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Inherently Chiral and Symmetrical Heteroatom-Doped Zigzag-Type Hydrocarbon Belts

2024; Chinese Chemical Society; Volume: 6; Issue: 5 Linguagem: Inglês

10.31635/ccschem.024.202403871

2096-5745

Xueyuan Wang, Xinyu Zhang, Shuo Tong, Qing‐Hui Guo, Mei‐Ling Tan, Chengjun Li, Mei‐Xiang Wang,

Molecular spectroscopy and chirality

Open AccessCCS ChemistryRESEARCH ARTICLES22 Feb 2024Inherently Chiral and Symmetrical Heteroatom-Doped Zigzag-Type Hydrocarbon Belts Xue-Yuan Wang†, Xin-Yu Zhang†, Shuo Tong, Qing-Hui Guo, Mei-Ling Tan, Cheng-Jun Li and Mei-Xiang Wang Xue-Yuan Wang† Key Laboratory of Bioorganic Phosphorous Chemistry and Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University, Beijing 100084 , Xin-Yu Zhang† Key Laboratory of Bioorganic Phosphorous Chemistry and Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University, Beijing 100084 , Shuo Tong *Corresponding authors: E-mail Address: [email protected] E-mail Address: [email protected] Key Laboratory of Bioorganic Phosphorous Chemistry and Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University, Beijing 100084 , Qing-Hui Guo Key Laboratory of Bioorganic Phosphorous Chemistry and Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University, Beijing 100084 , Mei-Ling Tan Key Laboratory of Bioorganic Phosphorous Chemistry and Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University, Beijing 100084 , Cheng-Jun Li Key Laboratory of Bioorganic Phosphorous Chemistry and Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University, Beijing 100084 and Mei-Xiang Wang *Corresponding authors: E-mail Address: [email protected] E-mail Address: [email protected] Key Laboratory of Bioorganic Phosphorous Chemistry and Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University, Beijing 100084 https://doi.org/10.31635/ccschem.024.202403871 SectionsSupplemental MaterialAboutAbstractPDF ToolsAdd to favoritesDownload CitationsTrack Citations ShareFacebookTwitterLinked InEmail Recent years have witnessed a resurgence of study in hydrocarbon belts due to their potential applications in carbon nanotechnology. By contrast, heteroatom-embedded zigzag hydrocarbon belts as advanced design strategies with fascinating structures and desirable, unique properties have remained largely unexplored, and inherently chiral ones are unknown. Herein, we report the synthesis of a diversity of symmetric and highly enantiopure inherently chiral O- and N-doped zigzag-type hydrocarbon belts starting from strainless macrocycles based on fjord-stitching strategy. The readily available pertriflated resorcin[6]arene underwent partial hydrolyses and intramolecular SNAr reactions to form a calix[3](9H-xanthene) derivative and a prochiral half-belt selectively. Straightforward transformations of calix[3](9H-xanthene) into C3v-symmetric molecular belts were achieved by closing the rest of the fjords with triple intramolecular SNAr reactions and Yamamoto homo coupling reactions, as well as palladium-catalyzed intermolecular acridination reactions with primary amines. The prochiral half-belt underwent enantioselective desymmetrizative mono-acridination to afford an inherently chiral N,O4-bridged pseudo-belt with an enantiomeric excess (ee) value of >99% under the catalysis of Pd(OAc)2 and (R)-Antphos. Ring closure reactions of the pseudo-belt produced diverse heteroatom-inlayed zigzag-type hydrocarbon belts of inherent chirality. Further, we showed the unique cavity structures of the belts and demonstrated interesting chiroptic properties of the inherently enantiopure chiral belts. This research opens the door for the exploration of novel and sophisticated symmetric and inherently chiral molecular nanobelt structures with outstanding physical and chemical properties, as well as potential applications. Download figure Download PowerPoint Introduction Hydrocarbon belts have been fascinating to the chemistry community for more than half a century because of their aesthetically appealing structures, tantalizing physical and chemical properties, and potential applications in the precision fabrication of carbon nanostructures at the atomic level. Due to the formidable challenge in the synthesis of conjugated hydrocarbon belts, the field has remained dormant for decades.1–4 Recent breakthroughs include the successful construction of armchairs,5–7 chiral,7,8 and especially zigzag hydrocarbon belts1,2,9–15 by means of either fjord-stitching reactions of strainless macrocycles10–12 or iterative Diels–Alder reactions9,13–15 of well-designed diene and dienophile precursors, leading to a resurgence of research in the field. As a result, a number of novel hydrocarbon belts consisting of various fused hexagonal1–4,16,17 and nonhexagonal18–26 carbocyclic rings have been prepared very recently. In contrast to hydrocarbon belts, heterocycle-containing or heteroatom-doped linear zigzag molecular belts have remained largely unexplored. In 2019, Wang and Miao27 attempted the synthesis of a tetraazapentacene-pyrene belt. Repetitive and two-directional condensation reactions between o-arylenediamine derivatives and C-shaped bis(o-benzoquinone)s afforded a box-like tetraepoxy belt. However, reductive aromatization reactions allowed the authors to only observe the formation of a 1,4-dihydropyrazine-embedded belt[18]arene derivative using matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry. Belts containing benzo[b][1,4]oxathiine and benzo[b][1,4]dithiine units were synthesized by Zhu and coworkers28,29 based on Ullmann coupling reactions and post-macrocyclization intramolecular electrophilic sulfurization reactions. We23,25,30 have developed a fjord-stitching strategy to construct diverse O/N-doped zigzag octahydrobelt[8]arenes from readily available resorcin[4]arene derivatives based on multiple intramolecular SNAr and intermolecular acridination reactions. Very recently, the construction of tetraaza-bridged octahydrobelt[8]arenes has been achieved by Wang and coworkers31 from fourfold palladium-catalyzed intramolecular C–N bond formation reactions of C4-symmetric resorcin[4]arenes consisting of a 4-amino-6-bromo-1,3-phenylene repeating unit. Further, it is worth noting the work of Chen,32 Itami,33 Wu,34 Tiefenbacher,35 and Tanaka36 who prepared pyrrole-, 1H-azepine-, 1,5-diazocine-, and 4H- and 2H-pyran-containing zigzag-type belts, respectively. Conceivably, the introduction of heteroatoms would generate a wide variety of zigzag belt structures. Particularly, precise inlaying various heteroatoms or site-selective replacing the carbon atoms with heteroatoms of distinct electronegativity would enable fine-tuning of the physical and chemical properties of molecular belts, leading to tailor-made materials useful in the field of supramolecular chemistry and advanced materials. Indeed, it has been shown that doping of heteroatom endowed the resulting zigzag and zigzag-type hydrocarbon belts with interesting photophysical property and molecular recognition ability.28–30,32 Another significant yet entirely unexplored aspect is the chirality of heteroatom-embedded zigzag belts. For example, the presence of different heteroatoms on the edges would desymmetrize the zigzag belt structures leading to antipodes, which are non-superimposable mirror images of each other. Evidently, such chiral belts differ completely from other well-known central, axial, planar, and helical molecules. They are also strikingly distinct from the shortest segments of chiral carbon nanotubes. We envisaged that a unique molecular chirality and unconventional chiral cavities would endow our proposed heteroatom-doped zigzag belts with interesting chiroptical and chiral recognition properties. Herein, we report the construction and structure of a diversity of symmetric and highly enantiopure zigzag-type hydrocarbon nanobelts incorporated with oxygen and nitrogen atoms along the edge from readily available resorcin[6]arenes as starting material. The resulting unprecedented chiral belts possessed large cylindroid cavities and exhibited a solvent-dependent circularly polarized luminescence (CPL) property. Experimental Section Procedure for the synthesis of half belt 3 Into a round bottom flask, complex 2 (4.96 g, 2 mmol), Na2CO3 (1.27 g, 12 mmol, 6 equiv), dimethylformamide (DMF; 30 mL), and H2O (108 mg, 6 mmol, 3 equiv) were added. After stirring for 6 h at 60 °C, the reaction was cooled to room temperature and quenched by adding water. Work-up gave 3 as a white solid (689 mg, 21% yield). Procedure for the synthesis of half belt 4 Into a round bottom flask, compound 2 (2.48 g, 1 mmol), Cs2CO3 (2.60 g, 8 mmol, 8 equiv), DMF (15 mL), and H2O (72–90 mg, 4–5 mmol, 4–5 equiv) were added and kept stirring for 6 h at 60 °C. After cooling to room temperature, the reaction was quenched by the addition of water. Work-up gave 4 as a white solid (434 mg, 32% yield). Procedure for the preparation of belt 7 (Method A) Into a round bottom flask, compound 3 (1.64 g, 1 mmol), K3PO4 (1.27 g, 6 mmol, 6 equiv), DMF (15 mL), and H2O (54 mg, 3 mmol, 3 equiv) were added. Then the mixture was heated for 10 h at 120 °C. After cooling to room temperature, the reaction was quenched by adding water. Work-up gave product 7 as a white solid (507 mg, 64% yield). General procedure for the synthesis of belt 9 A mixture of Pd(OAc)2 (9.0 mg, 0.04 mmol, 40 mol%), rac-(2,2′-bis(diphenylphosphino)-1,1′-binaphthyl) (rac-BINAP; 49.8 mg, 0.08 mmol, 80 mol%), 3 (164 mg, 0.1 mmol), primary amine 8 (0.6–1.0 mmol, 6–10 equiv) and Cs2CO3 (325 mg, 1.0 mmol, 10 equiv) in dry xylenes (17.5 mL) in a in a sealed tube was heated for 48 h at 145 °C under argon. After completion of the reaction, which was monitored by thin-layer chromatography (glass-supported Merck TLC silica gel 60 F254, the reaction was then cooled to room temperature and filtered through a Celite pad. Work-up gave the product 9. Procedure for the synthesis of belt 12 Under the protection of a nitrogen-regulated glovebox, Ni(cod)2 (330 mg, 1.2 mmol, 12 equiv) and a fresh DMF (5 mL) solution of 2,2′-bipyridine (bpy; 187 mg, 1.2 mmol, 12 equiv) were added into a dry Schlenk tube. After stirring at room temperature for 40 min, a dark purple solution was obtained and was then heated at 80 °C. A DMF (5 mL) solution of 3 (164 mg, 0.1 mmol) was added, and the resulting mixture was kept stirring at 80 °C for another 12 h. The reaction was quenched by cooling to room temperature, followed by adding a saturated NH4Cl aqueous solution. Work-up gave product 12 as a white solid (24.6 mg, 33% yield). A two-step-reaction procedure for catalytic enantioselective synthesis of (-)-14 Step 1. A mixture of Pd(OAc)2 (2.2 mg, 0.01 mmol, 20 mol %), (R)- L * (7.4 mg, 0.02 mmol, 40 mol %), 4 (67 mg, 0.05 mmol), 8e (7.4 mg, 0.06 mmol, 1.2 equiv) and Cs2CO3 (32.5 mg, 0.1 mmol, 2 equiv) in dry m-xylene (8.5 mL) in a sealed tube was heated for 12 h at 155 °C. The reaction was quenched by cooling to room temperature and filtering through a Celite pad. Work-up gave 13a and 13b as a mixture (53.9 mg, 81% yield). Step 2. A mixture of Pd(OAc)2 (2.2 mg, 0.01 mmol, 20 mol %), rac-BINAP (12.4 mg, 0.02 mmol, 40 mol %), a mixture of 13a and 13b (66.5 mg, 0.05 mmol) and Cs2CO3 (32.5 mg, 0.1 mmol, 2 equiv) in dry m-xylene (8.5 mL) in a sealed tube was heated at 145 °C for 2 h under argon. The reaction was cooled to room temperature and filtered through a Celite pad. Work-up and silica gel column chromatography gave (-)- 14 as a white solid (50.0 mg, 83% yield). Procedure for the synthesis of 15 A mixture of Pd(OAc)2 (2.2 mg, 0.01 mmol, 20 mol %), rac-BINAP (12.4 mg, 0.02 mmol, 40 mol %), (-)- 14 (59 mg, 0.05 mmol), 8d (8.9 mg, 0.075 mmol, 1.5 equiv) and Cs2CO3 (32.5 mg, 0.1 mmol, 2 equiv) in dry m-xylene (8.5 mL) in a sealed tube was heated for 2 h at 145 °C under argon. The reaction was quenched by cooling to room temperature and filtering through a Celite pad. Work-up gave product 15 (28.9 mg, 58% yield). Procedure for the synthesis of 17 Intermediate (-)- 14 (23.6 mg, 0.02 mmol), bis[(pinacolato)boryl]methane (0.03 mmol, 1.5 equiv), Pd(tBu3P)2 (0.001 mmol, 0.05 equiv), and 1.0 mL of dioxane were mixed in an oven-dried reaction flask. A NaOH aqueous solution (10 M, 10 μL, 5 equiv) was added and the mixture was kept stirring for 48 h at room temperature under nitrogen. After completion of the reaction, the mixture was filtered through a Celite pad. The filtrate was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography to afford product 17 as a colorless oil (10.0 mg, 55%). Further experimental details and full structural characterization of compounds can be found in Supporting Information. Results and Discussion Selective synthesis of oxygen-doped symmetric half-belt compounds Our initial aim was to construct an oxygen-doped zigzag-type belt of a larger size and a cavity following a fjord-stitching strategy developed in our laboratory.30 Resorcin[6]arene 1,37 which was obtained conveniently as a by-product in the synthesis of resorcin[4]arene from a condensation reaction between resorcinol and propionaldehyde was selected as the starting material because of its large and strainless macrocyclic structure. Exhaustive triflation of 1 with an excess amount of trifluoromethanesulfonic anhydride (Tf2O) using pyridine as a base in refluxing PhCF3 for 24 h produced pertriflated resorcin[6]arene 2 in 68% yield. Partial ring closure reactions took place yielding different half-belt products depending on the reaction conditions, especially, the base used. For instance, treatment of 2 with K3PO4 (6 equiv) in dry and warm DMF for 6 h led to 3 in 13% yield, along with the formation of a trace amount of 4. Replacing K3PO4 with Cs2CO3 gave rise to a mixture of 3 and 4 in 7% and 10%, respectively. After carefully surveying the reaction conditions, we were able to prepare half-belts 3 and 4 selectively in acceptable yields. As depicted in Scheme 1, in the presence of Na2CO3 (6 equiv) and H2O (3 equiv), pertriflated resorcin[6]arene 2 was converted to product 3 in 21% ( Supporting Information Table S1) while the isolation of 4 in 32% yield was achieved when Cs2CO3 (8 equiv) and H2O (4–5 equiv) were employed in the transformation of 2 under otherwise the same condition. The addition of water appeared critical to the formation of half-belt products, as the reaction in dry solvent gave much lower yields ( Supporting Information Table S2). Therefore, the formation of O-heterocycle proceeded through most probably a sequence of selective hydrolysis of triflate and spontaneous intramolecular nucleophilic aromatic substitution reaction (SNAr) between two proximal aromatic rings. Sodium and cesium ions might have played subtle templating roles dictating the reaction pathways of 2. It should be noted that the palladium-catalyzed reaction of 2 did not work for the selective synthesis of 3 and 4. From an attempted Pd(PPh3)4-catalyzed reaction of 2, a mixture of products 3 (1%) and 4 (5%) along with a partially hydrolyzed half-belt 5 (8%) were obtained in very low yields. Compound 5 could be the precursor of 4. In addition, a trace amount of compound 6 (Figure 1) was also isolated ( Supporting Information). Figure 1 | Half-belt compounds 5 and 6 isolated from Pd(PPh3)4-catalyzed reaction of 2. Download figure Download PowerPoint Scheme 1 | Selective synthesis of half-belt compounds 3 and 4 from 2. Download figure Download PowerPoint The spectroscopic data were in agreement with the structures of half-belt products 3- 6. 1H, 13C, and 19F-NMR spectra indicated symmetric structures of the compounds in solution. The structures of 3, 4, and 6 were also determined beyond any doubt using X-ray crystallography ( Supporting Information Figures S74–S76).a As illustrated in Figure 2a, half-belt 3, which could be viewed as a calix[3](9H-xanthene) derivative, adopted a cone conformation with roughly C3v-symmetry in the solid state. There were two triflate moieties in each fjord region. In the case of 4, four proximal benzene rings are linearly fused by three 4H-pyran rings in an alternative manner forming a seven-ring-fused C-shaped ribbon. The rest of the two benzene rings were connected by a 4H-pyran to form a 9H-xanthene segment, which tended to flip to nearly a horizontal position relative to the vertically orientated C-shaped ribbon (Figure 2b) because of the steric effect between triflate (OTf) groups in the fjord area. The presence of a mirror plane bisected the molecule. Half-belt 6 consisted of two pieces of curved 12,14-dihydrochromeno[3,2-b]xanthene fragment, generating an oval-shaped cavity (Figure 2c). In the cavity of 6, triphenylphosphine oxide (Ph3PO) was incorporated ( Supporting Information). It is noteworthy that there were short distances of phenoxy oxygen atoms to the proximal phenoxy carbons in all half-belt molecules (Figure 2), implying the possibility of facile intramolecular SNAr reaction, provided one of the triflate groups was hydrolyzed. Figure 2 | Single crystal X-ray molecular structures of 3, 4, and 6. Guest and solvent molecules in 6 were hidden for clarity. Download figure Download PowerPoint Synthesis of heteroatom-embedded symmetric zigzag belt compounds Having half-belt 3 in hand, we set to synthesize oxygen- and nitrogen-doped zigzag belts by closing the rest of the three fjords of resorcin[6]arene with oxygen and nitrogen atoms. Our first target was a symmetric belt that contained six oxygen atoms.30,38 As we expected, in the presence of K3PO4, compound 3 underwent selective hydrolysis and the subsequent SNAr reactions at 120 °C for 10 h in either dimethyl sulfoxide (DMSO) or DMF furnished belt 7 in good yields (Scheme 2). The facile formation of belt 7 inspired us to attempt the direct synthesis of 7 from pertriflated resorcin[6]arene 2 or even from starting resorcin[6]arene 1. Indeed, heating 2 with a mixture of K3PO4 (6 equiv) and water (6 equiv) at 120 °C for 24 h in DMF resulted in the formation of 7 albeit in a low yield of 6% ( Supporting Information). Since the formation of an oxygen-containing six-membered heterocycle was hypothetically due to an SNAr reaction between phenoxy and triflate, we envisioned that selective triflation of one of the phenol moieties in each fjord would probably be followed by a spontaneous ring closure reaction. To our delight, belt 7 was produced in 11% yield from the reaction of resorcin[6]arene 1 with phenyl triflimide (6.3 equiv) under basic conditions (Scheme 2). For a one-pot synthesis of 7 from 1 involving at least the formation of twelve chemical bonds, an overall yield of 11% was obtained, implying an efficiency higher than 83% for each bond-forming reaction. Scheme 2 | Synthesis of hexaoxa-embedded zigzag belt 7. Download figure Download PowerPoint Half-belt 3 was also used as a springboard to create N3,O3-inlayed zigzag belt structures. Scheme 3 depicts examples of the synthesis of symmetric belts by stitching all three fjords of calix[3](9H-xanthene) 3 through triple palladium-catalyzed ring-closing dual C–N bond cross-coupling reaction with nitrogen sources. Under the catalysis of Pd(OAc)2/BINAP, aromatic primary amines, including aniline 8a, 4′-(4,6-diphenyl-1,3,5-triazin-2-yl)aniline 8b, 4-fluoroaniline 8c, 4-aminobenzonitrile 8d and p-anisidine 8e reacted with 3 at 145 °C for 2 days in xylenes to form the corresponding triaza-trioxa-doped belts 9a- e with various aromatic substituents and chromophores decorating along the belt edge (infra vide). Satisfyingly, aliphatic primary amines such as n-butylamine 8f and benzylamine 8g acted as nitrogen sources to stitch the fjords delivering belt products 9f and 9g, respectively. Notably, careful control of the reaction conditions was crucial because a relatively high temperature was necessary for the synthesis. Very low yields or even failure in isolation of desired products were encountered if air (oxygen) was not strictly excluded. Catalytic hydrogenolysis of 9g led to the formation of NH-embedded belt 10, a valuable intermediate for the fabrication of diverse belt products simply based on the versatile reactivities of NH moieties. It is noteworthy that the bromination of 9a with N-bromosuccinimide (NBS) took place exclusively on the N-phenyl substituents to afford product 11 which bore transformable Caryl-Br bonds on the peripheral position. Besides the synthetic value of the method, the extraordinary selectivity of electrophilic aromatic bromination reaction on N-phenyl rather than on any skeletal aromatic ring suggested the latter was much less reactive than the former. In addition to N3,O3-linked zigzag belts, we were also able to synthesize belts, which contained pentagonal subrings by closing each fjord of 3 through a C–C bond forming reaction. As shown in Scheme 3, mediated by Ni(cod)2/2,2′-bypyridine, compound 3 underwent triple intramolecular Yamamoto coupling reactions to form three 5-membered alicyclic rings, affording belt 12 in 33% yield (Scheme 3). Scheme 3 | Synthesis of symmetric heteroatom-doped zigzag belts 9–12. Download figure Download PowerPoint The belt structures of products were determined unambiguously with the single crystal X-ray diffraction method (Figure 3a–f). A few structural features are worth addressing. First, the main core of all belt molecules consisting of hexagonal subrings, irrespective of 4H-pyran and 1,4-dihydropyridine, adopted a very similar C3v-symmetric hexagonal prism structure of roughly a regular hexagon cylinder cavity. The cavity size, which is defined by the distances between distal heteroatoms and between face-to-face paralleled benzene rings, varied within the range of 9.46–9.83 Å and a range of 8.56–8.80 Å, respectively (Figure 3a–f and Supporting Information Figures S77–S82). It should be pointed out that the cavity sizes on the other rim (all carbon rim) of the belts were slightly larger ( Supporting Information Figure S85) because of the longer C–C bonds in comparison with C–O and C–N bonds. Second, all unsaturated heterocyclic subrings gave a boat conformation, a beneficial structure that alleviated the overall macrocyclic strain. Six ethyl groups are axially and equatorially configured in an alternative fashion. Such configurations of ethyl substituents were inherited from the starting material, resorcin[6]arene 1.31 In addition, all N-phenyl groups in 9a are in axial position while all N-4-methoxylphenyls in 9e and benzyls in 9g were bonded in an equatorial position. The different configurations of N-substituents observed were most likely caused by molecular packing at the instant of nucleation. Furthermore, judging from the bond lengths and angles, embedded nitrogen and oxygen atoms did not form strong conjugations with their adjacent in-belt benzene rings. Instead, each nitrogen was conjugated with its aryl substituent on the edge. This accounted for the dominance of electrophilic aromatic bromination reaction occurring on N-phenyl groups when 9a reacted with NBS (infra supra). Evidently, the installation of N-substituents enabled the significant expansion of the belt cavity. Finally, differing from molecules 9- 11, belt 12 gave a bowl-like structure owing to the incorporation of five-membered carbocyclic units. The longest distance at the wider rim was >1 nm (Figure 3f). Figure 3 | Single crystal X-ray molecular structures of belts 7 (a), 9a (b), 9e (c), 9g (d), 10 (e), and 12 (f) with the top (top) and side (bottom) views. Solvent molecules in 9e and 12 were hidden for clarity. Download figure Download PowerPoint Asymmetric synthesis of inherently chiral heteroatom-embedded zigzag belts While half-belt 3 was a versatile platform for the construction of a diversity of C3v-symmetric belts, we expected that half-belt 4 would be an equally important intermediate in belt making, applying the same fjord-stitching reactions developed for 3. More interestingly, half-belt 4 served as a unique building block in the synthesis of inherently chiral heteroatom-doped zigzag belt molecules. Thus, we envisioned that stitching two last fjords of symmetric half-belt 4 using different doping agents would generate non-superimposable mirror-imaged molecular belts. To explore this tempting aspect, we studied the catalytic enantioselective desymmetrization of 4 by closing up one of the fjords through an acridination reaction with p-anisidine 8e. We found that in the presence of Cs2CO3 as a base, the complexes between Pd(OAc)2 and chiral bidentate phosphine ligands L1- L9 were able to catalyze the reaction in refluxing xylenes ( Supporting Information). However, product 14 was isolated in low to moderate yields with enantiomeric excess (ee) values hardly exceeding 70% (entries 1–9, Supporting Information Table S3). No generation of product 14 was observed when a chiral N,P-ligand L10 or a P-centered monodentate chiral phosphine L11 was used as a ligand (entries 10 and 11, Supporting Information Table S3). The use of (R)-4-(anthracen-9-yl)-3-(tert-butyl)-2,3-dihydrobenzo[d][1,3]oxaphosphole L* as a chiral ligand gave rise to highly enantiopure pseudo-belt 14 (ee >99%) in 8% yield. From the reaction, a mixture of inseparable isomers 13a and 13b ( Supporting Information Figure S1), which resulted from a single C–N cross-coupling reaction between 4 and p-anisidine 8e, was also obtained (entry 12, Supporting Information Table S3). Further screening of reaction parameters such as palladium sources, bases, solvents, and temperature (entries 13–29, Supporting Information Table S3) concluded the synthesis of 14 in 29% yield with 97.2% ee under the optimized conditions listed in Scheme 4. Since the transformation from 4 to 14 proceeded via intermediates 13a and 13b, an effort was then focused on two-step synthesis in order to improve the synthetic efficiency. After extensive examination of various conditions ( Supporting Information Table S4), a good yield of a mixture of 13a and 13b was obtained from the reaction between 4 and 8e (1.2 equiv) under the catalysis of Pd(OAc)2 (20 mol %) and L* (40 mol %) (Scheme 4). The measurement of the ee value of 13a or 13b was not successful because one pair of enantiomers was not resolved using the high-performance liquid chromatographic (HPLC) method, testing with various commercially available chiral stationary phase-coated columns. Fortunately, further intramolecular C–N bond cross-coupling reaction was promoted efficiently by a combination of Pd(OAc)2 and rac-BINAP, furnishing the desired acridine-bearing pseudo-belt product 14 in 83% yield with ee >99% (Scheme 4). Its structure, especially the absolute configuration, was established by employing X-ray crystallography (Scheme 4 and Supporting Information Figure S83). The high enantiopurity of 14 suggested excellent enantioselectivity of the desymmetrizative C–N bond formation reaction of 4 with p-anisidine 8e. Noteworthily, this represented an unprecedented example of creating inherent chirality of pseudo-belt molecules based on the transfer of a ligand's chirality in a catalytic fashion. Scheme 4 | Catalytic enantioselective synthesis of pseudo-belt (-)-14 and its single crystal X-ray molecular structure, showing the absolute configuration. Download figure Download PowerPoint Starting from enantioenriched pseudo-belt (-)- 14, which contained two perfectly predisposed triflate moieties (Scheme 4), novel highly enantiopure heteroatom-doped zigzag-type belt compounds were synthesized conveniently by means of efficacious fjord-stitching strategy. An example, demonstrated in Scheme 5 is the acridination of (-)- 14 with 4-cyanoaniline ( 8d) catalyzed by Pd(OAc)2/rac-BINAP. The reaction proceeded smoothly in refluxing m-xylene to afford a straightforward diazatetraoxa-bearing belt (+)- 15 in 58% yield. Remarkably, an inherent chirality was generated only from two different substituents, viz., methoxy and cyano, which were even remote from the belt core. In other words, a small variation of substituents at the remote position along the edge could break the symmetry of a belt. Another exciting example was the construction of the chiral molecule (-)- 16, a belt having a 5-membered alicyclic subring. In the presence of an excess amount of Ni(cod)2/2,2′-bipyridine, nickel-mediated intramolecular homo coupling reaction of pseudo-belt (-)- 14 took place efficiently to produce a good yield of 16. On the other hand, triflate groups of 14 were readily hydrolyzed under mild basic conditions to form bis-hydroxylated pseudo-belt 17. Taking advantage of the facile reactions of hydroxy groups of resorcin[4]arenes in the synthesis of well-known cavitands,38–40 we subjected 17 to the reaction with 2,3-dichloroquinoxaline. As anticipated, quinoxaline-fused belt compound