Chiral Iodoarenes Research Articles

Oxidative Remote Aryl Rearrangement of N-Cinnamyl-N-alkoxybenzyl Sulfonamides Using Hypervalent Iodine(III).

An oxidative remote aryl rearrangement of N-cinnamyl-N-alkoxybenzyl sulfonamides with a hypervalent iodine(III) compound was developed to furnish 5,6-disubstituted 1,3-oxazinanes in high yields. This reaction proceeded through the dearomatization of the alkoxybenzene ring on the benzyl group, which acts as a good aryl donor, inducing the regioselective installation of the aryl group and the oxygen atom via cascade transformation. An enantioselective oxidative remote aryl rearrangement using C2-symmetrical chiral iodoarene gave enantioenriched products with high enantioselectivity.

Electrochemical Asymmetric Diacetoxylation of Styrenes Mediated by Chiral Iodoarene Catalyst**

AbstractOrganocatalysis with chiral iodoarenes has emerged as a powerful approach for performing enantioselective transformations. However, it suffers from the need to utilize stoichiometric amounts of peroxy acids or similar high energy oxidants. Electrosynthesis enables eliminating stoichiometric redox reagents by replacing them with electric stimuli. In this context, an electrochemically‐promoted variant of the chiral iodoarene‐catalyzed asymmetric diacetoxylation of styrenes was evaluated. The screening of reaction parameters established a set of conditions under which, for the first time, an enantioselective electrochemical oxidation mediated by a chiral iodoarene achieving a catalytic turnover has been accomplished. The reaction was applied for the synthesis of an array of products in 15–60 % yields and 0–84 % ee. The modest efficiency of the electrocatalysis was traced to a partial direct oxidation of styrene substrates leading to racemic products and undesired dimeric side‐products. Cyclic voltammetry measurements demonstrated that such outcome originates from a somewhat difficult electrochemical oxidation of the applied iodoarene catalyst. Present work provides important insights and implications for the design of more efficient electrocatalytic systems employing chiral iodoarenes as mediators.

Iodine(III)-Mediated Enantioselective Oxidative Contraction of Dihydropyranones.

The γ-butyrolactone motif is promising in pharmaceuticals and natural products with various biological activities. The oxidative contraction of dihydropyranones mediated by hypervalent iodine (HVI) reagents is an efficient approach of preparing this motif. We show that, using readily available chiral HVI reagents, numerous enantioenriched γ-butyrolactones are accessible. The method provides generally high enantioselectivities and modest to high yields. The resulting chiral iodoarene is easily recovered and reused for the reaction multiple times, without loss of yield or enantioselectivities.

Synthesis of optical active tetramethyl-1,1′-spirobiindane-based iodoarenes and evaluation of their use as axially chiral organocatalysts

Three novel axially chiral iodoarenes based on the tetramethyl-1,1′-spirobiindane skeleton were successfully prepared starting from Bisphenol A. The reactivity and selectivity were evaluated in the asymmetric oxidative formation of CN bonds through an intramolecular desymmetrization strategy, resulting in ee’s up to 92% with high yield.

Sulfur-Based Chiral Iodoarenes: An Underexplored Class of Chiral Hypervalent Iodine Reagents

AbstractChiral hypervalent iodine reagents are active players in modern stereoselective organic synthesis. Structurally diverse chiral hypervalent iodine reagents have been synthesised and extensively studied, but hypervalent iodine reagents containing chiral sulfur stereogenic centre are scarce and their synthesis is challenging. A small library of iodoarenes containing chiral sulfinamide and chiral sulfoximine moieties has been synthesised using commercially available reagents. The oxidation of the chiral iodoarene precursors to iodine(III) reagents was cumbersome due to facile overoxidation of the sulfoxide moiety and hence loss of chirality under various oxidation conditions. Oxidation of chiral sulfonimidoyl derivatives to the corresponding hypervalent iodine reagents was successful and led to novel sulfur-based chiral iodine(III) reagents.

Aminolactonization of Unactivated Alkenes Catalyzed by Aryl Iodine.

A one-step protocol of the aryl iodine-catalyzed aminolactonization of unactivated alkenes under oxidation conditions was first reported to efficiently construct diverse amino lactones in a short time using HNTs2 as the compatible nitrogen source. In addition, we investigated the influence of the reaction rate based on the structure of the iodoarene precatalyst, which revealed the selective adjustment effect on aminolactonization and oxylactonization. Finally, preliminary experiments verified the feasibility of asymmetric aminolactonization catalyzed by a chiral iodoarene precatalyst.

C−N Axial Chiral Hypervalent Iodine Reagents: Catalytic Stereoselective α‐Oxytosylation of Ketones

A simple synthesis of a library of novel C−N axially chiral iodoarenes is achieved in a three‐step synthesis from commercially available aniline derivatives. C−N axial chiral iodine reagents are rarely investigated in the hypervalent iodine arena. The potential of the novel chiral iodoarenes as organocatalysts for stereoselective oxidative transformations is assessed using the well explored, but challenging stereoselective α‐oxytosylation of ketones. All investigated reagents catalyse the stereoselective oxidation of propiophenone to the corresponding chiral α‐oxytosylated products with good stereochemical control. Using the optimised reaction conditions a wide range of products was obtained in generally good to excellent yields and with good enantioselectivities.

Design and synthesis of chiral urea-derived iodoarenes and their assessment in the enantioselective dearomatizing cyclization of a naphthyl amide

Abstract A novel family of urea-derived chiral iodoarenes was designed and synthesized for use in enantioselective iodine(I/III) catalysis. Their preparation required the development of a bidirectional synthetic strategy. These new chiral iodoarenes were assessed as catalysts in the dearomatizing cyclization of a naphthyl amide and provided moderate yields of product in some cases with low enantioselectivities.

Hypervalent Iodine(III)-Catalysed Enantioselective α-Acetoxylation of Ketones.

An enantioselective catalytic synthesis of α‐acetoxylated ketones through I(I)/I(III) catalysis using a resorcinol/lactamide‐based chiral iodoarene is reported. Catalyst turnover by in situ generation of the active iodine(III) derivative is achieved by oxidation with mCPBA in the presence of acetic acid. The prior transformation of ketones to easily accessible acetyl enol ethers is beneficial and yields up to 97 % with enantioselectivities up to 88 % ee are obtained using only low catalyst loadings of only 5 mol % under mild reaction conditions.

An Enantioconvergent Benzylic Hydroxylation Using a Chiral Aryl Iodide in a Dual Activation Mode

The application of a triazole-substituted chiral iodoarene in a direct enantioselective hydroxylation of alkyl arenes is reported. This method allows the rapid synthesis of chiral benzyl alcohols i...

Carbohydrate-Based Chiral Iodoarene Catalysts: A Survey through the Development of an Improved Catalyst Design.

Iodoarene catalysts can be applied in versatile reactions, for instance in the construction of complex chiral molecules via dearomatization of simple aromatic compounds. Recently, we reported the synthesis of the first carbohydrate-based chiral iodoarene catalysts and their application in asymmetric catalysis. Here we describe the synthesis of some new and improved catalysts. An account on how we got to the improved catalyst design, as well as the X-ray structure of one of the carbohydrate-based iodoarenes, is given.

Enantioselective Intramolecular Dearomative Lactonization of Naphthols Catalyzed by Planar Chiral Iodoarene

A series of planar chiral iodoarenes based on [2.2]paracyclophane was synthesized. An efficient asymmetric intramolecular oxidative lactonization of naphthols enabled by a combination of these chiral iodoarenes and mCPBA as oxidant is reported. This reaction proceeds under mild conditions, allowing the formation of spirolactones bearing a tetrasubstituted stereocenter in moderate yields and good enantioselectivity.

Carbohydrate based chiral iodoarene catalysts for enantioselective dearomative spirocyclization

Organocatalysis using chiral iodoarenes enables many different enantioselective chemical reactions with cheap, easily accessible and robust catalysts. Carbohydrates have often been used as starting materials for the synthesis of chiral ligands for transition metal catalysts. Here, we now present the synthesis of the first carbohydrate based iodoarene catalysts which can be synthesized in one step starting from known compounds. These catalysts were used for oxidative spriolactonization of 3-(1-hydroxynaphthalen-2-yl)propanoic acid to afford the corresponding spirolactone in yields up to 77% and enantiomeric ratios er up to 80:20.

Synthesis of [7]Helicene Enantiomers and Exploratory Study of Their Conversion into Helically Chiral Iodoarenes and Iodanes.

The facile and convenient preparation of both enantiomers of a [7]helicene scaffold from inexpensive (l)-(+)-tartaric acid and 4-methylstyrene is described. These helical structures were transformed into bis-iodinated ether derivatives in order to explore their potential as precursors of novel chiral organoiodane reagents or as iodoarene pre-catalysts. Promising results were obtained in hydroxylative phenol dearomatization/[4+2] cycloaddition cascade and dearomative spirolactonization reactions with encouraging enantiomeric excesses.

Enantioselective Electrochemical Lactonization Using Chiral Iodoarenes as Mediators

The enantioselective electrochemical lactonization of diketo acid derivatives using chiral iodoarenes as redox mediators is reported for the first time. Good to high stereoselectivities are observed in the lactonization and also in intermolecular α-alkoxylations of diketo ester derivatives. This enantioselective process was then adapted to an electrochemical flow microreactor where only small amounts of supporting electrolyte were necessary.

Recent advances in hypervalent iodine(III)-catalyzed functionalization of alkenes

Hypervalent iodine(III) reagents have been well-developed and widely utilized in functionalization of alkenes, however, generally either stoichiometric amounts of iodine(III) reagents are required or stoichiometric oxidants such as mCPBA are employed to in situ generate iodine(III) species. In this review, recent developments of hypervalent iodine(III)-catalyzed functionalization of alkenes and asymmetric reactions using a chiral iodoarene are summarized.

Development of Planar Chiral Iodoarenes Based on [2.2]Paracyclophane and Their Application in Catalytic Enantioselective Fluorination of β-Ketoesters.

The design and synthesis of novel planar chiral iodoarenes based on [2.2]paracyclophane is reported. A process of highly enantioselective oxidative fluorination of a β-ketoester with 3HF-Et3N as a nucleophilic fluoride source mediated by these new hypervalent iodine catalysts has been developed. This represents the first highly enantioselective reaction catalyzed by planar chiral hypervalent iodine.

Metal-Free Catalytic Asymmetric Fluorination of Keto Esters Using a Combination of Hydrogen Fluoride (HF) and Oxidant: Experiment and Computation

A chiral iodoarene organocatalyst for the catalytic asymmetric fluorination has been developed. The catalyst was used in the asymmetric fluorination of carbonyl compounds, providing the products with a quaternary stereocenter with high enantioselectivities. Chiral hypervalent iodine difluoride intermediates were generated in situ by treatment of the catalyst with an oxidant and hydrogen fluoride as fluoride source. As such, the α-fluorination of a carbonyl compound was achieved with a nucleophilic fluorine source. A combined computational and experimental approach provided insight into the reaction mechanism and the origin of enantioselectivity.

Modular Synthesis of Triazole‐Based Chiral Iodoarenes for Enantioselective Spirocyclizations

AbstractA new triazole‐based C1‐symmetrical chiral iodoarene was synthesized in a highly modular route. Based on enzymatic kinetic resolution of an easily accessible propargylic alcohol both enantiomers were accessible in enantiopure form. By Huisgen‐type azide‐alkyne cycloaddtion a series of differently substituted iodoarenes was synthesized in high overall yields. Finally this novel iodoarene was successfully applied in the oxidative Kita cyclization of naphthol derivatives. Good yields and high ee values were obtained in the asymmetric spirocyclization via in situ generation of the hypervalent iodine species using mCPBA as the terminal oxidant.magnified image

Cover Picture: Modular Synthesis of Triazole‐Based Chiral Iodoarenes for Enantioselective Spirocyclizations (Adv. Synth. Catal. 17/2017)

The inside cover picture, provided by Pericàs and Nachtsheim, illustrates the development of novel C1-symmetric iodoarenes as precursors for chiral aryl-λ3-iodanes. The synthesis of these structures is highly modular and allows easy modification on all major substituents, namely the arene, the alkyl ether and the terminal triazole. This is not only the first example for a triazole-based chiral iodoarene but also the so far most efficient C1-symmetric catalyst for the oxidative enantioselective spirocyclization of 1-naphtholcarboxylic acids to spirolactones. Details can be found in the full paper on pages 2931–2941 (C. Hempel, C. Maichle-Moessmer, M. A. Pericàs, B. J. Nachtsheim, Adv. Synth. Catal. 2017, 359, 2931–2941; DOI: 10.1002/adsc.201700246).