Zinc‐Mediated Formation of Trifluoromethyl Ethers from Alcohols and Hypervalent Iodine Trifluoromethylation Reagents

A (fluor)ry of activity : The transfer of an intact trifluoromethyl group from a hypervalent iodine reagent to an aliphatic alcohol occurs smoothly upon activation by zinc bis(triflimide). This constitutes a straightforward method for the preparation of trifluoromethoxy alkyl derivatives, compounds otherwise difficult to access.

     

Lanthanum-Catalyzed Enantioselective Trifluoromethylation by Using an Electrophilic Hypervalent Iodine Reagent

A highly enantioselective catalytic method for the synthesis of quaternary α-trifluoromethyl derivatives of 3-oxo esters is described. The reaction uses lanthanum(III) triflate and chiral PyBOX-type C₂-symmetric ligands to generate intermediate La^III complexes that incorporate an enolate moiety of the starting 3-oxo ester and the trifluoromethylation transfer reagent. The enantioselectivity of the reaction stems from the efficient blockage of one of the prochiral faces of the La^III enolate by one unit of the C₂-symmetric ligand.     

Cyclic Hypervalent Iodine Reagents for Atom‐Transfer Reactions: Beyond Trifluoromethylation

Hypervalent iodine compounds are privileged reagents in organic synthesis because of their exceptional reactivity. Among these compounds, cyclic derivatives stand apart because of their enhanced stability. They have been widely used as oxidants, but their potential for functional‐group transfer has only begun to be investigated recently. The use of benziodoxol(on)es for trifluoromethylation (Togni's reagents) is already widely recognized, but other transformations have also attracted strong interest recently. In this Review, the development in the area since 2011 will be presented. After a short summary of synthetic methods to prepare benziodoxol(on)e reagents, their use to construct carbon–heteroatom and carbon–carbon bonds will be presented. In particular, the introduction of alkynes by using ethynylbenziodoxol(on)e (EBX) reagents has been highly successful. Breakthroughs in the introduction of alkoxy, azido, difluoromethyl, and cyano groups will also be described.     

从三氟甲基化反应的近年进展看有机氟化学的发展趋势

由于含三氟甲基的化合物在医药、农药等领域得到广泛应用,发展向有机分子引入三氟甲基的方法成为当前的热点研究课题.分别总结了国外和我国学者近年(主要是2009～2011年)在三氟甲基化反应研究领域取得的研究成果.从近年三氟甲基化反应的研究进展,作者提出一些值得关注的有机氟化学发展方向.     

Highly Efficient Method for Synthesis of Benzoquinones Using Hypervalent Iodine(III) Reagent and Sodium Bisulfate

A rapid, one-step, novel approach for the conversion of benzamides into benzoquinones using (diacetoxyiodo)benzene(III) and sodium bisulfate has been developed in aqueous acetonitrile at room temperature. The developed protocol is applicable to several types of substituted benzamide derivatives to get the corresponding benzoquinone products. The developed methodology offers mild reaction condition, short reaction time, and moderate to excellent yields. This is one of the most simple and environmentally benign protocols for synthesis of benzamide derivatives.

[Supplementary materials are available for this article. Go to the publisher's online edition of Synthetic Communications® for the following free supplemental resource(s): Full experimental and spectral details.]     

Study on the Degradation of the Highly Reactive Hypervalent Trifluoromethylation Iodine Reagent PhI(OAc)(CF3)

Degradation of the highly reactive hypervalent trifluoromethylation iodine reagent PhI(OAc)(CF₃), which can only be generated in situ with mixing PhI(OAc)₂ and TMSCF₃ in the presence of CsF, was studied by ESI‐MS and GC‐MS combined with ¹⁹F‐NMR. The important transient intermediate PhICF₃⁺ was determined by ESI‐MS, and the major volatile products containing CF₃ were identified with the authentic compounds by using GC‐MS, such as trifluoromethylbenzene, 2‐iodobenzotrifluoride, 3‐iodobenzotrifluoride, 4‐iodobenzotrifluoride. Meanwhile, more evidences obtained with ¹⁹F‐NMR were given for such degradation reaction. A possible rapid CF₃ radical transfer reaction pathway was proposed to clarify such degradation progress based on the experimental results. Therefore, this study may be helpful in elucidating the intrinsic reactivity of PhI(OAc)(CF₃) and the possible competing side reactions caused by such self‐degradation pathway.     

Isostrychnine Synthesis Mediated by Hypervalent Iodine Reagent

Althought there are several reported synthetic routes to strychnine, one of the most widely recognized alkaloids, we report an unexplored route with an oxidative dearomatizing process mediated by hypervalent iodine as the key step. The new syntheses of isostrychnine and strychnine have been achieved from an readily available phenol in nine and ten steps. In addition to the key step, these syntheses involve an aza Michael‐ether‐enol tandem transformation, two heck type cyclizations, a reductive isomerization, and a double reductive amination in cascade leading to the alkaloid main core.     

Novel 10-I-3 hypervalent iodine-based compounds for electrophilic trifluoromethylation

The synthesis of a new family of 10-I-3 hypervalent iodine compounds is described in which the CF3 functionality participates directly in the hypervalent bond. These materials are accessible by nucleophilic ligand substitution at iodine using Me3SiCF3 in the presence of a substoichiometric amount of fluoride. The expected T-shaped geometry at iodine was verified by X-ray crystallographic analyses of three of the products (1-trifluoromethyl-1,2-benziodoxol-3-(1 H)-one and two substituted 1-trifluoromethyl-1,3-dihydro-1,2-benziodoxoles). Preliminary results for the direct electrophilic transfer of the trifluoromethyl moiety onto organic nucleophiles show modest reactivity in polar aprotic solvents under relatively mild conditions. The overall process can be understood as a formal umpolung of the CF3 group.     

A Tunable Trifluoromethyliodonium Reagent

Four complexes of MCl₄ (M=Ti, Zr, Hf) with the hypervalent trifluoromethyl iodine reagent trifluoromethyl‐1,3‐dihydro‐3,3‐dimethyl‐1,2‐benziodoxole ( 1 ,=L) are described. With TiCl₄, an I?O bond cleavage occurs, leading to the formation of the trifluoromethyliodonium alcoholate complexes [Ti₂Cl₆(L)₄]Cl₂ ( 2 a ) and Ti₂Cl₈(L) ( 2 b ). Reactions with ZrCl₄ and HfCl₄ form the complexes ZrCl₄(L)₂ ( 3 ) and HfCl₄(L)₂ ( 4 ), respectively, wherein the original I?O bond is retained and elongated compared to that in free 1 . Therefore, the reactivity of 1 can be easily and practically fine‐tuned by addition of different metal chlorides, following the order ZrCl₄/HfCl₄<TiCl₄<2 TiCl₄. Complexes 2 a , 3 , and 4 are remarkably bench‐stable forms of activated reagent 1 , while 2 b is readily accessible in situ. 2 a and 2 b represent the first “real” trifluoromethyliodonium reagents derived from iodanes, that is, with the I?O bond being completely cleaved. The new complexes were shown to be useful for the trifluoromethylation of para‐toluenesulfonate under aprotic conditions.     

Intramolecular Fluorocyclizations of Unsaturated Carboxylic Acids with a Stable Hypervalent Fluoroiodane Reagent

A new class of fluorinated lactones was prepared by the intramolecular fluorocyclizations of unsaturated carboxylic acids by using the stable fluoroiodane reagent in combination with AgBF₄. This unique reaction incorporates a cyclization, an aryl migration, and a fluorination all in one step. The fluoroiodane reagent, prepared easily from fluoride, can also be used without a metal catalyst to give moderate yields within just 1 hour, thus demonstrating that it is a suitable reagent for developing new ¹⁸F‐labelled radiotracers for PET imaging.     

Lewis Base‐Promoted Ring‐Opening 1,3‐Dioxygenation of Unactivated Cyclopropanes Using a Hypervalent Iodine Reagent

A facile and effective system has been developed for the regio‐ and chemoselective ring‐opening/electrophilic functionalization of cyclopropanes through C?C bond activation by [bis(trifluoroacetoxy)iodo]benzene with the aid of the Lewis basic promoter p‐toluenesulfonamide. The p‐toluenesulfonamide‐promoted system works well for a wide range of cyclopropanes, resulting in the formation of 1,3‐diol products in good yields and regioselectivity.     

Pioneering Metal‐Free Oxidative Coupling Strategy of Aromatic Compounds Using Hypervalent Iodine Reagents

We started our hypervalent iodine research about 30 years ago in the mid‐1980s. We soon successfully developed the single‐electron‐transfer oxidation ability of a hypervalent iodine reagent, specifically, phenyliodine(III) bis(trifluoroacetate) (PIFA), toward aromatic rings of phenyl ethers for forming aromatic cation radicals. This was one of the exciting and unexpected events in our research studies so far, and the discovery was reported in 1991. It also led to the next challenge, developing the metal‐free oxidative couplings for C–H functionalizations and direct couplings between the C–H bonds of valuable aromatic compounds in organic synthesis. In order to realize the effective oxidative coupling, pioneering new aromatic ring activations was essential and several useful methodologies have been found for oxidizable arenes. The achievements regarding this objective obtained in our continuous research are herein summarized with classification of the aromatic ring activation strategies.     

S‐Trifluoromethylation of Thiols by Hypervalent Iodine Reagents: A Joint Experimental and Computational Study

The radical trifluoromethylation of thiophenol in condensed phase applying reagent 1 (3,3‐dimethyl‐1‐(trifluoromethyl)‐1λ³,2‐benziodoxol) has been examined by both theoretical and experimental methodologies. On the basis of ab initio molecular dynamics and metadynamics we show that radical reaction mechanisms favourably compete with polar ones involving the S‐centred nucleophile thiophenol, their free energies of activation, ΔF^≠, lying between 9 and 15 kcal mol^?1. We further show that the origin of the proton activating the reagent is important. Hammett plot analysis reveals intramolecular protonation of 1 , thus generating negative charge on the sulfur atom in the rate‐determining step. The formation of a CF₃ radical can be thermally induced by internal dissociative electron transfer, its activation energy, ΔF^≠, amounting to as little as 10.8 and 2.8 kcal mol^?1 for reagent 1 and its protonated form 2 , respectively. The reduction of the iodine atom by thiophenol occurs either subsequently or in a concerted fashion.     

Facile Oxidative Rearrangements Using Hypervalent Iodine Reagents

Aromatic substituents migrate in a novel oxidative cyclization mediated by iodine(III) reagents. 4-Arylbut-3-enoic acids are cyclized and rearranged to 4-arylfuran-2(5H)-ones by hypervalent iodine compounds in good to excellent yields under mild reaction conditions. Other ring sizes are also accessible. The mechanism of the reaction is described in detail, and calculations highlight the cationic nature of the intermediates in the rearrangement. The fast access to heavily substituted furanones is used for the synthesis of biologically active derivatives.