Achiral additives dramatically enhance enantioselectivities in the BINOL–Ti(IV) complex catalyzed aldol condensations of aldehydes with Chan’s diene

Achiral additives can dramatically enhance the enantioselectivities in the BINOL–Ti(IV) complex catalyzed aldol condensations of aldehydes with Chan’s diene. The best results were obtained by using 2.0 equiv of LiCl with respect to (S)-BINOL/Ti(Oi-Pr)₄ as the additive. In the presence of 4.0 mol % of LiCl and 2.0 mol % of BINOL/Ti(Oi-Pr)₄, all aldehydes tested gave δ-hydroxy-β-ketoesters as almost pure single enantiomers. Moreover, the present catalyst system was highly effective on reducing the catalyst loadings to 0.1 mol %.     

Henry reaction catalyzed by recoverable enantioselective catalysts based on copper(II) complexes of α-methoxypoly(ethylene glycol)-b-poly(l-glutamic acid) and imidazolidine-4-one ligands

Herein we describe the preparation and characterization of a recoverable catalyst for a Henry reaction based on a Cu(II) complex of block copolymer α-methoxypoly(ethylene glycol)-b-poly(l-glutamic acid) with (2R,5S)- or (2S,5R)-5-isopropyl-5-methyl-2-(pyridine-2-yl)imidazolidine-4-one. The reactions of substituted aldehydes with nitromethane catalyzed by these catalysts proceed with high chemical yield (70–98%) and with high enantioselectivity (61–92% ee). The reaction mixture is in the form of a colloid system and is formed by self-organized aggregates of the catalysts with average hydrodynamic particle size of 189 ± 3 nm (DLS). After sevenfold recycling, the catalyst exhibited no decrease in the enantioselectivity and only a slight decrease (ca. 18%) in the yield for the Henry reaction of nitromethane with 2-methoxybenzaldehyde.     

Iodine-catalyzed,one-pot,three-component aza-Friedel–Crafts reaction of electron-rich arenes with aldehyde/carbamate combinations

Iodine is shown to be an efficient catalyst for a one-step, three-component aza-Friedel–Crafts reaction of activated arenes or heteroarenes with benzyl or tert-butyl carbamates in combination with a wide variety of aldehydes in toluene under ‘open-flask’ and mild conditions. In the presence of 5 mol % of iodine in toluene at room temperature, the reaction gives the corresponding N-CBz or N-Boc protected α-branched amines, selectively, in good to excellent yields.     

Catalytic asymmetric cyano-phosphorylation of aldehydes using a YLi3tris(binaphthoxide) complex (YLB)

A highly enantioselective cyano-phosphorylation of aldehydes catalyzed by a YLi₃tris(binaphthoxide) complex YLB 1 is described. The slow addition of diethyl cyanophosphonate 4 to aldehydes 5 in the presence of YLB 1 (10 mol %), H₂O (30 mol %), tris(2,6-dimethoxyphenyl)phosphine oxide 3a (10 mol %), and BuLi (10 mol %) afforded cyanohydrin O-phosphates 6 in up to 98% yield and 97% ee. Mechanistic studies revealed that the addition of cyanide to aldehydes is irreversible and determines the enantioselectivity. The reaction mechanism is also discussed in detail.     

Synthesis,characterization, and structures of arylaluminum reagents and asymmetric arylation of aldehydes catalyzed by a titanium complex of an N-sulfonylated amino alcohol

A series of phenylaluminum reagents AlPh_xEt_3?x(L) (x = 1–3) containing adduct ligand L [Et₂O, THF, OPPh₃, or 4-dimethylaminopyridine (DMAP)] were synthesized and characterized. NMR studies showed that AlPh_xEt_3?x(L) (x = 1 or 2) exists as an equilibrium mixture of 3–4 species in solution. Solid-state structures of the phenylaluminum reagents reveal a distorted tetrahedral geometry. Asymmetric additions of phenylaluminum to 2-chlorobenzaldehyde were examined employing a titanium(IV) complex [TiL¹(OPrⁱ)₂]₂ 10 (H₂L¹ = (1R,2S)-2-(p-tolylsulfonylamino)-1,3-diphenyl-1-propanol) as a catalyst precursor. It was found that the adduct ligand L had a strong influence on the reactivity and the enantioselectivity in asymmetric phenyl additions to aldehydes. The phenylaluminum reagents with OPPh₃ or DMAP were unreactive toward aldehydes, and AlPh₃(THF) was found to be superior to AlPh₃(OEt₂) or AlPhEt₂(THF). Asymmetric aryl additions of AlAr₃(THF) to aldehydes employing a loading of 5 mol % titanium(IV) complex 10 with a strategy of a slow addition of the aldehydes over 20 min were conducted, and the reactions produced optically active secondary alcohols in high yields with excellent enantioselectivities of up to 94% ee.     

Decomposition of 14C containing organic molecules released from radioactive waste by gamma-radiolysis under repository conditions

Decomposition of ¹⁴C containing organic molecules into an inorganic compound has been investigated by γ-ray irradiation experiments under simulated repository conditions for radioactive waste. Lower molecular weight organic acids, alcohols, and aldehydes leached from metallic waste are reacted with OH radicals to give carbonic acid. A decomposition efficiency that expresses consumption of OH radicals by decomposition reaction of organic molecules is proposed. Decomposition efficiency increases with increasing concentration of organic molecules (1×10⁻⁶–1×10⁻³ mol dm⁻³) and is not dependent on dose rate (10–1000 Gy h⁻¹). Observed dependence indicates that decomposition efficiency is determined by reaction probability of OH radicals with organic molecules.     

Enantio- and diastereoselective hetero-Diels–Alder reactions between 4-methyl-substituted Rawal’s diene and aldehydes catalyzed by chiral dirhodium(II) carboxamidates: catalytic asymmetric synthesis of (−)-cis-aerangis lactone

The first catalytic asymmetric hetero-Diels–Alder (HDA) reaction between 3-tert-butyldimethylsilyloxy-1-dimethylamino-1,3-pentadiene (4-methyl-substituted Rawal’s diene) and aldehydes is described. With 3 mol % of dirhodium(II) tetrakis[N-benzene-fused-phthaloyl-(S)-piperidinonate], Rh₂((S)-BPTPI)₄, the cycloaddition reaction proceeded exclusively in an endo fashion and gave, after a novel sequential treatment with dimethyl acetylenedicarboxylate and acetyl chloride, the corresponding 2,3-cis-disubstituted dihydropyranones with up to 98% ee and perfect diastereoselectivity. The utility of this catalytic protocol was demonstrated by an asymmetric synthesis of the (−)-cis-aerangis lactone.     

Preparation of various xanthene derivatives over sulfonic acid functionalized imidazolium salts (SAFIS) as novel,highly efficient and reusable catalysts

In this work, some novel sulfonic acid functionalized imidazolium salts (SAFIS), as a new category of ionic liquids, are synthesized by eco-friendly and simple procedures, and used as highly efficient and reusable catalysts to promote the following one-pot multicomponent organic transformations under solvent-free conditions: (i) the synthesis of 14-aryl-14H-dibenzo[a,j]xanthenes from β-naphthol (2 eq.) and arylaldehydes (1 eq.), (ii) the preparation of tetrahydrobenzo[a]xanthene-11-ones from β-naphthol, arylaldehydes and dimedone, and (iii) the synthesis of 1,8-dioxo-octahydroxanthenes from dimedone (2 eq.) and aromatic aldehydes (1 eq.). Environmentally benign, simple methodologies, easy workup procedure, clean reaction, short reaction time, high yield and easy preparation of the catalysts are some advantages of this work.     

Chiral linear polymers bonded alternatively with salen and 1,4-dialkoxybenzene: synthesis and application for Ti-catalyzed asymmetric TMSCN addition to aldehydes

The synthesis of chiral linear polymers 1a–b having salen and 1,4-dioctyloxybenzene as alternate segments has been accomplished. The GPC analysis showed the molecular weights corresponding to ca. 15 (M_w = 10,999, M_n = 9165 and PDI = 1.20) repeating units for 1a and ca. 8 (M_w = 8547, M_n = 7883 and PDI = 1.08) repeating units for 1b. Polymers 1a–b have been studied with Ti(OⁱPr)₄ as a recyclable catalyst for the asymmetric addition of TMSCN to aldehydes while the selectivity of the polymer catalyst is identical to that of the monomer. The reactions are efficient affording the cyanohydrins with up to 88% ee. The selectivity of the polymer based catalyst 9a is found to be the same to that of the monomer 10a. The reaction provides the advantages of simplified product isolation and easy recovery and recyclability of polymer catalyst 9a without any loss of activity or selectivity.     

Enantioselective cyanoformylation of aldehydes organocatalyzed by recyclable cinchonidine ammonium salts

Enantiomerically enriched O-methoxycarbonyl cyanohydrins were obtained using an enantioselective addition of methyl cyanoformate to aldehydes organocatalyzed by a dimeric anthracenyldimethyl-derived cinchonidine ammonium salt (1 mol % catalyst loading) in the presence of substoichiometric amounts of triethylamine (20 mol %). Aromatic and heteroaromatic aldehydes usually afford high enantioselectivities (up to 96%) and quantitative yields of the corresponding O-methoxycarbonyl cyanohydrins, whereas aliphatic and α,β-unsaturated aldehydes give lower enantioselectivities (up to 60%) in high yields. The observed sense of the enantioselection was always the same, and the organocatalyst was almost quantitatively recovered by ether-promoted precipitation without any loss of activity. The use of resin-supported cinchonidine-derived ammonium salts as an organocatalyst in this transformation was also explored.     

Asymmetric nitroaldol reaction catalyzed by copper–diamine complexes: selective construction of two contiguous stereogenic centers

Chiral copper(II) complexes of secondary bisamines derived from 1,2-diaminocyclohexane were successfully used in the diastereoselective nitroaldol reaction. The reactions were carried out in the presence of 10 mol % of the Cu(II) complex and 7.7 mol % of i-Pr₂NEt in 2-propanol at ?30 °C. Good to excellent yields, enantioselectivities of up to 99%, and moderate to excellent diastereoselectivities were obtained for both aromatic or aliphatic aldehydes and various prochiral nitrocompounds forming the corresponding β-nitroalcohols with two contiguous stereocenters.     

Solvent-free multicomponent synthesis of 2-arylpyridines using p-sulfonic acid calix[6]arene as a reusable catalyst

An efficient methodology for obtaining 2-arylpyrimidines based on the use of p-sulfonic acid calix[6]arene as an organocatalyst is proposed. The methodology involves the formation of 1,2-dihydropyridine intermediates using a variety of aromatic aldehydes with methyl or ethyl acetoacetate and ammonium acetate, which are the same starting materials as in the Hantzsch reaction, under solvent-free reaction conditions, at 25 °C, followed by air oxidation for 12 h. The catalyst efficiency is not compromised after its successive use in reactions. Eleven examples were obtained with very good to excellent yields of 2-arylpyridines (92–62%). This is the first report about the use of calixarenes as catalysts in the multicomponent synthesis of 2-arylpyridines (molecules with potential biological activity).     

Optimization of the chemoenzymatic mono-epoxidation of linoleic acid using D-optimal design

Mono-epoxied linoleic acid 9(12)-10(13)-monoepoxy 12(9)-octadecanoic acid (MEOA) was synthesized and optimized by immobilized Candida antarctica lipase (Novozym 435®) using D-optimal design. For optimizing the reaction, response surface methodology (RSM) was employed with four reaction variables such as the effect of amount of hydrogen peroxide (μL), amount of enzyme (w) and reaction time (h). At optimum conditions the experiment to obtain a higher yield% with a medium OOC% of MEOA was predicted at an amount of H₂O₂ μL of 15, Novozym 435® of 0.12 g and 7 h of reaction time. At this condition, the yield of MEOA was 82.14%, 4.91% of OOC and 66.65 mg/g of iodine value (IV). The observed value was reasonably close to the predicted value. Hydrogen peroxide was found to have the most significant effect on the degree of epoxidation OOC% and yield%. The epoxy ring opening (–C–O–C–) has been observed by Fourier Transform Infrared Spectroscopy (FTIR) at 820 cm⁻¹ and the double band (–CC–) at 3009 cm⁻¹. ¹H NMR analyses confirmed that the oxirane ring (–CH–O–CH–) of MEOA at 2.92–3.12 ppm and four signals of methane (–CHCH–) was at 5.38–5.49 ppm while the ¹³C NMR showed the oxirane ring (–C–O–C–) at 54.59–57.29 ppm and the olefinic carbons at 124.02–132.89 ppm.     

Highly diastereo- and enantioselective direct aldol reaction under solvent-free conditions

An efficient, solvent-free protocol for the asymmetric aldol reaction between aldehydes and ketones using prolinamides 1–4 as organocatalysts is reported. Catalysts 2–4, in the presence of TFA (the ratio of catalyst and TFA = 1/1.5), proved to be excellent catalysts, giving the aldol products between aromatic aldehydes and ketones with nearly perfect diastereo- and enantioselectivities (up to >99:1 dr and >99% ee). This catalytic system can also be applied in the cross-aldol reaction of isatin with ketones and the Michael reaction between cyclohexane and nitroalkenes. A mechanism is proposed to account for the formation of the major enantiomer in this reaction.     

Quantitative NMR spectroscopy of binary liquid mixtures (aldehyde + alcohol). Part III: (1-decanal or 3-phenylpropanal or 2-chlorobenzaldehyde) + (methanol or ethanol or 1-propanol)

The thermodynamic properties of binary liquid mixtures of (aldehyde + alcohol) are strongly influenced by chemical reactions in particular around and below ambient temperature. In two previous publications the chemical reaction equilibrium was investigated by ¹³C – Fourier transform NMR-spectroscopy at temperatures between 255 K and 295 K for a series of aldehydes (acetaldehyde, 1-propanal, 1-butanal, 1-heptanal) with three alcohols (methanol, ethanol, 1-propanol). Here these investigations are extended to three more aldehydes (1-decanal, 3-phenylpropanal and 2-chlorobenzaldehyde, respectively). The results for the binary systems with decanal or 3-phenylpropanal as the aldehyde in the binary mixture (aldehyde + alcohol) confirm the expectations from the first parts of this series, i.e., that the majority of the constituents of the mixture is present as hemiacetal and the first two poly(oxymethylene) – hemiacetals. The numerical results for the chemical reaction equilibrium constants from the previous investigations can be used to predict quantitatively the speciation in binary systems of ((either 1-decanal or 3-phenylpropanal) + (either methanol or ethanol or 1-propanol)). However the experimental results with 2-chlorobenzaldehyde reveal a different behaviour. In all investigated systems (2-chlorobenzaldehyde + alcohol) the most important reaction product was the corresponding acetal whereas the amounts of hemiacetal were very small. While the amounts of hemiacteal could still be quantified, it was not possible to quantify the amount of any poly(oxymethylene) – hemiacetal.     

Sc(OTf)3/TsOH: a highly efficient catalytic system for the synthesis of 2,6-dioxabicyclo[3,2,1]octane derivatives

A variety of aldehydes undergo a tandem acetalization and intramolecular Prins cyclization with pent-4-ene-1,2-diol in the presence of 5 mol % scandium triflate and 15 mol % p-toluenesulfonic acid (TsOH) in dichloroethane at 80 °C to produce the corresponding bicyclic ethers, that is, 2,6-dioxabicyclo[3,2,1]octane derivatives in good yields and with high selectivity. The salient features of this methodology are higher yields, lower catalyst loadings, and faster reaction times. The combination of Sc(OTf)₃ and TsOH (1:3) was found to be more effective than either Sc(OTf)₃ or TsOH alone.     

Albumin-mediated asymmetric nitroaldol reaction of aromatic aldehydes with nitromethane in water

We succeeded in the asymmetric nitroaldol (Henry) reaction of aromatic aldehydes with nitromethane using human serum albumin (HSA) in water at neutral pH. The reaction of 4-nitrobenzaldehyde smoothly proceeded for 24 h at 30 °C to afford the corresponding (R)-2-nitro-1-(4-nitrophenyl)ethanol (27% ee). Lowering the reaction temperature to 0 °C improved the enantioselectivity (53% ee). Although the denatured HSA also catalyzed the coupling reaction, no enantioselectivity was observed. The reaction was also applicable to other substrates bearing various substitutions on the benzene ring, and the ee of (R)-1-(biphenyl-4-yl)-2-nitroethanol was up to 79% ee.     

Asymmetric Michael addition of aldehydes to nitroolefins catalyzed by l-prolinamide derivatives using phenols as co-catalysts

The asymmetric Michael addition of aldehydes to nitroolefins was investigated using l-prolinamide derivatives of 2-(2′-piperidinyl)pyridine as catalyst and a variety of phenols as co-catalyst. Extensive screening toward the effect of prolinamides, phenols, and solvents on this transformation revealed that a combination of (S)-2-(2′-piperidinyl)pyridine-derived trans-4-hydroxy-l-prolinamide 2c, (S)-1,1′-bi-2-naphthol, and dichloromethane was a promising system. This system was shown to be amenable to a rich variety of aldehydes and nitroolefins and afforded the nitroaldehyde products with excellent yield, enantiomeric excess (up to 99%) and diastereoselectivity ratio (up to 99/1), even in the case of 1 mol % catalyst loading and 1.5 equiv of aldehydes.     

Electrocatalytic multicomponent assembling of phthalhydrazide,aldehydes and malononitrile: An efficient approach to 1H-pyrazolo[1,2-b]phthalazine-5,10-diones

Electrocatalytic multicomponent transformation of phthalhydrazide, aromatic aldehydes and malononitrile in n-propanol in an undivided cell in the presence of sodium bromide as an electrolyte leads to 1H-pyrazolo[1,2-b]phthalazine-5,10-diones in short reaction times (4–8 min) and high yields (85–98%) at room temperature. The developed efficient electrocatalytic approach to the corresponding 1H-pyrazolo[1,2-b]phthalazine-5,10-diones is beneficial from the viewpoint of diversity-oriented large-scale processes and represents a new example of the ecologically pure synthetic concept for electrocatalytic multicomponent reactions strategy.     

Ultrasound-promoted,rapid, green,one-pot synthesis of 2′-aminobenzothiazolomethylnaphthols via a multi-component reaction,catalyzed by heteropolyacid in aqueous media

A one-pot, three-component condensation reaction of 2-aminobenzothiazole, 2-naphthol and appropriate aldehydes catalyzed by heteropolyacid (HPA) in an aqueous medium afforded the Mannich adduct 2′-aminobenzothiazolomethylnaphthols at 45 °C under ultrasound irradiation. This method provides several advantages such as simple work-up procedure, short reaction time and high yields.