New conformationally flexible and recyclable aryl iodine catalysts from inexpensive chiral source for asymmetric oxidations

doi:10.21203/rs.3.rs-2746569/v1

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New conformationally flexible and recyclable aryl iodine catalysts from inexpensive chiral source for asymmetric oxidations

https://doi.org/10.21203/rs.3.rs-2746569/v1

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Despite the remarkable advances in the research field of asymmetric catalytic oxidation reactions via hypervalent iodines with simple procedures, high level of efficiency and stereoselectivity over the past few decades, the development of their highly scalable, environmentally benign, and sustainable protocols under the greener organocatalysis paradigm for further industrial translations remains a long-standing synthetic organic chemistry and process engineering challenge. Herein, we design and synthesize a new library of conformationally flexible and recyclable aryl iodine catalysts by utilization of (i) industrial waste (chloramphenicol base) as the scaffold and (ii) inexpensive amino acid residue (threonine) as the chiral source. Our chiral aryl iodine(III) catalysts bearing H-bond donors and a tunable chiral pocket have been successfully applied in diverse robust asymmetric oxidative transformations, e.g., dearomatization, spirolactonization, direct C(sp²)−H/C(sp³)−H cross-coupling, and fluoridation. Our processes feature a column-isolation-free approach, easy-handling operation, and upscaling synthesis, with the catalysts being facilely recycled in particular via precipitation.

Physical sciences/Chemistry/Chemical synthesis

Physical sciences/Chemistry/Catalysis

Hypervalent iodines, possessing peculiar and unique properties, have lent themselves as versatile, hypotoxic, easy-handling, stable, and environmentally benign oxidants in organic synthesis, leading to numerous achievements of “metal-like” oxidative transformations to access significant scaffolds at the same or even in some cases higher level of efficiency than various transition metals.^1–12 In this matter, asymmetric oxidation reaction utilizing chiral organoiodines have presented themselves as the state-of-the-art field, conveying high applicability and versatility in modern organic synthesis.^13–21 The past decade has witnessed tremendous advancements of enantioselective hypervalent iodine catalysis in asymmetric organocatalytic oxidations, which have turned out to be a challenging research area because of the difficulty in achieving high stereoselectivity at related transition states compared with the metal-catalyzed and enzymatic counterparts.^15–21 Therefore, the development of highly efficient chiral organoiodine catalysts to fulfill various asymmetric transformations and obtain enantiopure structures remains highly desired and sought-after.^22–38

Since the pioneering discovery of a chiral iodoarenes-catalyzed enantioselective α-oxytosylation reported by Wirth and co-workers in 2007,³⁹ a variety of C₁- and C₂-symmetric iodoarenes, chiral spiro iodoarenes, as well as chiral planar iodoarenes have been developed.^17,40−49 Given the emergence of the first C₂-symmetric chiral iodoarene-catalyzed Kita oxidative spirolactonization reported by Ishihara,^40–41 the significant progress for the utilization of these conformationally flexible scaffolds as effective precatalysts to approach diversiform transformations has been well presented due to their suitable chiral environment and in situ-generated intramolecular interactions (Fig. 1A).^22–38 The represented structure of the C₂-symmetric chiral iodoarene is derived from substituted lactate, which may react with the oxidant and substrates to form the helical chiral intermediates (eg: Int-A) via intramolecular n-σ* interactions of the aryl iodine 1 between the Lewis basic group (carbonyl) and the electron-deficient iodine(III) centre, or intramolecular H-bond interactions (eg: Int-B) of catalyst 1 or 2 between the acidic hydrogen and the iodine(III) ligand.^{23,34,50−51} Though these catalyst precursors possess broad applicabilities in numerous exquisite transformations in organic synthesis, some challenges in the catalyst design and preparation remain yet to be solved, limiting the further applications and industrial translations of these catalysts. Synthetically, the large-scale processes to access precatalysts are rare,⁵² especially in the second-generation analogue synthesis (within 7 g), due to the fact that column isolation is unavoidable.^51,53−56 Structurally, the limited conventional chiral source made the reported catalysts possess only one chiral centre, which might decrease the richness and tunability of the catalysts’ chiral environment, leading to inhibition of their synthetic diversity and reactivities. Practicably, all the previous catalysts are unrecoverable without column purification, severely hampering the application of iodine-catalyzed oxidations at the industrial level. Hence, design and synthesis of a new conformationally flexible catalyst library that features facile availability, high reactivity, and recoverability would be absolutely acclaimed.

To approach more ideal chiral organoiodine catalysts, we intent to install an inexpensive chiral source that bearing multi chiral centres on the aryl iodine scaffold (Fig. 1B). Mechanistically, the precatalyst 3 can be oxidized to form the catalyst species Int-C self-assembling an active chiral pocket that its size and catalytic activity can be tuned by the H-bond interactions and the surrounding functional groups. Therefore, a controllable-chiral-pocket-based aryl iodine(III) enables the achievement of numerous highly enantioselective transformations. Naturally, the key to implementation of the above goal is the exploration of a concise, efficient, and scalable synthetic route to access the pivotal structure 4 which can be generated from inexpensive chiral sources. Based on our previous study, chloramphenicol base (ANP, 2-amino-1-(4-nitro-phenyl)propane-1,3-diol), as a privileged and unique chiral scaffold, has been widely applied in asymmetric transformations.^57–60 ANP is the crucial synthon in the industrial production of chloramphenicol (CAP), and only (1R,2R)-ANP is valuable for the construction of antibacterial active isomer of chloramphenicol, while (1S,2S)-ANP is left as a chiral waste. Recycling the industrial waste is conducive to pharmaceutical synthesis and environmental protection; therefore, (1S,2S)-ANP is the excellent and perfect chiral source. In view of the low price and availability of amino acid, threonine might also be a suitable scaffold to approach chiral aryl iodine catalyst.^61–62 Guided by all above-mentioned principles, the key structure 4 could be obtained through an easy-handing and upscaling process, leading to swift construction of the precatalyst library and final access to versatile applications in asymmetric oxidations.

Herein, we have developed a concise, facile, practical, and scalable procedure to access a new library of conformationally flexible aryl iodine catalysts from industrial waste and available chiral amino acid threonine. Significantly, the key intermediate 4 can be obtained in 100 grams scale without column isolation, thereby being smoothly transformed to an aryl iodine library in a large quantity. With our disclosed powerful and recyclable catalysts, various asymmetric oxidative reactions have been achieved, such as oxidative dearomatizations with carbon and oxygen nucleophiles, direct C(sp²)−H/C(sp³)−H oxidative cross-coupling reaction, and fluoridation (Fig. 1C). Our findings do pave a novel, efficient and more sustainable way for asymmetric organocatalytic oxidations with hypervalent iodine(III) catalysts towards more and further industrial scale applications.

General process for upscaling constructions of the aryl iodine precatalyst library. Intrigued by this outlook, we commenced our program on catalyst syntheses. The establishment of aryl iodine precatalyst library started with the previously known and facilely obtained industrial waste (1S,2S)-ANP 5, as summarized in Fig. 2. Thus, amino alcohol 5 was converted to its tert-butyl carbamate 6 in 91% yield and the latter was transformed to the corresponding silyl ether 7 through selective protection at the primary hydroxyl group. Subsequently, a reported Mitsunobu reaction utilizing 2-iodobenzene-1,3-diol 8 and silyl ether 7 enabled approach to the related diether Cat-1 accompanied by an intramolecular substituent aziridine 9. In this step, PPh₃ and DIAD were used in excess, and the separation of Cat-1 should be facilitated by the column isolation due to the complicated mixture of triphenylphosphine oxide, DIAD and its reduced byproduct. Therefore, we attempted to perform a concise S_N2 substitution to afford Cat-1.⁶³ Based on our previous work and experiment phenomena, we found that the scaffold of ANP and its derivates possessed the unique solubility (e.g., slightly soluble in methanol), leading to access a convenient route without column chromatography isolation. The revised procedure began with a protection to afford a cyclic N-Boc sulfamidite, which was subsequently converted to cyclic sulfamidate 10 in 86% yield over three steps from the product 6. An S_N2 substitution of the sodium anion of phenol 8 to the sulfamidate 10 led to a facile nucleophilic cleavage to furnish the intermediate N-sulfate which could be smoothly transformed to the Cat-1 via an acid-quenched step. A subsequent N-Boc deprotected process was readily achieved, resulting in the formation of a key amine structure 11 (> 99.9% ee) up to 106 grams scale. With the high-quality achievement of this upscaling operation, the pivotal scaffold 11 could be successfully transferred to an aryl iodine library bearing abundant of precatalysts with different hydrogen bonds, such as amides Cat-2 to Cat-4 and Cat-6 to Cat-11, ureas Cat-14 to Cat-17, and sulfamides Cat-18 to Cat-21. Moreover, the catalyst bearing the OTBDPS moiety could readily convert to other kind of catalysts, such as the ester (Cat-25 to Cat-34) and ether (Cat-37 to Cat-40) substituted precatalysts (for details, see the Supplementary Information page of P15). In particular, the column chromatograph isolation was unnecessary during the whole purification processes for synthesizing the ANP scaffold derived precatalyst which could be obtained via the recrystallization or precipitation; therefore, our route demonstrated the potential for industrialization. Furthermore, (1R,2R)-ANP could be smoothly utilized to construct the corresponding precatalyst (Cat-24) in high efficiency without column isolation. Notably, D- and L-threonine were also facilely applied to the corresponding aryl iodines (Cat-5, Cat-12 to Cat-13, and Cat-22 to Cat-23) through the similar procedures, and 5-Me/CO₂Me substituted 2-iodobenzene-1,3-diols smoothly reacted with the (1S,2S)-ANP 5 to furnish the related catalysts Cat-35 to Cat-36 (for details, see the Supplementary Information page of P16). The structures of 11 and Cat-8 were confirmed by the single crystal X-ray analysis (for details, see the Supplementary Information Figs. 5 and 6).

Applications of the new conformationally flexible aryl iodine catalyst library in asymmetric oxidations. With the new versatile class of precatalysts in hand, various asymmetric oxidations were consequently explored to verify the utility of the catalyst library. Firstly, the oxidative spirolactonization (Kita reaction)^{40,45,54,64−68} of phenol derivatives, considered as a benchmark reaction for the examination of the catalytic activity of hypervalent iodines, was investigated (Table 1). A series of aryl iodines were loaded to the oxidative conditions, in which m-chloroperbenzoic acid (^mCPBA) was used as oxidant at -30 ℃ (Table 1, Entries 1–7). These demonstrated the 2,4,6-trimethylbenzoyl amide substituted catalyst Cat-8 was the best catalyst leading to access the spirocyclic chiral product 13a in 77% yield with 98% ee (Table 1, Entry 4). Temperature investigations found elevating the temperature to -20 ℃ would increase the yield to 82% without erosion of the ee value (Table 1, Entries 4, 8–9). When the TBDPS substituent on the side arm of the catalyst was changed to the acetyl (Cat-33) with less steric hindrance, the efficiency to access desired product 13a would be decreased (Table 1, Entries 9–10). Solvent investigations demonstrated CH₂Cl₂ was the best solvent in this oxidative transformation (Table 1, Entries 8, 11–12). When five equivalent amounts of ethanol were added as additive to stabilize the hypervalent iodine(III) intermediate,⁵⁴ the product 13a would be furnished in 92% yield with 98% ee (Table 1, Entry 13). The fewer amount of precatalyst was loaded, the lower yield of compound 13a was afforded (Table 1, Entries 13–15). Increasing the solvent concentration led to slight reduction of the enantioselectivity (Table 1, Entry 16).

With the optimized conditions in hand, we examined the scope of the Kita reaction (Table 2). We initiated our efforts with substituted 3-(1-hydroxynaphthalen-2-yl)propanoic acids 12 to this transformation. 4-Halogeno substituted substrates were smoothly converted to the desired products in high yields with excellent enantioselectivities (Table 2, 13b-13c). The feedstocks bearing electron-withdrawing groups (EWGs), such as benzoyl and acetyl, were successfully transformed to the products 13d-13e in good chemical yields with high enantioselectivities. The 1-naphthol derivatives substituted with both 4-phenyl and 4-benzyl were tolerant of the standard conditions leading to access the desired products with 96% ee and good chemical yields (Table 2, 13f-13g). The utilization of other substrates bearing 4-alkyl and 6-methoxyl gave the corresponding products 13h-13l in moderate to high yields with excellent enantioselectivities. Subsequently, 3-(2-hydroxynaphthalen-1-yl)propanoic acids containing different kinds of functional groups were well tolerated to generate the counterparts 13m-13o in good yields with excellent ee values. Gratefully, gram-scale operation was successfully achieved by using lower catalyst loading of Cat-8 (5 mol%), leading to access 13a in 1.19 g with 80% yield and 99% ee via recrystallization along with recovery of the precatalyst in 96% yield (for details, please see the Supplementary Information page of P50). Moreover, the corresponding catalyst Cat-24 and Cat-22 prepared from (1R,2R)-ANP and L-threonine could facilely be utilized to this reaction system, leading to the generation of products 13g and 13i with opposite configuration in high efficiency, respectively. Importantly, our designed conformationally flexible chiral organoiodine(III) catalyst could also be applied to the oxidative cyclization of alcohols. Because of substrates incorporating EWGs presenting higher reactivity in Ciufolini’s work,⁶⁸ we focused on investigation of the lower reactive compounds bearing electron-donating groups (EDGs). All these substrates with EDGs could produce the desired products 14b-14f and 14j in moderate to high yield with excellent enantioselectivities. Compared with the reported catalysts, our catalyst presented the highest efficiency in this transformation (14g-14i) illustrating the proposed transition state would be more stable to inhibit its dissociation, which might result from its peculiar chiral pocket and intramolecular H-bond interactions.

Encouraged by the high efficiency of our developed catalyst in the oxidative dearomatization of substituted naphthols, we continued to expand applications of our catalyst library to other type of transformations (Table 3). Firstly, the C-attacked asymmetric spirocyclization of 1-hydroxy-N-aryl-2-naphthamide derivatives 15 was further employed to access functionalized spirooxindoles 16 bearing an all-carbon stereogenic center (Table 3 − 1). In this reaction, the selected precatalyst Cat-9 displayed the outstanding reactivity to furnish the desired products 16a-16d in moderate to good yields with excellent enantioselectivities under milder conditions (-10 ^oC) by using ^mCPBA as oxidant, trifluoroethanol (TFE) and water as additives, and nitromethane as solvent (for details, please see the Supplementary Information Table 2). Therefore, our catalyst possessed higher stereoselective efficiency than the previous catalyst reported by Gong and coworkers,⁶⁹ which further demonstrated the H-bond donor and the multiple tunable site installed on the chiral pocket were necessary. To facilitate the diversified application of our catalyst library, the direct C(sp²)−H/C(sp³)−H cross-coupling was subsequently engaged (Table 3 − 2), in which the anilide derivatives 17 was smoothly transformed to the spirooxindoles 18 by utilizing pivalamido-substitued precatalyst Cat-3, ^mCPBA as oxidant, CF₃CO₂H and H₂O as additives, and acetonitrile as solvent at room temperature (for details, please see the Supplementary Information Table 3). In this scenario, the more secure and available oxidant ^mCPBA was employed to replace CH₃CO₃H that was loaded in the previous work.²² The confused spirooxindoles 18a-18f could be furnished in moderate to high yields (41%-80%) with high enantioselectivities (82%-90% ee). Hence, our developed iodine catalyst further possessed high reactivity and practicability.

The installation of fluorine atom on organic molecules is a significant approach towards the adjustment of molecular properties, such as lipophilicity, membrane permeability, biokinetics, and biodynamics, within agrochemicals, pharmaceuticals, and materials.^70–75 Furthermore, hypervalent iodine catalysis has been successfully utilized in asymmetric fluorination, which provides a concise and inexpensive approach to access potential pharmaceuticals. Therefore, the development of new catalyst to achieve the formation of chiral fluorinated molecules is unquestionably beneficial. Our catalyst library was subsequently loaded to the enantioselective fluorination of keto esters 19.^46,76 To our delight, the aryl iodine Cat-38 bearing large steric hindrance groups was the optimized catalyst to access the asymmetric fluorination with high efficiency, in which 2,4,6-tribromobenzoyl and triphenylmethyl (Trt) were substituted on the amine and ether moieties, respectively (for details, please see the Supplementary Information Table 4). Hence, the excellent ee values and moderate yields of desired products 20a-20k could be obtained.

Catalyst recovery and recycling experiments in the oxidative dearomatization. Inspired by the concise and utility procedure of catalyst construction, the recovery and recycle of our developed catalyst might be feasible. A significant step in the evaluation of the sustainability characteristics of the precatalyst Cat-8 was the assessment of its recyclability (Table 5). To this end, a sample of Cat-8 was repeatedly utilized in the reaction of substrate 12a in the presence of ^mCPBA, ethanol, and CH₂Cl₂. At the end of each reaction of the cycle, the reaction mixture was quenched in the sequence of saturated Na₂S₂O₃ and NaHCO₃ aqueous solution. The organic layer was then extracted with CH₂Cl₂, washed with brine, dried over anhydrous Na₂SO₄. The mixture was concentrated in vacuo, the residue was subsequently dissolved by 30 mL of MeOH, H₂O (10 mL) was finally added to precipitate the catalyst which could enter the next cycle. The filtrate was concentrated in vacuo to get the crude product which could be further recrystallized by the mixture (10 mL, 1:300 volume ratio) of ethyl acetate and petroleum ether (for details, please see the Supplementary Information page of P48). Delightfully, Cat-8 presented greatly high reactivity and selectivity in 10 consecutive cycles, therefore indicating high robustness. Notably, aryl iodine Cat-8 was easily and efficiently recovered from reaction mixture with high efficiency (all cycles > 96% yield) over the whole operation period, while enantiospecificity of product 13a steadily maintained in 97% ee. Some 5.37 g (combined weight) of pure 13a was isolated over ten-cycle operations, which represented an accumulated TON of 83.6. These implements demonstrated our designed catalysts possessed high potential for industrial applications.

Investigation of the significance for H-bond interactions and a tunable chiral pocket. Based on our designed strategy to construct chiral aryl iodine catalyst, both the H-bond interaction and the tunable chiral pocket are essential (Fig. 1b, Int-C). To validate our hypothesis, the controlled experiments were conducted in turn (Table 6). Firstly, when the N−H bonds of the amide moiety on the optimized catalysts (Cat-41, Cat-43, Cat-45, and Cat-47) were changed to N−Me bonds, the yield and enantioselectivity of the corresponding products (13a, 16a, 18a, and 20a) would sharply decline, indicating the H-bond interactions in the key species were fundamental. D-threoninol derived aryl iodine catalysts (Cat-12, Cat-13, Cat-5, and Cat-48) were then applied to replace the (1S,2S)-ANP substituted analogues, leading to slight or dramatic decrease of the reactivities and enantioselectivities. These demonstrate that multi chiral centers were significant for the new catalyst scaffold. Finally, when the substituent R² (CH₂OTBDPS or CH₂OTrt) on the side arm of related catalysts (Cat-8, Cat-9, Cat-3, and Cat-38) were replaced by H atom (Cat-42, Cat-44, Cat-46, and Cat-49), the ee values of desired products would be reduced dramatically in most cases, which indicated that the chiral pocket forming from the structure of multi chiral centers via self-assembly was essential. Hence, both the H-bond interactions and tunable chiral pocket were indispensable for these types of catalyst skeleton.

In conclusion, we have developed a versatile and efficient synthetic process that allows the construction of various new conformationally flexible and recyclable aryl iodine catalysts bearing H-bond donors and a tunable chiral pocket. The synthesis of the key intermediate for the formation of catalyst library can be upscaled to more than 100 grams and is column-isolation free. Furthermore, our designed catalysts have achieved a series of highly enantioselective oxidative transformations, for example, C-/O-attacked intramolecular asymmetric dearomatization, direct C(sp²)−H/C(sp³)−H oxidative cross-coupling and fluoridation, to synthesize valuable functionalized products from different types of feedstocks. The catalyst recycling experiments and gram-scale operations of catalyst preparation are smoothly carried out to validate the great practicability of our protocol. Control experiments demonstrate that H-bond donors and the tunable chiral pocket are essential components for the aryl iodine catalysts. The promising utilities of these classes of chiral aryl iodine scaffolds in catalytic asymmetric oxidations and pharmaceutical syntheses are currently under investigation in our laboratories and will be reported in due course.

General methods. See Supplementary Methods for further details.

Representative procedure for the synthesis of oxidative dearomatization products 13. To a Schlenk tube containing Cat-8 (0.03 mmol, 15 mol%), ^mCPBA (0.3 mmol, 1.5 equiv.), and EtOH (1 mmol, 5 equiv.) were added CH₂Cl₂ (10 mL) and 12 (0.2 mmol, 1.0 equiv.), the reaction mixture was stirred at 0 to -20°C for 24–80 hours, which was then quenched in the sequence of saturated Na₂S₂O₃ and NaHCO₃ aqueous solution. The organic layer was subsequently extracted with CH₂Cl₂, washed with brine, dried over anhydrous Na₂SO₄. Finally, the mixture was concentrated in vacuo, and then the residue was purified by silica gel column chromatography to afford the product 13.

Representative procedure for the synthesis of oxidative spirolactonization products 16. To a Schlenk tube containing Cat-9 (0.03 mmol, 15 mol%), ^mCPBA (0.26 mmol, 1.3 equiv.), TFE (10 mmol, 50 equiv.), H₂O (2 mmol, 10 equiv.) and MeNO₂ (3 mL) were added 15 (0.2 mmol, 1.0 equiv.), the reaction mixture was stirred at -10°C for 72 hours, which was then quenched in the sequence of saturated Na₂S₂O₃ and NaHCO₃ aqueous solution. Finally, the organic layer was subsequently extracted with ethyl acetate, washed with brine, dried over anhydrous Na₂SO₄. The mixture was concentrated in vacuo, and then the residue was purified by silica gel column chromatography to afford the product 16.

Representative procedure for the synthesis of direct C(sp ² )-H/C(sp ³ )-H cross-coupling products 18. To a Schlenk tube containing Cat-3 (0.03 mmol, 15 mol%), ^mCPBA (0.52 mmol, 2.6 equiv.), TFA (0.6 mmol, 3 equiv.) and H₂O (0.6 mmol, 3 equiv.) and MeCN (3 mL) were added 17 (0.2 mmol, 1.0 equiv.), the reaction mixture was stirred at 25°C for 16 hours, which was then quenched in the sequence of saturated Na₂S₂O₃ and NaHCO₃ aqueous solution. The organic layer was subsequently extracted with ethyl acetate, washed with brine, dried over anhydrous Na₂SO₄. Finally, the mixture was concentrated in vacuo, and then the residue was purified by silica gel column chromatography to afford the product 18.

Representative procedure for the synthesis of fluorinated keto esters 20. To a Teflon tube containing β-ketoesters 19 (0.20 mmol, 1.0 equiv.), Cat-38 (0.03 mmol, 15 mol%), and CHCl₃ (8 mL) were added NEt₃∙3HF (2 mmol, 10 equiv.) and ^mCPBA (0.3 mmol, 1.5 equiv.) in turn, the reaction mixture was stirred at 25°C for 24–72 hours, which was then quenched in the sequence of saturated Na₂S₂O₃ and NaHCO₃ aqueous solution. The organic layer was subsequently extracted with CH₂Cl₂, washed with brine, dried over anhydrous Na₂SO₄. Finally, the mixture was concentrated in vacuo, and then the residue was purified by silica gel column chromatography to afford the desired product 20.

Data availability. The X-ray crystallographic coordinates for structures reported in this study have been deposited at the Cambridge Crystallographic Data Centre (CCDC), under deposition number CCDC 2236217 (Cat-8) and CCDC 2236218 (11). These data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.The authors declare that all data supporting the findings of this study are available within the article and Supplementary Information files, and are also available from the corresponding author on reasonable request.

Acknowledgements

This work was supported by the National Natural Science Foundation of China (No. 22208302), and the Natural Science Foundation of Zhejiang Province of China (Nos. LQ21B020006, ZJ2022039). We thank Dr. Wai-Lun Chan for helpful discussions, as well as proof reading of the manuscript and Supporting Information.

Author contributions

X.X. and F.-E.C. designed the project. X.X. and H.-J.Z. designed and carried out the experiments. Y.-P.Y., X.W., B.C., H.Z., and J.-A.C. contributed to part experiments. X.X. and F.-E.C. discussed the results, contributed to writing the manuscript, and commented on the manuscript. All authors approved the final version of the manuscript for submission.

Additional information

Competing ﬁnancial interests: The authors declare no competing ﬁnancial interests.

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Tables 1 to 6 are available in the Supplementary Files section.

There is NO Competing Interest.

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New conformationally flexible and recyclable aryl iodine catalysts from inexpensive chiral source for asymmetric oxidations. A concise, scalable and efficient process has been well established to access new conformationally flexible aryl iodine catalyst library by utilizing industrial waste and available amino acid as chiral source. These designed catalysts have been extensively loaded to a series of highly enantioselective oxidative transformations, such as C-/O-attacked intramolecular asymmetric dearomatization, direct C(sp²)-H/C(sp³)-H oxidative cross-coupling and fluoridation, leading to access various valuable molecules. Moreover, these catalysts can be facilely recycled, thereby possessing the potential for industrialization.
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New conformationally flexible and recyclable aryl iodine catalysts from inexpensive chiral source for asymmetric oxidations

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