The transformation of CO₂ into useful organic compounds has been generating increasing interest from both economic and environmental points of view arising from the utilization of renewable resources and the reduction of greenhouse gases [1-6]. One of the most successful methodologies for CO₂ fixation is the catalytic synthesis of cyclic carbonates via the cycloaddition of CO₂ to epoxides [7-16]. These epoxides are highly useful products that have been widely used in organic synthesis and as pharmaceutical/fine chemical intermediates, monomers, aprotic solvents, raw materials for plastics, and other such materials [17-23].

Biomimetic metalloporphyrins have been demonstrated to be effective catalysts for various organic reactions. Kruper et al. [24] have reported the coupling reaction of propylene oxide (PO) and CO₂ using a catalyst system composed of Cr(tetraphenylporphyrin [TPP])Cl with the co-catalyst 4-dimethylaminopyridine (DMAP), denoted generally as Cr(TPP)Cl/DMAP, to yield propylene carbonate (PC). In addition, Nguyen et al. [25] have developed the Co(TPP)X/DMAP catalyst system, and Srinivas et al. [26] have demonstrated the Cu(Ⅱ)porphyrin/DMAP catalyst system for conducting an equivalent coupling reaction. Recently, we have documented various porphyrin-Co/co-catalyst systems for the cycloaddition of CO₂ to epoxides [27-34].

Since the milestone work of Jacobsen et al. in 1997 [35] demonstrating the asymmetric ring-opening and kinetic resolution of aliphatic terminal epoxides, numerous examples of the synthesis of optically active cyclic carbonates by the catalytic kinetic resolution illustrated in Scheme 1 have been reported. Of these examples, chiral Schiff base Co complexes, particularly in the presence of nucleophilic reagents serving as co-catalysts, have been generally demonstrated to be the most effective catalysts for the coupling of CO₂ and epoxides [36-42]. In our previous work on CO₂ fixation, various types of bifunctional chiral catalysts were designed and prepared based on the chiral backbone of Co(Ⅲ)salen complexes that can catalyze this asymmetric coupling reaction of CO₂ and epoxides to generate chiral cyclic carbonates under mild conditions [43-50, 55]. However, the asymmetric synthesis of cyclic carbonates catalyzed by chiral metalloporphyrins has not been reported. Therefore, we designed and synthesized novel chiral basket-handle porphyrin-Co complexes with chiral picket-fence structures in the present work, and then successfully applied these complexes as catalysts for the asymmetric cycloaddition of CO₂ to epoxides.

The proposed chiral basket-handle porphyrin-Co complexes were fabricated according to the strategy depicted in Scheme 2. The precursor porphyrin 1 (meso-tetakis-(2-nitrophenyl) porphyrin); TNPP) was fabricated by the Lindsey method from pyrrole and 2-nitrobenzaldehyde, which was then reduced to porphyrin 2 (meso-tetakis-(2-aminophenyl) porphyrin); TAPP) according to previously reported methods [51, 52]. Phenylalanine was then introduced to porphyrin 2 to generate chiral porphyrin 4, which was linked by a second chiral group of (R)-2, 2'-dihydroxyl[1, 1']binaphthalenyl-3, 3'-dicarbaldehyde ((R)-5) to produce the target product of chiral basket-handle porphyrin 6a. The metalloporphyrin complex 6b was obtained by the reaction of porphyrin 6a with cobalt acetate, and was then oxidized by air in the presence of acetic acid to form the chiral cobaltoprophyrin acetate catalyst 6c. The chiral porphyrin catalysts 7a, 7b, and 7c shown in Fig. 1 were fabricated by an equivalent method. The synthesis of all remaining precursors is described as follows.

A solution of 1.46 g N, N'-dicyclohexyl carbodiimide (DCC; 7.1 mmol) in 80 mL of ethyl acetate was added into a round-bottomed flask containing N-boc-L-phenylalanine (1.70 g, 6.4 mmol) and TAPP (0.54 g, 0.8 mmol) dissolved in ethyl acetate (160 mL) at 25 ℃. The mixture was then stirred for 24 h at room temperature, filtered, and washed with ethyl acetate. The filtrate was evaporated under vacuum, and the residue obtained was purified by column chromatography with CH₂Cl₂-MeOH (50:1) as the eluent. The pure porphyrin 3 product of tetrakis[2-(N-tert-butoxycarbonyl-L-phenylalaninoyl-amido) phenyl] was obtained with a 97.3% yield (1.28 g) [53].

HRMS (ESI): calculated for C₁₀₀H₁₀₂N₁₂O₁₂[M+Na]⁺ 1685.7632, found 1685.7650; UV-vis: λ_max (CH₂Cl₂) 421, 515, 546, 590, and 654 nm.

Porphyrin 3 (0.83 g, 0.65 mmol) was dissolved in CH₂Cl₂ (10 mL) under Ar, and trifluoroacetic acid (4.5 mL) was added. After 30 min, the solvent was removed under vacuum. The pure porphyrin 4a product of tetrakis[2-(L-phenylalaninoylamido)phenyl]porphyrin was obtained in quantity (0.63 g) [54].

HRMS (ESI): calculated for C₈₀H₇₁N₁₂O₄[M+Na]⁺ 1285.5545, found 1285.5525; UV-vis: λ_max (CH₂Cl₂) 422 (Soret), 515, 548, 589, and 650 nm; FT-IR (KBr): ν_max 3325, 3063, 3032, 2928, 2853.2, 1679, 1629, 1581, 1525, 1445, 1205, 1136, 801, 723, and 700 cm^–1; [α]_D²¹: –36.4 (c = 0.10, in dimethylformamide (DMF)).

Porphyrin 4a (0.13 g, 0.1 mmol) and (R)-5/(S)-5 (0.068 g, 0.2 mmol) were dissolved in a mixed solvent (CH₂Cl₂:CH₃OH = 4:1, 120 mL). After 12 h refluxing, the mixture was evaporated under vacuum, and the residue obtained was purified by column chromatography in silica gel with CH₂Cl₂ and CH₂Cl₂-MeOH (50:1) as the eluent. Purple crystalline materials were obtained in a 10.6% yield (19.8 mg) for porphyrin 6a, and in an 18.8% yield (35.1 mg) for porphyrin 7a, respectively. The structure of these compounds is illustrated in Fig. 1.

Porphyrin 6a. ¹H NMR (400 MHz, CDCl₃): δ 8.95 (d, J = 8.4 Hz, 4H, 6-H), 8.80 (s, 4H, β-H), 8.69 (s, 4H, OH), 8.38 (s, 4H, β-H), 7.99 (s, 4H, NH), 7.62 (t, J = 8.4 Hz, 4H, 5-H), 7.56 (s, 4H, 8-H), 7.40 (d, J = 7.6 Hz, 4H, 15-H), 7.10 (m, 8H, 10, 14-H), 7.00 (dd, J = 8.4, 6.8 Hz, 4H, 13-H), 6.94 (d, J = 7.2 Hz, 8H, 21-H), 6.91 (d, J = 6.8 Hz, 4H, 22-H), 6.86 (d, J = 6.8 Hz, 8H, 20-H), 6.67 (t, J = 6.8 Hz, 4H, 4-H), 6.30 (d, J = 8.4 Hz, 4H, 12-H), 6.21 (d, J = 6.8 Hz, 4H, 3-H), 3.79 (dd, J = 14.0, 3.2 Hz, 4H, α′-H), 3.18 (d, J = 3.6 Hz, 2H, β′-H), 3.15 (d, J = 3.6 Hz, 2H, β′-H), 2.96 (dd, J = 14.0, 8.4 Hz, 2H, β′-H), 2.81 (dd, J = 14.0, 8.4 Hz, 2H, β′-H), –2.40 (s, 2H); ¹³C NMR (40 MHz, CDCl₃): δ 173.1 (7-C), 169.4 (18-C), 167.6 (8-C), 157.2 (α-C), 151.9 (2-C), 136.5 (6-C), 135.7 (19-C), 135.1 (16-C), 134.8 (10-C), 130.7 (1-C), 129.6 (β-C), 129.3 (12-C), 128.8 (4-C), 128.6 (21-C), 128.2 (20-C), 127.6 (22-C), 127.2 (11-C), 127.1 (3-C), 126.7 (5-C), 124.2 (14-C), 122.8 (15-C), 120.5 (13-C), 119.1 (9-C), 114.2 (17-C), 113.0 (m-C), 79.0 (α′-C), 41.3 (β′-C); DEPT-135^o (40 MHz, CDCl₃) δ 167.6 (8-C), 136.5 (6-C), 134.8 (10-C), 129.6 (β-C), 129.3 (12-C), 128.8 (4-C), 128.6 (21-C), 128.2 (20-C), 127.6 (22-C), 127.1 (3-C), 126.7 (5-C), 124.2 (14-C), 122.8 (15-C), 120.5 (13-C), 79.0 (α′-C), 41.3 (β′-C); HRMS (ESI): calculated for C₁₂₄H₉₁N₁₂O₈ [M+H]⁺ 1876.7116, found 1876.7123; UV-vis: λ_max (CH₂Cl₂) 229, 262, 310, 429 (Soret), 521, 558, 594, and 654 nm; FT-IR (KBr): ν_max 3420, 3369, 3307, 3059, 3027, 2923, 2852, 1768, 1706, 1682, 1625, 1580, 1514, 1440, 1300, 1259, 1088, 1025, 800, 747, and 698 cm^–1; MS (MALDI-TOF): calculated for C₁₂₄H₉₀N₁₂O₈ [M] 1875.7, found 1875.2; [α]_D²¹: –26.0 (c = 0.10, in DMF).

Porphyrin 7a. ¹H NMR (600 MHz, CDCl₃): δ 8.94 (d, J = 8.4Hz, 4H, 6-H), 8.79 (s, 4H, β-H), 8.68 (s, 4H, OH), 8.38 (s, 4H, β-H), 8.00 (s, 4H, NH), 7.65 (t, J = 8.4 Hz, 4H, 5-H), 7.55 (s, 4H, 8-H), 7.44 (s, 4H, 15-H), 7.08 (m, 8H, 10, 14-H), 7.02 (dd, J = 8.4, 6.8 Hz, 4H, 13-H), 6.94 (d, J = 6.8 Hz, 8H, 21-H), 6.89 (d, J = 6.8 Hz, 4H, 22-H), 6.85 (d, J = 6.8 Hz, 8H, 20-H), 6.67 (t, J = 8.4 Hz, 4H, 4-H), 6.30 (d, J = 8.4 Hz, 4H, 12-H), 6.23 (d, J = 8.4 Hz, 4H, 3-H), 4.01 (dd, J = 13.8, 3.0 Hz, 4H, α′-H), 3.30 (d, J = 3.0 Hz, 2H, β′-H), 3.27 (d, J = 3.0 Hz, 2H, β′-H), 2.93 (dd, J = 13.8, 3.0 Hz, 4H, β′-H), –2.40 (s, 2H); MS (MALDI-TOF): calculated for C₁₂₄H₉₀N₁₂O₈[M] 1875.7, found 1875.2; [α]_D²²: –3.0 (c = 0.10, in DMF).

A 25 mL three-neck round-bottom flask equipped with a water condenser and a magnetic stir bar was charged with DMF (10 mL), porphyrin (0.1 mmol), and Co(OAc)₂·4H₂O (0.3 mmol) under Ar, and the mixture was stirred at 130 ℃ for 3 h. After cooling to room temperature, it was quenched by the addition of ice-water. The amaranth precipitate of metalloporphyrin complexes 6b/7b illustrated in Fig. 2 were obtained by filtration, washed with water several times, and dried in vacuum.

Complex 6b. MS (ESI): calculated for C₁₂₄H₈₉CoN₁₂O₈[M+H]⁺ 1934.0, found 1933.9; UV-vis: λ_max (DMF) 267, 435 (Soret), 519, and 558 nm; FT-IR (KBr): ν_max 3394, 3061, 3030, 2928, 2844, 1689, 1608, 1578, 1419, 1341, 1047, 1026, 754, 699, 673, and 616 cm^–1; [α]_D²¹: –20.1 (c = 0.10, in DMF).

Complex 7b. MS (ESI): calculated for C₁₂₄H₈₉CoN₁₂O₈[M+H]⁺ 1934.0, found 1933.9; UV-vis: λ_max (DMF) 267, 435 (Soret), 519, and 558 nm; FT-IR (KBr): ν_max 3394, 3061, 3030, 2928, 2844, 1690, 1608, 1578, 1419, 1341, 1047, 1026, 754, 699, 673, and 616 cm^–1; [α]_D²²: –5.0 (c = 0.10, in DMF).

A suspension of porphyrin-Co(Ⅱ) (0.1 mmol) in 5 mL of toluene was added to glacial acetic acid (0.14 mL, 2 mmol, 20 equiv.), and then stirred for 4 h at room temperature under oxygen. The solvent and unreacted glacial acetic acid were removed under reduced pressure, leaving a reddish-brown solid that was washed with dichloromethane several times to yield pure chiral porphyrin-Co catalysts 6c/7c. Their configurations are presented in Fig. 2.

Catalyst 6c, (R)-Co(BINATAPP). MS (ESI): calculated for C₁₂₄H₈₈CoN₁₂O₈[M-OAc]⁺ 1933.0, found 1933.1; FT-IR (KBr): ν_max 3452.1, 3076.7, 2969.9, 2919.7, 2884.7, 2705.3, 2658.2, 2594.6, 2547.4, 1852.7, 1796.5, 1696.3, 1596.1, 1571.0, 1480.7, 1420.6, 1303.2, 1260.8, 1134.0, 1106.5, 1072.6, 915.8, 897.5, 847.9, 807.5, 749.5, 718.0, 667.7, 651.0, and 546.4 cm^–1; Elemental analysis: calculated for C₁₂₆H₉₁CoN₁₂O₁₀ C 75.97, H 4.60, N 8.44, found C 75.88, H 4.84, N 8.12; [α]_D²¹: –36.5 (c = 0.10, in DMF).

Catalyst 7c, (S)-Co(BINATAPP). MS (ESI): calculated for C₁₂₄H₈₈CoN₁₂O₈[M-OAc]⁺ 1933.0, found 1933.1; FT-IR (KBr): ν_max 3383.6, 3205.6, 3061.1, 2923.9, 2853.6, 1693.83, 1603.7, 1576.6, 1524.7, 1422.5, 1386.4, 1345.7, 1299.0, 1262.7, 1156.3, 1072.0, 1027.6, 999.0, 967.5, 897.6, 846.3, 801.9, 752.7, 700.9, 674.2, 598.2, and 503.9 cm^–1; Elemental analysis: calculated for C₁₂₆H₉₁CoN₁₂O₁₀ C 75.97, H 4.60, N 8.44, found C 75.76, H 4.79, N 8.19; [α]_D²²: +6.7 (c = 0.10, in DMF).

All reactions were conducted in a 100 mL stainless steel autoclave equipped with a magnetic stir bar, and submerged in an oil bath. The required catalyst, tetrabutylammonium chloride (TBAC) as the co-catalyst, epoxide, and CH₂Cl₂ were added to the reactor in turn. The reactor was then charged with CO₂ and vented three times, and finally pressurized with CO₂ to 1.0 MPa. The contents were then stirred at room temperature for an established period that depended on the selected substrate and catalyst, after which the reactor was carefully discharged to atmospheric pressure. The yield of cyclic carbonate was determined by the subtraction method or by comparison between the integral areas obtained by ¹H NMR spectroscopy for the cyclic carbonate and epoxide.

The asymmetric cycloaddition of CO₂ to rac-PO using the developed chiral Co-porphyrin catalysts was examined in detail, and the results are listed in Table 1. Firstly, employing the picket-fence catalyst 4c in this reaction produced PC and styrene carbonate (SC) in moderate yields (Table 1, entries 1 and 2). Unfortunately, these carbonates were both completely racemic owing to the limited asymmetric induction by L-phenylalanines. As the same as envision, catalyst 6c bearing (R)-BINOL obtained optically active (S)-PC with an enantiomeric excess (ee) of 33.0%. In contrast, catalyst 7c linking (S)-BINOL produced (R)-PC as the main enantiomer with an increased ee of 38.3% (Table 1, entry 3 versus 5). However, SC products were still obtained as racemates using either 6c or 7c as the catalyst (Table 1, entries 4 and 6) because the obvious steric hindrance affected the enantioselectivity of the epoxide to incorporate CO₂. This result is consistent with our previous work [44-50].

The metal-catalyzed coupling reaction of CO₂ and epoxides is generally thought to take place via a coordination-insertion mechanism [17-19, 43]. The epoxide is coordinated and activated by the metal complex, and then attacked by a nucleophilic group, leading to the formation of an intermediate metal-bonded alkoxide. The step coordinating the epoxide plays a significant role in determining the absolute configuration of the generated cyclic carbonate. The configurations of intermediates are depicted in Scheme 3, which was obtained from the work of Rose [56]. When (S)-PO approaches catalyst 7c-R forming intermediate Ⅰ, the linker of (R)-BINOL and (S)-PO is located in a favored position that allows for the formation of (S)-PC as the main product. However, for intermediate Ⅱ, it is clear that repulsion exists between the linker of (R)-BINOL and the methyl group of (R)-PO coordinated to the Co ion, which leads to the formation of (R)-PC. In contrast, (R)-PC is preferentially obtained by catalyst 7c-S bearing (S)-BINOL when coordinated with (R)-PO, and forms the favored intermediate Ⅲ. However, when coordinated with (S)-PO, catalyst 7c-S generates intermediate Ⅳ with a higher energy, and (S)-PC is obtained as a minor product. Therefore, we can see that the chirality of catalysts 6c-R and 7c-S inherited from (R)-BINOL/(S)-BINOL can be successfully transferred to the target PC products, which realizes the chiral resolution of PO. When styrene oxide (SO) is coordinated with the active catalyst region, as shown in Scheme 4, the plane of the phenyl group is restricted by the linker, and must lie parallel to the plane of porphyrin, such that they interact together with a face-to-face stacking of π-π interactions. Thus, intermediates Ⅰ and Ⅲ are very similar to intermediates Ⅱ and Ⅳ, respectively. This is why the ee values of the corresponding cyclic carbonates were negligible.

The proposed C₂ symmetric chiral basket-handle cobaltoporphyrin complexes are effective catalysts in the asymmetric cycloaddition of CO₂ to PO, yielding a relevant chiral PC with good enantioselectivity. The coupling reaction was performed with perfect atom economy under extremely mild conditions. Evidently, the stereochemistry control in the Co(BINATAPP)-catalyzed asymmetric cycloaddition reaction benefits from a synergistic effect between the chiral porphyrin catalysts and the PO substrate. To the best of our knowledge, this is the first example of chiral metalloporphyrin catalysts developed for the asymmetric cycloaddition of CO₂ to epoxide under very mild reaction conditions. Further structural optimization of these catalysts to enhance their enantioselectivity is underway in our laboratory.