The transition-metal-catalyzed asymmetric cyclopropanation of olefins with diazoacetates has become one of the most important methods for the synthesis of optically active cyclopropane derivatives, ...which are key pharmaceutical building blocks and present in a large number of natural products. To date, significant progress has been made in this area of research, and efficient stereocontrolled synthetic approaches to cyclopropane derivatives have been developed using rhodium, ruthenium, copper, and cobalt catalysts. However, the vast majority of these strategies are limited to electron-rich olefins, such as styrene derivatives, due to the electrophilicity of the metal–carbene intermediates generated from the reaction of the metal with the diazo compound. Recently, the D 2-symmetric Co(II)–phophyrin complexes developed by Zhang et al. were shown to be the most efficient catalysts for the asymmetric cyclopropanation of electron-deficient olefins. This catalytic system is mechanistically distinct from the previous rhodium and copper catalytic systems, proceeding via radical intermediates. However, the asymmetric cyclopropanation of vinyl carbamates, allenes, and α,β-unsaturated carbonyl compounds has rarely been reported. Therefore, the development of new powerful catalysts for the asymmetric cyclopropanation of a wide range of olefinic substrates is the next challenge in this field. In this Account, we summarize our recent studies on the Ru(II)–Pheox-catalyzed asymmetric cyclopropanation of various olefins, including vinyl carbamates, allenes, and α,β-unsaturated carbonyl compounds. We demonstrate that the developed catalytic system effectively promotes the asymmetric cyclopropanation of a wide variety of olefins to produce the desired cyclopropane products in high yields with excellent stereocontrol. The use of succinimidyl-, ketone-, and ester-functionalized diazoacetates as carbene sources was found to be crucial for the high stereoselectivity of the cyclopropanation reactions. In addition, we describe reusable chiral Ru(II)–Pheox catalysts, namely, water-soluble Ru(II)–hm-Pheox and polymer-supported PS-Ru(II)–Pheox, which can be reused at least five times in inter- and intramolecular cyclopropanation reactions without any significant loss of catalytic activity or enantioselectivity. These Ru(II)–Pheox-catalyzed asymmetric cyclopropanation reactions provide an elegant method to access a series of optically active cyclopropane derivatives, including cyclopropylamines, dicarbonyl cyclopropanes, alkylidenecyclopropanes, and cyclopropane-fused γ-lactones, which are intermediates in the syntheses of various biologically active compounds. The novel chiral Ru(II)–Pheox complexes are readily synthesized in high yield from inexpensive, commercially available benzoyl chloride and amino alcohols, then fully characterized using X-ray diffraction analysis, NMR, and elemental analysis. These catalysts are easy to handle and stable under ordinary temperatures and conditions and can be used after three months of storage without any loss of catalytic activity or stereoselectivity.
Syntheses of substituted pyridines and fluorinated compounds, which are often pharmaceutical targets, are important objectives in organic chemistry. Herein, we found that decarboxylative fluorination ...of lithium 2‐pyridylacetates occur under catalyst‐free conditions. The phenomenon can be applied to one‐pot transformation of substituted methyl 2‐pyridylacetate to 2‐(fluoroalkyl)pyridine by decarboxylative fluorination of the intermediate lithium 2‐pyridylacetate. This method was also applied to the syntheses of 2‐(difluoroalkyl)pyridines.
Substituted pyridines: Decarboxylative fluorination of lithium 2‐pyridylacetates occur under catalyst‐free conditions. The phenomenon was applied to one‐pot transformation of a substituted methyl 2‐pyridylacetate into a 2‐(fluoroalkyl)pyridine. The method was also applied to the syntheses of 2‐(difluoroalkyl)pyridines (see scheme).
Stereoselective halogenation is a highly useful organic transformation for multistep syntheses because the resulting chiral organohalides can serve as precursors for various medicinally relevant ...derivatives. Even though decarboxylative halogenation of aliphatic carboxylic acids is a useful and fundamental synthetic method for the preparation of a variety of organohalides, an enantioselective version of this reaction has not been reported. Here we report a highly enantioselective decarboxylative chlorination of β-ketocarboxylic acids to obtain α-chloroketones under mild organocatalytic conditions. The present method is also applicable for the enantioselective synthesis of tertiary α-chloroketones. The conversions of the resulting α-chloroketones into α-aminoketones and α-thio-substituted ketones via S
2 reactions at the tertiary carbon centres are also demonstrated. These results constitute an efficient approach for the synthesis of chiral organohalides and are expected to enhance the availability of enantiomerically enriched chiral compounds with heteroatom-substituted chiral stereogenic centres.
The first highly enantioselective intramolecular cyclopropanation of electron-deficient olefins, in the presence of Ru(II)–-Pheox catalyst, is reported. The corresponding cyclopropane-fused ...γ-lactones were obtained in high yields (up to 99%) with excellent enantioselectivities (ee up to 99%). Moreover, this method enables efficient access to enantioenriched dicarbonyl cyclopropane derivatives, which are important intermediates for the synthesis of various bioactive compounds.
The Ru(II)-Pheox-catalyzed asymmetric cyclopropanation of vinylcarbamates with diazoesters resulted in the corresponding cyclopropylamine derivatives in high yield and excellent diastereoselectivity ...(up to 96:4) and enantioselectivity (up to 99% ee).
Highly enantioselective gem-chlorofluorination of active methylene compounds was carried out by using a copper(II) complex of a chiral spiro pyridyl monooxazoline ligand. This reaction yielded ...α-chloro-α-fluoro-β-keto esters and α-chloro-α-fluoro-β-keto phosphonates with up to 92% ee. The resulting dihalo β-keto ester was converted into various α-fluoro-α-heteroatom-substituted carbonyl compounds via nucleophilic substitution without loss of optical purity. A fully protected β-amino acid with a gem-chlorofluoromethylene function was also synthesized.
Decarboxylative aldol reaction of aliphatic carboxylic acids is a useful method for C-C bond formation because carboxylic acids are an easily available class of compounds. In this study, we found ...that the decarboxylative aldol reaction of tertiary β-ketocarboxylic acids and trifluoropyruvates proceeded smoothly to yield the corresponding aldol products in high yields and with high diastereoselectivity in the presence of a tertiary amine catalyst. In this reaction, we efficiently constructed a quaternary carbon center and an adjacent trifluoromethylated carbon center. This protocol was also extended to an enantioselective reaction with a chiral amine catalyst, and the desired product was obtained with up to 73% enantioselectivity.
Ru(II)-Pheox-catalyzed asymmetric cyclopropanation of diethyl diazomethylphosphonate with alkenes, including α,β-unsaturated carbonyl compounds, afforded the corresponding optically active ...cyclopropylphosphonates in high yields and with excellent diastereoselectivity (up to 99:1) and enantioselectivity (up to 99% ee).
This work presented the efficient intramolecular aromatic C–H insertion of diazoacetamide. The 1a–1o diazo compounds (except for 1k) were converted into their corresponding oxindoles via an ...intramolecular C–H insertion reaction in the presence of a Ru catalyst. The Ru-Pheox catalyst was shown to be highly efficient in this transformation in terms of the regioselectivity, producing the desired products in excellent yield (99%). The efficiency of the Ru catalyst reached 580 (TON) and 156 min−1 (TOF).
This work presented the efficient intramolecular aromatic C–H bond insertion of diazoacetamide. The 1a–1o diazo compounds (except for 1k) were converted into their corresponding oxindoles via an intramolecular C–H insertion reaction in the presence of a Ru catalyst. The Ru-Pheox catalyst was shown to be highly efficient in this transformation in terms of the regioselectivity, producing the desired products in excellent yield (99%). The efficiency of the Ru catalyst reached 580 (TON) and 156 min−1 (TOF). Display omitted
•This is an operationally simple protocol to regioselectively synthesize oxindole derivatives.•In the presence of Ru(II)-Pheox, the intramolecular C–H insertion reactions of diazoamides proceed smoothly, rapidly under mild conditions, providing the corresponding products. And no other side reactions related to metal-carbene reactivity such as aromatic ring expansion, and Csp3-H on amide nitrogen insertion reaction, were observed.•The Ru-Pheox catalyst was shown to be highly efficient in this transformation in terms of the regioselectivity, producing the desired products in excellent yield (99%).
Six pesticides, azoxystrobin, boscalid, chlorfenapyr, imazalil, isoxathion, and nitenpyram, were simultaneously detected by using a surface plasmon resonance (SPR) immunosensor. The working ranges ...were 3.5 – 19 ng/mL for azoxystrobin, 4.5 – 50 ng/mL for boscalid, 2.5 – 25 ng/mL for chlorfenapyr, 5.5 – 50 ng/mL for imazalil, 3.5 – 50 ng/mL for isoxathion, and 8.5 – 110 ng/mL for nitenpyram. They showed adequate recovery results in tomato samples: 104 – 116% for azoxystrobin, 94 – 101% for boscalid, 90 – 112% for chlorfenapyr, 96 – 106% for imazalil, 107 – 119% for isoxathion, and 104 – 109% for nitenpyram. The correlation coefficient with liquid chromatography (HPLC or LC-MS/MS) using vegetable samples also agreed well: 0.91 – 0.99 as R2 without strong bias, except for nitenpyram for which the SPR immunosensor sensitivity was too low. The SPR immunosensor will have high applicability for pesticide residue analyses in vegetable samples.
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