The applications of hypervalent iodine(Ⅲ) reagents in the constructions of heterocyclic compounds through oxidative coupling reactions

Hypervalent iodine(Ⅲ)reagents have been vastly used in many useful organic transformations.In this review article,we highlight the strategies that used the common hypervalent iodine(Ⅲ)reagents as oxidants to synthesize the heterocyclic compounds,based on the patterns of bond formation during the construction of the heterocyclic backbones.

An environmentally benign benzylic oxidation catalyzed by hypervalent iodine intermediate in water

An effective and environmentally benign benzylic oxidation for transition of alkylarenes into the corresponding carbonyl compounds was reported. Alkylarenes were mixed and stirred with potassium bromide, m-chloroperbenzoic acid and a catalytic amount of iodobenzene in water at 60 ℃ for several hours, a series of the corresponding carbonyl compounds was obtained in moderate to good yields. In the reaction, iodobenzene was first oxidized by m-chloroperbenzoic acid into the hypervalent iodine intermediate which then reacted with potassium bromide to form the key radical initiator for the benzylic oxidation.

Hypervalent Iodine(Ⅲ)-Mediated Benzannulation of Enamines with Alkynes: an Efficient Synthesis of Substituted Aminonaphthoic Acid Derivatives

An intermolecular two C-C bond formation procedure for the synthesis of carbocycles mediated by hyperva-lent iodine(III)reagents was developed.This metal free protocol provided a new approach for the synthesis of use-ful substituted 1-amino-2-naphthoic acid derivatives via benzannulation reactions.Various N-unsubstituted and N-alkyl substituted aromatic enamines with terminal alkynes and non-terminal alkynes can be converted into corre-sponding 1-amino-2-naphthoic acid derivatives under mild reaction conditions.When meta-substituted phenyl enamines were employed in the reaction,two cyclization paths were detected in the reaction and ortho-cyclization products were the only or major products.Good functional group tolerance,readily available material and high atom utilization efficiency make this method a potential procedure which may find broad application in organic synthesis.

Hypervalent iodine-mediated gem-difluorination of vinyl halides enabled by exclusive 1,2-halo migration

β-Difluorinated alkyl halides are of significant value in the modular synthesis of gem-difluorinated molecules.An exclusive 1,2-halo migratory gem-difluorination of vinyl halides with in situ-generated PhIF_(2)·HF is described.This protocol provides a general and practical approach towards a wide variety ofβ-difluorinated alkyl bromides.Bothα-andβ-bromoalkyl alkenes are suitable substrates,leading to two distinct types of products.The extension of this protocol to vinyl chloride and iodide are also feasible.The synthetic versatility of this method has been highlighted by the late-stage modification of complex small molecules and further transformations of theβ-difluorinated alkyl halides to valuable CF_(2)-containing compounds.

Hypervalent iodine mediated C-H amination of quinoxalinones with heteroaromatic amines under metal-free conditions

An efficient and facile method for C-H amination of quinoxalinones with heteroaromatic amines under metal-free conditions has been described.In the presence of hypervalent PIDA reagent,the desired products with various groups were obtained with moderate to high yields.

Rhodium(Ⅲ)-catalyzed chelation-assisted C-H imidation of arenes via umpolung of the imidating reagent

Rh(Ⅲ)-catalyzed, chelation-assisted oxidative C-H imidation of arenes with N-H imide have been realized using PhI(OAc)2 as an oxidant. This transformation exhibits a broad substrate scope and tolerates various functional groups. The reaction proceeded via in situ generation of an iodine(Ⅲ) imido. DFT calculations suggest that this oxidative imidaton system proceeds via a Rh(Ⅲ)-Rh(Ⅴ)-Rh(Ⅲ) pathway.

Metal-free nucleophilic 7,8-dearomatization of quinolines:Spiroannulation of aminoquinoline protected amino acids

Atom-and step-economy in IBX assisted diversity-oriented synthesis is achieved with a versatile AQ auxiliary α-amino acid analogs offering rapid access to polycyclic spiro-quinolines featuring a quaternary stereocenter in 20%–91% yields under mild conditions via 7,8-dearomatization of quinolines. Free of a preinstalled activation group is highlight of this intramolecular oxidation spiroannulation tandem reaction. This type of N-heterospirocycles, traditionally difficult to access, may open the door to a potentially interest scaffold for synthetic and medicinal chemistry.

Fluoroalcohol-mediated reductive iodonio-Claisen rearrangement： Synthesis of complex ortho-substituted-allyl iodoarenes

Reductive iodonio-Claisen rearrangement （RICR） involving 23-iodanes and allyl or substituted-allyl silanes in fluoroalcohols, such as 1,1,1,3,3,3-hexafluoroi- sopropanol （HFIP） and 2,2,2-trifluoroethanol （TFE）, was studied for the synthesis of complex ortho-allyl or substituted-allyl iodoarenes. In comparison to the pre- viously reported condition involving boron trifluoride diethyl etherate, the RICR mediated by fluoroalcohols was found to proceed more effectively. The resulting complex ortho-allyl iodoarenes are useful synthetic intermediates and can be readily converted to various heterocyclic compounds.

Synthesis of polycyclic spiro-fused indolines via IBX-mediated cascade cyclization

We report a 2-iodoxybenzoic acid(IBX)-mediated intarmolecular oxidative spiro-fused tandem cyclization reaction of tryptophan analogs bearing an N-arylamides side-chain to rapidly afford polycyclic spiroindolines featuring multiple stereocenters including a quaternary stereocenters under mild reaction conditions.Among them,a novelty azaphosphol idine-containing spiroindoline compound is synthesized for the first time.It may open the door to azaphos pholidine-containing spiroindoline compound of potential interest in synthetic and medicinal chemistry.A plausible mechanism is proposed.

An efficient chlorination of aromatic compounds using a catalytic amount of iodobenzene

An efficient method was developed for chlorination of aromatic compounds with electron-donating groups using iodobenzene as the catalyst and m-chloroperbenzoic acid as the terminal oxidant in the presence of 4-methylbenzenesulfonic acid in THF at room temperature for 24 h,and a series of the monochlorinated compounds was obtained in good yields.In this protocol,the catalyst iodobenzene was first oxidized into the hypervalent iodine intermediate,which then treated with lithium chloride and finally reacted with aromatic compounds to form the chlorinated compounds.

PhI(OAc)2-promoted umpolung acetoxylation of enamides for the synthesis of α-acetoxy ketones

Umpolung is a fundamental concept in organic chemistry, which provides an alternative strategy for the synthesis of target compounds which were not easily accessible by conventional methods. Herein, a mild and efficient PhI(OAc)_2-promoted umpolung acetoxylation reactions of enamides was developed for the synthesis of α-acetoxy ketones. The reaction tolerates a wide range of functional groups and affords α-acetoxy ketones in good to excellent yields. PhI(OAc)_2 serves as a source of acetoxy in the reaction.

Skeletal contraction:A novel strategy to access multisubstituted cyclobutane

The polysubstituted and spirocyclic cyclobutanes were efficiently constructed by the utilization of a novel skeletal contraction strategy which only took one-step synthesis from the readily accessible pyrrolidines.The mechanistic studies indicated that a key intermediate N-aminated pyrrolidine was formed initially and subsequent extrusion of a nitrogen via a radical pathway completed the transformation.This practical methodology was further highlighted by the concise,formal synthesis of the cytotoxic natural product piperarborenine B.