2022 Volume 70 Issue 9 Pages 605-615
The preparation, optical resolution, and structural investigations of a series of axially chiral biaryl dicarboxylic acids bearing oxygen, sulfur, and selenium atoms were carried out. The crystal structures of sulfur- and selenium-containing derivatives revealed that the carboxy groups of these compounds are located in a co-planar geometry with the fused aromatic rings including the chalcogen atoms. These conformational controls were found to be achieved by chalcogen-bonding interactions between chalcogen atoms in the aromatic rings and oxygen atoms in the carboxy groups. Even in the case of a binaphthofuran derivative, in which the formation of chalcogen-bonding interactions was expected to be negligible, the carboxy groups were also found to be located in a co-planar geometry toward its fused cyclic rings. Natural bond orbital (NBO) analyses of these dicarboxylic acids indicated the formation not only for the chalcogen-bonding interactions for S and Se derivatives, but also the tetrel-bonding interactions between the oxygen atoms in the carboxy groups and the carbon atoms in the fused cyclic rings for all biaryl dicarboxylic acids. These tetrel-bonding interactions were thought to contribute to conformational control in the binaphthofuran derivative. Physical and chiroptical properties such as the racemization barriers and circular dichroism (CD) spectra of these biaryl dicarboxylic acids were also revealed.
The chalcogen-bonding interaction is known as an attractive non-covalent interaction between chalcogen atoms (S, Se, Te) and heteroatoms such as oxygen and nitrogen.1–5) This attractive interaction garnered significant attention as attractive forces for controlling molecular structures of bioactive compounds1,6) and organic materials,3,7,8) as well as driving forces for catalytic organic transformations.4,5,9–16)
We have recently developed chiral dirhodium(II) carboxylate complex 1 as a catalyst for asymmetric intramolecular C–H insertion reactions.17) A crystal structure showed the formation of chalcogen-bonding interactions between the sulfur atoms in the fused cyclic systems and the oxygen atoms of the carboxylate groups as well as the amide moieties in the D2 symmetric structure of catalyst 1 (Fig. 1). These chalcogen-bonding interactions were thought to work as a conformational lock for constructing the defined molecular space of the catalyst with uniform chiral environments around both the Rh(1) and Rh(2) catalytic centers (Fig. 1A). Furthermore, the effective chiral space was formed by the tilted aromatic rings (blue color) of the biaryl ligands toward the catalytic centers by virtue of the conformational lock through the chalcogen-bonding interactions (Fig. 1B). This uniform stereostructure and the conformational lock of 1 were thought to be key to the remarkable asymmetric induction in the intramolecular C–H insertion reactions of α-aryl-α-diazoacetate derivatives (Fig. 1C).
(A) Inclined side view of (S)-1. (B) Side view of (S)-1. (C) Intramolecular C–H insertion reactions catalyzed by (S)-1.
It is known that the chalcogen-bonding interaction becomes stronger in the order of the chalcogen atoms, tellurium > selenium > sulfur.5) We envisioned that if the rhodium complexes bearing other chalcogen atom including oxygen instead of sulfur are prepared, the significance and impact of the chalcogen-bonding interaction on the conformational control of 1 will be further clarified.
Catalyst 1 was prepared from axially chiral binaphthothiophene dicarboxyxlic acid 3 (Fig. 2) as a key intermediate17,18) and the preparation of axially chiral dicarboxylic acids bearing chalcogen atoms are indispensable for developing a series of dirhodium carboxylate complexes. This background motivated us to investigate the syntheses, structural features, and physical properties of optically active dicarboxylic acids 2, 4, 519–21) and 619) bearing oxygen and selenium atoms in their fused cyclic ring systems (Fig. 2). Herein, we report the syntheses, stereostructures, and physical properties of optically active axially chiral biaryl dicarboxylic acids 2, and 4–6 bearing chalcogen atoms.
First, we examined the synthesis and optical resolution of binaphthoselenophene dicarboxylic acid 4 according to the preparation of 318) (Chart 1). Naphthoselenophene bromide 8 was prepared from the cyclization of 7 in the presence of SeO2 according to the reported procedure.22) Ullmann coupling reaction of 8 and subsequent hydrolysis afforded (dl)-4 in 83% yield in two steps. We had previously developed a method for optical resolution of 3 by fractional crystallization of the corresponding diastereomeric salts with chiral diamine 9. This strategy was also applicable in this case. According to the procedure for (dl)-3, (dl)-4 was treated with 0.5 equivalent (equiv.) of diamine (S,S)-9 in acetone. While stirring the mixture at room temperature, one of the diastereomeric complexes, 4·(S,S)-9, was exclusively precipitated. From this complex, optically active dicarboxylic acid 4 was obtained in 25% yield with >99% ee after removal of (S,S)-9. Optical resolution with the enantiomeric amine (R,R)-9 gave (R)-4 in a similar manner. The absolute configuration of the axial chirality of 4 obtained with (S,S)-9 was determined to be S by its circular dichroism (CD) spectrum showing a similar Cotton effect to that of (S)-3, in which the absolute configuration was determined by X-ray analysis18) as described below.
This procedure for optical resolution was also applied for bibenzothiophene and bibenzoselenophene dicarboxylic acids 5 and 6. These cases, however, gave unsatisfactory results. Tanaka and Osuga reported the preparation of optically active biaryl bearing sulfur atoms, which is structurally similar to 3, through the separation of the diastereomers of the oxazoline derivatives.20,23) Inspired by this protocol, we prepared chiral oxazoline derivatives 10a, 10b,20) and 10c for optical resolution of 2, 5, and 6, respectively, from the corresponding carboxylic acids with L-valinol (for details, see Supplementary Materials). The Ullmann coupling reaction of these precursors gave the corresponding diastereomeric mixtures of biaryls (S,S,Ra)- and (S,S,Sa)-11a–c (Chart 2).
Opening of the oxazoline groups of 11a–c by treatment of trifluoroacetic acid (TFA) and subsequent acetylation afforded diastereomeric mixtures, which were separated by preparative HPLC to give (S,S,Ra)-12a–c and (S,S,Sa)-12a–c. Each separated diastereomer was hydrolyzed under basic conditions to give the corresponding enantiomer of 2, 5, and 6. The optical purities of these dicarboxylic acids were determined to be >99% ee by HPLC analyses with a chiral stationary phase. The absolute configuration of 2 was determined by comparing the CD spectrum with that of 3. Moreover, the absolute configuration of 6 obtained from (S,S,Sa)-12c was determined to be S by X-ray analysis as shown below.
X-Ray, Natural Bond Orbital (NBO) Analyses, and Physical PropertiesThe crystal structure of the S configured enantiomer in the racemic crystal of 3 is depicted in Fig. 3(B).18) This crystal structure exhibited a twisted biaryl system around the chiral axis with dihedral angles of 81.4(3)° (ϕa,b–c,d) as reported previously (Fig. 3B(1)). In this structure, both the carboxy groups were located in a co-planar geometry toward the naphthothiophene rings (the dihedral angle in upper side moiety I: ϕS,C–C,O = −3.4(2)° and the dihedral angle in lower side moiety II: ϕS,C–C,O = −15.8(2)°). These co-planar orientations were supposed to be achieved by the chalcogen-bonding interactions between sulfur atoms in the naphthothiophene rings and the oxygen atoms in the carboxy groups. Although the presence of the chalcogen-bonding interactions was supported by the short contacts between these sulfur atoms and the oxygen atoms (la = 2.810(2) Å, lb = 2.921(2) Å), both of which were shorter than the sum of the van der Waals radii of sulfur and oxygen atoms (3.32 Å), quantitative analysis has yet to be investigated.
In this study, NBO analysis was carried out based on the crystal structure of 3 for quantitative analysis of chalcogen-bonding interactions. As shown in Fig. 3B(2), delocalization of lone pairs of electrons on the oxygen atoms in the carboxy moieties into adjacent σ*S–C orbitals was observed. The corresponding second-order perturbation energies ES…O were determined to be 0.96 and 0.54 kcal/mol for the carboxy groups in moiety I and moiety II, respectively, at the ωB97XD/6-311G(d,p) level of the theory (for details, see Supplementary Materials). These orbital interactions obviously showed the formation of chalcogen-bonding interactions.24)
Interestingly, alternative orbital overlaps between lone pairs of the carbonyl groups and σ*C–S orbitals embedded in the naphthothiophene rings were also observed as shown in Fig. 3B(3) (EC…O = 1.09 kcal/mol for moiety I and 1.07 kcal/mol for moiety II). These orbital interactions involving carbon atoms are known as tetrel-bonding interactions.25) Therefore, the NBO analyses suggested that not only the chalcogen-bonding interactions, but also the tetrel-bonding interactions contributed to the conformational control of the carboxy groups in 3.
We further conducted X-ray and NBO analyses of binaphthofuran and binaphthoselenophene derivatives (R)-2 and (dl)-4 (Figs. 3A, 3C). The crystal structure of the R configured enantiomer in the racemic crystal of 4 is depicted in Fig. 3C. It was revealed that the naphthoselenophene rings were twisted in a perpendicular geometry around the chiral axis with dihedral angles of −94.9(5)° (ϕa,b–c,d) (Fig. 3C(1)). Similar to the crystal structure of 3, short contacts between the selenium atoms in the naphthoselenophene rings and the oxygen atoms in the carboxy groups (la = 2.933(3) Å, lb = 2.996(3) Å), which were shorter than the sum of the van der Waals radii of selenium and oxygen (3.42 Å), were observed. The carboxy groups were found to be located in co-planar geometries toward the naphthoselenophene rings (ϕSe,C–C,O in moiety I: –2.3(5)° and ϕSe,C–C,O in moiety II: 15.1(5)°), as observed in 3. NBO analyses supported the formation of chalcogen-bonding interactions (nO→σ*Se–C) between selenium and oxygen atoms as depicted in Fig. 3C(2) (ESe…O = 1.18 kcal/mol for moiety I and 1.15 kcal/mol for moiety II).24) Furthermore, tetrel-bonding interactions (nO→σ*C–Se) between the carbonyl groups and the naphthoselenophene rings were also observed (Fig. 3C(3), EC…O = 1.14 for moiety I and 0.63 kcal/mol for moiety II). These observations indicate that the carboxy groups of 4 were conformationally locked by both chalcogen-bonding as well as tetrel-bonding interactions.
On the other hand, in the case of binaphthofuran derivative 2, we initially expected that the co-planar conformation of the carboxy groups towards the naphthofuran rings could not be maintained, and the dihedral angles (ϕO,C–C,O) would be increased, because the electrostatic repulsion between the oxygen atoms of the carbonyl groups and the oxygen atoms in the naphthofuran rings might dominate over their attractive chalcogen-bonding interactions. However, contrary to our expectations, short contacts between the oxygen atoms (la = 2.668(6) Å, lb = 2.717(5) Å), both of which are less than the sum of the van der Waals radii of oxygen atoms (3.00 Å), were observed and the carbonyl groups and the naphthofuran rings were found to be in almost co-planar geometries (ϕO,C–C,O=−11.2(7)° for moiety I and ϕO,C–C,O=−14.7(8)° for moiety II) (Fig. 3A(1)). On the other hand, in accordance with our expectation, NBO analyses indicated no chalcogen-bonding interactions were formed between the oxygen atoms in the carboxy groups and the naphthofuran rings. However, tetrel-bonding interactions (nO→σ*C–O) were observed between the carbon atoms in naphthofuran rings and the oxygen atoms in the carboxy groups (EC…O = 1.22 kcal/mol for moiety I and 0.78 kcal/mol for moiety II) even in this case (Fig. 3A(3)). This observation suggested that the conformation of the carboxy groups of 2 was controlled by tetrel-bonding interactions rather than chalcogen-bonding interactions.26)
We further evaluated the crystal structures of bibenzothiophene and bibenzoselenophene dicarboxylic acids 5 and 6. The crystal structure of (R)-5 has already been reported as depicted in Fig. 4A.20) Further structural and NBO analyses were conducted in this study, using the reported crystal structure. As shown in Fig. 4A(1), the benzothiophene rings were twisted around the chiral axis at wider dihedral angles (ϕa,b-c,d=−121.7(2)°) than that of binaphthothiophene derivative 3 (ϕa,b–c,d = 81.4(3)°). On the other hand, similar to 3, short contacts between the sulfur atoms and the oxygen atoms of the carboxy groups (la = 2.978(2) Å, lb = 2.982(2) Å), and narrow dihedral angles between the carbonyl groups and the benzothiophene rings were observed (ϕS,C–C,O = 18.6(3)° in moiety I and ϕS,C–C,O = 18.5(2)° in moiety II). These structural properties indicated that formation of the chalcogen-bonding interactions, which were also supported by the NBO analyses as depicted in Fig. 4A(2) (ES…O = 0.57 kcal/mol for moiety I and 0.55 kcal/mol for moiety II).24) Furthermore, tetrel-bonding interactions (nO→σ*C–S) between the carbonyl groups and the benzothiophene rings were also observed (Fig. 4A(3), EC…O = 0.80 for moiety I and 0.68 kcal/mol for moiety II).
X-ray analysis of (S)-6 was successfully achieved and the absolute configuration of axial chirality was determined. As shown in Fig. 4B(1), the dihedral angle of the chiral axis (ϕa,b–c,d) was found to be 120(1)°, which is similar to that of (R)-5 (ϕa,b–c,d=−121.2(7)°). These wide dihedral angles could be one of the structural features of these bibenzochalcogenophene-type compounds. Short contacts between selenium atoms in the benzoselenophene rings and oxygen atoms in the carboxy groups were also observed (la = lb = 3.04(1) Å), and each dihedral angle around the C–C bond of the carboxy group (ϕSe,C–C,O) was found to be −15(1)°. NBO analysis proved the formation of the chalcogen-bonding interactions (nO→σ*Se–C) between selenium and oxygen atoms as shown in Fig. 4B(2) (ESe…O = 1.01 kcal/mol for moieties I and II).24) Moreover, tetrel-bonding interactions (nO→σ*C–Se) between the carbonyl groups and the benzothiophene rings were also observed in this crystal structure (Fig. 4A(3), EC…Se = 0.63 for moieties I and II).
Taking the non-covalent interactions presented in bicarcogenophene dicarboxylic acids 2–6 into account, the extent of conformational control of the carboxy groups in 3–6 bearing sulfur and selenium atoms were thought to be further effective than that of 2 through the additional chalcogen-bonding interactions, although the carboxy groups of 2 were also conformationally fixed through tetrel-bonding interactions. These differences in conformational control might affect the catalytic performance as well as asymmetric induction, if these derivatives are incorporated as chiral ligands of transition-metal catalysts or as a partial structure of organocatalysts.
13C-NMR spectra of these dicarboxylic acids also supported the formation of the chalcogen-bonding interactions. In the series of naphthocarcogenophene derivatives, the downfield shifts of the 13C signals of the carbonyl carbon atoms were observed in order from oxygen derivative 2 (162.1 ppm), sulfur derivative 3 (165.1 ppm), to selenium derivative 4 (166.2 ppm) in MeOH-d4, although all of these signals appeared in a upper field than that of 1,1′-binaphthalene-2,2′-dicarboxylic acid (13)27,28) (168.9 ppm) (Table 1). In the case of benzocarcogenophene derivatives, the 13C signal of selenium derivative 6 (166.3 ppm) also appeared in a slightly lower field than that of the sulfur derivative 5 (165.2 ppm). This tendency of 13C-NMR shifts is found to follow the order of the strength of the chalcogen-bonding interaction.14)
| Compound | 2 | 3 | 4 | 5 | 6 | 13 |
|---|---|---|---|---|---|---|
| 13C-NMR (ppm) | 162.1 | 165.1 | 166.2 | 165.2 | 166.3 | 168.9 |
| pKa1 | 2.26 | 2.52 | 3.26 | 2.73 | 2.93 | 2.58 |
| pKa2 | 4.19 | 4.56 | 6.00 | 4.55 | 6.01 | 6.31 |
We assumed that the acidity of these compounds might reflect the extent of the chalcogen-bonding interactions. The pKa values of 2–6 were measured in H2O/dimethyl sulfoxide (DMSO) by the capillary electrophoresis method.29) However, as shown in Table 1, each dicarboxylic acid gave similar 1st pKa (2.3–3.3) and 2nd pKa (4.2–6.3) values. The pKa value of 13 (1st pKa value (2.58) and 2nd pKa value (6.31)) as a comparative biaryl compound without chalcogen atoms was similar to those of 2–6. Contrary to our expectation, for the time being, the effects of chalcogen-bonding interactions on the acidity of the carboxylic acids could not be clarified.
Configurational Stabilities of Benzocarcogenophene Dicarboxylic AcidsConfigurational stability of axially chiral biaryls is essential information for applying them as chiral elements for asymmetric transformation as well as the study of chiral recognition. Particularly, configurational stabilities of benzocarcogenophene derivatives 5 and 6 have to be revealed, although naphthocarcogenophene derivatives 2–4 were expected to possess higher racemization barriers due to their wider fused aromatic rings.
As expected, racemization of 3 was not observed under reflux conditions in chlorobenzene (boiling point: 132 °C) for 3 d. On the other hand, 5 and 6 were found to racemize under the same conditions. Although the racemization barrier of 5 was reported previously,30) it was measured in our study for comparison to 6 under the same conditions. With continuous heating of (S)-5 in chlorobenzene under reflux conditions, decreases of optical purity was monitored by HPLC analysis equipped with the chiral stationary phase. The racemization barrier of 5 was determined to be 33.2 kcal/mol (132 °C) by the kinetic profile (for details, see Supplementary Materials). Under the same conditions, the racemization barrier of 6 was also measured and determined to be 33.8 kcal/mol (132 °C). These similar racemization barriers showed that differences in chalcogen atoms had no significant impact on the racemization process. Furthermore, the racemization barriers supported configurational stabilities of 5 and 6 are high enough to employ these as chiral elements for ligands or catalysts under ambient conditions.
CD Spectra for Determination of the Absolute Configurations of 2 and 4To determine the absolute configurations of 2 and 4, CD spectra of these compounds were measured and compared to those of (R)- and (S)-3, whose absolute configurations were determined by X-ray analysis in our previous report.18) As shown in Fig. 5A, (R)-3 showed a negative Cotton effect from 256 to 237 nm, and a positive Cotton effect from 236 to 218 nm; its enantiomer (S)-3 showed a spectrum which was an exact mirror image of CH3CN. By comparison against these spectra, we determined that the enantiomer of 2 that showed negative-to-positive Cotton effects from longer to shorter wavelengths was the R configuration, while the enantiomer exhibiting positive-to-negative Cotton effects from the longer wavelength was determined to be the S configuration (Fig. 5B). Similarly, the absolute configurations of the enantiomers of 4 were determined by comparison of their CD spectra with 3 as shown in Fig. 5C.
In conclusion, the preparation and optical resolution of axially chiral binaphtho-, as well as bibenzocarcogenophene dicarboxylic acids 2 and 4–6, bearing oxygen, sulfur, and selenium atoms in their fused aromatic rings were achieved. The crystal structures and NBO analyses revealed that not only the chalcogen-bonding interactions but also the tetrel-bonding interactions contributed to the conformational control of their carboxy groups. Transformations of 2 and 4–6 toward the corresponding dirhodium(II) carboxylate complexes are currently underway in our laboratory.
Uncorrected melting points were measured by using a Büchi Melting Point M-565. NMR spectra were obtained with a Bruker UltraShield 300 spectrometer, or a Bruker Ascend 500 spectrometer. Chemical shifts are given in units of ppm (1H-NMR in CDCl3: tetramethylsilane as the internal standard at 0 ppm, and CDCl3 as the internal standard at 7.26 ppm; 13C-NMR in CDCl3: CDCl3 as the internal standard at 77.16 ppm. 1H-NMR in acetone-d6: acetone-d6 as the internal standard at 2.05 ppm; 13C-NMR in acetone-d6: acetone-d6 as the internal standard at 29.84 ppm and 206.26 ppm. 1H-NMR in methanol-d4: methanol-d4 as the internal standard at 3.31 ppm; 13C-NMR in methanol-d4: methanol-d4 as the internal standard at 49.00 ppm. 1H-NMR in DMSO-d6: DMSO-d6 as the internal standard at 2.50 ppm; 13C-NMR in DMSO-d6: DMSO-d6 as the internal standard at 39.52 ppm). Spin–spin coupling constants are given in units of Hz. IR spectra were recorded on a JASCO FT-IR 4600 spectrometer. The high-resolution mass spectra (HRMS) were recorded on a JEOL GCmate II (for EI), a JEOL MStation JMS-700 spectrometer (for FAB), and a Shimadzu LCMS-IT-TOF (for ESI). The specific rotation was recorded on a JASCO P-2200 polarimeter. UV/Vis spectra were recorded on a JASCO V-550 UV/Vis spectrophotometer. CD spectra were recorded on a JASCO J-720W spectropolarimeter. All microwave experiments were performed with a Biotage Initiator+.
Column chromatography on silica gel was carried out using Silica gel 60 N (spherical, neutral, 63–210 µm, Kanto Chemical Co., Inc., Tokyo, Japan). TLC analyses and preparative TLC (PTLC) analyses were performed on commercial glass plates bearing a 0.25 mm layer or a 0.5 mm layer of Merck Kiesel-gel 60 F254, respectively. Analytical HPLC was carried out with a JASCO PU-4180 instrument equipped with a COSMOSIL CHiRAL 5A (4.6 × 250 mm) or a COSMOSIL CHiRAL 5B (4.6 × 250 mm) and a JASCO UV-4075 UV/Vis detector (detection: 254 nm). Preparative HPLC was run with a YMC Multiple Preparative HPLC LC-forte/R instrument equipped with a COSMOSIL 5SL-II (20 × 250 mm).
All chemical reagents were obtained from common commercially sources and used as received.
[1,1′-Binaphtho[2,1-b]thiophene]-2,2′-dicarboxylic Acid ((dl)-3)1H-NMR (300 MHz, CD3OD) δ: 6.90–7.00 (2H, m), 7.20–7.30 (4H, m), 7.80–7.90 (4H, m), 8.00 (2H, d, J = 8.7 Hz); 13C-NMR (75 MHz, CD3OD) δ: 121.7, 123.3, 126.4, 127.9, 130.0, 130.2, 130.6, 131.8, 133.4, 134.9, 141.7, 142.0, 165.1
Methyl 1-Bromonaphtho[2,1-b]selenophene-2-carboxylate (8)Selenium dioxide (8.86 g, 79.8 mmol, 2.00 equiv.) was dissolved in 48 wt% of aqueous hydrogen bromide (39.7 mL, 351 mmol, 8.80 equiv.) at room temperature (r.t.) After being stirred at r.t. for 30 min, a solution of 731) (8.39 g, 39.9 mmol, 1.00 equiv.) and cyclohexene (4.85 mL, 47.9 mmol, 1.20 equiv.) in 1,4-dioxane (200 mL) was added dropwise, and the reaction mixture was stirred at 70 °C for 12 h. Then, the resulting mixture was diluted with AcOEt and water, and extracted with AcOEt. The organic layer was washed with brine, dried over Na2SO4, filtered, and concentrated in vacuo to give a residue. The residue was purified by column chromatography (SiO2, n-hexane–AcOEt = 9 : 1), and the obtained solid was further washed with CHCl3/n-hexane to afford 8 (6.49 g, 44% yield).
Pale yellow solid; mp 130–131 °C; 1H-NMR (300 MHz, CDCl3) δ: 3.96 (3H, s), 7.55–7.74 (2H, m), 7.78–7.89 (2H, m), 7.89–8.00 (1H, m), 10.01 (1H, d, J = 8.7 Hz); 13C-NMR (75 MHz, CDCl3) δ: 52.8, 115.5, 123.0, 123.3, 126.2, 126.8, 129.3, 129.4, 129.6, 131.9, 132.6, 133.0, 143.2, 163.2; IR (neat) cm−1: 1718, 1480, 1212, 1192, 1047, 804, 787, 777, 752, 675; HR-EI-MS m/z: 367.8953 (M)+ (Calcd for C14H9BrO2Se: 367.8951).
[1,1′-Binaphtho[2,1-b]selenophene]-2,2′-dicarboxylic Acid ((dl)-4)A solution of 8 (4.88 g, 13.3 mmol, 1.00 equiv.) and Cu powder (4.21 g, 66.3 mmol, 5.00 equiv.) in DMF (20 mL) was refluxed for 7 h under a N2 atmosphere. After cooling to r.t., the reaction mixture was filtered, washed with CHCl3 to remove Cu, and concentrated in vacuo to give a residue. The residue was purified by column chromatography (SiO2, n-hexane–AcOEt = 4 : 1 to CHCl3 only) to afford (dl)-dimethyl [1,1′-binaphtho[2,1-b]selenophene]-2,2′-dicarboxylate as a solid containing DMF (3.70 g). The obtained solid was further washed with CHCl3/n-hexane to give (dl)-dimethyl [1,1′-binaphtho[2,1-b]selenophene]-2,2′-dicarboxylate for physical data collection (see Supplementary Materials).
To a solution of crude (dl)-dimethyl [1,1′-binaphtho[2,1-b]selenophene]-2,2′-dicarboxylate (3.70 g) in THF–MeOH–H2O (2 : 1 : 1, 200 mL), KOH (5.00 g, 75.7 mmol, 11.8 equiv.) was added at r.t. After being refluxed for 5 h, the reaction mixture was cooled to r.t., and washed with cyclopentyl methyl ether (CPME). The aqueous layer was acidified with 2N aq. HCl, and extracted with AcOEt. The organic layer was washed with brine, dried over Na2SO4, filtered, and concentrated in vacuo to give a residue. The residue was washed with CHCl3 to afford (dl)-4 (3.03 g, 83% yield in 2 steps from 8). The single crystal of (dl)-4 for X-ray analysis was obtained by recrystallization from MeOH.
Colorless solid; mp >300 °C; 1H-NMR (300 MHz, acetone-d6) δ: 7.04 (2H, ddd, J = 8.6, 6.9, 1.4 Hz), 7.25–7.50 (4H, m), 7.92–8.01 (4H, m), 8.30 (2H, d, J = 8.8 Hz), 11.20 (2H, br s); 13C-NMR (75 MHz, acetone-d6) δ: 123.3, 124.8, 126.3, 127.6, 129.4, 130.2, 133.0, 133.3, 134.1, 136.6, 144.8, 145.8, 164.3; 1H-NMR (300 MHz, CD3OD) δ: 6.88–6.98 (2H, m), 7.18–7.28 (2H, m), 7.31–7.40 (2H, m), 7.81 (4H, d, J = 8.5 Hz), 8.08 (2H, d, J = 8.7 Hz); 13C-NMR (75 MHz, CD3OD) δ: 123.6, 124.6, 126.4, 127.6, 129.7, 130.2, 133.3, 133.6, 134.4, 136.9, 145.2, 146.5, 166.2; IR (neat) cm−1: 1672, 1645, 1479, 1435, 1308, 1262, 1199, 796, 709, 455; HR-EI-MS m/z: 549.9223 (M)+ (Calcd for C26H14O4Se2: 549.9222).
Crystallographic data of (dl)-4: C26H14O4Se2, M = 548.29, 0.30 × 0.30 × 0.30 mm3, monoclinic, P21/n, a = 10.0447(3) Å, b = 10.1059(3) Å, c = 25.0609(7) Å, α = 90°, β = 95.305(7)°, γ = 90°, V = 2533.05(13) Å3, Z = 4, ρcalcd = 1.438 gcm–3, T = 293(2) K, 24413 reflections measured, 4612 unique. The final R1 and wR were 0.0565 and 0.1386 (all data). These data have been deposited with the Cambridge Crystallographic Data Center as CCDC 2144807.
Optical Resolution of (dl)-4Racemic 4 (500 mg, 912 µmol, 1.00 equiv.) was completely dissolved in acetone (100 mL) at r.t. To the solution, a solution of (1S,2S)-9 (96.8 mg, 456 µmol, 0.500 equiv.) in acetone (10 mL) was added at r.t. After being stirred at r.t. for 21 h, the precipitated solids were collected and washed with acetone. The obtained solids were dissolved in acetone/2N aq. HCl, and the solution was extracted with AcOEt. The organic layer was washed with brine, dried over Na2SO4, filtered, and concentrated in vacuo to give a residue. The residue was washed with CHCl3 to afford (S)-4 (124 mg, 25% yield). The enantiomeric excess (ee) of (S)-4 was determined to be >99% ee by HPLC analysis; HPLC (CHiRAL 5B (4.6 × 250 mm), n-hexane–EtOH–TFA = 90 : 10 : 0.1, flow rate = 1.0 mL/min, l = 254 nm) tR = 12.1 min (for (R)-4), 17.5 min (for (S)-4). (R)-4 was also obtained from (dl)-4 with (1R,2R)-9 instead of (1S,2S)-9.
(R)-4: [α]D19 +157.9 (c = 0.8, MeOH, >99% ee); CD λext (MeCN) nm (Δε): 345 (15.6), 330 (13.0), 293 (4.35), 272 (3.89), 246 (−90.0), 232 (98.8), 211 (−18.5); UV λmax (MeCN) nm (log ε): 338 (4.42), 327 (4.48), 290 (4.23), 236 (4.74), 205 (4.67).
(S)-4: CD λext (MeCN) nm (Δε): 345 (−14.8), 329 (−12.7), 293 (−4.25), 271 (−3.48), 246 (83.5), 232 (−93.1), 211 (15.0).
(Ra)- and (Sa)-Bis((S)-2-acetamido-3-methylbutyl) [1,1′-Binaphtho[2,1-b]furan]-2,2′-dicarboxylate ((S,S,Ra)-12a and (S,S,Sa)-12a)A solution of 10a (4.96 g, 12.2 mmol, 1.00 equiv.) and Cu powder (6.22 g, 97.9 mmol, 8.00 equiv.) in DMF (40 mL) was refluxed for 10 h under a N2 atmosphere. After cooling to r.t., the reaction mixture was filtered and washed with AcOEt to remove Cu. The filtrate was diluted with H2O, and extracted with AcOEt. The organic layer was washed with brine, dried over Na2SO4, filtered, and concentrated in vacuo to give a residue. The residue was purified by column chromatography (SiO2, n-hexane–AcOEt = 7 : 3 to 3 : 2) to afford diastereomeric mixture of (S,S,Ra)- and (S,S,Sa)-11a (1.88 g).
To a solution of diastereomeric mixture of 11a (1.88 g, 3.38 mmol, 1.00 equiv.) in THF (20 mL), TFA (10 mL, 130 mmol), H2O (2.0 mL, 111 mmol), and Na2SO4 (20 g, 141 mmol) were added at r.t. After being stirred at r.t. for 15 min, the reaction mixture was filtered, and concentrated in vacuo to give a residue. Then, to a solution of the residue in CH2Cl2 (20 mL), pyridine (10 mL, 124 mmol) and Ac2O (10 mL, 106 mmol) were added at r.t. under a N2 atmosphere. After being stirred at r.t. for 12 h, the reaction mixture was quenched with 2N aq. HCl, and extracted with CHCl3. The organic layer was washed with brine, dried over Na2SO4, filtered, and concentrated in vacuo to give a residue. The residue was purified by column chromatography (SiO2, CHCl3–MeOH = 10 : 1) to afford diastereomeric mixture of 12a. This diastereomeric mixture of 12a was separated by recycled prep. HPLC to give 1.10 g of (S,S,Ra)-12a (TLC-up isomer, 27% yield in 3 steps from 10a) and 849 mg of (S,S,Sa)-12a (TLC-down isomer, 21% yield in 3 steps from 10a); HPLC (COSMOSIL 5SL-II (20 mm×250 mm), CHCl3–acetone = 10 : 1, flow rate = 20 mL/min, l = 254 nm).
(S,S,Ra)-12a: Pale yellow amorphous; [α]D17 –116.2 (c = 0.7, CHCl3); 1H-NMR (300 MHz, CDCl3) δ: 0.38 (2H, dq, J = 9.7, 6.6 Hz), 0.56 (6H, d, J = 6.6 Hz), 0.67 (6H, d, J = 6.6 Hz), 1.24 (6H, s), 3.40–3.60 (2H, m), 3.91 (2H, d, J = 9.3 Hz), 4.10–4.25 (4H, m), 7.30 (2H, ddd, J = 8.3, 7.0, 1.3 Hz), 7.48 (2H, ddd, J = 8.3, 7.1, 1.3 Hz), 7.52–7.59 (2H, m), 7.94 (2H, d, J = 9.1 Hz), 7.97–8.03 (2H, m), 8.03–8.10 (2H, m); 13C-NMR (75 MHz, CDCl3) δ: 19.0, 19.3, 22.6, 28.5, 53.0, 65.9, 113.2, 120.7, 121.5, 122.3, 126.3, 128.2, 128.5, 129.7, 130.9, 131.2, 141.3, 154.1, 159.1, 169.4; IR (neat) cm−1: 1715, 1649, 1530, 1318, 1279, 1154, 806, 746, 517, 422; HR-FAB-MS m/z: 677.2870 (M + H)+ (Calcd for C40H41N2O8: 677.2863).
(S,S,Sa)-12a: Pale yellow amorphous; [α]D18 –174.5 (c = 0.5, CHCl3); 1H-NMR (300 MHz, CDCl3) δ: 0.16–0.37 (8H, m), 0.41–0.51 (6H, m), 1.92 (6H, s), 3.46–3.60 (2H, m), 4.01–4.21 (4H, m), 4.89 (2H, d, J = 9.0 Hz), 7.20–7.29 (2H, m), 7.45 (2H, ddd, J = 8.2, 7.0, 1.2 Hz), 7.53 (2H, dd, J = 8.3, 1.1 Hz), 7.90 (2H, d, J = 9.1 Hz), 7.94–8.01 (2H, m), 8.05 (2H, d, J = 9.1 Hz); 13C-NMR (75 MHz, CDCl3) δ: 18.7, 19.2, 23.1, 28.2, 53.2, 66.1, 112.6, 120.9, 121.8, 122.4, 126.1, 128.2, 128.5, 129.5, 131.1, 131.2, 141.1, 153.9, 159.5, 170.1; IR (neat) cm−1: 1715, 1649, 1530, 1320, 1279, 1153, 1067, 805, 746, 425; HR-ESI-MS m/z: 699.2669 (M + Na)+ (Calcd for C40H40NaN2O8: 699.2677).
(R)-[1,1′-Binaphtho[2,1-b]furan]-2,2′-dicarboxylic Acid ((R)-2)To a solution of (S,S,Ra)-12a (1.10 g, 1.63 mmol) in THF/MeOH (2 : 1, 30 mL), 2N aq. NaOH (10 mL) was added at r.t. After being stirred at r.t. for 11 h, the reaction mixture was washed with cyclopentyl methyl ether. The aqueous layer was acidified with 2N aq. HCl, and extracted with AcOEt. The organic layer was washed with brine, dried over Na2SO4, filtered, and concentrated in vacuo to give a residue. The residue was washed with CHCl3–n-hexane (1 : 9) to afford (R)-2 (565 mg, 82% yield). The enantiomeric excess of (R)-2 was determined to be >99% ee by HPLC analysis; HPLC (CHiRAL 5A (4.6 × 250 mm), n-hexane/EtOH/TFA = 90/10/0.1, flow rate = 0.5 mL/min, l = 254 nm) tR = 18.3 min (for (S)-2) and 22.3 min (for (R)-2).
Pale yellow solid (decomp.); 1H-NMR (500 MHz, CD3OD) δ: 7.12 (2H, ddd, J = 8.3, 6.9, 1.2 Hz), 7.34 (2H, ddd, J = 8.1, 6.9, 1.2 Hz), 7.48–7.54 (2H, m), 7.87 (2H, d, J = 9.1 Hz), 7.94 (2H, d, J = 8.1 Hz), 8.02 (2H, d, J = 9.1 Hz); 13C-NMR (126 MHz, CD3OD) δ: 113.6, 122.5, 122.9, 123.2, 126.4, 128.3, 129.9, 130.3, 131.2, 132.5, 143.1, 154.9, 162.1; IR (neat) cm−1: 2955, 1682, 1541, 1434, 1170, 1007, 954, 803, 744, 421; HR-EI-MS m/z: 422.0789 (M)+ (Calcd for C26H14O6: 422.0790); CD λext (MeCN) nm (Δε): 338 (−29.2), 325 (−17.2), 313 (−6.59), 301 (15.2), 292 (21.3), 250 (43.7), 225 (−336), 215 (220), 201 (−28.5); UV λmax (MeCN) nm (log ε): 336 (4.38), 322 (4.35), 304 (4.50), 293 (4.46), 242 (4.52), 223 (4.82), 203 (4.73).
Crystallographic data of (R)-2 recrystallized from CHCl3–n-hexane (one CHCl3 molecule is included in the crystal): C27H15Cl3O6, M = 541.74, 0.20 × 0.10 × 0.020 mm3, monoclinic, P21, a = 10.297(6) Å, b = 11.221(6) Å, c = 11.547(7) Å, α = 90°, β = 90.256(6)°, γ = 90°, V = 1334.2(13) Å3, Z = 2, ρcalcd = 1.349 gcm−3, T = 100(2) K, 22784 reflections measured, 6402 unique. The final R1 and wR were 0.1054 and 0.2533 (all data). These data have been deposited with the Cambridge Crystallographic Data Center as CCDC 2144806.
(S)-[1,1′-Binaphtho[2,1-b]furan]-2,2′-dicarboxylic Acid ((S)-2)To a solution of (S,S,Sa)-12a (1.16 g, 1.71 mmol) in THF–MeOH (2 : 1, 30 mL), 2N aq. NaOH (10 mL) was added at r.t. After being stirred at r.t. for 8 h, the reaction mixture was washed with cyclopentyl methyl ether. The aqueous layer was acidified with 2N aq. HCl, and extracted with AcOEt. The organic layer was washed with brine, dried over Na2SO4, filtered, and concentrated in vacuo to give a residue. The residue was washed with CHCl3–n-hexane (1 : 9) to afford (S)-2 (621 mg, 86% yield, >99% ee).
[α]D19 +205.5 (c = 0.7, MeOH, >99% ee); CD λext (MeCN) nm (Δε): 338 (30.5), 325 (17.1), 314 (6.30), 300 (−18.2), 292 (−23.8), 250 (−46.7), 225 (352), 215 (−229), 201 (28.2).
(Ra)- and (Sa)-Bis((S)-2-acetamido-3-methylbutyl) [3,3′-Bibenzo[b]thiophene]-2,2′-dicarboxylate ((S,S,Ra)-12b and (S,S,Sa)-12b)20)A solution of 10b (8.00 g, 21.5 mmol, 1.00 equiv.) and Cu powder (11.0 g, 172 mmol, 8.00 equiv.) in DMF (40 mL) was stirred at 100 °C for 21 h under a N2 atmosphere. After cooling to r.t., the reaction mixture was filtered, and washed with AcOEt to remove Cu. The filtrate was diluted with H2O, and extracted with AcOEt. The organic layer was washed with brine, dried over Na2SO4, filtered, and concentrated in vacuo to give a residue. The residue was purified by column chromatography (SiO2, n-hexane–AcOEt = 4 : 1 to 7 : 3) to afford diastereomeric mixture of (S,S,Ra)- and (S,S,Sa)-11b (4.34 g).
To a solution of diastereomeric mixture of 11b (4.34 g, 8.88 mmol, 1.00 equiv.) in THF (50 mL), TFA (10.0 mL, 130 mmol), H2O (2.00 mL, 111 mmol) and Na2SO4 (20.0 g, 141 mmol) were added at r.t. After being stirred at r.t. for 30 min, the reaction mixture was filtered, and concentrated in vacuo to give a residue. Then, to a solution of the residue in CH2Cl2 (50 mL), pyridine (10.0 mL, 124 mmol) and Ac2O (10.0 mL, 106 mmol) were added at r.t. under a N2 atmosphere. After being stirred at r.t. for 26 h, the reaction mixture was quenched with 2N aq. HCl, and extracted with CHCl3. The organic layer was washed with brine, dried over Na2SO4, filtered, and concentrated in vacuo to give a residue. The residue was purified by column chromatography (SiO2, CHCl3–MeOH = 10 : 1) to afford diastereomeric mixture of (S,S,Ra)- and (S,S,Sa)-12b. This diastereomeric mixture was separated by recycled prep. HPLC to give 1.34 g of (S,S,Ra)-12b (TLC-up isomer, 21% yield in 3 steps from 10b) and 2.60 g of (S,S,Sa)-12b (TLC-down isomer, 40% yield in 3 steps from 10b); HPLC (COSMOSIL 5SL-II (20 × 250 mm), CHCl3/acetone = 20/1, flow rate = 20 mL/min, l = 254 nm).
(S,S,Ra)-12b: Cololress amorphous; [α]D18 –77.7 (c = 0.8, CHCl3); 1H-NMR (300 MHz, CDCl3) δ: 0.65–0.79 (12H, m), 0.79–0.96 (2H, m), 1.67 (6H, s), 3.60–3.75 (2H, m), 3.99 (2H, dd, J = 11.6, 3.1 Hz), 4.22 (2H, dd, J = 11.5, 3.5 Hz), 4.45 (2H, d, J = 9.3 Hz), 7.27–7.32 (2H, m), 7.36 (2H, ddd, J = 8.0, 6.9, 1.0 Hz), 7.55 (2H, ddd, J = 8.2, 6.9, 1.4 Hz), 8.00 (2H, dt, J = 8.2, 0.9 Hz); 13C-NMR (75 MHz, CDCl3) δ: 19.1, 19.2, 23.2, 28.6, 53.0, 66.3, 123.1, 124.8, 125.6, 127.9, 131.6, 135.5, 139.9, 140.6, 162.4, 169.5; IR (neat) cm−1: 3274, 1718, 1697, 1641, 1546, 1372, 1276, 1229, 1113, 757, 734; HR-FAB-MS m/z: 609.2103 (M + H)+ (Calcd for C32H37N2O6S2: 609.2093).
(S,S,Sa)-12b: Cololress solid; mp 184–185 °C; [α]D18 –171.6 (c = 0.8, CHCl3); 1H-NMR (300 MHz, CDCl3) δ: 0.22–0.40 (2H, m), 0.47 (6H, d, J = 6.6 Hz), 0.57 (6H, d, J = 6.6 Hz), 1.94 (6H, s), 3.50–3.70 (2H, m), 4.00–4.20 (4H, m), 5.06 (2H, d, J = 9.2 Hz), 7.23–7.29 (2H, m), 7.34 (2H, ddd, J = 8.1, 6.9, 1.0 Hz), 7.54 (2H, ddd, J = 8.3, 7.0, 1.4 Hz), 7.97 (2H, dt, J = 8.2, 0.9 Hz); 13C-NMR (75 MHz, CDCl3) δ: 19.1, 19.2, 23.2, 27.9, 53.0, 66.7, 122.9, 125.0, 125.9, 128.1, 131.0, 135.7, 140.0, 140.1, 162.8, 170.0; IR (neat) cm−1: 1693, 1632, 1555, 1496, 1374, 1283, 1241, 1091, 758, 733; HR-FAB-MS m/z: 609.2112 (M + H)+ (Calcd for C32H37N2O6S2: 609.2093).
(R)-[3,3′-Bibenzo[b]thiophene]-2,2′-dicarboxylic Acid ((R)-5)20)To a solution of (S,S,Ra)-12b (253 mg, 416 µmol) in THF/MeOH (2 : 1, 15 mL), 2N aq. NaOH (5.0 mL) was added at r.t. After being stirred at r.t. for 2.5 h, the reaction mixture was washed with cyclopentyl methyl ether. The aqueous layer was acidified with 2N aq. HCl, and extracted with AcOEt. The organic layer was washed with brine, dried over Na2SO4, filtered, and concentrated in vacuo to give (R)-5 (137 mg, 93% yield). The enantiomeric excess of (R)-5 was determined to be >99% ee by HPLC analysis; HPLC (CHiRAL 5B (4.6 mm×250 mm), n-hexane/EtOH/TFA = 90/10/0.1, flow rate = 0.5 mL/min, l = 254 nm) tR = 15.0 min (for (R)-5) and 20.4 min (for (S)-5).
Colorless solid (decomp.); [α]D19 +80.3 (c = 0.7, MeOH, >99% ee); 1H-NMR (300 MHz, acetone-d6) δ: 7.28 (2H, ddd, J = 8.2, 1.3, 0.8 Hz), 7.37 (2H, ddd, J = 8.1, 6.9, 1.0 Hz), 7.56 (2H, ddd, J = 8.2, 7.0, 1.3 Hz), 8.10 (2H, dt, J = 8.2, 0.9 Hz), 11.42 (2H, br s); 13C-NMR (75 MHz, acetone-d6) δ: 123.7, 125.3, 126.0, 128.2, 131.8, 137.2, 140.7, 141.2, 163.3; 1H-NMR (300 MHz, CD3OD) δ: 7.15–7.25 (2H, m), 7.26–7.35 (2H, m), 7.45–7.55 (2H, m); 13C-NMR (75 MHz, CD3OD) δ: 123.7, 125.4, 126.0, 128.3, 132.5, 137.6, 141.1, 141.8, 165.2; IR (neat) cm−1: 2852, 1666, 1498, 1430, 1245, 1091, 754, 729, 582, 422; HR-EI-MS m/z 354.0021 (M)+ (Calcd for C18H10O4S2: 354.0021); CD λext (MeCN) nm (Δε): 337 (−3.73), 315 (5.94), 286 (36.2), 263 (−10.1), 245 (−8.54), 210 (−200), 200 (154); UV λmax (MeCN) nm (log ε): 316 (3.88), 283 (4.31), 233 (4.48), 205 (4.58).
(S)-[3,3′-Bibenzo[b]thiophene]-2,2′-dicarboxylic Acid ((S)-5)20)To a solution of 12b (TLC-down diastereomer) (398 mg, 654 µmol) in THF–MeOH (2 : 1, 15 mL), 2N aq. NaOH (5.0 mL) was added at r.t. After being stirred at r.t. for 3.5 h, the reaction mixture was washed with CPME. The aqueous layer was acidified with 2N aq. HCl, and extracted with AcOEt. The organic layer was washed with brine, dried over Na2SO4, filtered, and concentrated in vacuo to give (S)-5 (217 mg, 94% yield, >99% ee).
CD λext (MeCN) nm (Δε): 338 (4.34), 313 (−4.74), 285 (−32.9), 263 (8.50), 245 (6.87), 210 (180), 200 (−138).
(Ra)- and (Sa)-Bis((S)-2-acetamido-3-methylbutyl) [3,3′-Bibenzo[b]selenophene]-2,2′-dicarboxylate ((S,S,Ra)- and (S,S,Sa)-12c)In a vial for microwave irradiation, 10c (3.07 g, 8.27 mmol, 1.00 equiv.), Cu powder (4.21 g, 66.2 mmol, 8.00 equiv.) and DMF (15 mL) were added, and the resulting mixture was degassed with N2 stream, and sealed. The vial was placed into microwave reactor, and heated 200 °C for 4 h. Then, the reaction mixture was filtered, and concentrated in vacuo to give a residue. The residue was purified by column chromatography (SiO2, n-hexane–AcOEt = 4 : 1) to afford diastereomeric mixture of (S,S,Ra)- and (S,S,Sa)-11c (1.16 g).
To a solution of diastereomeric mixture of 11c (1.16 g, 1.99 mmol, 1.00 equiv.) in THF (20 mL), TFA (10.0 mL, 130 mmol), H2O (2.00 mL, 111 mmol) and Na2SO4 (20.0 g, 141 mmol) were added at r.t. After being stirred at r.t. for 25 min, the reaction mixture was filtered, and concentrated in vacuo to give a residue. Then, to a solution of the residue in CH2Cl2 (20 mL), pyridine (10.0 mL, 124 mmol) and Ac2O (10.0 mL, 106 mmol) were added at r.t. under a N2 atmosphere. After being stirred at r.t. for 12 h, the reaction mixture was quenched with 2N aq. HCl, and extracted with CHCl3. The organic layer was washed with brine, dried over Na2SO4, filtered, and concentrated in vacuo to give a residue. The residue was purified by column chromatography (SiO2, CHCl3–MeOH = 20 : 1) to afford diastereomeric mixture of (S,S,Ra)- and (S,S,Sa)-12c. This diastereomeric mixture was separated by recycled prep. HPLC to give 441 mg of (S,S,Ra)-12c (TLC-up isomer, 15% yield in 3 steps from 10c) and 738 mg of (S,S,Sa)-12c (TLC-down isomer, 25% yield in 3 steps from 10c); HPLC (COSMOSIL 5SL-II (20 × 250 mm), CHCl3–acetone = 15 : 1; flow rate = 20 mL/min, l = 254 nm).
(S,S,Ra)-12c: Colorless amorphous; [α]D19 −64.1 (c = 0.8, CHCl3); 1H-NMR (300 MHz, CDCl3) δ: 0.69–0.79 (12H, m), 0.91–1.08 (2H, m), 1.66 (6H, s), 3.60–3.80 (2H, m), 3.97 (2H, dd, J = 11.6, 3.1 Hz), 4.21 (2H, dd, J = 11.6, 3.5 Hz), 4.46 (2H, d, J = 9.4 Hz), 7.21–7.28 (2H, m), 7.33 (2H, ddd, J = 8.1, 7.0, 1.1 Hz), 7.48 (2H, ddd, J = 8.2, 7.0, 1.4 Hz), 8.03 (2H, dt, J = 8.0, 0.9 Hz); 13C-NMR (75 MHz, CDCl3) δ: 19.2, 19.3, 23.2, 28.7, 53.1, 66.5, 125.8, 126.1, 127.0, 128.0, 134.7, 140.2, 142.1, 142.3, 163.6, 169.5; IR (neat) cm−1: 1715, 1687, 1640, 1543, 1370, 1276, 1220, 1103, 756, 727; HR-ESI-MS m/z: 727.0777 (M + Na)+ (Calcd for C32H36NaN2O6Se2: 727.0803).
(S,S,Sa)-12c: Colorless amorphous; [α]D19 –169.9 (c = 0.9, CHCl3); 1H-NMR (300 MHz, CDCl3) δ: 0.18–0.33 (2H, m), 0.46 (6H, d, J = 6.6 Hz), 0.57 (6H, d, J = 6.6 Hz), 1.95 (6H, s), 3.50–3.70 (2H, m), 4.02 (2H, dd, J = 11.6, 2.9 Hz), 4.17 (2H, dd, J = 11.6, 3.2 Hz), 5.08 (2H, d, J = 9.2 Hz), 7.22 (2H, ddd, J = 8.1, 1.4, 0.6 Hz), 7.32 (2H, ddd, J = 8.1, 7.0, 1.1 Hz), 7.47 (2H, ddd, J = 8.2, 7.1, 1.4 Hz), 8.00 (2H, dt, J = 8.1, 0.9 Hz); 13C-NMR (75 MHz, CDCl3) δ: 19.2, 19.4, 23.2, 27.8, 53.1, 66.9, 125.9, 126.0, 127.2, 128.2, 133.9, 140.4, 141.6, 142.5, 163.9, 170.0; IR (neat) cm−1: 3276, 1689, 1649, 1507, 1370, 1271, 1217, 1068, 755, 728; HR-ESI-MS m/z: 727.0782 (M + Na)+ (Calcd for C32H36NaN2O6Se2: 727.0803).
(R)-[3,3′-Bibenzo[b]selenophene]-2,2′-dicarboxylic Acid ((R)-6)To a solution of (S,S,Ra)-12c (441 mg, 628 µmol) in THF–MeOH (2 : 1, 15 mL), 2N aq. NaOH (5.0 mL) was added at r.t. After being stirred at r.t. for 66 h, the reaction mixture was washed with cyclopentyl methyl ether. The aqueous layer was acidified with 2N aq. HCl, and extracted with AcOEt. The organic layer was washed with brine, dried over Na2SO4, filtered, and concentrated in vacuo to give a residue. The residue was washed with CHCl3–n-hexane (1 : 9) to afford (R)-6 (233 mg, 83% yield). The enantiomeric excess of (R)-6 was determined to be >99% ee by HPLC analysis; HPLC (CHiRAL 5B (4.6 × 250 mm), n-hexane–EtOH–TFA = 90 : 10 : 0.1, flow rate = 0.5 mL/min, l = 254 nm) tR = 16.1 min (for (R)-6) and 21.3 min (for (S)-6).
Pale yellow solid; mp 269–271 °C; 1H-NMR (500 MHz, acetone-d6) δ: 7.21 (2H, dd, J = 8.1, 1.1 Hz), 7.28–7.37 (2H, m), 7.42–7.52 (2H, m), 8.17 (2H, d, J = 8.0 Hz), 11.34 (2H, br s); 13C-NMR (126 MHz, acetone-d6) δ: 126.1, 126.9, 127.2, 128.1, 134.5, 142.1, 142.8, 143.2, 164.4; 1H-NMR (300 MHz, CD3OD) δ: 7.06–7.18 (2H, m), 7.20–7.30 (2H, m), 7.35–7.45 (2H, m), 8.02 (2H, d, J = 8.0 Hz); 13C-NMR (75 MHz, CD3OD) δ: 126.1, 126.9, 127.4, 128.3, 134.9, 142.7, 143.1, 143.4, 166.3; IR (neat) cm−1: 2851, 1659, 1506, 1275, 1246, 756, 744, 724, 445, 420; HR-EI-MS m/z: 449.8909 (M)+ (Calcd for C18H10O4Se2: 449.8909).
(S)-[3,3′-Bibenzo[b]selenophene]-2,2′-dicarboxylic Acid ((S)-6)To a solution of (S,S,Sa)-12c (738 mg, 1.05 mmol) in THF–MeOH (2 : 1, 15 mL), 2N aq. NaOH (5.0 mL) was added at r.t. After being stirred at r.t. for 68 h, the reaction mixture was washed with CPME. The aqueous layer was acidified with 2N aq. HCl, and extracted with AcOEt. The organic layer was washed with brine, dried over Na2SO4, filtered, and concentrated in vacuo to give a residue. The residue was washed with CHCl3–n-hexane (1 : 9) to afford (S)-6 (380 mg, 81% yield, >99% ee).
[α]D19 –104.7 (c = 0.2, MeOH, >99% ee).
Crystallographic data of (S)-6 recrystallized from THF/AcOEt/n-hexane: C9H5O2Se, M = 224.09, 0.30 × 0.30 × 0.30 mm3, orthorhombic, C2221, a = 11.9700(5) Å, b = 12.8292(6) Å, c = 13.9262(5) Å, α = 90°, β = 90°, γ = 90°, V = 2138.59(15) Å3, Z = 8, ρcalcd = 1.392 gcm−3, T = 296(2) K, 11536 reflections measured, 1966 unique. The final R1 and wR were 0.0542 and 0.1535 (all data). These data have been deposited with the Cambridge Crystallographic Data Center as CCDC 2144805.
1,1′-Binaphthyl-2,2′-dicarboxylic Acid ((dl)-13)1H-NMR (300 MHz, CD3OD) δ: 6.90–7.00 (2H, m), 7.20–7.30 (4H, m), 7.80–7.90 (4H, m), 8.00 (2H, d, J = 8.7 Hz); 13C-NMR (75 MHz, CD3OD) δ: 125.9, 126.2, 126.8, 127.25, 127.34, 127.6, 127.7, 133.0, 135.1, 140.4, 168.9.
This paper is dedicated to the memory of the late Prof. Toshiyuki Kan, who passed away July 24, 2021. This work was financially supported by a Grant-in-Aid for Scientific Research (B) (21H02611). We are grateful to Mr. Yukihiro Shigeta, Ms. Mami Iwasa, and Mr. Mitsuyoshi Kawashima of Nissan Chemical Corporation for the pKa measurement. We also thank Zeon Corporation for generously providing cyclopentyl metyl ether (CPME).
The authors declare no conflict of interest.
This article contains supplementary materials.
