7476-66-6Relevant articles and documents
A π–Cu(II)?π Complex as an Extremely Active Catalyst for Enantioselective α-Halogenation of N-Acyl-3,5-dimethylpyrazoles
Nishimura, Kazuki,Wang, Yanzhao,Ogura, Yoshihiro,Kumagai, Jun,Ishihara, Kazuaki
, p. 1012 - 1017 (2022/01/19)
Novel chiral π–copper(II)?π complex catalyzed enantioselective α-chlorination and -bromination of N-acyl-3,5-dimethylpyrazoles are described. The π–copper(II)?π complexation of Cu(OTf)2 with 3-(2-naphthyl)-l-alanine-derived amides greatly increases the Lewis acidity and triggers the in situ generation of enolate species without an external base, which has a suppressing effect for α-chlorination and -bromination due to undesired halogen bonding. This strategy provides facile access to α-halogenated compounds in high yield with excellent enantioselectivity. X-ray crystallographic and ESR analyses of the catalyst complexes suggest that the release of two counteranions (2TfO–) from the copper(II) center might be crucial for the efficient activation of N-acyl-3,5-dimethylpyrazoles.
Enantioselective α-Chlorination Reactions of in Situ Generated C1 Ammonium Enolates under Base-Free Conditions
Stockhammer, Lotte,Weinzierl, David,B?gl, Thomas,Waser, Mario
supporting information, p. 6143 - 6147 (2021/08/18)
The asymmetric α-chlorination of activated aryl acetic acid esters can be carried out with high levels of enantioselectivities utilizing commercially available isothiourea catalysts under base-free conditions. The reaction, which proceeds via the in situ formation of chiral C1 ammonium enolates, is best carried out under cryogenic conditions combined with a direct trapping of the activated α-chlorinated ester derivative to prevent epimerization, thus allowing for enantioselectivities of up to e.r. 99:1.
Straightforward Access to Terminally Disubstituted Electron-Deficient Alkylidene Cyclopent-2-en-4-ones through Olefination with α-Carbonyl and α-Cyano Secondary Alkyl Sulfones
Afri, Michal,Gruzman, Arie,Korshin, Edward E.,Leitus, Gregory,Palczewski, Krzysztof,Rothstein, Ayelet,Trifonov, Lena,Viskind, Olga
supporting information, p. 6725 - 6736 (2021/12/31)
Herein we report on a simplified synthesis of scarcely explored, terminally disubstituted electron-poor alkylidene cyclopent-2-en-4-ones through uncommon olefination. Secondary sulfones, activated by electron-withdrawing groups at the adjacent carbon atom, undergo K2CO3-promoted coupling with 4-acyloxy- and 4-tert-butyldimethylsilyloxycyclopent-2-en-1-ones giving directly, or after a separate dehydrosulfinylation step, alkylidene cyclopent-2-en-4-ones. A plausible mechanism for these transformations is proposed. Initially, β-arylsulfonyl esters as well as their acetyl or nitrile analogues are allylated by cyclopentenone derivatives via a tandem Michael addition of α-sulfonyl carbanions followed by proton migration and retro-Michael-type O-nucleofuge elimination. The primary allylation products are formed as two diastereomers whose configuration and conformation were elucidated using single crystal X-ray diffraction and NMR spectroscopy. Regardless of stereochemistry, both sets of diastereomers are subjected to Zaitsev-type retro-Michael vinylogous dehydrosulfinylation under either basic or thermal silica gel promoted conditions resulting in E/Z-alkylidene cyclopent-2-en-4-ones. In these reactions activated sulfones serve as bearing electron-withdrawing group alkylidene anion-radical synthons, whereas 4-oxy-substituted cyclopentenones represent cyclopent-2-en-4-one cation-radical surrogates.
Visible Light-Promoted Sulfoxonium Ylides Synthesis from Aryl Diazoacetates and Sulfoxides
Lu, Juan,Li, Lei,He, Xiang-Kui,Xu, Guo-Yong,Xuan, Jun
, p. 1646 - 1650 (2021/05/28)
A visible light-promoted reaction of donor/acceptor diazoalkanes with sulfoxides towards the synthesis of synthetically useful sulfoxonium ylides was reported. The reaction occurred under sole visible light irradiation without the need of any transition-metals or additives, affording the corresponding sulfoxonium ylides in moderate to good yields. The success of late-stage modification of natural isolates or drug candidates, scale-up reaction and transformation of sulfoxonium ylides to other useful molecules further rendered the approach valuable.
[3 + 2] Cycloaddition of α-Aryl-α-diazoacetates with Terminal Alkynes via the Cooperative Catalysis of Palladium and Acid
Guo, Hongyu,Zhang, Sheng,Yu, Xiaoqiang,Feng, Xiujuan,Yamamoto, Yoshinori,Bao, Ming
, p. 10789 - 10795 (2021/09/08)
Palladium and acid cooperative catalysis is presented as a strategy for the [3 + 2] cycloaddition of acceptor/donor-type diazo compounds with terminal alkynes. The [3 + 2] cycloaddition of α-aryl-α-diazoacetates with terminal alkynes proceeded smoothly to produce 2,3,5-trisubstituted furans with high yields. This synthesis method provided a direct and efficient pathway to prepare furan ring-containing organosilane and organoboron reagents. Synthetically valuable functional groups such as chloro and bromo atoms, methoxycarbonyl, and carbonyl remained intact during the [3 + 2] cycloaddition reaction.
Lewis Base Catalysis Enables the Activation of Alcohols by means of Chloroformates as Phosgene Substitutes
Zoller, Ben,Stach, Tanja,Huy, Peter H.
, p. 5637 - 5643 (2020/09/21)
Nucleophilic substitutions (SN) are typically promoted by acid chlorides as sacrificial reagents to improve the thermodynamic driving force and lower kinetic barriers. However, the cheapest acid chloride phosgene (COCl2) is a highly toxic gas. Against this background, phenyl chloroformate (PCF) was discovered as inherently safer phosgene substitute for the SN-type formation of C?Cl and C?Br bonds using alcohols. Thereby, application of the Lewis bases 1-formylpyrroldine (FPyr) and diethylcyclopropenone (DEC) as catalysts turned out to be pivotal to shift the chemoselectivity in favor of halo alkane generation. Primary, secondary and tertiary, benzylic, allylic and aliphatic alcohols are appropriate starting materials. A variety of functional groups are tolerated, which includes even acid labile moieties such as tert-butyl esters and acetals. Since the by-product phenol can be isolated, a recycling to PCF with inexpensive phosgene would be feasible on a technical scale. Eventually, a thorough competitive study demonstrated that PCF is indeed superior to phosgene and other substitutes.
A Phosphorus(III)-Mediated (4+1)-Cycloaddition of 1,2-Dicarbonyls and Aza-o-Quinone Methides to Access 2,3-Dihydroindoles
Eckert, Kaitlyn E.,Lepore, Antonio J.,Ashfeld, Brandon L.
, (2019/12/24)
A (4+1)-cycloaddition is reported between 1,2-dicarbonyls and aza-o-quinone methide precursors to access 2,3-dihydroindoles bearing a tetra-substituted carbon center. The utilization of dioxyphospholenes as carbene surrogates provided dihydroindoles in 20–90 % yield, wherein the electronic nature of the dioxyphospholene impacts its role in the reaction.
A General Catalytic Method for Highly Cost- and Atom-Efficient Nucleophilic Substitutions
Huy, Peter H.,Filbrich, Isabel
supporting information, p. 7410 - 7416 (2018/04/30)
A general formamide-catalyzed protocol for the efficient transformation of alcohols into alkyl chlorides, which is promoted by substoichiometric amounts (down to 34 mol %) of inexpensive trichlorotriazine (TCT), is introduced. This is the first example of a TCT-mediated dihydroxychlorination of an OH-containing substrate (e.g., alcohols and carboxylic acids) in which all three chlorine atoms of TCT are transferred to the starting material. The consequently enhanced atom economy facilitates a significantly improved waste balance (E-factors down to 4), cost efficiency, and scalability (>50 g). Furthermore, the current procedure is distinguished by high levels of functional-group compatibility and stereoselectivity, as only weakly acidic cyanuric acid is released as exclusive byproduct. Finally, a one-pot protocol for the preparation of amines, azides, ethers, and sulfides enabled the synthesis of the drug rivastigmine with twofold SN2 inversion, which demonstrates the high practical value of the presented method.
Systematic Evaluation of Sulfoxides as Catalysts in Nucleophilic Substitutions of Alcohols
Motsch, Sebastian,Schütz, Christian,Huy, Peter H.
supporting information, p. 4541 - 4547 (2018/09/13)
Herein, a method for the nucleophilic substitution (SN) of benzyl alcohols yielding chloro alkanes is introduced that relies on aromatic sulfoxides as Lewis base catalysts (down to 1.5 mol-%) and benzoyl chloride (BzCl) as reagent. A systematic screening of various sulfoxides and other sulfinyl containing Lewis bases afforded (2-methoxyphenyl)methyl sulfoxide as optimal catalyst. In contrast to reported formamide catalysts, sulfoxides also enable the application of plain acetyl chloride (AcCl) as reagent. In addition, it was demonstrated that weakly electrophilic carboxylic acid chlorides like BzCl promote Pummerer rearrangement of sulfoxides already at room temperature. This side-reaction also provided the explanation, why sulfoxide catalyzed SN-reactions of alcohols do not allow the effective production of aliphatic and electron deficient chloro alkanes. Comparison experiments provided further insight into the reaction mechanism.
A mild method for the replacement of a hydroxyl group by halogen. 1. Scope and chemoselectivity
Munyemana, Fran?ois,George, Isabelle,Devos, Alain,Colens, Alain,Badarau, Eduard,Frisque-Hesbain, Anne-Marie,Loudet, Aurore,Differding, Edmond,Damien, Jean-Marie,Rémion, Jeanine,Van Uytbergen, Jacqueline,Ghosez, Léon
, p. 420 - 430 (2015/12/31)
α-Chloro-, bromo- and iodoenamines, which are readily prepared from the corresponding isobutyramides have been found to be excellent reagents for the transformation of a wide variety of alcohols or carboxylic acids into the corresponding halides. Yields are high and conditions are very mild thus allowing for the presence of sensitive functional groups. The reagents can be easily tuned allowing therefore the selective monohalogenation of polyhydroxylated molecules. The scope and chemoselectivity of the reactions have been studied and reaction mechanisms have been proposed.
