CArâO Rotamers in 3,3â²-Disubstituted BINOL Esters - The Journal of

Subscriber access provided by University of Newcastle, Australia

Note Ar

C -O Rotamers in 3,3#-disubstituted BINOL esters Takeo Sakai, Junpei Matsuoka, Masayuki Shintai, and Yuji Mori J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.6b03035 • Publication Date (Web): 22 Feb 2017 Downloaded from http://pubs.acs.org on February 24, 2017

Just Accepted “Just Accepted” manuscripts have been peer-reviewed and accepted for publication. They are posted online prior to technical editing, formatting for publication and author proofing. The American Chemical Society provides “Just Accepted” as a free service to the research community to expedite the dissemination of scientific material as soon as possible after acceptance. “Just Accepted” manuscripts appear in full in PDF format accompanied by an HTML abstract. “Just Accepted” manuscripts have been fully peer reviewed, but should not be considered the official version of record. They are accessible to all readers and citable by the Digital Object Identifier (DOI®). “Just Accepted” is an optional service offered to authors. Therefore, the “Just Accepted” Web site may not include all articles that will be published in the journal. After a manuscript is technically edited and formatted, it will be removed from the “Just Accepted” Web site and published as an ASAP article. Note that technical editing may introduce minor changes to the manuscript text and/or graphics which could affect content, and all legal disclaimers and ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errors or consequences arising from the use of information contained in these “Just Accepted” manuscripts.

The Journal of Organic Chemistry is published by the American Chemical Society. 1155 Sixteenth Street N.W., Washington, DC 20036 Published by American Chemical Society. Copyright © American Chemical Society. However, no copyright claim is made to original U.S. Government works, or works produced by employees of any Commonwealth realm Crown government in the course of their duties.

Page 1 of 23

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

The Journal of Organic Chemistry

CAr-O Rotamers in 3,3′-disubstituted BINOL esters Takeo Sakai,* Junpei Matsuoka, Masayuki Shintai, Yuji Mori*

Faculty of Pharmacy, Meijo University, 150 Yagotoyama, Tempaku-ku, Nagoya 468-8503, Japan

E-mail: [email protected]; [email protected]

ABSTRACT

Rotamers around the CAr-O bond were disclosed in 3,3′-disubstituted BINOL esters by NMR spectroscopy. A bulky R1 group increased the rotational barrier. The pivalate showed two rotamers at 2 °C, and broad signals were observed close to room temperature when R2 = Ph. The highest rotational barrier was recorded for the (tetracyanocyclopentadienyl)carboxylate, and C-O rotamers were present at room temperature. DFT calculations indicated the presence of repulsion between R1 and R2 during rotation of the CAr-O bond.

Axial chirality around a carbon-heteroatom bond exists widely in natural products, pharmaceutical products, and catalysts.1 As such, the discovery of a novel class of axial chirality is of particular interest in organic chemistry, as it can lead to new useful chiral molecules and potential new applications.2 Carbanilides (Figure 1(a)) are a major class of non-biaryl atropisomers, where C-N bond ACS Paragon Plus Environment

1


1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 2 of 23

rotation is restricted by the ortho substituents (i.e., R2 and R3) on the aromatic ring, and by the two substituents (i.e., acyl and R4) on the nitrogen atom.3 In addition, C-O axial chirality has been reported in biaryl ethers, and is found in several antibiotics, such as vancomycin and teicoplanin.4 Atropisomers of biaryl ethers are separable and exist even at room temperature when the ortho positions of both aryl rings are unsymmetrically substituted with bulky groups (Figure 1(b)).5 In contrast, C-O chiral axes are rarely found outside the biaryl ethers, as the oxygen functional group can have only one substituent that plays a role of an anchor for bond rotation. Therefore, the discovery of other classes of molecules that contain C-O axial chirality is challenging. However, to date, two other types of C-O axial chirality have been observed as short-living rotational isomers. For example, Kawabata reported asymmetric intramolecular alkylation and conjugate addition using the C-O axial chirality present in aryloxy enolates (Figure 1(c)).6 In addition, Siddall III first reported slow rotation around the CAr-O bond of aryl esters by observing the diastereotopic isopropyl group of 2,6-disubstitutedphenyl esters at −30 °C (Figure 1(d)). 7 Furthermore, Mazzanti and Wolf reported three different conformations of 2,2′binaphthalene-1,1′-diol diisobutyrate due to the presence of slow CAr-O and CAr-CAr rotations.8 However, these C-O axial chiralities were observed only at very low temperatures because of the low C-O bond rotational barrier. During the course of our synthetic studies on 3,3′-disubstituted (R)-BINOL esters 1a–j, examination of the room temperature 1H NMR spectra showed that ester 1 exists as a mixture of rotamers. As ester 1 has a stable binaphthyl CAr-CAr chiral axis, we envisaged that the rotamers were attributed to diastereomeric conformations derived from slow rotation of the CAr-O bond of the ester functional group. We herein report our extensive studies into the effect of the acyl group (R1) and the 3,3′-substitutents (R2) of BINOL esters 1a–j on the formation of CAr-O rotamers through NMR signal shape analysis.

ACS Paragon Plus Environment

2

Page 3 of 23

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


Figure 1. Atropisomers around the carbon-heteroatom axis of (a) carbanilides and (b) diaryl ethers. Slow C-O rotation observed in (c) aryl enolates and (d) aryl esters. The slow rotating bonds are indicated in red and are formatted in bold.

(R)-3,3′-Diphenylbinaphthyl acetate, benzoate, mesitoate (2,4,6-trimethylbenzoate), and pivalate (1a–d) were synthesized by esterification of the corresponding (R)-3,3′-diphenylbinaphthol using an equimolar amount of acetic anhydride and the corresponding acyl chloride (Scheme 1). In addition, sodium carboxytetracyanocyclopentadienide (Na+[C5(CN)4COOH]−) BINOL esters 1e–j were prepared via condensation between the 3,3′-disubstituted (R)-BINOLs and Na+[C5(CN)4COOH]− 2 using 1-ethyl3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDCI). 9 Furthermore, the phenolic hydroxyl group in ester 1h was masked by a methyl group to give compound 3 to determine the effect of the protic functional group on the rotational barrier.


3


1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 4 of 23

SCHEME 1. Synthesis of BINOL esters 1a–j and 3

As shown in the 1H NMR spectra of the three representative esters 1a (R1 = Me), 1d (R1 = t-Bu), and 1h (R1 = C5(CN)4–Na+) (Figure 2), the size of acyl group R1 on the BINOL esters significantly influenced the signal pattern obtained. For example, the spectrum of acetate 1a obtained at 18 °C did not contain any signals corresponding to a rotamer (Figure 2(a)). Indeed, only sharp signals corresponding to a single compound were observed in the spectrum, which was similar to those of previously reported 3,3′-disubsitituted BINOL acetates.10 However, upon lowering the temperature to −10 °C, several broad peaks were observed, and a further decrease to −39 °C indicated the presence of two rotamers. Indeed, at −59 °C, a sharp, well-resolved spectrum corresponding to a 79:21 mixture of two rotamers was obtained. In contrast, the 1H NMR spectrum of the pivaloyl ester 1d contained broadened peaks in the aromatic region even at 24 °C, suggesting that 1d existed as a mixture of rotamers (Figure 2(b)). The presence of these rotamers was confirmed at 2 °C, while the rotamers were averaged at 57 °C. This finding is especially surprising, considering that no previous reports on BINOL pivalates discussed the presence of such rotamers.11 Furthermore, the spectra of benzoate 1b and mesitoate 1c also exhibited broadening at room temperature (e.g., 23−25 °C), as shown in the Supporting Information. Moreover, we found that (tetracyanocyclopentadienyl)carboxylate 1h provided a clear spectrum of rotamers at 23 °C (Figure 2(c)). ACS Paragon Plus Environment

4

Page 5 of 23

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


Elevating the temperature to 43 °C resulted in some broadening, while a further increase to 120 °C gave clear signals, confirming that 1h is a single compound.

Figure 2. Variable temperature (VT) NMR spectra of 1a (R1 = Me, R2 = Ph), 1d (R1 = t-Bu, R2 = Ph), and 1h (R1 = C5(CN)4−Na+, R2 = Ph). For clarity, all spectra are trimmed to show only the aromatic regions.

We then focused on analysis of the rotational barriers between the rotamers. The diastereomerization rates for transformation from the major rotamers12 to the minor rotamers at each temperature were measured by line shape analysis using WinDNMR Pro 7.1.13 The rotational enthalpy (∆H‡) and entropy (∆S‡) of the major rotamers were obtained from the standard Eyring plot,14 and the rotational free energies were calculated at 298 K (∆G‡298) using the previously obtained ∆H‡ and ∆S‡ values. The corresponding results for esters 1a–j and 3 are summarized in Table 1. Comparison of the rotational barriers of acetate 1a (13.3 kcal/mol, entry 1) with those of esters 1b–d (14.0–15.1 kcal/mol, entries 4–6) indicated the bulkiness of the acyl groups in comparison to the acetate group. In addition, for (tetracyanocyclopentadienyl)carboxylate ester 1h, whose 1H NMR spectrum confirmed the presence of rotamers at room temperature, a rotational barrier of 16.8 kcal/mol ACS Paragon Plus Environment

5


1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 6 of 23

(entry 10) was recorded, which was the highest among the various esters examined. We also found that the presence of bulky 3,3′-substitutents is critical for rotamer formation, as no signals corresponding to the rotamers of 1e were observed at −39 °C when the 3,3′-positions on the binaphthyl moiety were hydrogen (entry 7). Indeed, the extent of bulkiness of these substituents also affects the rotational barriers, with the methyl-, bromo-, phenyl-, 4-biphenyl-, and 9-anthracenyl-substituted BINOL esters (1f–1i) exhibiting rotational barriers of 15.8–16.8 kcal/mol at 25 °C (entries 8, 9, 12, and 13). It should be noted that the presence of methyl groups in the 3,3′-positions was sufficient to produce rotamers at 23 °C. In addition, the rotational barrier of 3, which is a methyl ether derivative of the phenolic hydroxyl ester 1h, was identical to that of 1h (entries 10 and 14), which indicates that any hydrogen bonds derived from phenolic hydroxyl groups contributed little to rotamer stability. Furthermore, slightly lower rotational barriers were observed in DMSO-d6, which may be attributed to stabilization of the rotational transition states by solvation effects (entries 11 and 12).15

Table 1. Rotational barriers between the major and minor rotamers

R1

R2

R3

rotamer ratiob

∆G‡298 ∆H‡ ∆S‡ (cal/ (kcal/ (kcal/ mol·K) mol) d mol) 1 Me Ph H CD2Cl2 79:21 (−39 °C) 13.3 11.1 −8 1a 2 Me Ph H CD3CN 66:34 (−39 °C) 12.5 11.3 −4 1a 3 Me Ph H CD3OD 64:36 (−39 °C) 12.7 11.8 −3 1a 4 Ph Ph H CDCl3 84:16 (−39 °C) 14.4 12.8 −5 1b 5 Mes Ph H CD3CN 72:28 (−39 °C) 14.0 12.4 −5 1c 6 t-Bu Ph H CD3CN 51:49 (1 °C) 15.1 11.0 −14 1d 7 C5(CN)4Na H H CD3CN –c 200 s−1 at −39 °C. d Diastereomerization energies for transformation from entry

solvent


6

Page 7 of 23

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


the major rotamer to the minor rotamer at 298 K (25 °C).

We

then

investigated

the

origin

of

the

higher

rotational

barrier

of

(tetracyanocyclopentadienyl)carboxylate ester 1f compared to ester 1e, the latter of which exhibited no rotamers at −39 °C. For this purpose, density functional theory (DFT) calculations were carried out using the B3LYP/6-31+G(d,p) level of theory in Gaussian 09 (Scheme 2).16 The two conformations found for 1e, i.e., the (1R,2S) and (1R,2R) conformers, exhibited dihedral angles of 87.7° and −127.7° between the naphthyl A ring and the ester group, respectively, indicating that both are CAr-O rotamers. As shown in Scheme 2, the cyclopentadienyl ring and the ester group lie in almost the same plane, which was demonstrated by the small values of the dihedral angles (θB) in both (1R,2S)- and (1R,2R)-1e. In addition, in rotational transition state 4 (TS) between the (1R,2S)- and (1R,2R)-1e conformers, the napthyl A ring, ester group, and cyclopentadienyl ring were arranged in a coplanar manner. Furthermore, the (R,S) and (R,R) rotamers of 1f adopted a similar conformation to those of (R,S)- and (R,R)-1e, respectively. However, four possible rotational transition states were found for 1f (see Supporting Information), in which the lowest energy conformation was the rotational transition state 5 (TS). In this case, the dihedral angle θB between the cyclopentadienyl ring and the ester group was 39.9°, which prevented repulsion between the methyl group on the napthyl C3 position and the cyano group on the cyclopentadienyl ring. This distorted conformation of 5 results in a larger rotational free energy than that of the coplanar conformation 4 by 4.5 kcal/mol, which is consistent with the experimental results that two rotamers were present for 1f at 23 °C, while no rotamer was observed for 1e even at −39 °C.

SCHEME 2. DFT calculations using the B3LYP/6-31+G(d,p) level of theory for determination of the conformations of (1R,2S)- and (1R,2R)-1e, (1R,2S)- and (1R,2R)-1f, and rotational transition states 4 and 5. Free energy differences were calculated at 298 K, and calculations were carried out without a sodium cation ACS Paragon Plus Environment

7


1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 8 of 23

In conclusion, through NMR spectroscopic analysis, we disclosed that the 3,3′-disubstituted BINOL esters exist as a mixture of rotamers along the CAr-O axis. Bulky esters, such as benzoate, mesitoate, and pivalate, yielded broadened signals at room temperature, with rotational barriers ranging from 14.0–15.1 kcal/mol at 298 K, as determined by line shape analysis of the VT NMR signals. Furthermore, (tetracyanocyclopentadienyl)carboxylates (e.g. 1f) produced rotational barriers of 15.8– 16.8 kcal/mol, and exist as rotamers at room temperature. Finally, DFT calculations suggested that rotational restriction around the CAr-O bond is responsible for the high rotation barrier of 1f, which could be explained by repulsion between the C3 substituent and the cyano “hands” of the tetracyanocyclopentadienide ring. We believe that our work provides key information that will help in better understanding the NMR spectra obtained during the application of BINOL and BINOL esters. Our findings also show that aryl esters bearing the CAr-O bond comprise a novel class of compounds exhibiting non-biaryl axial chirality.

Experimental Section General Experimental Methods. All air- and moisture-sensitive reactions were carried in dry solvents under an argon atmosphere. Flash chromatography was carried out using silica gel 60 (spherical, neutral, ACS Paragon Plus Environment

8

Page 9 of 23

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


40-50 µm). Melting points are uncorrected. Chemical shifts are reported in ppm relative to the solvent signals (δ 1.94 ppm for CD3CN, δ 2.50 ppm for DMSO-d6, δ 5.32 ppm for CD2Cl2) or internal TMS (δ 0.00 ppm for CDCl3) for 1H NMR spectra and to the solvent signals (δ 1.39 ppm for CD3CN, δ 77.0 ppm for CDCl3, 39.51 ppm for DMSO-d6) for

13

C NMR spectra. Coupling constants (J) are

reported in Hertz (Hz). Data are reported as follows: chemical shift, integration, and multiplicity (s = singlet, d = doublet, t = triplet, q = quartet, m = multiplet, br = broad). Low- and high-resolution mass spectra (MS) were recorded on magnetic sector fast atom bombardment (FAB) mass spectrometers. Unless otherwise noted, 1H and 13C NMR peak lists were recorded at room temperature ranging from 23 to 25 °C.

(R)-2′-Hydroxy-3,3′-diphenyl-[1,1′-binaphthalen]-2-yl acetate (1a). To a solution of (R)-3,3′diphenyl-1,1′-binaphthol (104 mg, 0.237 mmol) in pyridine (0.5 mL) was added Ac2O (25 µL, 0.26 mmol), and the mixture was stirred at room temperature for 4 h. The resulting mixture was concentrated under reduced pressure. Flash chromatography (25% benzene in n-hexane) afforded acetate 1a (62 mg, 55%) as a colorless solid. Mp 93–95 °C; [α]28D +113.1 (c 0.97, CHCl3); IR (film) νmax 3519, 3057, 1753, 1496, 1455, 1429, 1213, 1429, 750, 699 cm−1; 1H NMR (500 MHz, CDCl3) δ 8.06 (1H, s), 7.96 (1H, d, J = 7.8 Hz), 7.95 (1H, s), 7.86 (1H, d, J = 7.8 Hz), 7.73–7.71 (2H, m), 7.60–7.57 (2H, m), 7.49 (1H, ddd, J = 8.3, 4.6, 3.4 Hz), 7.46-7.42 (4H, m), 7.38–7.31 (5H, m), 7.26 (1H, ddd, J = 8.5, 6.9, 0.9 Hz), 7.15 (1H, d, J = 8.5 Hz), 5.45 (1H, brs), 1.57 (3H, s);

13

C NMR (150 MHz, CDCl3) δ 169.9,

149.4, 146.1, 137.9, 137.6, 134.8, 133.0, 132.9, 132.4, 131.1 (×2), 130.5, 129.6, 129.2, 129.0, 128.4, 128.3 (×2), 128.0, 127.7, 127.5, 127.3, 126.7, 126.6, 125.7, 124.6 (×2), 123.9, 115.3, 20.1; HRFABMS m/z [M+Na]+ Calcd for C34H24O3Na 503.1623; Found 503.1631. ACS Paragon Plus Environment

9


1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 10 of 23

(R)-2′-Hydroxy-3,3′-diphenyl-[1,1′-binaphthalen]-2-yl benzoate (1b). To a solution of (R)-3,3′diphenyl-1,1′-binaphthol (35 mg, 0.080 mmol) and Et3N (12 µL, 0.088 mmol) in CH2Cl2 (1 mL) was added benzoyl chloride (10 µL, 0.088 mmol). The resulting mixture was stirred at room temperature for 0.5 h, after which time the reaction was quenched with saturated aqueous NaHCO3 solution, and the resulting mixture was extracted with ethyl acetate (EtOAc). The organic layer was washed with brine, dried over anhydrous Mg2SO4, filtered, and concentrated under reduced pressure. Flash chromatography (5% EtOAc in n-hexane) afforded benzoate 1b (39 mg, 90%) as colorless solid. Mp 109–112 ºC; [α]D22 +85.0 (c 1.95, CHCl3); IR (CHCl3) νmax 3533, 3061, 3012, 1733, 1266, 1241 cm−1; 1H NMR (CDCl3, 500 MHz) δ 8.13 (1H, s), 8.01 (1H, d, J = 8.3 Hz), 7.75 (1H, s), 7.75 (1H, m), 7.63 (2H, d, J = 7.2 Hz), 7.56 (2H, d, J = 7.5 Hz), 7.52 (1H, ddd, J = 8.3, 6.8, 1.4 Hz), 7.48 (2H, d, J = 7.2 Hz), 7.41–7.24 (13H, m), 7.11 (2H, t, J = 7.7 Hz), 5.53 (1H, brs); 13C NMR (CDCl3, 125 MHz) δ 165.9, 149.4, 146.5, 137.9, 137.5, 135.0, 133.13, 133.06, 132.9, 132.4, 131.2 (×2), 130.5, 129.59, 129.55, 129.2, 129.0, 128.6, 128.4, 128.3, 128.2, 128.0 (×2), 127.6, 127.4, 127.3, 126.59, 126.58, 125.8, 124.7, 124.5, 123.7, 115.4; HRFABMS m/z [M+H]+ Calcd for C39H27O3 543.1960; Found 543.1944.

(R)-2′-Hydroxy-3,3′-diphenyl-[1,1′-binaphthalen]-2-yl 2,4,6-trimethylbenzoate (1c). To a solution of (R)-3,3′-diphenyl-1,1′-binaphthol (100 mg, 0.228 mmol) in pyridine (1.0 mL) was added 2,4,6trimethylbenzoyl chloride (42 µL, 0.25 mmol) and N,N-dimethylaminopyridine (DMAP) (2 mg, ACS Paragon Plus Environment

10

Page 11 of 23

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


0.02 mmol), and the reaction mixture was stirred at room temperature for 6 h. The reaction was quenched with saturated aqueous NaHCO3 solution, and the resulting mixture was extracted with EtOAc. The organic layer was washed with brine, dried over anhydrous MgSO4, filtered, and concentrated under reduced pressure. Flash chromatography (10% acetone in n-hexane) afforded mesitoate 1c (119 mg, 89%) as a colorless solid. Mp 113–114 °C; [α]28D –51.0 (c 1.03, CHCl3); IR (film) νmax 3502, 3057, 3030, 2968, 2924, 2856, 1732, 1238, 1050, 751, 699 cm−1; 1H NMR (600 MHz, CDCl3, 50 °C) δ 8.09 (1H, s), 7.97 (1H, d, J = 8.3 Hz), 7.94 (1H, s), 7.85 (1H, d, J = 8.1 Hz), 7.68–7.66 (2H, m), 7.63–7.61 (2H, m), 7.50 (1H, ddd, J = 8.1, 5.5, 2.6 Hz), 7.41 (2H, t, J = 7.0 Hz), 7.36–7.31 (7H, m), 7.28–7.23 (2H, m), 6.51 (2H, s), 5.67 (1H, brs), 2.10 (3H, s), 1.20 (6H, s); 13C NMR (150 MHz, CDCl3, 50 °C) δ 168.9, 149.9, 146.5, 139.7, 138.0, 136.8 (×2), 135.2, 133.7, 133.2, 132.5, 131.7, 130.6, 129.9, 129.7, 129.4, 128.6, 128.5 (×2), 128.4, 128.2 (×2), 128.0, 127.9, 127.43, 127.36, 126.8, 126.7, 125.9, 125.3, 124.6, 124.0, 116.3, 20.9, 18.5; HRFABMS m/z [M+H]+ Calcd for C42H33O3 585.2430; Found 585.2437.

(R)-2'-Hydroxy-3,3'-diphenyl-[1,1'-binaphthalen]-2-yl pivalate (1d). To a solution of (R)-3,3′diphenyl-1,1′-binaphthol (162 mg, 0.369 mmol) in pyridine (1.3 mL) was added pivaloyl chloride (50 µL, 0.41 mmol), and the reaction mixture was stirred at room temperature for 2.5 h. The reaction was quenched with saturated aqueous NaHCO3 solution, and the resulting mixture was extracted with EtOAc. The organic layer was then washed with brine, dried over anhydrous MgSO4, filtered, and concentrated under reduced pressure. Flash chromatography (10% acetone in n-hexane) afforded pivalate 1d (158 mg, 82%) as a colorless solid. Mp 86–88 °C; [α]28D +85.0 (c 1.11, CHCl3); IR (film) νmax 3510, 3057, 2971, 1737, 1114, 749 cm−1; 1H NMR (500 MHz, CD3CN, 50 °C) δ 8.16 (1H, s), 8.08 (1H, d, J = 8.3 Hz), 7.95 (1H, s), 7.89 (1H, d, J = 7.9 Hz), 7.66 (2H, d, J = 7.5 Hz), 7.59 (2H, d, J = ACS Paragon Plus Environment

11


1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 12 of 23

7.3 Hz), 7.56 (1H, ddd, J = 8.3, 6.8, 1.1 Hz), 7.49–7.45 (4H, m), 7.42–7.38 (3H, m), 7.36–7.22 (3H, m), 7.08 (1H, brs), 6.34 and 5.85 (total 1H, brs, OH), 0.53 (9H, s); 13C NMR (150 MHz, CD3CN, 50 °C) δ 177.9 and 176.5 (broad peaks of the rotamers), 151.1, 147.6, 139.6, 138.8, 136.7, 134.4, 134.3, 133.6, 132.7, 131.7, 131.4, 130.8, 130.5, 130.2, 129.6, 129.4 (×2), 129.1, 128.9, 128.6, 128.3, 127.6, 127.5, 126.5, 126.2 and 125.3 (broad peaks of the rotamers), 126.0, 124.9, 116.4, 39.4, 26.9; HRFABMS m/z [M+Na]+ Calcd for C37H30O3Na 545.2093; Found 545.2099.

General Procedure for the Synthesis of C5(CN)4 Esters 1e–1j

(R)-Sodium 1,2,3,4-tetracyano-5-(((2′-hydroxy-(1,1′-binaphthalen)-2-yl)oxy)carbonyl) cyclopentadienide (1e). To a suspension of carboxylic acid 2 (50 mg, 0.22 mmol, 1.0 equiv), DMAP (4 mg, 0.03 mmol, 0.1 equiv), and (R)-BINOL (82 mg, 0.43 mmol, 2.0 equiv) in THF (1 mL) was added 1-ethyl-3-(3dimethylaminopropyl)carbodiimide hydrochloride (EDCI) (82 mg, 0.43 mmol, 2.0 equiv) in a single portion, and the reaction mixture was stirred at room temperature for 3 h. The reaction was quenched with a 10% aqueous HCl (2 mL) solution, and the resulting mixture was extracted with EtOAc. The organic layer was then washed with saturated NaHCO3 solution and brine, dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. Flash chromatography (EtOAc) afforded (87 mg, 81%) of 1e as a yellow solid. Rf = 0.4 (10% MeCN in EtOAc); Mp 244–246 °C; [α]28D +74.9 (c 1.15, MeOH); IR (KBr) νmax 3464, 2222, 1708, 1621, 1478, 1250, 1209, 1096 cm−1; 1H NMR (CD3CN, 500 MHz) δ 8.13 (1H, d, J = 8.9 Hz), 8.03 (1H, d, J = 8.3 Hz), 7.87 (1H, d, J = 8.9 Hz), 7.81 (1H, d, J = 8.0 Hz), 7.60 (1H, d, J = 8.9 Hz), 7.51 (1H, dd, J = 8.0, 7.2 Hz), 7.34 (1H, dd, J = 8.3, 7.2 Hz), 7.28 (1H, d, J = 8.9 Hz), 7.27 (1H, dd, J = 8.0, 7.2 Hz), 7.21 (1H, dd, J = 8.3, 7.2 Hz), 7.20 (1H, d, J = 8.9 Hz), 7.05 (1H, d, J = 8.3 Hz), 6.61 (1H, brs);

13

C NMR (CD3CN, 125 MHz) δ 160.6, 153.5, 146.4, 134.8,


12

Page 13 of 23

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


134.7, 133.2, 130.9, 130.7, 129.7, 129.3, 128.9, 127.9, 127.5, 127.0, 126.5, 125.6, 125.5, 124.2, 123.4, 121.8, 119.3, 115.2, 114.9, 114.8, 104.1, 101.7; HRFABMS m/z [M–Na]− Calcd for C30H13N4O3 477.0988; Found 477.0984.

(R)-Sodium

1,2,3,4-tetracyano-5-(((2′-hydroxy-3,3′-dimethyl-[1,1′-binaphthalen]-2-yl)oxy)carbonyl)

cyclopentadienide (1f). According to the procedure described for 1e, 1f was synthesized using carboxylic acid 2 (134 mg, 0.578 mmol, 1.0 equiv), DMAP (9 mg, 0.08 mmol, 0.1 equiv), (R)-3,3′dimethyl-1,1′-binaphthol (200 mg, 0.636 mmol, 1.1 equiv), and EDCI (222 mg, 1.16 mmol, 2.0 equiv) in THF (9 mL) at room temperature over 14 h. Flash chromatography (0 → 10% MeCN in EtOAc) afforded 1f (257 mg, 84%) as a pale yellow solid. Rf = 0.4 (10% MeCN in EtOAc); Mp 280–283 °C; [α]25D +214.4 (c 1.16, acetone); IR (KBr) νmax 3504, 2223, 1708, 1477, 1252, 1230, 1101, 751 cm−1; 54:46 rotamer ratio at room temperature in CD3CN; 1H NMR for the major rotamer (600 MHz, CD3CN) δ 8.00 (1H, s), 7.92 (1H, d, J = 8.3 Hz), 7.71–7.67 (2H, m), 7.47–7.45 (1H, m), 7.28–7.18 (3H, m), 7.13–7.06 (2H, m), 6.98 (2H, d, J = 8.4 Hz), 6.10 (1H, brs), 2.49 (3H, s), 2.42 (3H, s); 1H NMR for the minor rotamer (600 MHz, CD3CN) δ 7.97 (1H, s), 7.92 (1H, d, J = 8.3 Hz), 7.71–7.67 (2H, m), 7.47– 7.45 (1H, m), 7.28–7.18 (2H, m), 7.13–7.06 (3H, m), 6.98 (2H, d, J = 8.4 Hz), 6.18 (1H, brs), 2.45 (6H, s);

13

C NMR for the major rotamer (150 MHz, CD3CN) δ 160.9, 152.5, 148.6, 133.6, 133.4, 133.3,

131.4, 131.1, 130.5, 129.9, 128.7, 128.6, 128.1, 127.4, 127.2, 126.8, 126.1, 125.6, 125.1, 124.4, 121.2, 115.2, 115.0, 114.7, 104.2, 101.9, 17.6, 17.4;

13

C NMR for the minor rotamer (150 MHz, CD3CN) δ

159.6, 152.6, 148.7, 133.6, 133.5, 133.3, 132.0, 130.8, 130.2, 129.7, 128.6, 128.4, 128.0, 127.1, 127.0, 126.4, 126.0, 125.9, 125.8, 124.0, 121.5, 115.2, 114.8, 114.7, 104.1, 101.6, 17.7 (×2); HRFABMS m/z [M–Na]− Calcd for C32H17N4O3 505.1301; Found 505.1291. ACS Paragon Plus Environment

13


1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

(R)-Sodium

Page 14 of 23

1,2,3,4-tetracyano-5-(((3,3′-dibromo-2′-hydroxy-[1,1′-binaphthalen]-2-yl)oxy)carbonyl)

cyclopentadienide (1g). According to the procedure described for 1e, 1g was synthesized using carboxylic acid 2 (114 mg, 0.409 mmol, 1.0 equiv), DMAP (8 mg, 0.05 mmol, 0.1 equiv), (R)-3,3′dibromo-1,1′-binaphthol (204 mg, 0.450 mmol, 1.1 equiv), and EDCI (171 mg, 0.450 mmol, 2.0 equiv) in THF (6 mL) at room temperature over 5 h. Flash chromatography (0 → 10% MeCN in EtOAc) afforded 1g (286 mg, 95%) as a pale yellow solid. Rf = 0.5 (10% MeCN in EtOAc); Mp 293–295 °C; [α]28D +94.4 (c 1.03, acetone); IR (KBr) νmax 3483, 2223, 1718, 1475, 1242, 1221, 1088, 749 cm−1; 1H NMR for the major rotamer (600 MHz, CD3CN) δ 8.48 (1H, s), 8.23 (1H, s), 8.01 (1H, d, J = 8.3 Hz), 7.75 (1H, d, J = 8.1 Hz), 7.57 (1H, t, J = 7.2 Hz), 7.38 (1H, t, J = 7.9 Hz), 7.30 (1H, t, J = 7.3 Hz), 7.22 (1H, t, J = 7.3 Hz), 7.10 (1H, d, J = 8.4 Hz), 7.01 (1H, d, J = 8.4 Hz), 6.72 (1H, brs); 58:42 rotamer ratio at room temperature in CD3CN; 1H NMR for the minor rotamer (600 MHz, CD3CN) δ 8.51 (1H, s), 8.23 (1H, s), 8.01 (1H, d, J = 8.3 Hz), 7.77 (1H, d, J = 8.1 Hz), 7.58 (1H, t, J = 7.0 Hz), 7.42 (1H, t, J = 7.5 Hz), 7.35 (1H, t, J = 7.7 Hz), 7.31 (1H, t, J = 7.2 Hz), 7.17 (1H, d, J = 8.4 Hz), 7.04 (1H, d, J = 8.4 Hz), 6.66 (1H, brs);

13

C NMR for the major rotamer (150 MHz, CD3CN) δ 159.0, 149.8, 145.7,

133.9 (×2), 133.7, 133.6, 133.5, 130.2, 128.7, 128.6, 128.2 (×2), 128.0, 127.8, 126.6, 126.1, 125.4, 120.7, 117.1, 116.3, 115.1, 114.7, 113.9, 104.4, 101.8;

13

C NMR for the minor rotamer (150 MHz,

CD3CN) δ 159.6, 149.7, 145.7, 134.4, 134.2, 133.9, 133.6 (×2), 130.3, 120.0, 128.6, 128.5, 128.4, 128.0, 127.7, 126.4, 125.6, 125.5, 120.3, 116.4, 116.2, 115.1, 114.7, 113.3, 104.5, 102.2; HRFABMS m/z [M– Na]− Calcd for C30H11Br2N4O3 632.9198; Found 632.9171.


14

Page 15 of 23

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

(R)-Sodium


1,2,3,4-tetracyano-5-(((2′-hydroxy-3,3′-diphenyl-[1,1′-binaphthalen]-2-yl)oxy)carbonyl)

cyclopentadienide (1h). According to the procedure described for 1e, 1h was synthesized using carboxylic acid 2 (510 mg, 2.19 mmol, 1.0 equiv), DMAP (30 mg, 0.22 mmol, 0.10 equiv), (R)-3,3′diphenyl-1,1′-binaphthol (1.10 g, 2.42 mmol, 1.1 equiv), and EDCI (850 mg, 4.38 mmol, 2.0 equiv) in THF (30 mL) at room temperature over 3.5 h. Flash chromatography (5 → 20% MeCN in EtOAc) afforded 1h (1.01 g, 76%) as a pale yellow solid. Rf = 0.4 (5% MeCN in EtOAc); Mp 284–286 ºC; [α]D27 +35.9 (c 3.0, MeOH); IR (KBr) νmax 3503, 2955, 2364, 2220, 1707, 1623, 1474, 1239, 1178, 1091, 896, 764, 701 cm−1; 51:49 rotamer ratio at room temperature in CD3CN; 1H NMR (CD3CN, 500 MHz) δ 8.23 (0.5H, s), 8.21 (0.5H, s), 8.12 (0.5H, s), 8.10 (0.5H s), 7.88 (0.5H, s), 7.87 (0.5H, s), 7.86 (0.5H, m), 7.82 (0.5H, d, J = 8 Hz), 7.78–7.73 (3H, m), 7.59–7.55 (2H, m), 7.50 (1H, t, J = 7.5 Hz), 7.45–7.30 (7H, m), 7.27 (0.5H, t, J = 7.45 Hz), 7.26 (0.5H, d, J = 8.3 Hz), 7.20–7.16 (1.5H, m), 7.00 (0.5H, d, J = 8.6 Hz), 6.41 (0.5H, s), 6.01 (0.5H, s);

13

C NMR (CD3CN, 125 MHz) δ 160.6, 159.2, 151.1, 150.8,

147.0, 146.7, 139.4, 139.3, 138.8, 138.4, 136.4, 135.9, 134.3, 134.1, 134.0, 133.7, 133.6, 132.6 (×2), 132.4, 132.0, 131.5, 131.4, 131.2, 130.8, 130.7, 130.5, 130.1, 129.9, 129.7, 129.6, 129.5 (×2), 129.4, 129.3 (×2), 129.2, 129.0, 128.9, 128.8, 128.7, 128.4, 128.3 (×2), 128.0 (×2), 127.7, 127.4, 127.1, 126.6, 126.5, 126.3, 126.0, 125.4, 124.9, 124.5, 121.5, 120.7, 116.5, 115.7, 115.2, 115.1, 114.8, 114.7, 104.2, 104.0, 101.8, 101.4; HRFABMS m/z [M–Na]− Calcd for C42H21O3N4 629.1619; Found 629.1643.

(R)-Sodium

1,2,3,4-tetracyano-5-(((3,3′-di([1,1′-biphenyl]-4-yl)-2′-hydroxy-[1,1′-binaphthalen]-2ACS Paragon Plus Environment

15


1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 16 of 23

yl)oxy)carbonyl)cyclopentadienide (1i). According to the procedure described for 1e, 1i was synthesized using carboxylic acid 2 (120 mg, 0.519 mmol, 1.0 equiv), DMAP (8 mg, 0.07 mmol, 0.1 equiv), (R)3,3′-di([1,1′-biphenyl]-4-yl)-1,1′-binaphthol (337 mg, 0.571 mmol, 1.1 equiv), and EDCI (199 mg, 1.04 mmol, 2.0 equiv) in THF (30 mL) at room temperature over 2 h. Flash chromatography (5 → 20% MeCN in EtOAc) afforded 1i (1.01 g, 76%) as a pale yellow solid. Rf = 0.5 (5% MeCN in EtOAc); Mp 287–290 °C; [α]28D –173.0 (c 1.19, MeOH); IR (KBr) νmax 3522, 3057, 3030, 2222, 1714, 1240, 1092, 767 cm−1; 52:48 rotamer ratio at room temperature in CD3CN; 1H NMR (CD3CN, 600 MHz) δ 8.30 (0.5H, s), 8.28 (0.5H, s), 8.12 (1H, d, J = 8.5 Hz), 7.96 (0.5H, s), 7.95 (0.5H, s), 7.90–7.83 (4H, m), 7.77–7.69 (6H, m), 7.67–7.64 (2H, m), 7.59–7.55 (1H, m), 7.50–7.44 (4H, m), 7.42–7.34 (4H, m), 7.29– 7.25 (1.5H, m), 7.22 (0.5H, d, J = 7.9 Hz), 7.20 (0.5H, ddd, J = 8.2, 6.8, 1.1 Hz), 7.04 (0.5H, d, J = 8.5 Hz), 6.54 (0.5H, brs), 6.17 (0.5H, brs); 13C NMR (CD3CN, 150 MHz, 15 °C) δ 160.7, 159.3, 151.1, 150.7, 147.0, 146.5, 141.3, 141.2, 141.0, 140.8 (×3), 140.58, 140.56, 138.4, 138.2, 137.7, 137.3, 135.8, 135.2, 134.2, 134.02, 134.00, 133.9, 133.6, 133.5, 132.04, 131.96, 131.8, 131.6, 131.40, 131.36, 131.21, 131.20, 131.0, 130.5, 129.9, 129.83 (×2), 129.81 (×2), 129.7, 129.5 (×2), 129.01, 128.96, 128.49, 128.47, 128.35 (×2), 128.33, 128.05, 128.03, 127.83, 127.82, 127.77, 127.75, 127.69, 127.66, 127.62, 127.59, 127.5, 127.4, 127.1, 126.50, 126.46, 126.2, 125.9, 125.4, 125.0, 124.5, 121.6, 120.7, 116.6, 115.6, 115.3, 115.2, 114.8, 114.6, 104.3, 104.1, 101.9, 101.5; HRFABMS m/z [M–Na]− Calcd for C54H29N4O3 781.2240; Found 781.2265.

(R)-Sodium

1,2,3,4-tetracyano-5-(((3,3′-di(anthracen-9-yl)-2′-hydroxy-[1,1′-binaphthalen]-2-

yl)oxy)carbonyl)cyclopentadienide (1j). According to the procedure described for 1e, 1j was synthesized using carboxylic acid 2 (81 mg, 0.35 mmol, 1.0 equiv), DMAP (6 mg, 0.05 mmol, 0.1 equiv), (R)-3,3′-


16

Page 17 of 23

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


di(anthracen-9-yl)-1,1′-binaphthol (245 mg, 0.383 mmol, 1.1 equiv), and EDCI (133 mg, 0.696 mmol, 2.0 equiv) in THF (5 mL) at room temperature over 19 h. Flash chromatography (20% MeCN in CH2Cl2) afforded 1j (161 g, 54%) as a pale yellow solid. Rf = 0.4 (20% MeCN in CH2Cl2); Mp 318– 320 °C; [α]28D +183.4 (c 1.05, MeOH); IR (KBr) νmax 3479, 3052, 2218, 1707, 1622, 1472, 1442, 1246, 1093, 737 cm−1; 64:36 rotamer ratio at room temperature in CD3CN; 1H NMR for the major rotamer (600 MHz, CD3CN, 15 °C) δ 8.57 (1H, s), 8.39 (1H, s), 8.15 (1H, s), 8.08 (1H, d, J = 8.2 Hz), 8.04 (1H, d, J = 8.5 Hz), 8.02 (1H, d, J = 8.5 Hz), 7.98 (1H, d, J = 9.0 Hz), 7.95 (1H, d, J = 8.4 Hz), 7.93 (1H, d, J = 8.6 Hz), 7.87 (1H, d, J = 8.7 Hz), 7.843 (1H, s), 7.836 (1H, d, J = 8.7 Hz), 7.834 (1H, d, J = 8.7 Hz), 7.67 (1H, d, J = 8.5 Hz), 7.581 (1H, d, J = 8.7 Hz), 7.577 (1H, dd, J = 8.7, 6.8 Hz), 7.53 (1H, dd, J = 8.7, 6.8 Hz), 7.50 (1H, dd, J = 8.6, 6.4 Hz), 7.49 (2H, dd, J = 8.6, 6.4 Hz), 7.47 (1H, dd, J = 8.6, 6.4 Hz), 7.46 (1H, dd, J = 8.6, 6.4 Hz), 7.41 (1H, dd, J = 8.6, 6.4 Hz), 7.40 (1H, dd, J = 8.6, 6.4 Hz), 7.38 (1H, dd, J = 8.6, 6.4 Hz), 7.33 (1H, dd, J = 8.6, 6.4 Hz), 7.14 (1H, d, J = 8.6 Hz), 7.09 (1H, dd, J = 8.6, 6.4 Hz), 6.19 (1H, brs); 1H NMR for the minor rotamer (600 MHz, CD3CN, 15 °C) δ 8.62 (1H, s), 8.36 (1H, s), 8.12 (1H, d, J = 8.1 Hz), 8.093 (1H, d, J = 7.7 Hz), 8.086 (1H, d, J = 8.5 Hz), 8.08 (1H, s), 8.02 (1H, d, J = 8.5 Hz), 7.92 (1H, d, J = 8.3 Hz), 7.88 (1H, d, J = 8.5 Hz), 7.848 (1H, s), 7.84 (1H, d, J = 8.7 Hz), 7.80 (1H, d, J = 8.5 Hz), 7.78 (1H, d, J = 8.5 Hz), 7.62 (1H, d, J = 8.6 Hz), 7.58 (1H, dd, J = 8.7, 6.8 Hz), 7.529 (1H, d, J = 8.5 Hz), 7.526 (1H, dd, J = 8.7, 6.8 Hz), 7.48 (1H, dd, J = 8.7, 6.4 Hz), 7.47 (2H, dd, J = 8.7, 6.4 Hz), 7.45 (1H, dd, J = 8.6, 6.4 Hz), 7.44 (1H, d, J = 8.5 Hz), 7.43 (1H, dd, J = 8.6, 6.4 Hz), 7.36 (1H, dd, J = 8.6, 6.4 Hz), 7.35 (1H, dd, J = 8.6, 6.4 Hz), 7.34 (1H, dd, J = 8.6, 6.4 Hz), 7.26 (1H, dd, J = 8.6, 6.4 Hz), 7.22 (1H, dd, J = 8.6, 6.4 Hz), 6.17 (1H, brs);

13

C NMR for the major

rotamer (150 MHz, CD3CN, 15 °C) δ 159.5, 152.4, 148.4, 134.7, 134.5, 134.4, 133.7, 133.6, 133.3, 133.0, 132.5, 132.3 (×2), 132.2, 132.0, 131.7, 131.59, 131.55, 131.46, 129.7, 129.4, 129.3, 129.2, 129.1, 129.0, 128.7 (×2), 128.5, 128.4 (×2), 128.2, 127.9, 127.8, 127.7, 127.5, 127.3, 126.9 (×2), 126.8, 126.6, 126.5, 126.3 (×3), 126.2, 126.1, 126.0, 124.9, 120.0, 115.9, 114.6, 114.4, 103.7, 101.6; 13C NMR for the minor rotamer (150 MHz, CD3CN, 15 °C) δ 158.7, 152.3, 148.2, 134.8, 134.7, 134.3, 133.4, 133.2 (×2),


17


1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 18 of 23

133.1, 132.6, 132.5, 132.3 (×2), 131.9, 131.8, 131.7 (×2), 131.2, 129.7, 129.4, 129.3, 129.1 (×2), 128.8 (×2), 128.7, 128.4 (×3), 128.2 (×2), 127.6, 127.4 (×2), 127.33, 127.28, 127.0 (×2), 126.9, 126.8, 126.7, 126.38, 126.36, 126.3, 126.1 (×2), 124.8, 120.5, 116.2, 114.71, 114.66, 103.6, 101.2; HRFABMS m/z [M–Na]− Calcd for C58H29N4O3 829.2240; Found 829.2250.

(R)-Sodium

1,2,3,4-tetracyano-5-(((2′-methoxy-3,3′-diphenyl-[1,1′-binaphthalen]-2-

yl)oxy)carbonyl)cyclopentadienide (3). To a solution of ester 1h (50 mg, 0.077 mmol) and MeI (48 µL, 0.77 mmol) in DMF (1 mL) was added NaH (60% dispersion in mineral oil, 6 mg, 0.2 mmol). After stirring for 2 h, dimethyl sulfate (40 µL, 0.38 mmol) and NaH (60% dispersion in mineral oil, 15 mg, 0.38 mmol) were added, and the mixture was stirred at room temperature for 22 h. After this time, the reaction was quenched with saturated aqueous NH4Cl solution, and the resulting mixture was extracted with EtOAc. The organic layer was washed with brine, dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. Purification by flash chromatography (0–15% MeCN in EtOAc) afforded methyl ether 3 (48 mg, 94%) as pale yellow solid. Rf = 0.4 (5% MeCN in EtOAc); Mp 279– 282 ºC; [α]24D –89.4 (c 1.00, MeOH); IR (KBr) νmax 3483, 2221, 1710, 1476, 1239, 1093 cm−1; 64:36 rotamer ratio at room temperature in CD3CN; 1H NMR for the major rotamer (150 MHz, CD3CN) δ 8.17 (1H, s), 8.10 (1H, d, J = 8.3 Hz), 7.98 (1H, s), 7.88 (1H, d, J = 8.2 Hz), 7.78 (2H, d, J = 7.2 Hz), 7.73 (2H, d, J = 7.2 Hz) 7.56 (1H, ddd, J = 8.1, 6.8, 1.3 Hz), 7.50 (2H, t, J = 7.5 Hz), 7.42 (1H, t, J = 7.5 Hz), 7.40 (2H, t, J = 7.5 Hz), 7.39 (1H, dd, J = 8.6, 6.4 Hz), 7.36 (1H, dd, J = 8.6, 6.4 Hz), 7.32 (1H, t, J = 7.5 Hz), 7.27 (1H, d, J = 8.9 Hz), 7.23 (1H, ddd, J = 8.6, 6.6, 0.9 Hz), 7.20 (1H, d, J = 8.3 Hz), 3.24 (3H, s); 1H NMR for the minor rotamer (150 MHz, CD3CN) δ 8.17 (1H, s), 8.10 (1H, d, J = 8.3 Hz), 7.95 (1H, s), 7.93 (1H, d, J = 8.6 Hz), 7.77 (2H, d, J = 7.9 Hz), 7.56 (1H, ddd, J = 8.1, 6.8, ACS Paragon Plus Environment

18

Page 19 of 23

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


1.3 Hz), 7.455 (2H, d, J = 7.8 Hz), 7.446 (1H, dd, J = 8.7, 6.8 Hz), 7.43 (2H, t, J = 7.5 Hz), 7.42 (2H, t, J = 7.5 Hz), 7.39 (1H, dd, J = 8.6, 6.4 Hz), 7.375 (1H, t, J = 8.6, 6.4 Hz), 7.368 (1H, d, J = 7.7 Hz), 7.35 (1H, dd, J =8.6, 6.4 Hz), 7.34 (1H, t, J = 7.5 Hz), 7.28 (1H, d, J = 8.9 Hz), 2.99 (3H, s);

13

C NMR for

the major rotamer (150 MHz, CD3CN) δ 159.4, 155.2, 145.9, 139.8, 138.9, 136.2, 136.1, 134.2, 133.8, 133.1, 131.7 (×2), 130.8, 130.4, 130.2, 129.5, 129.41, 129.36, 128.9, 128.7, 128.5, 128.3, 127.9, 127.4, 127.1, 126.8, 126.7, 126.2, 125.1, 121.4, 115.2, 114.8, 104.0, 101.3, 61.5;

13

C NMR for the minor

rotamer (150 MHz, CD3CN) δ 159.2, 155.3, 145.6, 139.8, 139.1, 136.2, 135.6, 134.2, 134.1, 133.1, 132.1, 131.7, 130.9, 130.2, 130.0, 129.48, 129.47, 129.4, 129.0, 128.7, 128.4, 128.0, 127.9, 127.8, 127.3, 127.1, 126.6, 126.1, 124.5, 122.0, 115.1, 114.8, 103.8, 101.5, 61.2; HRFABMS m/z [M–Na]− Calcd for C43H23N4O3 643.1770; Found 643.1781.

VT NMR and Line Shape Simulations Temperatures were calibrated using MeOH (from −80 °C to 25 °C) and 80% ethylene glycol in DMSO-d6 (from 25 °C to 120 °C) according to the Bruker instrument manual. The populations of rotamers A (pA) and B (pB)17 and the diastereomerization constant from rotamer A to B (kAB) shown in eq 1 were determined by line shape analysis using WinDNMR Pro 7.1 (Figures S1–S13(b) in the Supporting Information).

Rotamer A (pA)

kAB (s–1) kBA (s–1)

Rotamer B (pB)

(eq 1)

The activation parameters were determined by plotting ln(kAB/T) versus 1/T (Figures S1–S13(c) in the Supporting Information), wherein the activation enthalpy (∆H‡) was determined from the slope of the plot using eq 2: ∆H‡ = −R × slope

(eq 2)

where R is the gas constant, 1.987 cal/mol. The activation entropy (∆S‡) was then determined from the intercept using eq 3:


19


1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

∆S‡ = R × (intercept − ln (h/kB))

Page 20 of 23

(eq 3)

where h is Plank’s constant, kB is the Boltzmann constant, and ln (h/kB) = 23.7600. Finally, the rotational free energy at 298 K (∆G‡298) was calculated from the calculated ∆H‡ and ∆S‡ values according to eq 4: ∆G‡ = ∆H‡ – T∆S‡

(eq 4)

Supporting Information VT NMR spectra, line shape simulations, and Eyring plots. Copies of 1H and 13

C NMR spectra of all new compounds. Cartesian coordinates and energies of the optimized geometries.

Cartesian coordinates, energies, and imaginary frequencies of the rotational transition states. This material is available free of charge via the Internet at http://pubs.acs.org.

Notes The authors declare no competing financial interest.

Acknowledgments This research was partially supported by Grant-in-Aids for Scientific Research (C) (16K08182 and 16K08183) from the Japan Society for the Promotion of Science (JSPS). References 1

(a) Clayden, J.; Moran, W. J.; Edwards, P. J.; LaPlante, S. R. Angew. Chem. Int. Ed. 2009, 48, 6398–

6401. (b) Bringmann, G.; Gulder, T.; Gulder, T. A. M.; Breuning, M. Chem. Rev. 2011, 111, 563–639. (c) LaPlante, S. R.; Fader, L. D.; Fandrick, K. R.; Fandrick, D. R.; Hucke, O.; Kemper, R.; Miller, S. P. F.; Edwards, P. J. J. Med. Chem. 2011, 54, 7005–7022. (d) Zask, A.; Murphy, J.; Ellestad, G. A. Chirality, 2013, 25, 265–274. (e) Nalbandian, C. J.; Hecht, D. E.; Gustafson, J. L. Synlett, 2016, 27, 977–983. (f) Wipf, P.; Skoda, E. M.; Mann, A. Conformatioonal Restriction and Steric Hinderance in Medicinal Chemistry. In The Practice of Medicinal Chemistry, 4th Ed.; Elsevier: UK, 2015; pp 279–299. 2

Leading review for nonbiaryl and heterobiaryl atropisomers: Kumarasamy, E.; Raghunathan, R.; Sibi, ACS Paragon Plus Environment

20

Page 21 of 23

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


M.; Sivaguru, J. Chem. Rev. 2015, 115, 11239–11300. 3

Reviews: (a) Clayden, J. Angew. Chem. Int. Ed. Engl. 1997, 36, 949–951. (b) Campolo, D.; Gastaldi,

S.; Roussel, C.; Bertrand, M. P.; Nechab, M. Chem. Soc. Rev. 2013, 42, 8434–8466. (c) Tanaka, K.; Shibata, T. Synthesis of Axially Chiral Aromatic Compounds via [2+2+2] Cycloaddition. In TransitionMetal-Mediated Aromatic Ring Construction; Tanaka, K., Ed.; John Wiley & Sons, Inc., Hoboken, NJ, USA, 2013; pp 255–279. (d) Takahashi, I.; Suzuki, Y.; Kitagawa, O. Org. Prep. Proced. Int. 2014, 46, 1– 23. (e) Bencivenni, G. Synlett 2015, 26, 1915–1922. 4

(a) Nicolaou, K. C.; Boddy, C. N. C.; Bräse, S.; Winssinger, N. Angew. Chem. Int. Ed. 1999, 38, 2096–

2152. (b) Crowley, B. M.; Boger, D. L. J. Am. Chem. Soc. 2006, 128, 2885–2892. 5

(a) Betson, M. S.; Clayden, J.; Worrall, C. P.; Peace, S. Angew. Chem. Int. Ed. 2006, 45, 5803–5807.

(b) Fuji, K.; Oka, T.; Kawabata, T.; Kinoshita, T. Tetrahedron Lett. 1998, 39, 1373–1376. Asymmetric synthesis: (c) Clayden, J.; Worrall, C. P.; Moran, W. J.; Helliwell, M. Angew. Chem. Int. Ed. 2008, 47, 3234–3237. (d) Yuan, B.; Page, A.; Worrall, C. P.; Escalettes, F.; Willies, S. C.; McDouall, J. J. W.; Turner, N. J.; Clayden, J. Angew. Chem. Int. Ed. 2010, 49, 7010–7013. (e) Page, A.; Clayden, J. Beilstein J. Org. Chem. 2011, 7, 1327–1333. 6

(a) Yoshimura, T.; Tomohara, K.; Kawabata, T. J. Am. Chem. Soc. 2013, 135, 7102–7105. (b)

Tomohara, K.; Kasamatsu, K.; Yoshimura, T.; Furuta, T.; Kawabata, T. Chem. Pharm. Bull. 2016, 64, 899–906. 7

Siddall III, T. H.; Stewart, W. E.; Good, M. L. Can. J. Chem. 1967, 45, 1290–1293.

8

Mazzanti, A.; Chiarucci, M.; Bentley, K. W.; Wolf, C. J. Org. Chem. 2014, 79, 3725–3730.

9

Tetracyanocyclopentadienides (C5R(CN)4−) are stable as superacid anions: (a) Webster, O. W. J. Am.

Chem. Soc. 1966, 88, 3046–3050. (b) Sakai, T.; Seo, S.; Matsuoka, J.; Mori, Y. J. Org. Chem. 2013, 78, 10978–10985. (c) Sakai, T.; Bito, M.; Itakura, M.; Sato, H.; Mori, Y. Chem. Pharm. Bull. 2016, 64, 930– 934. 10

(a) Nakano, D.; Hirano, R.; Yamaguchi, M.; Kabuto, C. Tetrahedron Lett. 2003, 44, 3683–3686. (b)


21


1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 22 of 23

Jiang, H.; Lin, W. J. Am. Chem. Soc. 2004, 126, 7426–7427. (c) Hua, J.; Lin, W. Org. Lett. 2004, 6, 861– 864. (d) Qin, Y.-C.; Liu, L.; Pu, L. Org. Lett. 2005, 7, 2381–2383. (e) Caricato, M.; Leza, N. J.; Gargiulli, C.; Gattuso, G.; Dondi, D.; Pasini, D. Beilstein J. Org. Chem. 2012, 8, 967–976. (f) Ye, P.; Li, Q.; Bai, Z.; Dong, K.; Liu, Q. Heterocycles, 2015, 91, 1986–1995. 11

Rotamers were not observed in 3,3′-dimethyl- and 3,3′-di(alkoxymethyl)-BINOL pivalates synthesized

previously at room temperature. (a) Matsu-ura, M.; Tani, F.; Naruta, Y. J. Am. Chem. Soc. 2002, 124, 1941–1950. (b) Hocke, H.; Uozumi, Y. Tetrahedron 2003, 59, 619–630. (c) Reddy, J. J.; Ohta, T.; Naruta, Y. Tetrahedron Lett. 2009, 50, 3418–3421. Syntheses of 3,3′-diaryl-BINOL pivalates including 1d were reported in two patents, although NMR data were not reported. (d) Tokunaga, M.; Hamazaki, A.; Yamamoto, E.; Sakuma, T.; Omura, N.; Nagai, A.; Nakamura, R. Jpn. Kokai Tokkyo Koho JP 2012148983, 2012. (e) Lee, J.-W.; List, B.; Opwis, K.; Mayer-Gall, T.; Gutmann, J. S. Int. Patent WO2013/178640 A1, 2013. 12

Relative configuration of the major rotamer was not determined. We attempted to carry out difference

NOE experiments for pivaloyl ester 1d at −40 °C; however, no conclusive data were obtained between the major and minor rotamers as shown in the Supporting Information, Figure S14. 13

Reich, H. J. WinDNMR: Dynamic NMR Spectra for Windows. J. Chem. Educ. Software 1996, 3D, 2.

14

(a) Casarini, D.; Lunazzi, L.; Mazzanti, A. Eur. J. Org. Chem. 2010, 2035–2056. (b) Sandström, J.

Dynamic NMR Spectroscopy, Academic Press: London, 1982. 15

Mishiro, K.; Furuta, T.; Sasamori, T.; Hayashi, K.; Tokitoh, N.; Futaki, S.; Kawabata, T. J. Am. Chem.

Soc. 2013, 135, 13644–13647. 16

Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb, M. A.; Cheeseman, J. R.;

Scalmani, G.; Barone, V.; Mennucci, B.; Petersson, G. A.; Nakatsuji, H.; Caricato, M.; Li, X.; Hratchian, H. P.; Izmaylov, A. F.; Bloino, J.; Zheng, G.; Sonnenberg, J. L.; Hada, M.; Ehara, M.; Toyota, K.; Fukuda, R.; Hasegawa, J.; Ishida, M.; Nakajima, T.; Honda, Y.; Kitao, O.; Nakai, H.; Vreven, T.; Montgomery, Jr., J. A.; Peralta, J. E.; Ogliaro, F.; Bearpark, M.; Heyd, J. J.; Brothers, E.; Kudin, K. N.; Staroverov, V. N.;


22

Page 23 of 23

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


Keith, T.; Kobayashi, R.; Normand, J.; Raghavachari, K.; Rendell, A.; Burant, J. C.; Iyengar, S. S.; Tomasi, J.; Cossi, M.; Rega, N.; Millam, J. M.; Klene, M.; Knox, J. E.; Cross, J. B.; Bakken, V.; Adamo, C.; Jaramillo, J.; Gomperts, R.; Stratmann, R. E.; Yazyev, O.; Austin, A. J.; Cammi, R.; Pomelli, C.; Ochterski, J. W.; Martin,

R. L.; Morokuma, K.; Zakrzewski, V. G.; Voth, G. A.; Salvador, P.;

Dannenberg, J. J.; Dapprich, S.; Daniels, A. D.; Farkas, O.; Foresman, J. B.; Ortiz, J. V.; Cioslowski, J.; Fox, D. J. Gaussian 09, Revision E.01; Gaussian, Inc., Wallingford, CT, 2013. 17

In several samples, the population of the rotamers varied slightly depending on the temperature due to

the small entropy difference between these two rotamers. A dramatic temperature-dependent change in population was recently reported for secondary 2,2′-bisanilides: Mazzanti, A.; Chiarucci, M.; Prati, L.; Bentley, K. W.; Wolf, C. J. Org. Chem. 2016, 81, 89–99.


23

CArâO Rotamers in 3,3â²-Disubstituted BINOL Esters - The Journal of

Recommend Documents

CArâO Rotamers in 3,3â²-Disubstituted BINOL Esters - The Journal of