Chemo- and Enantioselective Arylation and Alkenylation of Aldehydes Enabled by Nickel/ <i>N</i> -Heterocyclic Carbene Catalysis

Abstract

Open AccessCCS ChemistryCOMMUNICATION1 Apr 2022Chemo- and Enantioselective Arylation and Alkenylation of Aldehydes Enabled by Nickel/N-Heterocyclic Carbene Catalysis Zi-Chao Wang, Jian Gao, Yuan Cai, Xiaodong Ye and Shi-Liang Shi Zi-Chao Wang State Key Laboratory of Organometallic Chemistry, Center for Excellence in Molecular Synthesis, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200032 , Jian Gao State Key Laboratory of Organometallic Chemistry, Center for Excellence in Molecular Synthesis, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200032 , Yuan Cai State Key Laboratory of Organometallic Chemistry, Center for Excellence in Molecular Synthesis, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200032 , Xiaodong Ye State Key Laboratory of Organometallic Chemistry, Center for Excellence in Molecular Synthesis, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200032 and Shi-Liang Shi *Corresponding author: E-mail Address: [email protected] State Key Laboratory of Organometallic Chemistry, Center for Excellence in Molecular Synthesis, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200032 School of Pharmacy, Fudan University, Shanghai 201203 https://doi.org/10.31635/ccschem.021.202101001 SectionsSupplemental MaterialAboutAbstractPDF ToolsAdd to favoritesDownload CitationsTrack Citations ShareFacebookTwitterLinked InEmail Herein, we report the first highly enantioselective Ni-catalyzed arylation and alkenylation of simple aldehydes using readily available and stable organoboronic esters. This protocol provides various chiral secondary alcohols in high yields and enantioselectivities (up to 97% ee) with a broad scope of substrates, functional groups, and heterocycles. The use of a bulky N-heterocyclic carbene (NHC) ligand for nickel catalyst is the key to high enantiocontrol. The competitive Ni-catalyzed transformations, including Tishchenko reaction, dehydrogenation/hydrogenation reaction, and Suzuki–Miyaura couplings, are avoided. The excellent chemoselectivity is likely due to the application of mild base CsF and η2-coordination of aldehydes with nickel. Download figure Download PowerPoint Introduction Optically active secondary alcohols are common structural motifs in pharmaceutical molecules, natural products, and fine chemicals (Figure 1a).1–3 They can undergo various selective transformations to afford a wide range of significant stereodefined compounds.4,5 Moreover, they also serve as key building blocks for chiral ligand designs for asymmetric catalysis.6 Therefore, asymmetric synthesis of them has attracted tremendous attention over the past few decades.7,8 Transition metal-catalyzed asymmetric additions of organometallic reagents to aldehydes have been recognized as fundamental and straightforward methods due to simultaneous construction of the carbon–carbon bond and stereocenter. Organometallic reagents, including organomagnesium,9,10 -zinc,11,12 -lithium,13 -silane,14,15 and -boron,16–25 have been used in these addition reactions. Particularly, organoborons remain one of the most attractive reagents because of their stability in air and moisture, easy availability, nontoxicity, low cost, and excellent tolerance of various functional groups. Figure 1 | (a–c) Construction of chiral secondary alcohols via asymmetric addition of organoboronic esters to aldehydes. Download figure Download PowerPoint In 1998, Miyaura and co-workers16 reported the first example of Rh(I)-catalyzed asymmetric 1,2-addition to aldehydes with arylboronic acids. Since then, important contributions of the asymmetric addition of organoboron reagents to aldehyde have been made from Zhou et al.,17 Hayashi et al.,18 Amii et al.,19 and Hu et al.20 through the design of chiral ligands for Rh(I) catalysts.8 Ru(II)-catalyzed asymmetric arylborations of aldehydes were also developed by the groups of Miyaura21 and Tang,22 respectively (Figure 1b). Moreover, Bolm and co-workers24,25 developed an efficient synthesis of diaryl secondary alcohols from aldehydes using arylzinc species generated in situ from arylboronic acids and diethylzinc. Despite this significant progress, considerable limitations remain in this field. For example, most of these methodologies require noble metal catalysts, and only a few examples use first-row transition metal catalysts.26,27 More importantly, the substrate scope of these reactions is usually limited to simple aryl groups for organoborons, simple benzaldehydes for the aldehyde partners, arylation of aliphatic aldehydes, or heteroaryl aldehydes with organoborons remain elusive. Furthermore, the asymmetric alkenylboration of aldehydes is rarely explored.28 These methods generally proceed through a traditional η1-coordinating activation of carbonyls by chiral Lewis acidic metal catalysts. While improving the electrophilicity of aldehyde, this activation manner might also facilitate deleterious coordination to heteroatom and enolization of alkyl aldehydes, leading to the limitations mentioned above. Different from Lewis acidic metals, and as an earth-abundant and cost-effective first-row transition metal, nickel has been widely applied to catalyze cross-coupling reactions. Moreover, low-valent nickel has been well-established to enable aldehyde η2-coordination and oxidative cyclization, although the corresponding enantioselective variant is relatively rare.29–39 Recently, Ogoshi and co-workers38 developed an elegant Ni(0)/N-heterocyclic carbene (NHC)-catalyzed enantioselective intramolecular arylation of organosilane reagent. However, Ni(0)-catalyzed intermolecular enantioselective arylboration of simple aldehydes remains elusive, probably due to the lack of suitable chiral ligands. In this context, our group has developed a series of bulky C2-symmetric chiral NHCs,40 termed 7,9-bis(4-methyl-2,6-bis((R)-1-phenylethyl)phenyl)-7H-acenaphtho[1,2-d]imidazol-9-ium-8-ide (ANIPE)- and 1,3-bis(4-methyl-2,6-bis((R)-1-phenylethyl)phenyl)-4,5-dihydro-1H-imidazol-3-ium-2-ide) (SIPE)-type ligands and applied to asymmetric nickel catalysis.41–49 Recently, we disclosed the first general asymmetric arylboration of simple ketones to prepare chiral tertiary alcohols using Ni/NHC catalysis and a rare enantioselective η2-coordinating activation of ketones.47,50–57 Given the importance of chiral secondary alcohols, we became interested in developing asymmetric aldehyde addition of organoborons as a general and efficient approach to prepare chiral secondary alcohols. Compared with ketone addition, Ni-catalyzed aldehyde addition seems trivial; however, it would confront considerable challenges in chemo- and enantiocontrol (Figure 1c). First, different from ketones, aldehydes are more likely to undergo the aldol reaction and would be readily transferred into esters via the Tishchenko reaction in the presence of Ni/NHC catalysis, as has been reported by Ogoshi and co-workers.58 Moreover, unlike tertiary alcohols, secondary alcohols would readily undergo dehydrogenation and further derivatization in the presence of Ni/NHC catalysts.42,59–64 Furthermore, Ni-catalyzed Suzuki–Miyaura couplings of various electrophiles are well-developed,65 posing further challenges for chemoselectivity control. Finally, it would be nontrivial to control enantioselectivity for an intermolecular arylation of aldehyde in a η2-activation manner.38 Herein, we describe a general and efficient Ni/NHC-catalyzed chemo- and enantioselective arylation and alkenylation of aldehydes with readily available organoboronic esters, delivering chiral secondary alcohols in high yields with excellent functional group tolerance and broad substrate scope (Figure 1c). This protocol could be applied for the synthesis of several biologically relevant molecules. Results and Discussion Reaction optimization To assess the feasibility, we evaluated the model reaction of 2-naphthaldehyde ( 1a) with 5,5-dimethyl-2-phenyl-1,3,2-dioxaborinane (PhBneo, 2a) in the presence of 2.0 mol % of Ni(COD)2 and chiral ligand. The reaction was performed in c-hexane at ambient temperature for 16 h using CsF and tBuONa as a base (Table 1). First, we tested some commercially available chiral privileged ligands and found none of them could efficiently deliver the desired product (see Supporting Information for details). However, when chiral NHC L1 [1,3-bis(4-methyl-2,6-bis((R)-1-phenylethyl)phenyl)-1H-imidazol-3-ium-2-ide) (IPE)] was used as the ligand, the desired product alcohol 3a was obtained in 79% yield with 65% ee (entry 1). When switching to the saturated SIPE-type ligand, the enantioselectivity was improved to 75% ee. Although the ligand backbone change to an acenaphthyl group did not affect the enantioselectivity ( L3, entry 3), further increases in the steric hindrance of N-substituents on NHC dramatically improved the enantioselectivity, delivering product 3a in 94% ee (entry 4). During reaction optimization, as expected, significant amounts of byproducts, including diaryl ketone ( B), 2-naphthalenemethanol ( C), and homocoupled esters ( D), were observed. A solvent screening (entries 5–13) proved that c-hexane is the best choice for this transformation, providing 3a with high chemoselectivity [90∶10, 3a∶( B + C + D)] and enantioselectivity (94% ee), although ether-type solvents lead to higher ee value (entries 5 and 6). Intensive examination of the base effect (entries 14–24) revealed that excellent chemoselectivity (97∶3) could be achieved when used CsF as the single base for in situ catalyst generation and activator of PhBneo, offering the product in nearly quantitative yield (95% isolated yield) with excellent enantioselectivity (94% ee). CsF presumably facilitates the transmetalation of organoboron to the Ni catalyst, thus retarding the formation of ester byproduct D. Moreover, the presence of CsF might inhibit the generation of undesired Ni–H complex, which leads to fewer amounts of B and C. Finally, controlled experiments using other organoboron [PhBpin or PhB(OH)2] gave low yield or no detectable products (entries 25 and 26). The use of a divalent nickel source (NiCl2) instead of Ni(COD)2 resulted in no conversions, indicating the critical role of a low-valent nickel for oxidative cyclization (entry 27). Table 1 | Reaction Optimization Entry NHC Solvent Base Conv. (%)a 3a∶ B∶ C∶ Da ee (%)b of 3a 1 L1 c-Hexane CsF >99 79∶10∶11∶0 65 2 L2 c-Hexane CsF >99 79∶8∶8∶5 75 3 L3 c-Hexane CsF >99 89∶4∶7∶0 74 4 L4 c-Hexane CsF >99 90∶5∶5∶0 94 5 L4 THF CsF >99 48∶12∶12∶28 95 6 L4 2-Me-THF CsF >99 53∶21∶21∶5 96 7 L4 CPME CsF 88 0∶44∶44∶12 — 8 L4 Toluene CsF 99 71∶13∶11∶5 89 9 L4 PhCF3 CsF 75 36∶33∶34∶25 91 10 L4 tBuOH CsF >99 52∶22∶22∶4 93 11 L4 Dioxane CsF >99 47∶21∶20∶13 92 12 L4 iPr2O CsF >99 75∶10∶10∶5 95 13 L4 TBME CsF 68 35∶46∶15∶4 96 14 L4 c-Hexane Cs2CO3 99 75∶10∶10∶6 96 15 L4 c-Hexane CsOH·H2O 99 28∶25∶47∶0 91 16 L4 c-Hexane tBuONa 99 24∶19∶21∶36 40 17 L4 c-Hexane Na2CO3 99 43∶21∶21∶15 73 18 L4 c-Hexane NaOH 99 25∶22∶28∶25 50 19 L4 c-Hexane KOH 99 22∶41∶37∶0 17 20 L4 c-Hexane CH3OK 99 45∶25∶15∶15 71 21 L4 c-Hexane K3PO4 60 12∶45∶43∶0 96 22 L4 c-Hexane Et3N 99 54∶13∶16∶17 85 23 L4 c-Hexane TMSOK 99 57∶15∶15∶13 11 24c L4 c-Hexane CsF >99(95) 97∶1.5∶1.5∶0 94 25c,d L4 c-Hexane CsF 44 0∶27∶27∶45 — 26c,e L4 c-Hexane CsF 34 22∶34∶34∶10 7 27c,f L4 c-Hexane CsF <2 — — Note: THF, tetrahydrofuran; CPME, cyclopentyl methyl ether; TMSOK, potassium trimethylsilanolate; TBME, methyl tert-butyl ether; HPLC, high-performance liquid chromatography. aDetermined by 1H NMR analysis of reaction crude mixture using 1,3,5-trimethylbenzene as an internal standard, isolated yield shown in the parenthesis. bDetermined by HPLC analysis with a chiral stationary phase. cWithout tBuONa. dUsing PhBpin. eUsing PhB(OH)2. fUsing NiCl2. Substrate scope With optimized reaction conditions in hand, we first investigated the substrate scope of aldehyde partners. As shown in Figure 2, various commercially available aldehydes efficiently underwent the arylation reaction, delivering chiral secondary alcohols in excellent chemo- and enantioselectivities (89–96% ee). The reaction was not sensitive to steric effect; bulky aromatic aldehydes bearing ortho-substituents worked well ( 3b– 3d and 4o). We found that both electron-donating groups on aromatic aldehydes, such as ether ( 3d and 3e), thioether ( 3i), dimethylamine ( 3f), and electron-withdrawing groups, including fluoride ( 3h), chloride ( 4p), BPin ( 3j), ketone ( 3k), amide ( 3l), and ester ( 3m), were well tolerated, delivering products in high yields and excellent enantioselectivities. Notably, an aldehyde was selectively arylated in a substrate possessing a ketone group ( 3k) because of the higher reactivity of aldehyde under the mild reaction condition. Interestingly, BPin was found intact under the reaction condition, illustrating the high selectivity between Bneo and BPin ( 3j), probably due to steric effects. In the case of methyl 2-formylbenzoate, lactonization product ( 3m) was obtained from the corresponding secondary alcohol in a single operation. Moreover, heteroaromatic aldehydes, such as pyridine ( 3n), pyrimidine ( 3o), benzofuran ( 3p), benzothiophene ( 3q), indole ( 3r), and carbazole ( 3s), efficiently participated in the reaction, furnishing products in excellent yields and enantioselectivities (89–94% ee). In addition to aromatic aldehydes, the use of challenging aliphatic aldehydes ( 3t– 3y) also delivered products in moderate to good yields and enantioselectivities (54–90% ee). The corresponding byproducts derived from the aldol reaction or Tishchenko reaction were not detected, indicating the mildness of this method. Finally, we successfully conducted a gram-scale reaction (6 mmol scale, 3a) to give the alcohol product in similar high yield and enantioselectivity (95%, 94% ee). Figure 2 | Substrate scope. aIsolated yields are reported. bUsing 5 mol % catalyst. Download figure Download PowerPoint Next, we surveyed the scope of organoboron components. A wide variety of arylboronic acids were readily converted to chiral diarylmethanols (86–97% ee). Many functional groups, such as trifluoromethyl ( 4a), cyano ( 4b), chloride ( 4c), ether ( 4s), thioether ( 4d), ketone ( 4e), ester ( 4f), amide ( 4g), bromide ( 4h), fluoride ( 4i and 4q), and alkenyl ( 4j), were found to be compatible. Several heteroaryl boronic acids, including thiophene ( 4l and 4p), benzothiophene ( 4o), furan ( 4n), and benzofuran ( 4m), were also competent substrates, affording chiral secondary alcohols in excellent enantioselectivities (90–96% ee). Importantly, this catalytic addition method is applicable to alkenylboron coupling components. Several chiral secondary allylic alcohols derived from aryl, heteroaryl, alkyl, or dialkyl-substituted alkenylboronates ( 5a– 5g) were furnished in high yields and enantioselectivities (82–91% ee). Also, aliphatic aldehydes ( 5h and 5i) could be used in this alkenylation method, although enantioselectivity is moderate for a challenging linear substrate (50–84% ee). It bears mentioning that the control of chemoselectivity in all reactions mentioned earlier was perfect. Except for the potential aldol reaction, Tishchenko reaction, and dehydrogenation reaction, this arylation reaction is orthogonal to Ni-catalyzed Suzuki–Miyaura cross-coupling. Many well-established electrophiles,65 including aryl chlorides, bromides, fluorides, ethers, esters, nitriles, amides, and benzylic alcohol and allylic alcohol derivatives, were compatible under these reaction conditions, providing opportunities for further transformations. We ascribe this exceptional chemoselectivity to the robust η2-coordination and oxidative cyclization of nickel and aldehydes.29–37 Synthetic application To further demonstrate the synthetic utility of the current arylation protocol, we applied it in the asymmetric synthesis or formal synthesis of several drugs. For example, chiral alcohol product 3c would be readily transformed to an anticholinergic drug (R)-orphenadrine through a known alkylation reaction66 (Figure 3a). Furthermore, chiral alcohol 6, a key intermediate for the synthesis of sleeping-inducing agent 7, was obtained in high enantioselectivity and efficiency using the arylation method (Figure 3b).67 CDP-840, a selective phosphodiesterase IV inhibitor, could be synthesized following the literature procedure68 from chiral alcohol 9. 9 was obtained in excellent enantioselectivity via the arylation of aldehyde 8, which was prepared through a Mitsunobu reaction (Figure 3c). Our method was also applied to a three-step synthesis of chiral benzo[c]chromene 12, for which only a few synthetic methods available.69 A Suzuki coupling of two commercially available reagents gave aldehyde 10, which, upon our asymmetric arylation reaction, furnished chiral alcohol 11 in 87% yield with 98% ee. Finally, cyclization with tBuOK yielded 12 in high enantioselectivity (96% ee) (Figure 3d). Figure 3 | (a–d) Synthetic applications of the asymmetric arylation reaction. Download figure Download PowerPoint Based on literature reports and our observations,29–39,47 we proposed catalytic cycles for this arylation reaction, as depicted in Figure 4. The use of electron-rich NHC ligands for Ni(0) catalysts would favor the enantioselective η2-coordination and oxidative cyclization to form an oxanickelacycle. CsF facilitates transmetalation of the organoboronic ester to nickel to form the Ni-alkyl species. Finally, reductive elimination of the Ni-alkyl species occurs to provide the chiral alcohol product with concomitant regeneration of the Ni(0) catalyst. Remarkably, aldol reaction and three other side reactions that also catalyzed by nickel catalyst are prevented: (1) ester formation through Tishchenko reaction,58 (2) dehydrogenation of the secondary alcohol to form a ketone, and (3) hydrogenation of aldehyde substance. Figure 4 | Proposed mechanisms of the product and byproducts. Download figure Download PowerPoint Conclusions We have developed the first general highly chemoselective and enantioselective Ni-catalyzed arylboration and alkenylboration of simple aldehydes to access a wide range of chiral secondary alcohols. This methodology displays a broad substrate scope and exceptional functional group compatibility. The use of bulky chiral NHC is critical for high levels of enantiocontrol; using aldehyde η2-coordination and mild base CsF is essential to sustain excellent chemoselectivity. Moreover, this methodology was successfully applied to the asymmetric (formal) syntheses of bioactive molecules. Further applications of this rare efficient enantioselective η2-coordinating activation of carbonyls are underway in our laboratory. Supporting Information Supporting Information is available and includes experimental procedures, spectroscopic data, and NMR spectra of products. Conflict of Interest There is no conflict of interest to report. Funding Information The authors gratefully acknowledge the financial support from the National Natural Science Foundation of China (grant nos. 91856111, 21871288, 21690074, and 21821002) and the Strategic Priority Research Program of the Chinese Academy of Sciences (grant no. XDB 20000000). References 1. Barouth V.; Dall H.; Petal D.; Hite G.Stereochemical Aspects of Antihistamine Action. 4. Absolute Configuration of Carbinoxamine Antipodes.J. Med. Chem.1971, 14, 834–836. Google Scholar 2. Casy A. F.; Drake A. F.; Ganellin C. R.; Mercer A. D.; Upton C.Stereochemical Studies of Chiral h-1 Antagonists of Histamine: The Resolution, Chiral Analysis, and Biological Evaluation of Four Antipodal Pairs.Chirality1992, 4, 356–366. Google Scholar 3. Klaholz B. P.; Mitschler A.; Moras D.Structural Basis for Isotype Selectivity of the Human Retinoic Acid Nuclear Receptor.J. Mol. Biol.2000, 302, 155–170. Google Scholar 4. Harris M. R.; Hanna L. E.; Greene M. A.; Moore C. E.; Jarvo E. R.Retention or Inversion in Stereospecific Nickel-Catalyzed Cross-Coupling of Benzylic Carbamates with Arylboronic Esters: Control of Absolute Stereochemistry with an Achiral Catalyst.J. Am. Chem. Soc.2013, 135, 3303–3306. Google Scholar 5. Zhou Q.; Srinivas H. D.; Dasgupta S.; Watson M. P.Nickel-Catalyzed Cross-Couplings of Benzylic Pivalates with Arylboroxines: Stereospecific Formation of Diarylalkanes and Triarylmethanes.J. Am. Chem. Soc.2013, 135, 3307–3310. Google Scholar 6. Zhou Q.-L.Privileged Chiral Ligands and Catalysts; Wiley-VCH: Weinheim, 2012. Google Scholar 7. Schmidt F.; Stemmler Bolm and Google Scholar P.; 2, Google Scholar 9. F.; R.; R.; of Chiral via of to 6, Google Scholar P.; A.; A. in Organometallic Google Scholar to Google Scholar and In Organometallic E. Google Scholar In Organometallic E. Google Scholar S.; of to Google Scholar D.; R.; Alkenylation and by a Chiral Am. Chem. Google Scholar Miyaura of to Chem. Google Scholar Shi Q.; Zhou of Arylboronic to Aldehydes Chiral 8, Google Scholar H.; Hayashi of Chiral Ligands and to the Arylation of Google Scholar S.; Amii Chiral with a for Arylation of 12, Google Scholar P.; Hu of Arylboronic with to Chiral Google Scholar Miyaura for Enantioselective Arylation of Aldehydes with Arylboronic Chem. Google Scholar Hu R.; Yuan Chiral for of Arylboronic to Google Scholar R.; Q.; Shi Chiral Carbene (NHC) Arylation of Aldehydes with Arylboronic Google Scholar Bolm to Aldehydes with as Am. Chem. Google Scholar H. Bolm B. and to Aldehydes by a Chiral A on the a and an of the Google Scholar Reaction of with Enantioselective of Google Scholar D.; of and by a Chiral Enantioselective Alkenylation and Arylation of Google Scholar Enantioselective of and Am. Chem. Google Scholar Ogoshi of Aldehydes with through and Chem. Google Scholar E. A.; between and Chem. Google Scholar and Chem. Google Scholar Hayashi Suzuki H.; Ogoshi of and through by Chem. 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Google Scholar D.; Shi Enantioselective of and with Google Scholar Cai A.; Shi and Arylation of with Enabled by Nickel/N-Heterocyclic Carbene Chem. Google Scholar For a concomitant of A. Enantioselective Enabled by a Carbene Am. Chem. Google Scholar Wang Shi Cross-Coupling via Enabled by a Chiral Chem. Google Scholar Wang Enantioselective of to of Chem. Google Scholar Wang Zhou of Arylboronic to Chem. Google Scholar Cai F.; V.; A.; in Am. Chem. Google Scholar Enantioselective of to and Chiral Chem. Google Scholar R.; Hayashi of and to Chem. Google Scholar Enantioselective of Arylboronic to A of Optically Am. Chem. Google Scholar D.; of Based on the of Catalysis to a Am. Chem. Google Scholar Ni Gao of to Enantioselective of Google Scholar Ogoshi of Different Aldehydes to Am. Chem. Google Scholar H.; D. A.; and of at by Google Scholar of from Google Scholar H.; by Chem. Google Scholar for the of to and Google Scholar E. S.; by a Nickel-Catalyzed Cross-Coupling of Am. Chem. Google Scholar F.; Shi of via of and Google Scholar Suzuki–Miyaura Cross-Coupling A from to Google Scholar D. S.; of with Google Scholar F.; S.; F.; D.; S.; S.; M. L. Wang H.; E.; A.; A.; D.; of for Evaluation in the of Med. Google Scholar R.; F.; D. D.; A.; at of 6, Google Scholar S.; A.; A.; R.; R.; H. M. D.; A. for the of Med. Google Scholar Information Chinese secondary NHC

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