In situ phosphine oxide reduction: a catalytic Appel reaction

Several important reactions in organic chemistry thrive on stoichiometric formation of phosphine oxides from phosphines. To avoid the resulting burden of waste and purification, cyclic phosphine oxides were evaluated for new catalytic reactions based on in situ regeneration. First, the ease of silane-mediated reduction of a range of cyclic phosphine oxides was explored. In addition, the compatibility of silanes with electrophilic halogen donors was determined for application in a catalytic Appel reaction based on in situ reduction of dibenzophosphole oxide. Under optimized conditions, alcohols were effectively converted to bromides or chlorides, thereby showing the relevance of new catalyst development and paving the way for broader application of organophosphorus catalysis by in situ reduction protocols.     

Efficient and economic halogenation of aryl amines via arenediazonium tosylate salts

Arenediazonium tosylate salts have been successfully employed as a new and efficient reagent in halogenation reactions. A novel and economic protocol has been developed for the bromination and chlorination of various anilines using arenediazonium tosylate salts. A wide variety of reaction conditions were studied in acetonitrile at either room temperature or 60 °C in the presence or absence of catalyst with good to excellent yields. A surprising result showed the formation of acetanilides as a major product of aniline and methyl-substituted aniline halogenations in high yields.     

Catalytic Access to Alkyl Bromides,Chlorides and Iodides via Visible Light‐Promoted Decarboxylative Halogenation

Herein is reported the catalytic, visible light‐promoted, decarboxylative halogenation (bromination, chlorination, and iodination) of aliphatic carboxylic acids. This operationally‐simple reaction tolerates a range of functional groups, proceeds at room temperature, and is redox neutral. By employing an iridium photocatalyst in concert with a halogen atom source, the use of stoichiometric metals such as silver, mercury, thallium, and lead can be circumvented. This reaction grants access to valuable synthetic building blocks from the large pool of cheap, readily available carboxylic acids.     

Photoredox-Catalyzed Decarboxylative Bromination,Chlorination and Thiocyanation Using Inorganic Salts

Decarboxylative halogenation reactions of alkyl carboxylic acids are highly valuable reactions for the synthesis of structurally diverse alkyl halides. However, many reported protocols rely on stoichiometric strong oxidants or highly electrophilic halogenating agents. Herein, we describe visible-light photoredox-catalyzed decarboxylative halogenation reactions of N-hydroxyphthalimide-activated carboxylic acids that avoid stoichiometric oxidants and use inexpensive inorganic halide salts as the halogenating agents. Bromination with lithium bromide proceeds under simple, transition-metal-free conditions using an organic photoredox catalyst and no other additives, whereas dual photoredox-copper catalysis is required for chlorination with lithium chloride. The mild conditions display excellent functional-group tolerance, which is demonstrated through the transformation of a diverse range of structurally complex carboxylic acid containing natural products into the corresponding alkyl bromides and chlorides. In addition, we show the generality of the dual photoredox-copper-catalyzed decarboxylative functionalization with inorganic salts by extension to thiocyanation with potassium thiocyanide, which was applied to the synthesis of complex alkyl thiocyanates.     

Visible-Light-Induced Catalytic Selective Halogenation with Photocatalyst

Halide moieties are essential structures of compounds in organic chemistry due to their popularity and wide applications in many fields such as natural compounds, agrochemicals, and pharmaceuticals. Thus, many methods have been developed to introduce halides into various organic molecules. Recently, visible-light-driven reactions have emerged as useful methods of organic synthesis. Particularly, halogenation strategies using visible light have significantly improved the reaction efficiency and reduced toxicity, as well as promoted reactions under mild conditions. In this review, we have summarized recent studies in visible-light-mediated halogenation (chlorination, bromination, and iodination) with photocatalysts.     

Fluorinations, chlorinations and brominations of organic compounds in micro reactors

This paper gives an overview of the application of micro reactors for fluorination and chlorination of organic compounds supplemented by reporting about first investigations by the authors on the topic of bromination reactions in a micro reactor system. After a brief introduction illuminating the status of micro-chemical processing in general and covering the basic advantages of microstructured reactors, the different micro reactors used so far for halogenation reactions will be described with respect to fabrication, range of operation and performance. Thereafter, investigated reaction systems will be described and discussed.All the reactions have in common that halogenation is achieved by using elemental halogens. Beside one gas phase chlorination, the described fluorinations and chlorinations are gas/liquid processes investigated in specialised gas/liquid micro reactors. In contrast, bromination reactions were performed in a micro mixer/tube set-up not specially adopted e.g. to gas/liquid conditions. Phase conditions here are quite complex through evaporated bromine and gaseous hydrogen bromide formed during the reaction.The range of reactions comprises aromatic electrophilic substitutions and free radical substitutions of alkanes and in the side chain of aromatic compounds. The experimental results underpin the benefits of micro reactors for halogenation reactions as improved process control, process safety, improved selectivity and yields, shortening of syntheses and higher space-time yields. Furthermore, another aspect is the potential for an accelerated process development.     

Catalytic asymmetric bromination and chlorination of beta-ketoesters

The first general catalytic asymmetric bromination and chlorination of beta-ketoesters has been developed. The reactions proceed for both acyclic and cyclic beta-ketoesters catalyzed by chiral bisoxazolinecopper(II) complexes giving the corresponding optically active alpha-bromo- and alpha-chloro-beta-ketoesters in high yields and moderate to good enantioselectivities. For the optically active chlorinated products the isolated yields are in the range of 88-99 % and the enantiomeric excesses up to 77 % ee, while the optically active brominated adducts are formed in 70-99 % isolated yield and up to 82 % ee. Based on the absolute configuration of the optically active products, the face selectivity for the catalytic enantioselective halogenation is discussed based on a bidentate coordination of the beta-ketoester to the chiral catalyst and a X-ray structure of chiral alpha,gamma-diketoesterenolatebisoxazolinecopper(II) complex.     

Ruthenium-catalyzed propargylic substitution reactions of propargylic alcohols with oxygen-, nitrogen-, and phosphorus-centered nucleophiles

The scope and limitations of the ruthenium-catalyzed propargylic substitution reaction of propargylic alcohols with heteroatom-centered nucleophiles are presented. Oxygen-, nitrogen-, and phosphorus-centered nucleophiles such as alcohols, amines, amides, and phosphine oxide are available for this catalytic reaction. Only the thiolate-bridged diruthenium complexes can work as catalysts for this reaction. Results of some stoichiometric and catalytic reactions indicate that the catalytic propargylic substitution reaction proceeds via an allenylidene complex formed in situ, whereby the attack of nucleophiles to the allenylidene C(gamma) atom is a key step. Investigation of the relative rate constants for the reaction of propargylic alcohols with several para-substituted anilines reveals that the attack of anilines on the allenylidene C(gamma) atom is not involved in the rate-determining step and rather the acidity of conjugated anilines of an alkynyl complex, which is formed after the attack of aniline on the C(gamma) atom, is considered to be the most important factor to determine the rate of this catalytic reaction. The key point to promote this catalytic reaction by using the thiolate-bridged diruthenium complexes is considered to be the ease of the ligand exchange step between a vinylidene ligand on the diruthenium complexes and another propargylic alcohol in the catalytic cycle. The reason why only the thiolate-bridged diruthenium complexes promote the ligand exchange step more easily with respect to other monoruthenium complexes in this catalytic reaction should be that one Ru moiety, which is not involved in the allenylidene formation, works as an electron pool or a mobile ligand to another Ru site. The catalytic procedure presented here provides a versatile, direct, and one-step method for propargylic substitution of propargylic alcohols in contrast to the so far well-known stoichiometric and stepwise Nicholas reaction.     

Halogenation of Some Alkyl-Substituted 4-Aroyloxyimino- and 4-Arylsulfonyloxyimino-2,5-cyclohexadienones

The chlorination and bromination of 2,3-dimethyl-, 3-methyl-6-isopropyl-, and 2,6-diisopropyl-4-aroyl(or arylsulfonyl)oxyimino-2,5-cyclohexadienones follow the proposed rules of halogenation of 4-aroyl(or arylsulfonyl)oxyimino-2,5-cyclohexadienones: the reaction occurs preferentially at the cis-CÍC bond of the quinoid ring; simultaneous halogenation at both double bonds is not observed; halogen adds mainly across unsubstituted CÍC bond; no halogenation occurs at the double bond already substituted by a halogen; bromination of the CÍC bond with an alkyl substituent is more difficult than chlorination; the second halogen molecule adds only after regioselective dehydrohalogenation.     

流动化学在卤化反应中的应用

有机物的卤化反应是有机合成中最重要的转化之一.传统釜式卤化反应存在高放热及选择性差等问题,且卤化试剂一般具有毒性和腐蚀性.流动化学在传质和传热方面具有显著优势,可精确控制反应温度及试剂用量,并且可在线淬灭危险试剂,避免其暴露.按有机化合物卤化反应分类,系统地归纳了流动化学在氟化反应、氯化反应、溴化反应和碘化反应中的应用进展,并展望了其发展趋势.     

A Convenient and Selective Palladium‐Catalyzed Aerobic Oxidation of Alcohols

An efficient procedure for the oxidation of primary and secondary alcohols to aldehydes and ketones, respectively, with molecular oxygen under ambient conditions has been achieved. By applying catalytic amounts of Pd(OAc)₂ in the presence of tertiary phosphine oxides (O?PR₃) as ligands, a variety of substrates are selectively oxidized without formation of ester byproducts. Spectroscopic investigations and DFT calculations suggest stabilization of the active palladium(II) catalyst by phosphine oxide ligands.     

Catalytic, asymmetric alpha-chlorination of acid halides

We present a full account of a tandem catalytic, asymmetric chlorination/esterification process that produces highly optically enriched alpha-chloroesters from inexpensive, commercially available acid halides using cinchona alkaloid derivatives as catalysts and polychlorinated quinones as halogenating agents. We have performed kinetics and control experiments to investigate the reaction mechanism and establish conditions under which the reactions can be best performed. We have developed NaH and NaHCO3 shuttle base systems as the easiest and most cost-effective ways of conducting the reactions, rendering the methodology economically competitive with known chiral halogenation procedures. We have also demonstrated the utility of our reactions by converting the products to synthetically useful derivatives.     

Synthesis of Nitro,Amino, and Halo Derivatives of 2-Ethyl-2-methyl-2,3-dihydro-1H-indole

Russian Journal of Organic Chemistry - The nitration, oxidative halogenation, and radical bromination and chlorination of 2-ethyl-2-methyl-2,3-dihydro-1H-indole afforded the corresponding nitro,...     

Recent topics of phosphine-mediated reactions

Phosphines constitute key organophosphorus reagents that are being widely used in industry as well as in research laboratories since over a century. Specifically, in last two decades, there have been numerous reports on phosphine-mediated and phosphine-catalyzed reactions. In terms of industrial application, phosphine-mediated reactions have received much attention when compared to the catalytic versions for the synthesis of a variety of structurally diverse organic frameworks. In this digest review, we wish to summarize the recent advances (2014–2017) in phosphine-mediated reactions that are primarily based on stoichiometric application of phosphine.     

Direct and enantioselective organocatalytic alpha-chlorination of aldehydes

The first direct enantioselective catalytic alpha-chlorination of aldehydes has been accomplished. The use of enamine catalysis has provided a new organocatalytic strategy for the enantioselective chlorination of aldehydes to generate alpha-chloro aldehydes, an important chiral synthon for chemical and medicinal agent synthesis. The use of imidazolidinone 3 as the asymmetric catalyst has been found to mediate the halogenation of a large variety of aldehyde substrates with the perchlorinated quinone 1 serving as the electrophilic chlorinating reagent. A diverse spectrum of aldehyde substrates can also be accommodated in this new organocatalytic transformation. The capacity of catalyst 3 to override the inherent bias of resident stereogenicity in the chlorination of enantiopure beta-chiral aldehydes is also described. Catalyst quantities of 5 mol % were generally employed in this study.     

Organocatalytic Mitsunobu reactions

A catalytic Mitsunobu reaction system is described in which the azo reagent is used as an organocatalyst and iodosobenzene diacetate is used as the stoichiometric oxidant. In this system, iodosobenzene diacetate oxidizes the formed hydrazine byproduct to regenerate the azo reagent. Yields obtained in the catalytic reactions using a variety of carboxylic acids and alcohols were slightly lower than those obtained from corresponding stoichiometric reactions. Both primary and secondary alcohols can be used as substrates in this reaction system, with the secondary alcohols affording products with inverted stereochemistry at the carbinol center.     

氯过氧化物酶的手性催化活性在有机合成中的应用

氯过氧化物酶（CPO）作为过氧化物酶家族中的一员对多种有机底物表现出了广泛的催化活性。自上世纪60年代被发现以来，CPO在有机合成中的应用一直是一个研究热点。它作为一种生物催化剂能催化广泛的底物合成手性化合物，且有高的产率和高的对映选择率。本文综述了氯过氧化物酶在手性有机合成中的应用，重点关注了卤化、醇氧化、羟基化、环氧化、磺化氧化等反应，并讨论了目前在该领域所面临的问题及今后的发展趋势。     

B(C6F5)3‐Catalyzed Selective Chlorination of Hydrosilanes

The chlorination of Si−H bonds often requires stoichiometric amounts of metal salts in conjunction with hazardous reagents, such as tin chlorides, Cl₂, and CCl₄. The catalytic chlorination of silanes often involves the use of expensive transition‐metal catalysts. By a new simple, selective, and highly efficient catalytic metal‐free method for the chlorination of Si−H bonds, mono‐, di‐, and trihydrosilanes were selectively chlorinated in the presence of a catalytic amount of B(C₆F₅)₃ or Et₂O⋅B(C₆F₅)₃ and HCl with the release of H₂ as a by‐product. The hydrides in di‐ and trihydrosilanes could be selectively chlorinated by HCl in a stepwise manner when Et₂O⋅B(C₆F₅)₃ was used as the catalyst. A mechanism is proposed for these catalytic chlorination reactions on the basis of competition experiments and density functional theory (DFT) calculations.     

Mitsunobu Reactions Catalytic in Phosphine and a Fully Catalytic System

The Mitsunobu reaction is renowned for its mild reaction conditions and broad substrate tolerance, but has limited utility in process chemistry and industrial applications due to poor atom economy and the generation of stoichiometric phosphine oxide and hydrazine by‐products that complicate purification. A catalytic Mitsunobu reaction using innocuous reagents to recycle these by‐products would overcome both of these shortcomings. Herein we report a protocol that is catalytic in phosphine (1‐phenylphospholane) employing phenylsilane to recycle the catalyst. Integration of this phosphine catalytic cycle with Taniguchi’s azocarboxylate catalytic system provided the first fully catalytic Mitsunobu reaction.     

Fluorous solvent as a new phase-screen medium between reagents and reactants in the bromination and chlorination of alcohols

[reaction: see text] A perfluorohexane layer regulates the rate of reagent transport in the bromination and chlorination of alcohols. A fluorous triphasic U-tube method is effective for lighter reagents; the thionyl chloride layer (yellow) vanishes, and the chlorides are obtained from the right top organic layer in the chlorination of alcohols.