quaternary ammonium salt and Cs2CO3, while that of ECMP in the absence of catalyst and solvent using K2CO3. MW irradiation was beneficial in both cases. During the alkylation of ECMP, by-products coming from the alcoholysis of the diethyl ester were also identified. © 2011 Wiley Periodicals, Inc. Heteroatom Chem 22:174–179, 2011; View this article online at wileyonlinelibrary.com. DOI 10.1002/hc.20673

The solid–liquid phase alkylation of a variety of five-membered N-heterocycles (carbazole, imidazole, benzimidazole, and indole-3-carbaldehyde) was carried out under different conditions. The use of alkali carbonate in dimethylformamide or in MeCN (in the latter case, in the presence of a phase-transfer catalyst) is a suitable method to prepare the corresponding N-alkylated products in an efficient way. In most cases, the solventless, microwave-assisted reaction is an environmentally friendly alternative to traditional methods.

The synthesis of hydroxy-methylenebisphosphonates (2a–c) by the addition of dialkyl phosphite to the carbonyl group of the corresponding α-oxophosphonate (1a–c) was studied under microwave irradiation (MW) and solventless conditions in the presence of dialkylamine as the catalyst. After optimization, products 2a and 2b were obtained selectively and in good yields avoiding the formation of the phosphonate-phosphate by-product (3a and 3b) that is the result of a rearrangement. The MW-assisted synthesis of hydroxybisphosphonates (2a and 2b) offers complete conversions and a chemoselectivity of 100% as compared to the not so efficient thermal reaction. At the same time, the phenyl-substituted methylenebisphosphonate 2c could be obtained in only 75% selectivity. © 2009 Wiley Periodicals, Inc. Heteroatom Chem 20:350–354, 2009; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.20558

The outcome of the solvent-free benzylation of phenol and 4-substituted phenols (such as 4-cresol and 4-chlorophenol) under MW irradiation was found to depend on the absence or presence of the base (K 2 CO 3 ) and catalyst (triethylbenzylammonium chloride (TEBAC)). Reaction of benzyl halides at 80–120 °C in the presence of K 2 CO 3 and TEBAC resulted in O-alkylation in high (89–96%) chemoselectivities. In the absence of TEBAC, the proportion of C-alkylation was considerable (16–34%). Omitting also K 2 CO 3 from the reaction mixture, C-alkylation became predominant. In the case of 4- tert -butylphenol, the presence of TEBAC promoted C-alkylation. The selectivity of the alkylations can be fine-tuned by choosing the appropriate conditions.

The solid–liquid phase C-alkylation of active methylene containing compounds with C=O or P=O functions under phase transfer catalysis or microwave conditions has been summarized in this minireview. The mono- and dialkylation of the methylene containing derivatives was investigated under microwave (MW) conditions. It was found that in many cases, there was no need to use phase transfer catalyst under MW conditions. Moreover, most of the reactions were carried out without any solvent. These results mean a serious green chemical advantage.

The (R)- and (S)-enantiomers of a binaphthyl-appended calix[4]crown-6 ether with two 2,4-dinitrophenylazo chromophore units ((R)-1 and (S)-1) as chiral hosts were tested in their reactions with the enantiomers of alpha-methylbenzylamine ((R)-MBA, (S)-MBA)) and phenylglycinol ((R)-PGL, (S)-PGL) as chiral guests. The visible absorption spectra indicate a two-step process: the first is a nonenantioselective proton transfer from the host to the guest, which is followed by the enantioselective real complexation. In the visible range of the CD spectra a positive/negative band belongs to the absorption of pure (R)-1/(S)-1, and a negative/positive exciton couplet to the absorption of (R)-1-(S)-MBA/(S)-1-(R)-MBA complexes. The latter phenomenon suggests that the complexation of amines is accompanied by a chiral arrangement of the two chromophore units in the hosts. The UV fluorescence of (R)-1/(S)-1 arising from the binaphthyl moiety is quenched by K+ ions, but not by the amine guests, showing that the interaction between the binaphthyl group and the complexed amines is weak.

Novel chromogenic 1,3-calix[4](crown-6) derivatives comprised of 1,1′-binaphthyl-, methyl-α- d -glucoside-and d -mannitol moieties in the crown ether ring have been synthesized. UV–vis spectroscopic measurements of the 2,4-dinitrophenylazo chromogenic molecules indicated noticeable chiral discrimination associated with coloration towards primary amine enantiomers.

The synthesis of the drug alendronate from γ-aminobutyric acid and phosphorus trichloride/phosphorous acid as the P-reagents is revisited using methanesulfonic acid and sulfolane as solvents and ionic liquids (ILs) as additives according to a novel approach. Besides elaborating efficient synthetic methods with a record yield of up to 80%, the misleading literature data were also clarified. It is a novel trend to use ILs as only catalysts or additives and not as solvents.

We report on the synthesis and trace analytical application of ionophore–gold nanoparticle conjugates as a basis of a new concept in confining ionophores to ion-selective membranes using inert nanoparticle carriers.

Six active 4-aryl-5-nitro-pentan-2-ones were synthesized enantioselectively from the corresponding 5-aryl-butenones by asymmetric Michael addition of nitromethane using an imidazolidine-type enantioselective organocatalyst. The ee ratio of the products were between 67 and 100%, determined by HPLC with Chiracel OD. Molecular and crystal structure of 3,4-methylenedioxy-phenyl-5-nitro-pentan-2-one has been studied by single crystal X-ray diffraction. Chirality, 2008. © 2008 Wiley-Liss, Inc.

Enantioenriched (S)-phosphoglutaminic acid derivatives with up to 72% ee were obtained in the catalytic enantioselective Michael reaction of the achiral phosphoglycine synthon. The scope and limitation of the process in terms of the catalyst (diverse (R,R)-TADDOL derivatives) and the base (solid alkali metal tert-butoxides) were examined. The nature of the transition complex was also investigated.