Enantioselective Decarboxylative Arylation of α-Amino Acids via the Merger of Photoredox and Nickel Catalysis.

Transition metal-catalyzed cross-coupling reactions have become one of the most utilized carbon–carbon and carbon–heteroatom bond-forming reactions in chemical synthesis. More recently, nickel catalysis has been shown to participate in a wide variety of C–C bond forming reactions, most notably Negishi, Suzuki–Miyaura, Stille, Kumada, and Hiyama couplings1,2. Despite the tremendous advances in C–C fragment couplings, the ability to forge C–O bonds in a general fashion via nickel catalysis has been largely unsuccessful. The challenge for nickel-mediated alcohol couplings has been the mechanistic requirement for the critical C–O bond forming step (formally known as the reductive elimination step) to occur via a Ni(III) alkoxide intermediate. In this manuscript, we demonstrate that visible light-excited photoredox catalysts can modulate the preferred oxidation states of nickel alkoxides in an operative catalytic cycle, thereby providing transient access to Ni(III) species that readily participate in reductive elimination. Using this synergistic merger of photoredox and nickel catalysis, we have developed a highly efficient and general carbon–oxygen coupling reaction using abundant alcohols and aryl bromides. More significantly, we have developed a general strategy to “switch on” important yet elusive organometallic mechanisms via oxidation state modulations using only weak light and single-electron transfer (SET) catalysts.

A ligand-free cross-coupling of vinyl halides and α-silylamines toward tertiary allylic alkylamines by merging nickel and photoredox catalysis is developed. A variety of (E)-vinyl electrophiles including conjugate divinyl halides and sterically hindered vinyl halides are coupled smoothly with α-silylamines to afford allylic amines under mild conditions with good yields and E-selectivity. Moreover, by simply modifying the photocatalyst or prolonging the irradiation time, the reaction can afford Z-selective allylic amines as major products via photochemically driven E → Z isomerization. This radical-based coupling strategy provides an alternative and efficient pathway to construct tertiary allylic alkylamines with good and tunable Z/E selectivity.

Key words late-stage modification - phosphotyrosine mimetics - photoredox catalysis - nickel catalysis - chloroalkyl compounds

Key words alkynyl bromides - nickel catalysis - phosphonates - photoredox catalysis - reductive cross-coupling

Key words acetate - alkyl thiols - aryl chlorides - cross-coupling - nickel catalysis - thioethers

Review: 12 refs.

The report of a light-activated catalyst that generates usually inaccessible nickel intermediates provides a general strategy that might allow elusive catalytic reactions to be realized. See Letter p.330 Despite advances in carbon–carbon fragment couplings, the ability to create carbon–oxygen bonds via nickel catalysis has been largely unsuccessful. Here David MacMillan and colleagues show that visible-light-excited photoredox catalysts can provide transient access to Ni(III) species that readily participate in reductive elimination. Using this synergistic merger of photoredox and nickel catalysis, the authors develop a highly efficient and general carbon–oxygen coupling reaction using alcohols and aryl bromides.

Open AccessCCS ChemistryCOMMUNICATION1 May 2022Nickel-Catalyzed Reductive Asymmetric Aryl-Acylation and Aryl-Carbamoylation of Unactivated Alkenes Youxiang Jin, Pei Fan and Chuan Wang Youxiang Jin Hefei National Laboratory for Physical Science at the Microscale and Department of Chemistry, University of Science and Technology of China, Hefei, Anhui 230026 , Pei Fan Hefei National Laboratory for Physical Science at the Microscale and Department of Chemistry, University of Science and Technology of China, Hefei, Anhui 230026 School of Chemical and Materials Engineering, Huainan Normal University, Huainan, Anhui 232038 and Chuan Wang *Corresponding author: E-mail Address: [email protected] Hefei National Laboratory for Physical Science at the Microscale and Department of Chemistry, University of Science and Technology of China, Hefei, Anhui 230026 Center for Excellence in Molecular Synthesis of CAS, Hefei, Anhui 230026 https://doi.org/10.31635/ccschem.021.202101040 SectionsSupplemental MaterialAboutAbstractPDF ToolsAdd to favoritesDownload CitationsTrack Citations ShareFacebookTwitterLinked InEmail Herein we report a nickel-catalyzed asymmetric two-component reductive aryl-acylation and aryl-carbamoylation of aryl-iodide-tethered unactivated alkenes, which utilize ortho-pyridinyl esters and isocyanates as the electrophilic acyl sources, respectively. Under the catalysis of a nickel–pyrox complex with zinc powder as the reductant, a variety of chiral indanes, indolines, and dihydrobenzofurans bearing a quaternary stereogenic center were prepared in moderate to high efficiency and good to excellent enantioselectivities. The utility of this method is demonstrated by various simple derivatizations of the attached carbonyl group, particularly the sequential benzylic oxidation and pinacol coupling, which provide a concise entry to the benzene-fused bicyclic bridged ring framework containing three challenging tetrasubstituted stereocenters in high stereocontrol. Download figure Download PowerPoint Introduction In the last decade, transition metal-catalyzed enantioselective dicarbofunctionalizations of tethered alkenes have evolved into a reliable method to construct the scaffold of chiral benzene-fused cyclic compounds.1–6 The majority of these reactions rely on a facially selective Heck-type arylmetallation of the pendant olefinic unit as the enantiodetermining step,7 followed by trapping of the generated σ-alkyl metal species with either a nucleophile or an electrophile. Based on this strategy, asymmetric aryl-alkylation,8–10 diarylation,10–13 aryl-benzylation,14 aryl-alkenylation,15,16 and aryl-alkynylation13,17,18 of incorporated alkenes have been developed under palladium, copper, or nickel catalysis. As an important subset of various dicarbofunctionalization reactions, olefin aryl-acylation or aryl-carbamoylation allows for the synthesis of structurally complex carbonyl compounds directly starting from alkenes, and considerable progress has been accomplished in this domain.19–34 However, enantioselective variants of these reactions are still rare.31–34 In 2012, Dong et al.31 reported a one-component asymmetric version of aryl-acylation of alkenes employing strained benzocyclobutanones with a pendant olefinic unit as the precursors, which was efficiently catalyzed by a chiral rhodium complex (Figure 1a, equation 1). In recent years, Correia32 and Guan33 developed palladium-catalyzed carbonylative Heck reactions using carbon monoxide in combination with aryl boronic acids or anilines as the terminating agents, providing a series of highly enantioenriched carbonyl-containing dihydrobenzofurans and oxindoles (Figure 1a, equation 2). Very recently, Ye and co-workers34 described a nickel-catalyzed olefin aryl-carbamoylation, which successfully converted carbamoyl-fluoride-tethered alkenes and aryl boronic acids into a wide range of chiral γ-lactams in a highly enantioselective manner (Figure 1a, equation 3). Figure 1 | Asymmetric aryl-acylation and aryl-carbamoylation of tethered alkenes. Download figure Download PowerPoint The three aforementioned general approaches for asymmetric aryl-acylation or aryl-carbamoylation in the redox-neutral reaction pathway are plagued by one or more of the following disadvantages: (1) the requirement of preformation of organometallics; (2) the high cost of noble metal (rhodium or palladium) as the catalyst; (3) the use of highly toxic odorless carbon monoxide gas, which is arguably undesirable on the laboratory scale of synthesis; and (4) basic reaction conditions leading to incompatibility of base-sensitive functionalities. To address the issues mentioned above, we turned our attention to establish a reductive strategy35–42 for asymmetric aryl-acylation and aryl-carbamoylation that could avoid the use of pregenerated organometallics by using earth-abundant nickel as the catalyst under base-free conditions. We envisioned that the target reaction would be achieved via the use of an appropriate electrophilic acyl source as a coupling partner in the reaction with aryl-halide-tethered alkenes under the reductive catalysis of a chiral nickel catalyst with a stoichiometric reductant. This reductant would offer a new entry to prepare benzene-annulated cyclic compounds bearing a synthetically useful carbonyl group in an asymmetric fashion (Figure 1b). Results and Discussion Optimization First, we focused on the development of asymmetric olefin aryl-acylation. To realize the target reaction, we initially screened various electrophilic acylating agents including the ortho-pyridinyl ester 2a,43,44 the acid chloride 2a- 1,45–50 the acid fluoride 2a- 2,51 the acid anhydride 2a- 3,52–54 the thioester 2a- 4,55,56 and the activated amide 2a- 5,57 which have proven successful in different cross-electrophile coupling reactions43–57 (Table 1). These reactions with the aryl-iodide-tethered alkene 1a as the coupling partner were performed in DMA at 40 °C using NiBr2·glyme as a precatalyst, the chiral Pyrox L1 as a ligand, and Zn as a reductant. The best outcome in terms of both efficiency and asymmetric induction was achieved in the case of the ortho-pyridinyl ester 2a wherein the desired product 3aa was obtained in 25% yield and 95% ee. Table 1 | Preliminary Screening of the Electrophilic Acylating Agentsa–c aUnless otherwise specified, reactions were performed on a 0.2 mmol scale of the aryl-iodide-tethered alkene 1a using 2.0 equiv of electrophilic acylating agents 2a–2a- 5, 10 mol % NiBr2·glyme, and 15 mol % Pyrox L1 in 0.5 mL DMA at 40 °C for 12 h. bYields of isolated product through column chromatography. cEnantiomeric excesses were determined by High-Performance Liquid Chromatography (HPLC) analysis on a chiral stationary phase. Encouraged by these initial results, we continued to optimize the reaction conditions by varying various reaction parameters (Table 2). To improve the reaction efficiency, we first conducted the reaction at a higher temperature. Indeed, the yield was elevated to 31% while the enantioselectivity remained high (Entry 1). Subsequently, a series of chiral ligands were examined for the studied reaction (Entries 2–10). In general, the Pyrox and bis(oxazoline) (BiOX) ligands L2– 8 were able to promote the desired reaction in moderate yields and enantiomeric excesses ranging from 31% to 89% (Entries 2–8). In contrast, the reactions employing the bis(oxazoline)-pyridine (PyBOX) L9 or phosphine–oxazoline (PHOX) L10 as a ligand failed to deliver compound 3aa (Entries 9 and 10). Next, several Ni(II) salts and bis(cyclooctadiene)nickel(0) (Ni(COD)2) were surveyed (Entries 11–14), and the highest enantioselectivity was achieved in the case of NiBr2·diglyme (Entry 14). In this case, the yield was also increased to 38%. Although the reaction using Ni(COD)2 gave the best yield, the enantiomeric excess diminished to 92% (Entry 13). At this juncture, we decided to carry out the reaction with 2 equiv of the alkene 1a, which turned out to have a high propensity to undergo dimerization after the initial cyclization. Gratifyingly, the yield was improved to 61% based on the o-pyridinyl ester 2a (Entry 15). A brief solvent screening was undertaken, and no better result was provided (Entries 16–18). Performing the reaction at 80 °C resulted in a higher yield, but asymmetric induction declined to a moderate level (Entry 19). Replacing Zn with Mn as the reducing agent led to an inferior result (Entry 20). Moreover, the reaction with the bromo analog of 1a as a precursor was also able to deliver 3aa, albeit in a much lower yield (Entry 21). Table 2 | Optimization of the Reaction Conditionsa Entry Ligand Ni-precatalyst Solvent Yield (%)b ee (%)c 1 L1 NiBr2·glyme DMA 31 95 2 L2 NiBr2·glyme DMA 27 55 3 L3 NiBr2·glyme DMA 29 63 4 L4 NiBr2·glyme DMA 24 31 5 L5 NiBr2·glyme DMA trace n.d.d 6 L6 NiBr2·glyme DMA 11 89 7 L7 NiBr2·glyme DMA 26 72 8 L8 NiBr2·glyme DMA 35 80 9 L9 NiBr2·glyme DMA 0 – 10 L10 NiBr2·glyme DMA 0 – 11 L1 NiBr2 DMA 31 95 12 L1 NiCl2 DMA 30 95 13 L1 Ni(COD)2 DMA 50 92 14 L1 NiBr2·diglyme DMA 38 96 15e L1 NiBr2· diglyme DMA 61 96 16e L1 NiBr2·diglyme DMF 41 95 17e L1 NiBr2·diglyme NMP 60 94 18e L1 NiBr2·diglyme THF 19 95 19e,f L1 NiBr2·diglyme DMA 64 80 20e,g L1 NiBr2·diglyme DMA 16 88 21h L1 NiBr2·diglyme DMA 32 95 aUnless otherwise specified, reactions were performed on a 0.2 mmol scale of the aryl-iodide-tethered alkene 1a using 2.0 equiv of ortho-pyridinyl ester 2a, 10 mol % Ni-precatalyst, and 15 mol % ligand L in 0.5 mL solvent at 60 °C for 12 h. bYields of isolated product through column chromatography. cDetermined by HPLC analysis on a chiral stationary phase. dNot determined. eThe reaction was preformed with 2 equiv of the aryl-iodide-tethered alkene 1a. fThe reaction was performed at 80 °C. gMn was used as reductant instead of Zn. hThe bromo analogue of 1a (2 equiv) was used instead 1a. Substrate scope After establishing the optimum reaction conditions, we started to investigate the substrate scope of this Ni-catalyzed reductive aryl-acylation (Table 3). First, an array of o-pyridinyl benzoates 2a- n bearing electron-donating or electron-withdrawing substitution on different positions were reacted with the aryl-iodide-tethered alkene 1a under the standard conditions. To our delight, all these reactions proceeded smoothly, furnishing the products 3aa– an in moderate to good yields and good to excellent enantioselectivities. Of note is that organometallics- and base-sensitive ester ( 3ah– am) and nitrile ( 3an) moieties were well tolerated, which were not reported in the previous palladium-catalyzed reaction using arylboronic acids under basic conditions.32,33 Furthermore, the use of naphthoate as a substrate posed no problem, providing the product 3ao in moderate efficiency and high enantiomeric excess. The o-pyridinyl 2-furonate 2p, 2 -thiophenecarboxylate 2q, and indole-2-carboxylate 2r also proved to be pertinent precursors, enabling the incorporation of heterocycles into the backbone of the coupling products ( 3ap– ar) with a high level of asymmetric induction. Unfortunately, no desired product was formed when o-pyridinyl alkanoates were utilized as precursors. Table 3 | Evaluation of the Substrate Scope of Asymmetric Aryl-Acylationa–c aUnless otherwise specified, reactions were performed on a 0.2 mmol scale of the ortho-pyridinyl esters 2 using 2.0 equiv of the aryl-iodide-tethered alkenes 1, 10 mol % NiBr2·diglyme, and 15 mol % Pyrox L1 in 0.5 mL DMA at 60 °C for 12 h. bYields of the isolated products after column chromatography. cEnantiomeric excesses were determined by HPLC analysis on a chiral stationary phase. dThe reaction was performed on a 4-mmol scale of the ortho-pyridinyl ester 2a. eThe reaction was performed at 40 °C. Next, we varied the structure of the aryl-iodide-tethered alkenes. No significant impact was observed when increasing the bulkiness of geminal substitution on the olefinic unit ( 3bd, 3bm, and 3cd). Either electron-donating or electron-withdrawing groups could be introduced to the phenyl ring of the aryl iodides, yielding the products 3fd, 3fm, 3gd, and 3gm in moderate efficiency and excellent enantiocontrol. Moreover, our method is applicable for the construction of chiral indoline scaffold ( 3hd– jd) wherein decreasing enantioselectivity with ascending bulkiness of N-substitution was noticed. In addition, this reaction could be simply scaled up to 4 mmol, affording compound 3aa in 60% yield and 94% ee. At this juncture, we turned our attention to establishing a method to introduce a carbamoyl moiety across the olefinic unit. However, reactions using carbamoyl chlorides turned out to be unsuccessful. To our delight, however, isocyanates58–60 proved to be a competitive electrophilic carbamoylating agent in our catalytic system under slightly modified conditions. The scope of this asymmetric aryl-carbamoylation reaction was explored, and the results are summarized in Table 4. In general, aryl isocyanates bearing either electron-donating or electron-withdrawing substitution were well accommodated, furnishing the chiral benzamides 5aa– ak in moderate to high yields and high to excellent enantiomeric excesses. Notably, keto and nitrile moieties remained intact during the reaction. In contrast, the reactions using aliphatic isocyanates as precursors failed to yield the target products. On the other hand, the broad scope of the tethered alkenes allowed the efficient synthesis of various benzene-annulated cyclic compounds ( 5ba– oa) containing an amide group, and high enantioselectivities were achieved in most cases. Table 4 | Evaluation of the Substrate Scope of Asymmetric Aryl-Carbamoylationa–c aUnless otherwise specified, reactions were performed on a 0.2 mmol scale of the the aryl-iodide-tethered alkenes 1 using 1.5 equiv of the isocyanates 4, 10 mol % NiBr2·diglyme, 15 mol % Pyrox L1, and 1.0 equiv of NEt3 in 0.5 mL DMA at 30 °C for 12 h. bYields of the isolated products after column chromatography. cEnantiomeric excesses were determined by HPLC analysis on a chiral stationary phase. dThe reaction was performed without NEt3. Derivatization of the cross-coupling products To demonstrate the utility of this method, various derivatizations of the aryl-carbonylation products were conducted (Figure 2). First, compound 3aa was subjected to Wittig olefination, delivering a chiral alkene 6 in 71% yield (Figure 2a, equation 1). Moreover, meta-Chloroperoxybenzoic acid (mCPBA)-mediated Baeyer–Villiger oxidation smoothly converted compound 3aa into the corresponding phenolic ester 7 in 64% yield. Subsequently, hydrolysis of 7 afforded a chiral carboxylic acid 8 in 88% yield, which is present as the core structure in GPR40 agonists61 (Figure 2a, equation 2). Furthermore, ruthenium-catalyzed benzylic oxidation of the indane products furnished a set of chiral indanones 9 in moderate to good yields.62 Taking advantage of the two keto moieties of 9, we successfully transformed them into diverse benzene-annulated bicyclic bridged rings 10 bearing three challenging tetrasubstituted stereogenic centers in excellent diastereocontrol through a samarium-mediated intramolecular pinacol-coupling reaction (Figure 2b).63 Besides, reduction of the amide 5aa with LiAlH4 provided an amine 11 in 75% yield (Figure 2c). In addition, a one-pot aza-annulation of 5aa with styrene followed by DDQ-mediated oxidation enabled the installation of the quinolone moiety onto the chiral indane structure ( 12) in good efficiency (Figure 2d).64 Figure 2 | Derivatizations of the aryl-acylation and aryl-carbamoylation products. (a) mCPBA (10 equiv), para-toluenesulfonic acid monohydrate (pTsOH•H2O) (1 equiv), dichloroethane (DCE), 60 °C, 5 h. (b) LiOH (5 equiv), MeOH/H2O = 10:1, 45 °C, 12 h. (c) RuCl3 (0.16 mol %), phenyl iodide (PhI) (10 mol %), oxone (2 equiv), MeCN/H2O (1:1), room temperature, 24 h. (d) Samarium (Sm) (1.2 equiv), trimethylsilyl chloride (1.2 equiv), THF, 67 °C, 20 h. Download figure Download PowerPoint Proposed reaction mechanism On the basis of the previous reports,12,14,65 we proposed a plausible reaction mechanism for this Ni-catalyzed aryl-carbonylation reaction (Figure 3). Initially, a Ni(0) species was generated under the reductive condition, which underwent oxidative addition with the tethered aryl iodide 1. Next, the resultant Ni(II) complex I performed a facially selective arylnickelation to the pendant olefinic unit, to accomplish the construction of the benzene-fused cyclic scaffold with a quaternary stereocenter. Subsequently, Zn-mediated reduction of the generated Ni(II) intermediate II delivered a Ni(I) species III, to which o-pyridinyl esters 2 conducted oxidative addition. Facile reductive elimination from the Ni(III) complex IV afforded the aryl-acylation products 3. Finally, the Ni(I) o-pyridinylate V was reduced by Zn, to regenerate the Ni(0) species for the next catalytic cycle. In the case of aryl-carbamoylation, the Ni(I) species III performed migratory insertion into the C–N double bond of isocyanates 4 to install the amide moiety. Reduction of the intermediate VI by zinc and the protonation after the completion of the reaction yielded the aryl-carbamoylation products 5. Figure 3 | Proposed reaction mechanism. Download figure Download PowerPoint Conclusion In conclusion, we developed a highly enantioselective reductive aryl-acylation and aryl-carbamoylation of pendant unactivated alkenes with ortho-pyridinyl esters and isocyanates as the electrophilic carbonylating agent, respectively. These reactions were catalyzed by a Ni/Pyrox system with a facially selective arylnickelation as the key enantiodetermining step. By circumventing the use of pregenerated organometallics, strong bases, and carbon monoxide gas, this method allowed the synthesis of diverse chiral indanes, indolines, and dihydrobenzofurans bearing a quaternary stereogenic center with a high functionality tolerance. The utility of this method was further demonstrated through various derivatizations of the coupling products. Particularly, benzene-fused bicyclic bridged rings bearing three challenging tetrasubstituted stereogenic centers were prepared in high stereocontrol via a benzylic oxidation/pinacol-coupling sequence. Supporting Information Supporting Information is available and includes experimental procedures, characterization data, and 1H NMR, 13C NMR, 19F NMR, and HPLC chromatograms for products (PDF). Conflict of Interest The authors declare no competing interests. Acknowledgments This work is supported by start-up funds from the Young Scholar 1000 Talents Plan, the National Natural Science Foundation of China (21772183 and 22071230), the Fundamental Research Funds for the Central Universities (WK2060190086), the Project Funded by China Postdoctoral Science Foundation (2020M682006), as well as the University of Science and Technology of China.

Key words acyl chlorides - alkenes - alkyltrifluoroborates - carboacylation - nickel catalysis - photoredox catalysis

Key words organoboron nucleophiles - nickel catalysis - photoredox catalysis

Key words α-acylation - carboxylic acids - enantioselectivity - nickel catalysis - photoredox catalysis

Key words allylic C(sp3)–H arylation - cross-coupling - nickel catalysis - photoredox catalysis

An enantioselective, decarboxylative C(sp3)—C(sp3) cross‐coupling reaction of α‐amino acids with aryl halides by synergistic iridium‐photoredox and nickel catalysis is presented.

A novel and efficient C-P bond formation reaction of diarylphosphine oxides with aryl iodides was achieved by combining nickel catalysis and visible-light-induced photoredox catalysis. This dual-catalytic reaction showed a broad substrate scope, excellent functional group tolerance, and afforded the corresponding products in good to excellent yields. Compared with the previously reported use of photoredox/nickel dual catalysis in the construction of C-C bonds, the methodology described herein was observed to be the first to allow for C-heteroatom bond formation.

A mechanism that enables direct aldehyde C-H functionalization has been achieved via the synergistic merger of photoredox, nickel, and hydrogen atom transfer catalysis. This mild, operationally simple protocol transforms a wide variety of commercially available aldehydes, along with aryl or alkyl bromides, into the corresponding ketones in excellent yield. This C-H abstraction coupling technology has been successfully applied to the expedient synthesis of the medicinal agent haloperidol.