Variable-Sized bis(4-spiro-fused-β-lactam)-Based Unsaturated Macrocycles: Synthesis and Characterization

Abstract

The synthesis with structural identifications including NMR and HRMS spectral data along with single-crystal X-ray diffraction analysis (for 20b, 23b, 25b–27b) of a family of 14 new syn/anti bis-4-spiro-β-lactam-based unsaturated macrocycles (19a,b–27a,b), obtained by multistep synthesis including (i) diimine formation, (ii) Staudinger [2 + 2] ketene–imine cycloaddition, and (iii) ring-closing metathesis (RCM), is reported.

Introduction

Among azaheterocyclic ring systems, C3 and C4 spiro-fused β-lactams (azetidin-2-one) (Figure 1)¹⁻⁴ are uniquely important for their presence in a family of marine natural products, e.g., chartellines and chartelamides,⁵ for their prominence in synthetic chemistry as versatile building blocks in the synthesis of α/β-amino acids,⁶ alkaloids,⁷ heterocycles,⁸ toxoids, and other relevant molecular structures⁹ and for their medicinal chemistry in synthesis of many biologically vital materials that behave as β-turn mimetics,¹⁰ enzyme inhibitors,¹¹ and precursors of α,α-disubstituted β-amino acids,¹² as well as their biological activities including antibacterial agents,¹³ active against HIV-1 and plasmodium,¹⁴ along with cholesterol absorption inhibitors.¹⁵

Figure 1.

General representation of C3 and C4 spiro-fused azetidin-2-ones.

In the light of their remarkable structural, chemical, and biological properties and applications, much attention has been devoted by our research group for demonstrating more complexed materials,¹⁶ that is, bis-4-spiro-β-lactams containing unsaturated macrocycles (Figure 2).

Figure 2.

Chemical structures of bis(4-spiro-fused-β-lactam)-based unsaturated macrocycles.

During our recent interest in the construction of new types of azacrown ethers,¹⁷⁻¹⁹ a wide spectrum of macrocycles composed of two β-lactam sites, which are covalently linked with various organic and organometallic linkers through their 1,3-,1,4-, 3,4-, and 1,3,4-positions, have been achieved and reported in literature.²⁰ However, examples of macrocycles incorporating bis-4-spiro-β-lactams moieties in their backbone core structures are still limited. Recently, however, six bis-4-spiro-β-lactam-based macrocycles (Figure 2) have been successfully synthesized and utilized by our group following the classical sequential diimination, Staudinger [2 + 2] ketene–imine cycloaddition, and ring-closing metathesis (RCM) synthetic approach.

Continuing our work in architecting innovative (bis-4-spiro-β-lactam)-based azacrowns, a family of 14 new unsaturated macrocycles (seven syn/anti20, 21, 23–27configurational isomers) are described (Scheme 1). Azacrowns 28–30 were previously reported, and they are used for comparison with those newly prepared compounds. The structures of all macrocycles were established from their respective NMR and HRMS spectroscopic data along with their single-crystal X-ray diffraction analysis (for 20b, 23b, 25b, 26b, and 27b). Complete data are presented in the Supporting Information (SI) section.

Scheme 1. Synthesis of bis(4-Spiro-fused-β-lactam)-based Unsaturated Macrocycles (19–30).

Results and Discussion

Scheme 1 illustrates the synthetic procedure for the synthesis of the target syn/anti isomeric macrocycles. At first, the reaction of 1-tetralone or 9-fluorenone with 1,2-diaminoethane, 1,4-diaminobutane, and 2,2′-(ethylenedioxy)-bis(ethylamine) in the presence of para-toluene sulfonic acid (PTSA) in refluxing ethanol afforded the diamine derivatives (1–6). The complimentary diimines were then treated with 2-allyloxyacetyl chloride or (2-allyloxy)phenoxyacetyl chloride with triethylamine (TEA) in dichloromethane (DCM) at room temperature to result in the syn/anti acyclic diene isomers (7a,b–18a,b), which upon RCM in the presence of a Grubbs (II) catalyst in refluxing DCM resulted in the formation of the desired syn/anti isomeric bis-4-spiranic macrocycles (20, 21, and 23–30). Diimines 1–3, acyclic dienes 7–15, and macrocycles 20, 21, and 23–27 are reported for the first time (SI).

Regarding the acyclic structures, dienes 7b, 10a, and 10b were isolated in their pure isomeric forms by the fractional crystallization method. Their single-crystal X-ray diffraction (10a was obtained as a precipitate, and no appreciable crystals have been demonstrated), molecular packing, and ¹H-NMR spectra are presented in Figures 3–5, respectively, while the remaining dienes (8, 9, 11, 12, 14, 15, and 16) were attained as a mixture of both syn/anti isomers. The thermal ellipsoid representation (50% probability) of the crystal samples 7b and 10b along with their various crystallographic parameters are provided in the Supporting Information.

Figure 3.

Crystal structures of (A) 7b and (B) 10b. Color code: blue—nitrogen; gray—carbon; red—oxygen; black—hydrogen.

Figure 5.

Partial ¹H NMR spectra of acyclic dienes (A) anti7b, (B) syn10b, and (C) anti10b.

Figure 4.

Packing pattern of anti7b and anti10b in their crystal network; view along the (A) a, (B) b, and (C) c directions. Color code: red—oxygen; blue—nitrogen; gray—carbon (hydrogens are hidden for clarity).

The ratio between the syn/anti configurations has been established from their spiro-fused 2-azitadinone protons (H_a) (Figure 6: full ¹H-NMR spectra of the allyloxy containing acyclic dienes 8, 9, 11, and 12, Table 1) which were allocated based on the crystal structures of the isolated anti isomers 7b and 10b.

Figure 6.

1H NMR spectra of acyclic dienes (A) syn/anti8, (B) syn/anti9, (C) syn/anti11; and (D) syn/anti12.

Table 1. Yield and H_a Chemical Shifts of Syn/Anti Acyclic Dienes 7–15 and Macrocycles 20, 21, and 23–27.

compound	isomer	yield (%)	δHa (ppm)
7a	syn	29 (7a,b, 92)	4.33 (s)
7b	anti	63 (7a,b, 92)	4.25 (s)
8a	syn	45 (8a,b, 90)	4.28 (s)
8b	anti	45 (8a,b, 90)	4.27 (s)
9a	syn	46 (9a,b, 92)	4.28 (s)
9b	anti	46 (9a,b, 92)	4.27 (s)
10a	syn	45 (10a,b, 90)	4.90 (s)
10b	anti	45 (10a,b, 90)	4.83 (s)
11a	syn	41 (11a,b, 82)	4.907 (s)
11b	anti	41 (11a,b, 82)	4.90 (s)
12a	syn	40 (12a,b, 80)	4.91 (s)
12b	anti	40 (12a,b, 80)	4.90 (s)
13a	syn	39 (13a,b, 78)	5.10 (s)
13b	anti	39 (13a,b, 78)	5.02 (s)
14a	syn	44 (14a,b, 88)	4.28 (s)
14b	anti	44 (14a,b, 88)	4.27 (s)
15a	syn	43 (15a,b, 86)	5.02 (s)
15b	anti	43 (15a,b, 86)	5.01 (s)
20a,b	syn/anti	(90)	4.90 (s)
21a,b	syn/anti	(88)	4.70 (s)
23a,b	syn/anti	(90)	5.70 (s)
24a,b	syn/anti	(87)	5.49 (s)
25a	syn	50 (25a,b, 93)	5.31 (s)
25b	anti	43 (25a,b, 93)	5.26 (s)
26a	syn	23 (26a,b, 93)	5.28 (s)
26b	anti	68 (26a,b, 91)	5.26 (s)
27a	syn	22 (27a,b, 92)	5.18 (s)
27b	anti	70 (27a,b, 92)	5.25 (s)

For the macrocyclic structures, no RCM formation took place for dienes 7a,b and 10a,b, and their corresponding macrocycles 19a,b and 22a,b were not formed. This can be explained from the crystal structures along with the ¹H-NMR spectra of both acyclic dienes 7b (anti) and 10b (anti) (Figures 3 and 5). Clearly, from the crystal structures (Figure 3), it can be observed that the short ethylene linker joining the two lactams together through their N atoms has a major role in rigidifying the diene structures, thus forcing the allyl groups to point away from each other. Moreover, the rigidity of the acyclic diene’s backbones can be further supported from their ¹H-NMR spectra (Figure 5), by means of their multiplicity: two sets of triplets of triplets, of the allyloxy protons (H_b, −OCH₂CH=CH₂). Owing to the lack of flexibility of the diene overall structures and the resulting outward facing of the allyloxy active sites, no metathesis reaction took place and no appreciable product formation has been attained.

Such limitation can be simply resolved by elongating the covalent spacers between the N atom conjugating the two lactam units together and/or by flexing the ethylene substituents based on the lactam centers. As expected, replacing the short alkyl likers −(CH₂)₂– with −(CH₂)₄ or −(CH₂)₂O(CH₂)₂O(CH₂)₂– spacers and/or substituting the allyloxy groups with phenoxy-containing allyloxy substituents afforded the macrocyclic structures 20a,b–27a,b (Scheme 1). All compounds were achieved as a mixture of syn/anti, though macrocycles 20,23, and 25–27 were further isolated in their pure isomeric structures by fractional crystallization. Single-crystal X-ray diffraction (Figure 7) of the anti-isomers 20b, 23b, and 25b–27b was effectively gained, and their molecular packing is presented in Figure 8.

Figure 7.

Crystal structures of (A) 20b; (B) 23b; (C) 25b; (D) 26b; and (E) 27b. Color code: blue—nitrogen; gray—carbon; red—oxygen; black—hydrogen; green—chlorine.

Figure 8.

Packing patterns of anti20b, anti23b, anti25b, anti26b, and anti27b in their crystal network; view along the (A) a, (B) b, and (C) c directions. Color code: red—oxygen; blue—nitrogen, gray—carbon (hydrogens are hidden for clarity). The thermal ellipsoid representation (50% probability) of the crystal samples 20b, 23b, 25b, 26b, and 27b are depicted in the Supporting Information. The molecular structure information of these compounds obtained from the single-crystal X-diffraction method is in good agreement with the predicted synthetic protocol and other characterization techniques like NMR and mass spectroscopy. Various crystallographic and refinement parameters of these crystals are provided in the Supporting Information.

In conclusion, a family of 14 (seven syn and seven anti configurational isomers) unsaturated macrocycles (20, 21, 23–27) bearing two 4-spiro-fused-β-lactam sites in their backbone structures has been successfully obtained following the traditional sequential organic transformations, that is, diimine formation, Staudinger [2 + 2] ketene–imine cycloaddition, and RCM reactions. All compounds have been characterized and utilized from their respective NMR and HRMS spectral data along with single X-ray diffraction analysis (for anti20b, anti23b, anti25b, anti26b, and anti27b).

Experimental Section

General

All reactions were carried out under nitrogen atmosphere unless otherwise noted, and all analyses were determined in the Research Sector Projects Unit (RSPU) at the Faculty of Science, Kuwait University. Thin layer chromatography (TLC) was performed using Polygram SIL G UV254 TLC plates, and visualization was carried out by ultraviolet lights at 254 and 350 nm. Column chromatography was performed using Merck silica gel 60 of mesh sizes 0.040–0.063 mm. H and C NMR spectra were recorded using Bruker DPX 600 at 600 MHz. Single-crystal data collection was made on a Bruker X8 Prospector diffractometer. Melting points were determined via differential scanning calorimetry (DSC) analyses on Shimadzu DSC-50.

Crystal Structure Analysis

Single crystals of 7b, 10b, 20b, 23b, 25b, 26b, and 27b were grown by the slow solvent evaporation method. Single-crystal data collection was made on the Bruker X8 Prospector diffractometer by Cu-Kα radiation at room temperature. The reflection frames were then integrated with the Bruker SAINT Software package using a narrow-frame algorithm. Finally, the structure was solved using the Bruker SHELXTL Software Package and refined using SHELXL-2017/1. All non-hydrogen atoms were refined anisotropically.

Materials

All reagents were used with no further purification unless otherwise specified. Anhydrous solvents were either supplied from Sigma-Aldrich or dried as described by Perrin et al.²¹

General Procedures

Synthesis of Diimines

A mixture of the appropriate ketone (2 mmol) and the appropriate diamine (1 mmol) in toluene (50 mL) was heated under reflux for 3–15 h, and water was removed using a Dean–Stark apparatus. The solvent was removed in vacuo, and the reaction mixture was kept in an oven at 70 °C overnight to yield a pale-yellow viscous liquid, which was characterized and used in the subsequent step without further purification.

Diimine 1

White solid in 0.29 g (93%); mp 58–60 °C; ¹HNMR (600 MHz, CDCl₃-d6, 50 °C) δ = 8.23 (d, 2H, J 7.8), 7.32–7.30 (td, 2H, J 7.2, 1.2),7.25 (t, 2H, J 7.2), 7.14 (d, 2H, J 7.8), 3.97 (s, 4H), 2.79 (t, 4H, J 6.6), 2.74 (t, 4H, J 6.6), 1.96–1.92 (qui, 4H, J 6.0); ¹³C{1H} NMR (150 MHz, CDCl₃-d6, 50 °C) δ = 165.5, 140.7, 135.0, 133.5, 128.9, 127.3, 126.8, 52.6, 39.3, 29.9, 23.5; EIMS m/z (%) 316 (M⁺,4), 171 (8), 158 (100), 129 (14), 116 (5); HRMS (ESI) [m]⁺ calcd for C₂₂H₂₄N₂ 316.1934, found 316.1934.

Diimine 2

Pale yellow solid in 0.33 g (89%); mp 68–70 °C; ¹HNMR (600 MHz, CDCl₃, 50 °C) δ = 8.29 (s, 2H), 7.33–7.23 (m, 6H), 7.16 (d, 2H, J 7.2), 3.52 (t, 4H, J 6.6), 2.83 (t, 4H, J 6.0), 2.63 (t, 4H, J 6.0), 1.99–1.95 (m, 4H), 1.82 (t, 4H, J 6.6), 1.56–1.51 (m, 4H); ¹³C{1H} NMR (150 MHz, CDCl₃, 50 °C) δ = 164.2, 140.5, 133.6, 129.6, 128.4, 126.5, 125.7, 51.2, 39.3, 31.3, 30.0, 27.8, 22.8; EIMS m/z (%) 371 (M⁺,3), 226 (100), 214 (32), 172 (22), 158 (46), 146 (36), 129 (20), 97 (7); HRMS (ESI) [m]⁺ calcd for C₂₆H₃₂N₂ 372.2560, found 372.2560.

Diimine 3

White solid in 0.36 g (90%); mp 72–73 °C; ¹HNMR (600 MHz, CDCl₃, 50 °C) δ = 8.17 (d, 2H, J 7.8), 7.30–7.27 (td, 2H, J 7.2, 1.2), 7.22 (t, 2H, J 7.2),7.12 (d, 2H, J 7.8), 3.90 (t, 4H, J 6.6), 3.74 (s, 4H), 3.66 (t, 4H, J 6.6), 2.80 (t, 4H, J 6.6), 2.59 (t, 4H, J 6.6), 1.96–1.92 (qui, 4H, J 6.0); ¹³C{1H} NMR (150 MHz, CDCl₃, 50 °C) δ = 165.8, 140.6, 134.9, 129.7, 128.4, 126.4, 125.8, 72.1, 70.8, 51.3, 29.9, 22.7; EIMS m/z (%) 404 (M⁺,4), 232 (5), 216 (13), 172(25), 158 (100), 129 (36), 116 (15), 91 (7); HRMS (ESI) [m]⁺ calcd for C₂₆H₃₂O₂N₂ 404.2458, found 404.2457.

Synthesis of β-Lactams

A solution of allyloxyacetyl chloride or o-allyloxyphenoxyacetyl chloride (4 mmol) in dry CH₂Cl₂ (5 mL) was purged with nitrogen and cooled to 0 °C, then a solution of TEA (8 mmol) in dry CH₂Cl₂ (5 mL) was added dropwise with a syringe. The mixture was stirred for 30 min, and a solution of the corresponding diimine (1 mmol) in dry CH₂Cl₂ (5 mL) was added dropwise over a period of 2 h. The reaction mixture was then stirred overnight at room temperature. The organic layer was washed with water and Na₂CO₃ solution (10%) till no effervescence and then dried over anhydrous Na₂SO₄. The solvent was then removed in vacuo, and the crude product was purified by chromatography with eluent petroleum ether (60–80)/EtOAc.

Compound 7a

Colorless oil in 0.14 g (29%); R_f = 0.55 (ethyl acetate/petroleum ether 2:3); ¹HNMR (600 MHz, CDCl₃, 50 °C) δ = 7.28–7.13 (m, 8H), 5.59–5.51 (m, 2H), 5.03–4.99 (m, 4H), 4.33 (s, 2H), 3.78–3.75 (tdd, 2H, J 1.2, 6.0, 12.0), 3.64–3.61 (tdd, 2H, J 1.2, 6.0, 12.6), 3.51–3.48 (m, 2H), 3.05–3.03 (m, 2H), 2.92–2.83 (m, 4H), 2.20–2.18 (m, 4H), 1.84–1.79 (m, 4H); ¹³C{1H} NMR (150 MHz, CDCl₃, 50 °C) δ = 167.7, 139.1, 133.5, 132.2, 129.2, 128.3, 128.2, 125.7, 117.8, 90.7, 71.3, 67.6, 39.0, 32.5, 29.3, 21.2; EIMS m/z (%) 512 (M⁺, 4), 453 (5), 396 (7), 200 (39), 185 (100), 159 (54), 129 (59), 91 (17); HRMS (ESI) [m]⁺ calcd for C₃₂H₃₆O₄N₂ 512.2670, found 512.2674.

Compound 7b

White solid in 0.30 g (63%); mp 71–72 °C; R_f = 0.57 (ethyl acetate/petroleum ether 2:3); ¹HNMR (600 MHz, CDCl₃, 50 °C) δ = 7.28–7.26 (dd, 2H, J 1.2, 7.2), 7.25–7.22 (dt, 2H, J 1.2, 7.2), 7.18 (t, 2H, J 7.2), 7.13 (d, 2H, J 7.2), 5.56–5.50 (m, 2H), 5.02–4.96 (m, 4H), 4.25 (s, 2H), 3.73–3.70 (tdd, 2H, J1.2, 6.0, 12.0), 3.58–3.55 (tdd, 2H, J 1.2, 6.0, 12.6), 3.45–3.42 (m, 2H), 3.16–3.13(m, 2H), 2.92–2.83 (m, 4H), 2.19–2.14 (dt, 2H, J 3.0, 13.2), 2.09–2.06 (m, 2H), 1.89–1.87 (dd, 2H, J 3.0, 13.2), 1.82–1.78 (m, 2H); ¹³C{1H} NMR (150 MHz, CDCl₃, 50 °C) δ = 167.1, 139.0, 133.4, 131.9, 129.2, 128.4, 128.3, 125.8, 118.1, 90.8, 71.3, 67.3, 38.6, 32.7, 29.3, 21.2; EIMS m/z (%) 512 (M⁺, 4), 453 (5), 396 (7), 200(39), 185 (100), 159 (54), 129 (59), 91 (17); HRMS (ESI) [m]⁺ calcd for C₃₂H₃₆O₄N₂ 512.2670, found 512.2674.

Compound 8a,b

Colorless oil in 0.51 g (90%); R_f = 0.73 (ethyl acetate/petroleum ether 2:3); ¹HNMR (600 MHz, CDCl₃, 50 °C) δ = δ_H(600 MHz, CDCl₃) 7.34–7.32 (td, 2H, J 1.8, 7.8), 7.22–7.17 (m, 4H), 7.12 (d, 2H, J 7.2), 5.58–5.51 (m, 2H), 5.02–4.96 (m, 4H), 4.28 (s, 1H), 4.27 (s, 1H), 3.74–3.71 (dd, 2H, J 6.0, 12.0), 3.58–3.55 (ddt, 2H, J 1.2, 6.0, 12.6), 3.20–3.16 (quin,2H, J 7.2), 2.93–2.86 (m, 6H), 2.16–2.11 (dt, 2H, J 3.0, 7.2), 2.09–2.06 (m, 2H), 1.85–1.80 (m, 4H), 1.63–1.38 (m, 4H), 1.26–1.23 (m, 4H); ¹³C{1H} NMR (150 MHz, CDCl₃, 50 °C) δ = 167.1, 138.8, 133.5, 132.4, 129.0, 128.7, 128.1, 125.6, 117.9, 90.9, 71.3, 67.1, 39.8, 32.7, 29.4, 29.0, 27.0, 21.2; EIMS m/z (%) 568 (M+, 4), 510 (19), 452 (23), 411 (11), 373 (6), 283 (14), 200 (86), 159 (91), 131 (100), 91 (22); HRMS (ESI) [m]⁺ calcd for C₃₆H₄₄O₄N₂ 568.3296, found 568.3295.

Compound 9a,b

Colorless oil in 0.55 g (92%); R_f = 0.74 (ethyl acetate/petroleum ether 2:3); ¹HNMR (600 MHz, CDCl₃, 50 °C) δ = 7.37–7.35 (d, 2H, J 7.2), 7.27–7.17 (m, 4H), 7.11–7.09 (d, 2H, J 7.2), 5.57–5.51 (m, 2H), 5.02–4.96 (m, 4H), 4.28 (s, 1H), 4.27 (s, 1H), 3.64–3.61 (m, 2H), 3.48–3.36 (m, 6H), 3.29–3.21 (m, 4H), 3.16–3.13 (m, 4H), 2.79–2.76 (m, 4H), 6.16–2.13 (t, 2H, J 16.2), 1.99–1.94 (m, 2H), 1.80–1.78 (m, 4H); ¹³C{1H} NMR (150 MHz, CDCl₃, 50 °C) δ = 167.3, 138.8, 133.5, 132.6, 128.9, 128.6, 128.0, 125.5, 117.9, 91.0, 71.2, 70.1, 68.4, 67.3, 39.6, 32.2, 29.5, 21.2; EIMS m/z (%) 600 (M+, 13), 542 (25), 501 (20), 483 (15), 443 (9), 303 (38), 200 (96), 185 (100), 159 (93), 91 (27); HRMS (ESI) [m]⁺ calcd for C₃₆H₄₄O₆N₂ 600.3194, found 600.3193.

Compound 10a

Colorless oil in 0.26 g (45%); R_f = 0.69 (ethyl acetate/petroleum ether 2:3); ¹HNMR (600 MHz, CDCl₃, 50 °C) δ =7.64–7.63 (dt, 4H, J 7.8, 0.6), 7.49 (d, 2H, J 7.2), 7.43–7.39 (m, 4H), 7.27–7.19 (m, 6H), 5.39–5.34 (m, 2H), 4.82–4.79 (m, 2H), 4.83 (s, 2H), 4.87–4.84 (m, 2H), 3.58–3.55 (ddt, 2H, J 12.0, 6.0, 1.2), 3.39–3.35 (ddt, 2H, J 12.6, 6.0, 1.2), 2.91–2.88 (m, 2H), 2.69–2.66 (m, 2H); ¹³C{1H} NMR (150 MHz, CDCl₃, 50 °C) δ = 167.1, 142.1, 140.9, 140.4, 139.3, 132.8, 129.85, 129.81, 128.1, 127.8, 126.7, 123.3, 120.5, 120.2, 118.5, 89.2, 72.4, 71.9, 39.6; EIMS m/z (%) 580 (M⁺, 6), 522 (8), 483 (5), 385 (7), 249 (56), 219 (43), 193 (37), 165 (100), 151 (3), 70 (4); HRMS (ESI) [m]⁺ calcd for C₃₈H₃₂O₄N₂ 580.2357, found 580.2358.

Compound 10b

White solid in 0.26 g (45%); mp 181–182 °C; R_f = 0.70 (ethyl acetate/petroleum ether 2:3); ¹HNMR (600 MHz, CDCl₃, 50 °C) δ =7.64–7.63 (dd, 4H, J 7.8, 1.2), 7.56 (d, 2H, J 7.2), 7.43–7.38 (m, 6H), 7.31–7.28 (td, 2H, J 7.2, 0.6), 4.25–7.22 (td, 2H, J 7.2, 0.6), 5.42–5.35 (m, 2H), 4.90 (s, 2H), 4.87–4.79 (m, 4H), 3.61–3.57 (ddt, 2H, J 12.0, 6.0, 1.2), 3.40–3.37 (ddt, 2H, J 12.6, 6.0, 1.2), 2.92–2.88 (m, 2H), 2.68–2.64 (m, 2H); ¹³C{1H} NMR (150 MHz, CDCl₃, 50 °C) δ = 167.3, 142.1, 141.1, 140.3, 139.5, 132.8, 129.8, 129.7, 128.3, 127.6, 126.6, 123.9, 120.4, 120.2, 118.5, 89.2, 72.6, 71.9, 40.0; EIMS m/z (%) 580 (M+, 5), 522 (7), 483 (4), 385 (6), 249 (58), 219 (47), 193 (39), 165 (100), 151 (3), 70 (4); HRMS (ESI) [m]⁺ calcd for C₃₈H₃₂O₄N₂ 580.2357, found 580.2355.

Compound 11a,b

White solid in 0.55 g (82%); mp 135–136 °C; R_f = 0.77 (ethyl acetate/petroleum ether 2:3); ¹HNMR (600 MHz, CDCl₃, 50 °C) δ = 7.69 (d, 4H, J 7.8), 7.58 (d, 2H, J 7.2), 7.43 (t, 4H, J 7.2), 7.37 (t, 2H, J 7.2), 7.33–7.29 (m, 4H), 5.44–5.38 (m, 2H), 4.91 (s, 1H), 4.90 (s, 1H), 4.89–4.81 (m,4H), 3.59–3.56 (m, 2H), 3.39–3.35 (m, 2H), 2.94–2.89 (m, 2H), 2.82–2.77 (quin, 2H, J 6.6), 1.00 (quin, 4H, J 6.6), 0.85 (quin, 4H, J 7.2); ¹³C{1H} NMR (150 MHz, CDCl₃, 50 °C) δ = 166.99 (166.97), 142.45 (142.43), 140.97 (140.94), 140.36 (140.34), 140.0, 132.8, 129.75 (129.71), 128.08 (128.07), 127.5, 126.7, 123.17 (123.15), 120.5, 120.2, 118.5, 89.4, 72.4, 71.9, 40.65 (40.62), 28.1, 26.45 (26.43); EIMS m/z (%) 636 (M+, 4), 578 (10), 539 (11), 441 (4), 305 (10), 234 (42), 193 (26),165 (100); HRMS (ESI) [m]⁺ calcd for C₄₂H₄₀O₄N₂ 636.2983, found 636.2981.

Compound 12a,b

Pale yellow oil in 0.53 g (80%); R_f = 0.61 (ethyl acetate/petroleum ether 2:3); ¹HNMR (600 MHz, CDCl₃, 50 °C) δ = 7.67–7.65 (m, 4H), 7.61–7.60 (dt, 2H, J 7.8, 1.2), 7.44–7.39 (m, 6H), 7.32–7.29 (m, 4H), 5.42–5.36 (m, 2H), 4.91 (s, 1H), 4.90 (s, 1H), 4.88–4.86 (dd,2H, J 10.2, 1.2), 4.83–4.80 (dd, 2H, J 17.4, 1.2), 4.37–4.28 (m, 2H), 3.37–3.34 (m, 2H), 3.19–3.17 (m, 2H), 3.10–3.00 (m, 6H), 2.91–2.86 (m, 4H); ¹³C{1H} NMR (150 MHz, CDCl₃, 50 °C) δ = 167.02 (167.01), 142.48 (142.47), 140.98 (140.96), 140.28 (140.27), 139.99 (139.98), 132.7, 129.6, 129.5, 127.99 (127.98), 127.47 (127.45), 126.67 (126.66), 123.2, 123.1, 120.4, 120.1, 118.5, 89.6, 72.6, 71.8, 69.7, 67.73 (67.72), 40.2; EIMS m/z (%) 668 (M⁺, 15), 610 (7), 571 (16), 473 (3), 337 (22), 234 (61), 219 (52), 193 (35), 165 (100), 70 (7); HRMS (ESI) [m]⁺ calcd for C₄₂H₄₀O₆N₂ 668.2881, found 668.2882.

Compound 13a

Pale yellow oil in 0.27 g (78%); R_f = 0.69 as (ethyl acetate/petroleum ether 2:3); ¹HNMR (600 MHz, CDCl₃, 50 °C) δ = 7.37–7.35 (dd, 2H, J 7.8, 1.8), 7.29–7.23 (m, 4H), 7.14 (d, 2H, J 7.2), 6.92–6.89 (td, 2H, J 7.8, 1.8), 6.82–6.81 (dd, 2H, J 9.6, 1.2), 6.75–6.72 (td, 2H, J 7.8, 1.2), 6.51–6.49 (dd, 2H, J 7.8, 1.2), 5.92–5.86 (m, 2H), 5.28–5.25 (dq, 2H, J 10.8, 1.8), 5.18–5.16 (dq, 2H, J 17.4, 1.2), 5.10 (s, 2H), 4. 34–4.28 (m, 4H), 3.67–3.65 (m, 2H), 3.10–3.07 (m, 2H), 2.85–2.82 (m, 2H), 2.72–2.69 (dd, 2H, J 16.8, 4.2), 2.33(d, 2H, J 13.2), 2.21–2.16 (td, 2H, J 13.2, 3.0), 1.98–1.94 (m, 2H), 1.62–1.59 (m, 2H); ¹³C{1H} NMR (150 MHz, CDCl₃, 50 °C) δ = 167.2, 149.6, 147.4, 139.8, 133.5, 132.7, 129.4, 128.3, 127.9, 125.9, 123.9, 121.8, 120.5, 117.2, 116.0, 90.8, 70.4, 68.0, 39.3, 32.7, 29.2, 20.9; EIMS m/z (%) 696 (M⁺, 15), 547 (95), 507 (17), 397 (18), 292 (26), 255 (100), 212 (51), 171 (55), 129 (57), 91 (19); HRMS (ESI) [m]⁺ calcd for C₄₄H₄₄O₆N₂ 696.3194, found 696.3195.

Compound 13b

Pale yellow oil in 0.27 g (78%); R_f = 0.67 as (ethyl acetate/petroleum ether 2:3); ¹HNMR (600 MHz, CDCl₃, 50 °C) δ = 7.42–7.40 (dd,2H, J 7.2, 1.8), 7.29–7.24 (m, 4H), 7.14–7.12 (dd, 2H, J 9.0, 6.6), 6.91–6.88 (td, 2H, J 7.8, 1.8), 6.82–6.80 (dd, 2H, J 7.8, 1.2), 6.70–6.67 (td, 2H, J 7.8, 1.8), 6.30–6.29 (dd, 2H, J 7.8, 1.2), 5.93–5.87 (m, 2H), 5.29–5.26 (dq, 2H, J 17.4, 1.2), 5.19–5.17 (dq, 2H, J 10.8, 1.8), 5.02 (s, 2H), 4.36–4.30 (m, 4H), 3.60–3.57 (q, 2H, J 5.4), 3.25–3.22 (q, 2H, J 5.4), 2.84–2.81 (m, 2H), 2.68–2.64 (dd, 2H, J 16.8, 4.8), 2.19–2.14 (m, 2H), 1.93–1.90 (dt, 2H, J 9.6, 3.6), 1.51–1.49 (m, 2H); ¹³C{1H} NMR (150 MHz, CDCl₃, 50 °C) δ = 166.6, 149.7, 147.2, 139.6, 133.4, 132.4, 129.3, 128.4, 128.2, 125.9, 124.1, 121.7, 120.8, 117.3, 115.9, 91.0, 70.4, 67.7, 38.8, 32.9, 29.1, 20.9; EIMS m/z (%) 696 (M⁺, 6), 605 (5), 547 (31), 507 (14), 419 (15), 397 (23), 292 (56), 255 (85), 212 (74), 185 (83), 129 (100), 91 (45); HRMS (ESI) [m]⁺ calcd for C₄₄H₄₄O₆N₂ 696.3194, found 696.3195.

Compound 14a,b

Pale yellow oil in 0.66 g (88%); R_f = 0.63 as (ethyl acetate/petroleum ether 2:3); ¹HNMR (600 MHz, CDCl₃, 50 °C) δ = 7.47–7.45 (m, 2H), 7.27–7.25 (m, 4H), 7.13–7.11 (m, 2H), 6.90–6.88 (td, 2H, J 7.2, 1.2), 6.82–6.80 (dd, 2H, J 7.8, 1.2), 6.72–6.69 (td, 2H, J 7.2, 1.2), 6.41–6.39 (dt, 2H, J 7.8, 1.2), 5.92–5.88 (m, 2H), 5.29–5.26 (dd, 2H, J 17.4, 1.8), 5.19–5.17 (dd, 2H, J 10.8, 1.2), 5.03 (s, 1H), 5.02 (s, 1H), 4.34–4.30 (qt, 4H, J 6.6, 1.8), 3.34–3.29 (m, 2H), 2.97–2.92 (m, 2H), 2.83–2.79 (m, 2H), 2.69–2.65 (dd, 2H, J 16.8, 4.8), 2.14–2.09 (td, 2H, J 12.0, 1.8), 1.93–1.91 (m, 4H), 1.58–1.55 (m, 6H), 1.32–1.30 (m, 4H); ¹³C{1H} NMR (150 MHz, CDCl₃, 50 °C) δ = 166.5, 149.6, 147.5, 139.4, 133.5, 132.9, 129.1, 128.4, 128.2, 125.7, 123.8, 121.8, 120.60 (120.61), 117.3, 116.1, 91.0, 70.4, 67.4, 39.9, 32.9, 29.2, 29.0, 27.08 (27.09), 20.9; EIMS m/z (%) 752 (M⁺, 5), 603 (84), 562 (36), 453 (32), 413 (56), 373 (86), 311 (71), 292 (32), 214 (36), 171 (51), 158 (56), 144 (100), 129 (71), 115 (31), 91 (19); HRMS (ESI) [m]⁺ calcd for C₄₈H₅₂O₆N₂ 752.3820, found 752.3820.

Compound 15a,b

Pale yellow oil in 0.67 g (86%); R_f = 0.60 as (ethyl acetate/petroleum ether 2:3); ¹HNMR (600 MHz, CDCl₃, 50 °C) δ = 7.49–7.47 (m, 2H), 7.27–7.19 (m, 4H), 7.09–7.08 (m, 2H), 6.83–6.82 (td, 2H, J 7.8, 1.2), 6.79 (d, 2H, J 7.8), 6.68 (t, 2H, J 7.8), 6.37–6.36 (dd, 2H, J 7.2, 1.2), 5.92–5.85 (m, 2H), 5.28–5.16 (m, 4H), 5.02 (s, 1H), 5.01 (s, 1H), 4.32–4.28 (qd, 4H, J 10.2, 4.8), 3.56–3.23 (m, 12H), 2.77–2.73 (td, 2H, J 11.4, 5.4), 2.65–2.62 (dd, 2H, J 13.2, 3.6), 2.18 (t, 2H, J 14.4), 1.89–1.85 (m, 4H), 1.51–1.49 (m, 2H); ¹³C{1H} NMR (150 MHz, CDCl₃, 50 °C) δ = 166.6, 149.5, 147.3, 139.3, 133.4, 133.0, 128.9, 128.3, 127.9, 125.5, 123.8, 121.6, 120.4, 117.1, 115.9, 91.0, 70.2, 70.0, 68.3, 67.5, 39.6, 32.3, 29.2, 20.7; EIMS m/z (%) 784 (M⁺, 5), 635 (93), 594 (20), 485 (20), 445 (30), 405 (35), 343 (46), 292 (35), 274 (8), 212 (100), 158 (72), 144 (61), 91 (17); HRMS (ESI) [m]⁺ calcd for C₄₈H₅₂O₈N₂ 784.3718, found 784.3715.

General Procedures of RCM

Grubb’s catalyst II (6.0 mg, 5 mol %) was added into a solution of the appropriate bis-β-lactam (0.5 mmol) in DCM (10 mL). The reaction mixture was heated to 40 °C in an oil bath overnight. After completion, the solvent was removed in vacuo, and the product was purified by column chromatography using (2:3) ethyl acetate/petroleum ether.

Compound 20a,b

Pale yellow solid in 0.48 g (90%); mp 172–173 °C; R_f = 0.71 as (ethyl acetate/petroleum ether 2:3); ¹HNMR (600 MHz, CDCl₃, 50 °C) δ = 7.27–7.14 (m, 8H), 5.94–5.93 (m, 2H), 4.89 (s, 2H), 4.22 (d, 2H, J 12), 3.80–3.77 (m, 2H), 3.70–3.64 (td, 2H, J 13.2, 3.0), 2.89–2.87 (m, 4H), 2.79–2.75 (dt, 2H, J 14.4, 3.0), 2.44–2.41 (m, 2H), 2.13–2.07 (m, 4H), 1.87–1.77 (m, 4H), 1.61–1.56 (m, 2H), 1.44–1.34 (m, 4H); ¹³C{1H} NMR (150 MHz, CDCl₃, 50 °C) δ = 170.5, 139.6, 134.0, 133.2, 129.5, 127.8, 127.0, 125.9, 90.7, 73.2, 68.3, 37.1, 33.8, 29.6, 29.5, 25.7, 21.5; EIMS m/z (%) 540 (M⁺, 36), 523 (7), 469 (15), 452 (31), 411(29), 373 (14), 311 (69), 271 (22), 228 (21), 185 (47), 129 (100), 91 (38); HRMS (ESI) [m]⁺ calcd for C₃₄H₄₀O₄N₂ 540.2983, found 540.2983.

Compound 21a,b

Yellow oil in 0.51 g (88%); R_f = 0.72 as (ethyl acetate/petroleum ether 2:3); ¹HNMR (600 MHz, CDCl₃, 50 °C) δ = 7.30–7.16 (m, 8H), 5.85–5.84 (m, 2H), 4.70 (s, 2H), 4.17 (d, 2H, J 11.4), 3.78–3.66 (m, 4H), 3.60–3.58 (dd, 2H, J 10.2, 1.8), 3.51–3.24 (m, 6H), 2.89–2.77 (m, 6H), 2.23–2.10 (m, 6H), 1.86–1.82 (m, 2H); ¹³C{1H} NMR (150 MHz, CDCl₃, 50 °C) δ = 168.9, 158.9, 139.5, 133.1, 129.4, 127.9, 127.7, 125.8, 89.0, 71.4, 70.8, 68.4, 39.8, 33.2, 29.5, 21.5; EIMS m/z (%) 572 (M⁺, 10), 530 (4), 501 (6), 443 (8), 413 (14), 343 (60), 303 (24), 211 (54), 185 (100), 172 (34), 129 (73), 91 (24); HRMS (ESI) [m]⁺ calcd for C₃₄H₄₀O₆N₂ 572.2881, found 572.2881.

Compound 23a,b

White solid in 0.55 g (90%); mp 310–311 °C; R_f = 0.71 as (ethyl acetate/petroleum ether 2:3); ¹HNMR (600 MHz, CDCl₃, 50 °C) δ = 8.29–8.28 (m, 2H), 7.73 (d, 2H, J 7.2), 7.71–7.69 (m, 2H), 7.53 (d, 2H, J 7.2), 7.47–7.44 (m, 6H), 7.38–7.36 (td, 2H, J 7.2, 1.2), 6.05–6.04 (m, 2H), 5.70 (s, 2H), 4.27 (d, 2H, J 12.6), 3.79–3.70 (m, 4H), 2.50–2.47 (dt, 2H, J 15.0, 3.0), 1.99–1.95 (quin, 2H, J 6.0), 1.23–1.21 (m, 2H), 1.09–1.07 (m, 4H); ¹³C{1H} NMR (150 MHz, CDCl₃, 50 °C) δ = 171.4, 143.7, 142.0, 140.7, 140.6, 133.2, 129.55, 129.52, 128.3, 127.5, 126.2, 125.4, 120.2, 119.9, 88.5, 73.9, 73.0, 37.8, 27.8, 24.6; EIMS m/z (%) 608 (M⁺, 18), 551 (10), 481 (4), 415 (21), 345 (23), 305 (13), 219 (6), 180 (16), 165 (100), 129 (3), 83 (3); HRMS (ESI) [m]⁺ calcd for C₄₀H₃₆O₄N₂ 608.2670, found 608.2668.

Compound 24a,b

Yellow oil in 0.55 g (87%); R_f = 0.75 as (ethyl acetate/petroleum ether 2:3); ¹HNMR (600 MHz, CDCl₃, 50 °C) δ = 8.04 (d, 2H, J 7.2), 7.74 (d, 2H, J 7.2), 7.69 (d, 2H, J 7.8), 7.56 (d, 2H, J 7.8), 7.54–7.51 (td, 2H, J 7.2, 1.2), 7.48–7.45 (m, 4H), 7.38–7.35 (td, 2H, J 7.8, 1.2), 5.76–5.74 (m, 2H), 5.49 (s, 2H), 4.17 (d, 2H, J 13.2), 4.04–3.99 (td, 2H, J 11.4, 3.6), 3.64–3.61 (ddd, 2H, J 12.0, 6.0, 3.0), 3.39–3.33 (m, 4H), 3.21–3.18 (m, 2H), 2.85–2.81 (td, 2H, J 10.8, 2.4), 2.65–2.62 (dt, 2H, J 15.0, 3.0); ¹³C{1H} NMR (150 MHz, CDCl₃, 50 °C) δ = 169.2, 143.5, 142.0, 139.9, 139.7, 132.9, 129.6, 129.5, 128.9, 127.3, 126.7, 125.6, 120.2, 119.7, 87.8, 72.4, 72.0, 70.3, 66.6, 39.9; EIMS m/z (%) 640 (M⁺, 64), 570 (11), 447 (8), 377 (35), 246 (68), 219 (72), 165 (100), 114 (5),70 (30); HRMS (ESI) [m]⁺ calcd for C₄₀H₃₆O₆N₂ 640.2568, found 640.2567.

Compounds 25a

Pale yellow oil in 0.31 g (50%); R_f = 0.74 as (ethyl acetate/petroleum ether 2:3); ¹HNMR (600 MHz, CDCl₃, 50 °C) δ = 7.42–7.40 (dd, 2H, J 7.2, 1.2), 7.32–7.27 (m, 4H), 7.20 (d, 2H, J 7.2), 7.0–6.97 (td, 2H, J 7.8, 1.8), 6.90–6.88 (dd, 2H, J 8.4, 1.2), 6.63–6.60 (td, 2H, J 7.8, 1.2), 6.41 (t, 2H, J 1.8), 5.75–5.74 (dd, 2H, J 7.8, 1.2), 4.66 (d, 2H, J 11.4), 5.31 (s, 2H), 4.57 (d, 2H, J 11.4), 3.84 (d, 2H, J 11.4), 2.95 (d, 2H, J 12.6), 2.85–2.78 (m, 2H), 2.71–2.67 (dd, 2H, J 17.4, 5.4), 2.07–2.02 (td, 2H, J 13.2, 3.0), 1.90–1.87 (m, 4H), 1.24–1.19 (m, 2H); ¹³C{1H} NMR (150 MHz, CDCl₃, 50 °C) δ = 168.2, 150.6, 146.5, 139.6, 134.4, 129.3, 128.4, 128.1, 127.4, 127.1, 126.0, 124.9, 122.8, 120.7, 113.3, 91.0, 70.1, 67.7, 40.7, 31.2, 29.9, 20.8; EIMS m/z (%) 668 (M⁺, 14), 559 (7), 507 (16), 457 (8), 397 (53), 357 (9), 255 (52), 212 (100), 185 (93), 171 (51), 120 (57), 91 (16); HRMS (ESI) [m]⁺ calcd for C₄₂H₄₀O₆N₂ 668.2881, found 668.2883.

Compounds 25b

White solid in 0.26 g (43%); mp 244–246 °C; R_f = 0.75 as (ethyl acetate/petroleum ether 2:3); ¹HNMR (600 MHz, CDCl₃, 50 °C) δ = 7.42–7.40 (dd, 2H, J 7.2, 1.2), 7.32–7.27 (m, 4H), 7.20 (d, 2H, J 7.2), 7.0–6.97 (td, 2H, J 7.8, 1.8), 6.90–6.88 (dd, 2H, J 8.4, 1.2), 6.63–6.60 (td, 2H, J 7.8, 1.2), 6.41 (t, 2H, J 1.8), 5.75–5.74 (dd, 2H, J 7.8, 1.2), 4.66 (d, 2H, J 11.4), 5.26 (s, 2H), 4.57 (d, 2H, J 11.4), 3.84 (d, 2H, J 11.4), 2.95 (d, 2H, J 12.6), 2.85–2.78 (m, 2H), 2.71–2.67 (dd, 2H, J 17.4, 5.4), 2.07–2.02 (td, 2H, J 13.2, 3.0), 1.90–1.87 (m, 4H), 1.24–1.19 (m, 2H); ¹³C{1H} NMR (150 MHz, CDCl₃, 50 °C) δ = 168.1, 150.6, 146.5, 139.6, 134.4, 129.3, 128.4, 128.1, 127.4, 127.1, 126.0, 124.9, 122.8, 120.7, 113.3, 92.1, 70.1, 68.1, 40.7, 31.2, 29.2, 21.3; EIMS m/z (%) 668 (M⁺, 14), 559 (7), 507 (16), 457 (8), 397 (53), 357 (9), 255 (52), 212 (100), 185 (93), 171 (51), 120 (57), 91 (16); HRMS (ESI) [m]⁺ calcd for C₄₂H₄₀O₆N₂ 668.2881, found 668.2883.

Compounds 26a

Pale yellow oil in 0.17 g (23%); R_f = 0.77 as (ethyl acetate/petroleum ether 2:3); ¹HNMR (600 MHz, CDCl₃, 50 °C) δ = 7.58–7.56 (dd, 2H, J 7.8, 0.6), 7.33 (t, 2H, J 7.8), 7.14–7.16 (td, 2H, J 7.8, 1.2), 7.07 (d, 2H, J 7.2), 6.93–6.89 (td, 2H, J 7.2, 1.8), 6.83–6.81 (td, 2H, J 7.2, 1.2), 6.64–6.61 (td, 2H, J 7.8, 1.8), 6.13 (t, 2H, J 2.4), 6.05–6.04 (dd, 2H, J 7.8, 1.2), 5.28 (s, 2H), 4.53–4.48 (m, 2H), 3.37–3.33 (m, 2H), 3.02–2.99 (m, 2H), 2.82–2.76 (m, 2H), 2.65–2.61 (dd, 2H, J 16.8, 3.6), 2.15–2.13 (dd, 2H, J 13.2, 3.0), 2.06–2.04 (m, 2H), 1.91–1.88 (m, 2H), 1.60–1.57 (m, 4H),1.47–1.45 (m, 6H); ¹³C{1H} NMR (150 MHz, CDCl₃, 50 °C) δ = 166.9, 150.0, 146.6, 139.6, 133.1, 128.9, 128.7, 128.2, 128.0, 125.9, 123.9, 121.0, 120.6, 113.8, 90.8, 68.6, 67.6, 39.1, 32.4, 29.4, 28.6, 26.3, 21.0; EIMS m/z (%) 724 (M⁺, 16), 615 (10), 562 (38), 453 (88), 413 (52), 311 (82), 283 (29), 185 (56), 171 (72), 121 (100), 91 (21); HRMS (ESI) [m]⁺ calcd for C₄₆H₄₈O₆N₂ 724.3507, found 724.3504.

Compounds 26b

White solid in 0.49 g (68%); mp 258–260 °C; R_f = 0.78 as (ethyl acetate/petroleum ether 2:3); ¹HNMR (600 MHz, CDCl₃, 50 °C) δ = 7.55–7.53 (dd, 2H, J 7.8, 1.2), 7.33 (t, 2H, J 7.8), 7.28–7.25 (td, 2H, J 7.8, 1.2), 7.08 (d, 2H, J 7.2), 6.93–6.89 (td, 2H, J 7.2, 1.8), 6.83–6.81 (td, 2H, J 7.2, 1.2), 6.69–6.66 (td, 2H, J 7.8, 1.8), 6.25–6.24 (dd, 2H, J 7.8, 1.2), 6.13 (t, 2H, J 2.4), 5.26 (s, 2H), 4.53–4.48 (m, 2H), 3.37–3.33 (m, 2H), 3.02–2.99 (m, 2H), 2.82–2.76 (m, 2H), 2.65–2.61 (dd, 2H, J 16.8, 3.6), 2.15–2.13 (dd, 2H, J 13.2, 3.0), 2.06–2.04 (m, 2H), 1.91–1.88 (m, 2H), 1.60–1.57 (m, 4H), 1.47–1.45 (m, 6H); ¹³C{1H} NMR (150 MHz, CDCl₃, 50 °C) δ = 166.7, 149.8, 146.8, 139.4, 132.8, 129.1, 128.9, 128.7, 128.2, 126.0, 123.9, 121.2, 120.4, 114.5, 90.6, 68.9, 67.4, 39.3, 32.9, 29.4, 28.7, 26.5, 21.0; EIMS m/z (%) 724 (M⁺, 16), 615 (10), 562 (38), 453 (88), 413 (52), 311 (82), 283 (29), 185 (56), 171 (72), 121 (100), 91 (21); HRMS (ESI) [m]⁺ calcd for C₄₆H₄₈O₆N₂ 724.3507, found 724.3504.

Compounds 27a

Pale yellow oil in 0.17 g (22%); R_f = 0.78 as (ethyl acetate/petroleum ether 2:3); ¹HNMR (600 MHz, CDCl₃, 50 °C) δ = 7.57–7.55 (dd, 2H, J 7.8, 1.2), 7.31–7.27 (m, 4H), 7.09–7.08 (dd, 2H, J 7.2, 0.6), 6.92–6.90 (td, 2H, J 7.2, 1.2), 6.82–6.80 (dd, 2H, J 8.4, 1.2), 6.68–6.65 (td, 2H, J 7.8, 1.2), 6.25–6.23 (dd, 2H, J 8.4, 1.8), 6.05 (t, 2H, J 3.0), 5.18 (s, 2H), 4.45 (d, 2H, J 0.6), 3.60–3.20 (m, 12H), 2.77–2.75 (m, 2H), 2.65–2.62 (dd, 2H, J 16.8, 4.8), 2.22–2.15 (td, 2H, J 13.2, 2.4), 1.97 (d, 2H, J 13.2), 1.90–1.87 (m, 2H), 1.62–1.51 (m, 2H); ¹³C{1H} NMR (150 MHz, CDCl₃, 50 °C) δ = 166.7, 149.9, 146.7, 139.5, 133.0, 129.0, 128.8, 128.6, 128.2, 125.8, 124.1, 121.3, 121.2, 114.5, 91.1, 70.4, 68.9, 68.5, 67.6, 40.1, 32.4, 29.3, 20.9; EIMS m/z (%) 756 (M⁺, 55), 647 (23), 595 (28), 485 (21), 445 (41), 343 (80), 303 (24), 212 (76), 185 (100), 158 (76), 121 (72), 70 (15); HRMS (ESI) [m]⁺ calcd for C₄₆H₄₈O₈N₂ 756.3405, found 756.3405.

Compounds 27b

White solid in 0.53 g (70%); mp 268–270 °C; R_f = 0.79 as (ethyl acetate/petroleum ether 2:3); ¹HNMR (600 MHz, CDCl₃, 50 °C) δ = 7.55–7.53 (dd, 2H, J 7.8, 1.2), 7.28 (t, 2H, J 7.8), 7.24–7.21 (td, 2H, J 7.8, 1.2), 7.08 (d, 2H, J 7.8), 6.94–6.91 (td, 2H, J 7.8, 1.8), 6.84–6.83 (dd, 2H, J 7.8, 1.8), 6.60–6.57 (td, 2H, J 7.8, 1.8), 6.15 (t, 2H, J 3.0), 5.90–5.89 (dd, 2H, J 9.6, 1.8), 5.25 (s, 2H), 4.54 (s, 4H), 3.67–3.44 (m, 10H), 3.19–3.15 (m, 2H), 2.79–2.73 (m, 2H), 2.58–2.54 (dd, 2H, J 16.8, 4.8), 2.19–2.14 (td, 2H, J 13.2, 3.0), 1.99 (d, 2H, J 13.8), 1.93–1.91 (m, 2H), 1.48–1.35 (m, 2H); ¹³C{1H} NMR (150 MHz, CDCl₃, 50 °C) δ = 166.7, 150.4, 146.2, 139.8, 133.2, 129.1, 128.6, 128.5, 128.1, 125.8, 124.4, 122.1, 121.1114.0, 91.2, 70.4, 68.9, 68.4, 67.9, 40.1, 32.4, 29.3, 20.9; EIMS m/z (%) 756 (M⁺, 54), 647 (23), 595 (28), 485 (21), 445 (41), 343 (80), 303 (24), 212 (76), 185 (100), 158 (76), 121 (72), 70 (15); HRMS (ESI) [m]⁺ calcd for C₄₆H₄₈O₈N₂ 756.3405, found 756.3405.

Supporting Information Available

The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acsomega.2c05212.

• X-ray data of seven samples (ZIP)

• NMR and HRMS (ESI) spectral data of diimines (1–3) and compounds 7–15a,b, 20a,b, 21a,b, and 23–27a,b; single-crystal X-ray diffraction studies of macrocycles 7b, 10b, 20b, 23b, 25b, 26b, and 27b (PDF)

The authors declare no competing financial interest.