1 Introduction
As a class of highly active intermediates, transition- metal carbenes have been extensively utilized in catalytic transformations for constructing diverse molecular frameworks.[1-11] Consequently, developing corresponding asym- metric catalytic methodologies involving metal-carbene intermediates has been a major pursuit since the early days of asymmetric catalysis.[12-14] This field has now evolved into a critically important area for the efficient synthesis of valuable chiral compounds.[2,6,15-24] While many racemic versions exist, the development of metal-catalyzed asymmetric couplings involving metal-carbene intermediates is significantly less advanced.[23-33] Notably absent are efficient three-component (or three-functional-group-in-two- components) couplings (3FGC) that utilize the benzyl-Pd intermediate formed from carbene migratory insertion (CMI) (Scheme 1a).[24,29-34] A key obstacle is the lack of chiral ligands or catalytic systems that can orchestrate these transformations with high efficiency, enantioselectivity, and controlled reaction sequences. This precision is critical to avoid side reactions and achieve high chemo- selectivity, making the development of such asymmetric 3FGC reactions a substantial ongoing challenge.
Palladium-catalyzed couplings via metal-carbene intermediates are a powerful method for forging two new C—C bonds at the carbene center, enabling access to diverse molecular skeletons. However, effective asymmetric versions of these transformations remain scarce.[24] Notably, the Zhang group demonstrated two elegant 3FGC reactions based on a carbene migratory insertion/Sonogashira or Suzuki cascade,[29,30] which were achieved using their chiral sulfinamide-phosphine ligand (SadPhos) (Scheme 1b). Meanwhile, the amphiphilic nature of metal-carbenes also makes them excellent C1-dipoles for coupling two building blocks into cyclic compounds.[1,18,24] In this context, the Xu group developed a Pd-catalyzed cyclization via a domino sequence of Heck reaction, C—H activation, and carbene insertion, which was also applied in asymmetric catalysis (Scheme 1c).[35] However, this system afforded the major diastereomer with only low enantiomeric excess, underscoring the difficulty of achieving high stereocontrol in such annulations. Consequently, successful and general examples of Pd-catalyzed asymmetric annulations using carbene precursors as C1-dipoles remain scarce and highly desirable. Capitalizing on the emerging concept of dynamic multiligand relay catalysis (DMRC)[36] reported by Dai[37] and others[38-44] within Pd-catalysis, we recently achieved the first highly efficient, Pd-catalyzed asymmetric [4+1] annulation using a carbenoid as the C1 dipole (Scheme 1d).[45-47] This transformation was enabled by a tailored asymmetric ligand relay strategy, delivering chiral indanones efficiently.
The indane ring system constitutes a key structural motif in numerous natural products and pharmaceuticals (Figure 1).[48] For instance, Ramelteon bearing a chiral indane skeleton belongs to a class of drugs known as melatonin receptor agonists.[49] Furthermore, chiral indane motifs serve as essential scaffolds for ligands in asymmetric catalysis.[48] Consequently, the development of efficient syn-thetic methods for constructing this skeleton has attracted considerable interest. The Liang group has reported a racemic synthesis of indanes via a Pd-catalyzed [4+1] annulation,[50] proceeding through a tandem CMI/Tsuji-Trost reaction.[51-57] This prompted us to question whether our dynamic multiligand relay asymmetric catalysis strategy could be adapted to address the broader challenge of asymmetric Pd-catalyzed annulations employing carbene precursors as C1 dipoles to forge two C—C bonds. Achie- ving such asymmetric induction remains a challenge, as different tandem processes may demand specific ligand combinations to precisely control the individual reaction steps, catalytic activity, and stereochemical outcome. Moreover, the highly reactive nature of the Pd-carbene intermediate is prone to undesired side reactions when integrated with the Tsuji-Trost process, further complicating the development of an asymmetric variant. Building on the ongoing efforts in the development of asymmetric annulations,[45,58,59] we herein report the development of a ligand relay-enabled, Pd-catalyzed asymmetric [4+1] annulation via a CMI/Tsuji-Trost cascade (Scheme 1e). In this system, a bidentate Pyrox ligand promotes the initial oxidative addition, while a monodentate Feringa-type phosphoramidite ligand governs the enantioselective carbenation/migratory insertion and the subsequent Tsuji-Trost step.
2 Results and discussion
Our investigation was commenced by screening reaction conditions using 2-(2-iodobenzyl)malonate 1a and N-Ts- hydrazone 2a as model substrates (Table 1). Initial screening focused on a single-ligand system with various phosphoramidite ligands, employing K2CO3 as base and MTBE as solvent at 65 °C. The evaluation of ligands L1a and L1b, which possess opposite axial chirality, revealed that the diol backbone of the ligand predominantly governs the enantioselectivity. Subsequent testing of phosphoramidite ligands with different backbones indicated that those based on H8-BINOL and spiro-bisindane skeletons (L1c and L1d) afforded lower enantioselectivity and yield. While the chiral ethylene glycol-derived ligand L1e enhanced reactivity, it resulted in diminished enantioselectivity. An inverse correlation was observed between the reaction yield and the steric bulk of the phosphoramidite ligand, with larger ligands generally affording lower yields (see series L1a, L1e, L1f, L1g, L1h). Modifications involving different chiral amine components (L1f, L1g, L1h) were found to be ineffective at improving enantioselectivity. Additionally, substitution at both ortho-positions of the BINOL skeleton negatively impacted the enantioselectivity (L1i and L1j).
Table 1 Ligand screening a |
| Without L2 |
|---|
 |
| With L1a |
 |
a The reaction was conducted with 1a (0.10 mmol, 1.0 equiv.), 2a (0.225 mmol, 2.25 equiv.), [Pd(C3H5)Cl]2 (5 mol %), L1 (20 mol %), L2 (10 mol %), MTBE (3.0 mL), K2CO3 (0.525 mmol), stirred for 10 h. The yield was determined by 1H NMR using 1,1,2,2-tetrachloroethane as an internal standard, and the er values were determined by chiral HPLC analysis on a chiral stationary phase. b 2a (0.30 mmol, 3.0 equiv.), K2CO3 (0.55 mmol), MTBE (1.5 mL). MTBE=methyl tert-butyl ether. |
Having identified L1a as the optimal first ligand, bidentate nitrogen second ligands (L2a~L2f) were screened. Pyrox-type ligands L2a and L2b delivered higher activity than other bidentate nitrogen ligands while preserving enantioselectivity. With L2a established, the reaction concentration was next optimized. Decreasing the MTBE volume to 1.5 mL (0.10 mmol scale 1a) improved the yield to 99% (83∶17 er). The necessity of the ligand relay was confirmed by a control reaction with L1a alone, which afforded only 61% yield under identical conditions. Based on these results, the reaction employing L1a/L2a ligand relay in MTBE (0.1 mmol/1.5 mL) at 65 °C was defined as optimal.
Having established the optimal reaction protocol, the substrate generality for the synthesis of chiral indanes was explored via this [4+1] annulation (Table 2). A range of N-Ts-hydrazones 2 were initially examined. Aryl-subs- tituted cinnamaldehyde-type hydrazones proved to be excellent substrates, delivering products 3a~3m in 76%~99% yields with enantiomeric ratios (er) ranging from 76∶24 to 86.5∶13.5. The CF₃-substituted derivative stood out as the sole exception, exhibiting an er lower than 80∶20. Notably, ortho-substitution on the aryl ring marginally reduced yield slightly but left enantioselectivity largely unaffected (3j and 3k vs 3c and 3f). However, the reaction proved much less efficient with an alkyl substituent (3n) or a methyl group introduced at the vinyl 2-posi- tion (3o and 3p), resulting in significantly lower reactivity. Subsequently, the scope of 4C coupling partner 1 was explored. Substitution with a methyl group at C2 or C3 compromised enantioselectivity (3q and 3t), while halogen atoms (F, Cl) at these positions were well-tolerated (3r, 3s, 3u, 3v, 3y). A chloro substituent at C1 provided the product in 79% yield with maintained enantioselectivity (3w, 83∶17 er). In a contrasting trend, the C4 position appeared highly sensitive to substitution, as evidenced by the low yield of 3x. This may be attributed to steric interference with the oxidative addition step. The size of the ester group also played a role: employing ethyl or isopropyl esters (3z and 3aa) led to reduced yield and enantioselectivity compared to methyl esters. This trend suggests that increased steric bulk around the reacting center is detrimental, which is consistent with the results of P-ligand screening. Lastly, a malononitrile analogue of 1 was evaluated but proved unreactive in this transformation (3ab).
Table 2 Substrate scopea |
 |
a The reaction was conducted with 1 (0.10 mmol, 1.0 equiv.), 2 (0.30 mmol, 3.0 equiv.), [Pd(C3H5)Cl]2 (5 mol %), L1a (20 mol %), L2a (10 mol %), K2CO3 (0.55 mmol), MTBE (1.5 mL), stirred for 10 h at 65 °C under N2 atmosphere. Isolated yields were reported. The er values were determined by chiral HPLC analysis on a chiral stationary phase. |
The practical utility of this method was confirmed through a scale-up experiment (Scheme 2). The reaction demonstrated excellent scalability, proceeding smoothly on a 10 mmol scale to provide 3a in 98% yield with 83∶17 er, efficiency comparable to that of the small-scale (0.10 mmol) procedure. Subsequent recrystallization enabled the optical purity to be increased to nearly enantiomerically pure. To underscore the synthetic value of the products, compound 3a was further derivatized. Catalytic reduction furnished 4a in quantitative yield, albeit with a marginal decrease in enantiopurity. Complete reduction of the ester groups with LiAlH4 afforded the corresponding diol 4b. Finally, a hydrolysis/decarboxylation sequence cleanly delivered the indanyl mono-acid 4c.
Based on our previous work,[45] the mechanism proposed is outlined in Scheme 3. The cycle begins with oxidative addition (OA) of 1a to the Pyrox-ligated Pd(0) species I, forming intermediate II. Subsequent ligand exchange with the phosphoramidite ligand L1a yields intermediate III, which features a coordinatively unsaturated Pd(II) center. It should be noted that similar ligand exchange process has been studied by NMR in our previous report.[45] Meanwhile, hydrazone 2a reacts with K2CO3 to generate a diazo compound in situ. This diazo species reacts with III to form the putative Pd(II)-carbene IV, which likely exists transiently during a concerted carbene transfer/migratory insertion to give the enolate-bound species V. Intramolecular attack of the enolate on the Pd-allyl moiety then delivers the product 3a and regenerates a Pd(0) species coordinated by L1a. A final ligand exchange with L2a restores the more OA-active catalyst I to complete the catalytic cycle.
3 Conclusions
In summary, we have established a dynamic multiligand relay asymmetric catalysis for the Pd-catalyzed synthesis of chiral indanes via a [4+1] annulation. The key to success lies in the synergistic use of two very different ligands: a bidentate Pyrox ligand promotes oxidative addition, while a monodentate Feringa-type phosphoramidite ligand dictates the stereochemistry of the carbenation/carbene migratory insertion and Tsuji-Trost steps. The reaction delivers products in high yields with enantiomeric ratios generally higher than 80∶20, which are amenable to further enhancement by recrystallization. This strategy establishes a practical and efficient route to enantioenriched vicinal substituted indanes.
4 Experimental section
4.1 Instruments and reagents
Unless otherwise stated, all reagents and solvents were purchased from commercial suppliers and used without further purification. 1H NMR, 13C NMR and 19F NMR spectra were recorded at 400, 500 or 600 MHz NMR spectrometer using CDCl3 as solvent and TMS as internal standard.
4.2 General procedure for the ligand relay-enabled asymmetric [4+1] annulation for the preparation of 3
To an 8.0 mL vial equipped with a magnetic stir bar were added diester 1 (0.10 mmol, 1.0 equiv), N-Ts-hydrazone 2 (0.30 mmol, 3.0 equiv), [Pd(allyl)Cl]2 (0.0050 mmol, 5.0 mol %), L1a (0.020 mmol, 20 mol %), L2a (0.010 mmol, 10 mol %), K2CO3 (0.55 mmol, 5.5 equiv), and dry MTBE (1.5 mL) under a nitrogen atmosphere. The suspension was stirred at room temperature for 15 min, then at 65 °C for 10 h. TLC analysis showed complete consumption of substrate 1. The reaction mixture was diluted with EtOAc and filtered, and the solvent was removed under reduced pressure. The enantiomeric ratio was determined by chiral HPLC. Purification of the residue by silica gel column chromatography afforded the title product 3.
Dimethyl (E)-1-styryl-1,3-dihydro-2H-indene-2,2-dicar- boxylate (3a): Pale yellow solid (31.9 mg, 95% yield). m.p.107.5~108.6 °C. 1H NMR (500 MHz, CDCl3) δ: 7.35~7.31 (m, 2H), 7.31~7.26 (m, 2H), 7.25~7.21 (m, 3H), 7.20 (m, 2H), 6.60 (d, J=15.6 Hz, 1H), 6.09 (dd, J=9.4 Hz, J=15.7 Hz, 1H), 4.79 (d, J=9.4 Hz, 1H), 3.93 (d, J=16.7 Hz, 1H), 3.76 (s, 3H), 3.64 (s, 3H), 3.41 (d, J=16.7 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ:: 172.0, 170.3, 142.7, 139.5, 137.0, 132.9, 128.7, 127.7, 127.4, 126.6, 125.0, 124.5, 65.6, 54.7, 53.1, 52.7, 39.4. HRMS (ESI) calcd for C21H20O4 [M+Na]+ 359.1259, found 359.1267. Optical rotation: [α]20 D–138.1 (c 1.0, CHCl3). HPLC (Chiralpak AD-H): n-Hexane/i-PrOH (V/V=97/3), flow rate 1.0 mL/min, T=40 °C, λ=254 nm, tR1=11.6 min (minor), tR2=15.0 min (major), 83∶17 er.
Dimethyl (E)-1-(4-methoxystyryl)-1,3-dihydro-2H-inde- ne-2,2-dicarboxylate (3b): Pale yellow oil (30.4 mg, 83% yield). 1H NMR (600 MHz, CDCl3) δ: 7.31~7.24 (m, 2H), 7.24~7.11 (m, 4H), 6.82 (d, J=8.4 Hz, 2H), 6.53 (d, J=15.6 Hz, 1H), 5.94 (dd, J=9.4, 15.6 Hz, 1H), 4.76 (d, J=9.4 Hz, 1H), 3.92 (d, J=16.6 Hz, 1H), 3.79 (s, 3H), 3.75 (s, 3H), 3.63 (s, 3H), 3.39 (d, J=16.6 Hz, 1H); 13C NMR (150 MHz, CDCl3) δ: 171.9, 170.2, 159.3, 142.8, 139.4, 132.2, 129.8, 127.6, 127.5, 127.2, 125.1, 125.0, 124.5, 114.0, 65.6, 55.3, 54.7, 53.0, 52.6, 39.3. HRMS (ESI) calcd for C22H22O5 [M+Na]+ 389.1429, found 389.1426; Optical rotation: [α]20 D–151.5 (c 1.0, CHCl3); HPLC (Chiralpak AD-H): n-Hexane/i-PrOH (V/V=97/3), flow rate 1.0 mL/min, T=40 °C, λ=254 nm, tR1=15.4 min (minor), tR2=19.6 min (major), 86.5∶13.5 er.
Dimethyl (E)-1-(4-methylstyryl)-1,3-dihydro-2H-inde- ne-2,2-dicarboxylate (3c): Pale yellow solid (33.9 mg, 97% yield). m.p. 110.0~111.6 °C; 1H NMR (600 MHz, CDCl3) δ: 7.25~7.20 (m, 4H), 7.20~7.17 (m, 2H), 7.09 (d, J=8.0 Hz, 2H), 6.56 (d, J=15.7 Hz, 2H), 6.03 (dd, J=9.4 Hz, J=15.6 Hz, 1H), 4.77 (d, J=9.4 Hz, 1H), 3.93 (d, J=16.7 Hz, 1H), 3.75 (s, 3H), 3.63 (s, 3H), 3.40 (d, J=16.6 Hz, 1H), 2.32 (s, 3H); 13C NMR (150 MHz, CDCl3) δ: 172.0, 170.3, 142.8, 139.5, 137.5, 134.2, 132.8, 129.3, 127.6, 127.3, 126.5, 126.3, 125.1, 124.5, 65.6, 54.7, 53.1, 52.7, 39.4, 21.3. HRMS (ESI) calcd for C22H22O4 [M+ Na]+ 373.1416, found 373.1416. Optical rotation: [α]20 D–139.1 (c 1.0, CHCl3). HPLC (Chiralpak AD-H): n-Hexane/ i-PrOH (V/V=97/3), flow rate 1.0 mL/min, T=40 °C, λ=254 nm, tR1=13.7 min (minor), tR2=17.2 min (major), 83∶17 er.
Dimethyl (E)-1-(4-isopropylstyryl)-1,3-dihydro-2H-in- dene-2,2-dicarboxylate (3d): Pale yellow oil (34.1 mg, 90% yield). 1H NMR (600 MHz, CDCl3) δ: 7.26~7.25 (m, 2H), 7.24~7.16 (m, 4H), 7.15~7.14 (m, 2H), 6.57 (d, J=15.7 Hz, 1H), 6.03 (dd, J=9.4, 15.6 Hz, 1H), 4.77 (d, J=9.4 Hz, 1H), 3.92 (d, J=16.6 Hz, 1H), 3.75 (s, 3H), 3.64 (s, 3H), 3.39 (d, J=16.7 Hz, 1H), 2.90~2.85 (m, 1H), 1.24 (s, 3H), 1.22 (s, 3H); 13C NMR (150 MHz, CDCl3) δ: 172.0, 170.3, 148.6, 142.8, 139.5, 134.7, 132.8, 127.6, 127.3, 126.7, 126.6, 126.4, 125.1, 124.5, 65.6, 54.8, 53.1, 52.7, 39.4, 34.0, 24.1; HRMS (ESI) calcd for C24H26O4 [M+Na]+ 401.1729, found 401.1737. Optical rotation: [α]20 D–122.1 (c 1.0, CHCl3). HPLC (Chiralpak AD-H): n-Hexane/i-PrOH (V/V=97/3), flow rate 1.0 mL/min, T=40 °C, λ=254 nm, tR1=9.6 min (minor), tR2=11.0 min (major), 81.5∶18.5 er.
Dimethyl (E)-1-(2-([1'-biphenyl]-4-yl)vinyl)-1,3-dihy- dro-2H-indene-2,2-dicarboxylate (3e): Pale yellow solid (33.4 mg, 81% yield). m.p. 136.5~137.4 °C; 1H NMR (600 MHz, CDCl3) δ: 7.60~7.58 (m, 2H), 7.54 (d, J=8.3 Hz, 2H), 7.46~7.39 (m, 4H), 7.34 (t, J=7.4 Hz, 1H), 7.26~7.19 (m, 4H), 6.65 (d, J=15.7 Hz, 1H), 6.15 (dd, J=9.4 Hz, J=15.7 Hz, 1H), 4.82 (d, J=9.4 Hz, 1H), 3.95 (d, J=16.8 Hz, 1H), 3.77 (s, 3H), 3.67 (s, 3H), 3.43 (d, J=16.7 Hz, 1H); 13C NMR (150 MHz, CDCl3) δ: 172.0, 170.3, 142.7, 140.8, 140.5, 139.5, 136.0, 132.4, 128.9, 127.7, 127.5, 127.43, 127.38, 127.3, 127.04, 126.98, 125.1, 124.5, 65.7, 54.8, 53.1, 52.8, 39.4. HRMS (ESI) calcd for C27H24O4 [M+Na]+ 435.1572, found 435.1572. Optical rotation: [α]20 D–130.8 (c 1.0, CHCl3). HPLC (Chiralpak AD-H): n-Hexane/i-PrOH (V/V=97/3), flow rate 1.0 mL/min, T=40 °C, λ=254 nm, tR1=17.6 min (minor), tR2=22.5 min (major), 83∶17 er.
Dimethyl (E)-1-(4-fluorostyryl)-1,3-dihydro-2H-indene- 2,2-dicarboxylate (3f): Pale yellow solid (35.4 mg, 99% yield). m.p. 106.1~107.6 °C; 1H NMR (600 MHz, CDCl3) δ: 7.28 (m, 2H), 7.25~7.16 (m, 4H), 6.97 (t, J=8.6 Hz, 2H), 6.55 (d, J=15.7 Hz, 1H), 6.00 (dd, J=9.4 Hz, J=15.6 Hz, 1H), 4.77 (d, J=9.4 Hz, 1H), 3.91 (d, J=16.7 Hz, 1H), 3.75 (s, 3H), 3.63 (s, 3H), 3.40 (d, J=16.7 Hz, 1H). 13C NMR (150 MHz, CDCl3) δ: 171.9, 170.3, 162.4 (d, J=245.2 Hz), 142.6, 139.3, 133.2 (d, J=3.4 Hz), 131.7, 128.1 (d, J=7.9 Hz), 127.8, 127.4, 127.2 (d, J=2.1 Hz), 125.0, 124.5, 115.6 (d, J=21.5 Hz), 65.6, 54.6, 53.1, 52.7, 39.4; 19F NMR (565 MHz, CDCl3) δ: –114.38~–114.48 (m). HRMS (ESI) calcd for C21H19FO4 [M+ Na]+ 377.1165, found 377.1168. Optical rotation: [α]20 D–144.6 (c 1.0, CHCl3). HPLC (Chiralpak AD-H): n-Hexane/ i-PrOH (V/V=96/4)), flow rate 1.0 mL/min, T=40 °C, λ=254 nm, tR1=11.5 min (minor), tR2=16.4 min (major), 83.5∶16.5 er.
Dimethyl (E)-1-(4-chlorostyryl)-1,3-dihydro-2H-indene- 2,2-dicarboxylate (3g): Pale yellow solid (37.0 mg, 99% yield). m.p. 116.8~118.2 °C; 1H NMR (600 MHz, CDCl3) δ: 7.29~7.16 (m, 8H), 6.56 (d, J=15.7 Hz, 1H), 6.08 (dd, J=9.4 Hz, J=15.7 Hz, 1H), 4.79 (d, J=9.4 Hz, 1H), 3.93 (d, J=16.7 Hz, 1H), 3.77 (s, 3H), 3.64 (s, 3H), 3.42 (d, J=16.7 Hz, 1H); 13C NMR (150 MHz, CDCl3) δ: 171.9, 170.2, 142.4, 139.5, 135.5, 133.4, 131.7, 128.8, 128.1, 127.8, 127.7, 127.4, 125.0, 124.6, 65.6, 54.6, 53.1, 52.7, 39.4. HRMS (ESI) calcd for C21H19ClO4 [M+Na]+ 393.0870, found 393.0872; Optical rotation: [α]20 D–123.2 (c 1.0, CHCl3). HPLC (Chiralpak AD-H): n-Hexane/i- PrOH (V/V=97/3)), flow rate 1.0 mL/min, T=40 °C, λ=254 nm, tR1=13.6 min (minor), tR2=22.1 min (major), 81.5∶18.5 er.
Dimethyl (E)-1-(4-bromostyryl)-1,3-dihydro-2H-indene- 2,2-dicarboxylate (3h): Pale yellow solid (40.1 mg, 97% yield). m.p. 121.3~121.8 °C; 1H NMR (600 MHz, CDCl3) δ: 7.46~7.36 (m, 2H), 7.25~7.15 (m, 6H), 6.53 (d, J=15.6 Hz, 1H), 6.09 (dd, J=9.4, J=15.7 Hz, 1H), 4.77 (d, J=9.4 Hz, 1H), 3.94~3.89 (d, J=16.7 Hz, 1H), 3.75 (s, 3H), 3.63 (s, 3H), 3.40 (d, J=16.7 Hz, 1H); 13C NMR (150 MHz, CDCl3) δ: 171.8, 170.2, 142.4, 139.5, 135.9, 131.8, 131.7, 128.3, 128.1, 127.8, 127.4, 125.0, 124.6, 121.5, 65.6, 54.6, 53.1, 52.7, 39.4. HRMS (ESI) for C21H19BrO4 [M+Na]+ 437.0364, found 437.0363; Optical rotation: [α]20 D–101.5 (c 1.0, CHCl3); HPLC (Chiralpak AD-H): n-Hexane/i-PrOH (V/V=97/3)), flow rate 1.0 mL/min, T=40 °C, λ=254 nm, tR1=14.2 min (minor), tR2=23.8 min (major), 82.5∶17.5 er.
Dimethyl (E)-1-(4-(trifluoromethyl)styryl)-1,3-dihydro- 2H-indene-2,2-dicarboxylate (3i): Pale yellow solid (34.7 mg, 86% yield). m.p. 103.3~105.0 °C; 1H NMR (600 MHz, CDCl3) δ: 7.53 (d, J=8.1 Hz, 2H), 7.42 (d, J=8.1 Hz, 2H), 7.25~7.16 (m, 4H), 6.62 (d, J=15.7 Hz, 1H), 6.20 (dd, J=9.4, J=15.7 Hz, 1H), 4.81 (d, J=9.4 Hz, 1H), 3.92 (d, J=16.7 Hz, 1H), 3.76 (s, 3H), 3.63 (s, 3H), 3.42 (d, J=16.7 Hz, 1H); 13C NMR (150 MHz, CDCl3) δ: 171.8, 170.2, 142.1, 140.5, 139.6, 131.6, 130.3, 129.6 (q, J=32.0 Hz), 127.9, 127.5, 126.7, 125.7 (q, J=3.7 Hz), 125.0, 124.6, 124.3 (q, J=270.0 Hz), 65.6, 54.6, 53.2, 52.8, 39.5; 19F NMR (565 MHz, CDCl3) δ: –62.52. HRMS (ESI) calcd for C22H19F3O4 [M+Na]+ 427.1133, found 427.1129. Optical rotation: [α]20 D–83.9 (c 1.0, CHCl3). HPLC (Chiralpak AD-H): n-Hexane/i-PrOH (V/ V=97/3)), flow rate 1.0 mL/min, T=40 °C, λ=254 nm, tR1=10.5 min (minor), tR2=16.3 min (major), 76∶24 er.
Dimethyl (E)-1-(3,5-dimethylstyryl)-1,3-dihydro-2H-in- dene-2,2-dicarboxylate (3j): Pale yellow solid (31.9 mg, 91% yield). m.p. 78.0~78.6 °C; 1H NMR (600 MHz, CDCl3) δ: 7.32 (d, J=7.1 Hz, 1H), 7.25~7.19 (m, 4H), 7.15~7.09 (m, 3H), 6.80 (d, J=15.5 Hz, 1H), 5.95 (dd, J=9.4 Hz, J=15.5 Hz, 1H), 4.80 (d, J=9.4 Hz, 1H), 3.93 (d, J=16.7 Hz, 1H), 3.76 (s, 3H), 3.66 (s, 3H), 3.41 (d, J=16.7 Hz, 1H), 2.34 (s, 3H); 13C NMR (150 MHz, CDCl3) δ: 172.0, 170.3, 142.8, 139.4, 136.3, 135.5, 131.0, 130.3, 128.8, 127.7, 127.6, 127.4, 126.2, 126.0, 125.0, 124.5, 65.6, 55.0, 53.1, 52.8, 39.4, 19.9. HRMS (ESI) calcd for C22H22O4 [M+Na]+ 373.1416, found 373.1418. Optical rotation: [α]20 D–143.2 (c 1.0, CHCl3). HPLC (Chiralpak IM): n-Hexane/i-PrOH (V/V=99/1), flow rate 0.5 mL/min, T=40 °C, λ=254 nm, tR1=18.9 min (minor), tR2=23.6 min (major), 84.5∶15.5 er.
Dimethyl (E)-1-(2-fluorostyryl)-1,3-dihydro-2H-indene- 2,2-dicarboxylate (3k): Pale yellow solid (30.4 mg, 86% yield). m.p. 76.5~78.0 °C; 1H NMR (600 MHz, CDCl3) δ: 7.40~7.31 (m, 1H), 7.25~7.20 (m, 2H), 7.20~7.13 (m, 3H), 7.08~6.95 (m, 2H), 6.75 (d, J=15.8 Hz, 1H), 6.15 (dd, J=9.5, 15.8 Hz, 1H), 4.79 (d, J=9.5 Hz, 1H), 3.92 (d, J=16.7 Hz, 1H), 3.75 (s, 3H), 3.66 (s, 3H), 3.40 (d, J=16.7 Hz, 1H); 13C NMR (150 MHz, CDCl3) δ: 171.9, 170.2, 160.3 (d, J=247.8 Hz), 142.5, 139.5, 130.1 (d, J=4.6 Hz), 129.0 (d, J=8.3 Hz), 127.8, 127.7 (d, J=3.7 Hz), 127.4, 125.5 (d, J=3.3 Hz), 125.0, 124.8 (d, J=7.8 Hz), 124.5, 124.2 (d, J=3.5 Hz), 115.8 (d, J=21.8 Hz), 65.7, 55.1, 53.1, 52.7, 39.4; 19F NMR (565 MHz, CDCl3) δ: –117.93. HRMS (ESI) calcd for C21H19FO4 [M+Na]+ 377.1165; Found 377.1168; Optical rotation: [α]20 D–129.8 (c 1.0, CHCl3); HPLC (Chiralpak IM): n-Hexane/ i-PrOH (V/V=99/1), flow rate 0.5 mL/min, T=40 °C, λ=254 nm, tR1=19.4 min (minor), tR2=24.5 min (major), 82∶18 er.
Dimethyl (E)-1-(4-methylstyryl)-1,3-dihydro-2H-inde- ne-2,2-dicarboxylate (3l): Pale yellow solid (34.6 mg, 95% yield). m.p. 81.5~83.5 °C; 1H NMR (600 MHz, CDCl3) δ: 7.25~7.15 (m, 4H), 6.95 (s, 2H), 6.86 (s, 1H), 6.53 (d, J=15.7 Hz, 1H), 6.05 (dd, J=9.4, 15.6 Hz, 1H), 4.76 (d, J=9.5 Hz, 1H), 3.93 (d, J=16.6 Hz, 1H), 3.75 (s, 3H), 3.64 (s, 3H), 3.40 (d, J=16.7 Hz, 1H), 2.28 (s, 6H); 13C NMR (150 MHz, CDCl3) δ: 172.0, 170.3, 142.9, 139.4, 138.1, 136.9, 133.0, 129.5, 127.7, 127.4, 126.9, 125.1, 124.48, 124.45, 65.6, 54.8, 53.1, 52.8, 39.4, 21.4. HRMS (ESI) calcd for C23H24O4 [M+Na]+ 387.1572, found 387.1571. Optical rotation: [α]20 D–89.4 (c 1.0, CHCl3). HPLC (Chiralpak IM): n-Hexane/i-PrOH (V/V=99/1), flow rate 0.5 mL/min, T=40 °C, λ=254 nm, tR1=16.3 min (minor), tR2=21.3 min (major), 80∶20 er.
Dimethyl (E)-1-(2-(furan-2-yl)vinyl)-1,3-dihydro-2H-in- dene-2,2-dicarboxylate (3m): Pale yellow oil (24.7 mg, 76% yield). 1H NMR (600 MHz, CDCl3) δ: 7.29 (s, 1H), 7.24~7.15 (m, 4H), 6.39~6.30 (m, 2H), 6.19 (d, J=3.2 Hz, 1H), 6.04 (dd, J=9.2, 15.7 Hz, 1H), 4.73 (d, J=9.2 Hz, 1H), 3.88 (d, J=16.6 Hz, 1H), 3.74 (s, 3H), 3.66 (s, 3H), 3.37 (d, J=16.6 Hz, 1H); 13C NMR (150 MHz, CDCl3) δ: 171.9, 170.1, 152.5, 142.4, 142.1, 139.6, 127.7, 127.3, 126.0, 125.0, 124.5, 121.4, 111.3, 108.0, 65.7, 54.4, 53.1, 52.7, 39.3. HRMS (ESI) calcd for C19H18O5 [M+ Na]+ 349.1053, found 349.1052. Optical rotation: [α]20 D–78.2 (c 1.0, CHCl3). HPLC (Chiralpak AD-H): n-Hexane/i- PrOH (V/V=96/4), flow rate 1.0 mL/min, T=40 °C, λ=254 nm, tR1=10.1 min (minor), tR2=16.0 min (major), 82.5∶17.5 er.
Dimethyl (E)-5-methyl-1-styryl-1,3-dihydro-2H-indene- 2,2-dicarboxylate (3q): Pale yellow solid (32.2 mg, 92% yield). m.p. 74.0~75.6 °C; 1H NMR (600 MHz, CDCl3) δ: 7.32 (d, J=7.3 Hz, 2H), 7.28 (t, J=7.4 Hz, 2H), 7.21 (t, J=7.2 Hz, 1H), 7.09~7.04 (m, 2H), 7.01 (d, J=7.7 Hz, 1H), 6.58 (d, J=15.7 Hz, 1H), 6.08 (dd, J=9.4, 15.7 Hz, 1H), 4.74 (d, J=9.4 Hz, 1H), 3.88 (d, J=16.7 Hz, 1H), 3.75 (s, 3H), 3.63 (s, 3H), 3.35 (d, J=16.6 Hz, 1H), 2.33 (s, 3H); 13C NMR (150 MHz, CDCl3) δ: 172.0, 170.3, 139.7, 139.6, 137.5, 137.1, 132.7, 128.6, 128.2, 127.7, 127.6, 126.5, 125.2, 124.8, 65.8, 54.4, 53.1, 52.7, 39.3, 21.5. HRMS (ESI) calcd for C22H22O4 [M+Na]+ 373.1416, found 373.1414. Optical rotation: [α]20 D–108.8 (c 1.0, CHCl3). HPLC (Chiralpak AD-H): n-Hexane/i- PrOH (V/V=97/3), flow rate 1.0 mL/min, T=40 °C, λ=254 nm, tR1=13.9 min (minor), tR2=16.0 min (major), 77∶23 er.
Dimethyl (E)-5-fluoro-1-styryl-1,3-dihydro-2H-indene- 2,2-dicarboxylate (3r): Pale yellow solid (31.8 mg, 90% yield). m.p. 81.0-82.6 °C; 1H NMR (600 MHz, CDCl3) δ: 7.35~7.31 (m, 2H), 7.30~7.27 (m, 2H), 7.23 (t, J=7.1 Hz, 1H), 7.17 (dd, J=5.1, 8.2 Hz, 1H), 6.94~6.84 (m, 2H), 6.59 (d, J=15.7 Hz, 1H), 6.06 (dd, J=9.3, 15.7 Hz, 1H), 4.75 (d, J=9.3 Hz, 1H), 3.86 (d, J=16.4 Hz, 1H), 3.76 (s, 3H), 3.64 (s, 3H), 3.35 (d, J=16.4 Hz, 1H); 13C NMR (150 MHz, CDCl3) δ: 171.8, 170.0, 162.6 (d, J=242.8 Hz), 144.9 (d, J=7.9 Hz), 136.8, 134.9 (d, J=2.4 Hz), 133.5, 128.7, 127.9, 126.6, 126.5, 125.5 (d, J=8.6 Hz), 114.8 (d, J=22.5 Hz), 112.1 (d, J=22.6 Hz), 66.1, 54.6, 53.2, 52.8, 38.7; 19F NMR (565 MHz, CDCl3) δ: –115.74. HRMS (ESI) calcd for C21H19FO4 [M+Na]+ 377.1165, found 377.1160. Optical rotation: [α]20 D–135.6 (c 1.0, CHCl3). HPLC (Chiralpak ADH): n-Hexane/i-PrOH (V/V=97/3), flow rate 1.0 mL/min, T=40 °C, λ=254 nm, tR1=10.5 min (minor), tR2=13.9 min (major), 82∶18 er.
Dimethyl (E)-5-chloro-1-styryl-1,3-dihydro-2H-indene- 2,2-dicarboxylate (3s): Pale yellow oil (35.5 mg, 96% yield). 1H NMR (600 MHz, CDCl3) δ: 7.34~7.27 (m, 4H), 7.25~7.21 (m, 2H), 7.18 (d, J=8.1 Hz, 1H), 7.10 (d, J=8.2 Hz, 1H), 6.58 (d, J=15.7 Hz, 1H), 6.05 (dd, J=9.3, 15.7 Hz, 1H), 4.74 (d, J=9.3 Hz, 1H), 3.89 (d, J=16.9 Hz, 1H), 3.76 (s, 3H), 3.64 (s, 3H), 3.37 (d, J=16.9 Hz, 1H); 13C NMR (150 MHz, CDCl3) δ: 171.6, 169.9, 141.5, 141.2, 136.8, 133.44, 133.36, 128.7, 127.9, 127.7, 126.7, 126.6, 126.2, 124.8, 65.8, 54.1, 53.2, 52.8, 39.2. HRMS (ESI) calcd for C21H19ClO4 [M+Na]+ 393.0870, found 393.0865. Optical rotation: [α]20 D–105.3 (c 1.0, CHCl3). HPLC (Chiralpak AD-H): n-Hexane/i-PrOH (V/V=97/3), flow rate 1.0 mL/min, T=40 °C, λ=254 nm, tR1=10.9 min (minor), tR2=13.9 min (major), 83.5∶16.5 er.
Dimethyl (E)-6-methyl-1-styryl-1,3-dihydro-2H-indene- 2,2-dicarboxylate (3t): Pale yellow solid (29.8 mg, 85% yield). m.p. 63.1~64.0 °C; 1H NMR (600 MHz, CDCl3) δ: 7.35~7.32 (m, 2H), 7.28 (t, J=7.4 Hz, 2H), 7.22 (t, J=7.3 Hz, 1H), 7.12 (d, J=7.6 Hz, 1H), 7.02 (d, J=7.8 Hz, 1H), 7.00 (s, 1H), 6.60 (d, J=15.7 Hz, 1H), 6.08 (dd, J=9.5, 15.6 Hz, 1H), 4.73 (d, J=9.5 Hz, 1H), 3.88 (d, J=16.4 Hz, 1H), 3.75 (s, 3H), 3.64 (s, 3H), 3.36 (d, J=16.6 Hz, 1H), 2.30 (s, 3H); 13C NMR (150 MHz, CDCl3) δ: 172.0, 170.3, 142.8, 137.07, 137.05, 136.4, 132.8, 128.7, 128.6, 127.7, 127.5, 126.6, 125.6, 124.2, 65.8, 54.7, 53.1, 52.7, 39.1, 21.4. HRMS (ESI) calcd for C22H22O4 [M+ Na]+ 373.1416, found 373.1422; Optical rotation: [α]20 D–75.3 (c 1.0, CHCl3); HPLC (Chiralpak AD-H): n-Hexane/i- PrOH (V/V=97/3), flow rate 1.0 mL/min, T=40 °C, λ=254 nm, tR1=8.4 min (major), tR2=9.1 min (minor), 25∶ 75 er.
Dimethyl (E)-6-fluoro-1-styryl-1,3-dihydro-2H-indene- 2,2-dicarboxylate (3u): Pale yellow solid (30.1 mg, 85% yield). m.p. 67.0~68.6 °C; 1H NMR (600 MHz, CDCl3) δ: 7.34~7.30 (m, 2H), 7.30~7.26 (m, 2H), 7.24~7.20 (m, 1H), 7.11 (dd, J=5.2, 8.3 Hz, 1H), 6.95~6.86 (m, 2H), 6.57 (d, J=15.7 Hz, 1H), 6.06 (dd, J=9.3, 15.7 Hz, 1H), 4.73 (d, J=9.3 Hz, 1H), 3.89 (d, J=16.9 Hz, 1H), 3.76 (s, 3H), 3.64 (s, 3H), 3.37 (d, J=16.9 Hz, 1H); 13C NMR (150 MHz, CDCl3) δ: 171.7, 170.0, 162.8 (d, J=243.1 Hz), 141.6 (d, J=8.5 Hz), 138.2 (d, J=2.4 Hz), 136.9, 133.1, 128.7, 127.8, 127.1, 126.6, 126.2 (d, J=8.9 Hz), 114.4 (d, J=22.5 Hz), 111.6 (d, J=22.5 Hz), 66.0, 53.9, 53.2, 52.8, 39.3; 19F NMR (565 MHz, CDCl3) δ: –115.44~–115.53 (m). HRMS (ESI) calcd for C21H19FO4 [M+Na]+ 377.1165, found 377.1167. Optical rotation: [α]20 D–111.8 (c 1.0, CHCl3). HPLC (Chiralpak AD-H): n-Hexane/i- PrOH (V/V=97/3), flow rate 1.0 mL/min, T=40 °C, λ=254 nm, tR1=9.0 min (minor), tR2=12.2 min (major), 82.5∶17.5 er.
Dimethyl (E)-6-chloro-1-styryl-1,3-dihydro-2H-indene- 2,2-dicarboxylate (3v): Pale yellow oil (29.2 mg, 79% yield). 1H NMR (600 MHz, CDCl3) δ: 7.35~7.32 (m, 2H), 7.31~7.27 (m, 2H), 7.25~7.21 (m, 1H), 7.20~7.17 (m, 1H), 7.16~7.13 (m, 2H), 6.60 (d, J=15.7 Hz, 1H), 6.05 (dd, J=9.4, 15.7 Hz, 1H), 4.75 (d, J=9.4 Hz, 1H), 3.86 (d, J=16.9 Hz, 1H), 3.76 (s, 3H), 3.64 (s, 3H), 3.35 (d, J=16.9 Hz, 1H); 13C NMR (150 MHz, CDCl3) δ: 171.7, 169.9, 144.7, 138.0, 136.7, 133.6, 133.1, 128.7, 128.0, 127.9, 126.6, 126.4, 125.6, 125.3, 65.8, 54.5, 53.2, 52.8, 38.9. HRMS (ESI) calcd for C21H19ClO4 [M+Na]+ 393.0870, found 393.0865. Optical rotation: [α]20 D–79.5 (c 1.0, CHCl3). HPLC (Chiralpak AD-H): n-Hexane/i-PrOH (V/V=97/3), flow rate 1.0 mL/min, T=40 °C, λ=254 nm, tR1=8.5 min (minor), tR2=9.9 min (major), 83:17 er.
Dimethyl (E)-4-chloro-1-styryl-1,3-dihydro-2H-indene- 2,2-dicarboxylate (3w): Pale yellow oil (29.2 mg, 79% yield). 1H NMR (400 MHz, CDCl3) δ: 7.34~7.25 (m, 4H), 7.24~7.18 (m, 2H), 7.14 (t, J=7.4 Hz, 1H), 7.07 (d, J=7.3 Hz, 1H), 6.59 (d, J=15.6 Hz, 1H), 6.05 (dd, J=9.4, 15.6 Hz, 1H), 4.84 (d, J=9.4 Hz, 1H), 3.95 (d, J=17.4 Hz, 1H), 3.77 (s, 3H), 3.63 (s, 3H), 3.45 (d, J=17.4 Hz, 1H); 13C NMR (125 MHz, CDCl3) δ: 171.7, 169.9, 144.7, 138.0, 136.8, 133.4, 130.6, 129.0, 128.7, 127.9, 127.8, 126.7, 126.6, 123.4, 64.8, 55.3, 53.2, 52.8, 38.8. HRMS (ESI) calcd for C21H19ClO4 [M+Na]+ 393.0870, found 393.0868. Optical rotation: [α]20 D–146.1 (c 1.0, CHCl3). HPLC (Chiralpak AD-H): n-Hexane/i-PrOH (V/V=97/3), flow rate 1.0 mL/min, T=40 °C, λ=254 nm, tR1=6.8 min (minor), tR2=9.0 min (major), 83:17 er.
Dimethyl (E)-6-fluoro-1-(4-fluorostyryl)-1,3-dihydro- 2H-indene-2,2-dicarboxylate (3y): Pale yellow oil (33.8 mg, 91% yield). 1H NMR (500 MHz, CDCl3) δ: 7.29 (dd, J=5.4, 8.7 Hz, 2H), 7.16 (dd, J=5.2, 8.2 Hz, 1H), 6.98 (t, J=8.7 Hz, 2H), 6.94~6.83 (m, 2H), 6.55 (d, J=15.7 Hz, 1H), 5.98 (dd, J=9.4, 15.7 Hz, 1H), 4.73 (d, J=9.4 Hz, 1H), 3.84 (d, J=16.5 Hz, 1H), 3.76 (s, 3H), 3.63 (s, 3H), 3.34 (d, J=16.6 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ: 171.7, 170.0, 162.64 (d, J=242.8 Hz), 162.55 (d, J=245.6 Hz), 144.8 (d, J=7.8 Hz), 134.9 (d, J=2.5 Hz), 133.0 (d, J=3.4 Hz), 132.3, 128.1, 126.4 (d, J=2.1 Hz), 125.6 (d, J=8.6 Hz), 115.6 (d, J=21.5 Hz), 114.8 (d, J=22.4 Hz), 112.1 (d, J=22.6 Hz), 66.1, 54.5, 53.2, 52.8, 38.7; 19F NMR (471 MHz, CDCl3) δ: –114.12, –115.69. HRMS (ESI) calcd for C21H18F2O4 [M+Na]+ 395.1071, found 395.1068. Optical rotation: [α]20 D–152.8 (c 1.0, CHCl3). HPLC (Chiralpak AD-H): n-Hexane/i-PrOH (V/V=97/3), flow rate 1.0 mL/min, T=40 °C, λ=254 nm, tR1=12.0 min (minor), tR2=17.2 min (major), 84:16 er.
Diethyl (E)-1-styryl-1,3-dihydro-2H-indene-2,2-dicar- boxylate (3z): Pale yellow oil (26.9 mg, 74% yield). 1H NMR (600 MHz, CDCl3) δ: 7.34~7.30 (m, 2H), 7.29~7.26 (m, 2H), 7.25~7.15 (m, 5H), 6.59 (d, J=15.7 Hz, 1H), 6.11 (dd, J=9.5, 15.7 Hz, 1H), 4.78 (d, J=9.4 Hz, 1H), 4.30~4.22 (m, 1H), 4.20~4.15 (m, 1H), 4.15~4.05 (m, 2H), 3.93 (d, J=16.7 Hz, 1H), 3.39 (d, J=16.7 Hz, 1H), 1.25 (t, J=7.1 Hz, 3H), 1.14 (t, J=7.1 Hz, 3H); 13C NMR (150 MHz, CDCl3) δ: 171.5, 169.9, 142.9, 139.6, 137.0, 132.8, 128.6, 127.64, 127.63, 127.5, 127.3, 126.5, 125.0, 124.5, 65.5, 61.8, 61.6, 54.6, 39.4, 14.3, 14.2. HRMS (ESI) calcd for C23H24O4 [M+Na]+ 387.1572, found 387.1579. Optical rotation: [α]20 D–156.6 (c 1.0, CHCl3). HPLC (Chiralpak AD-H): n-Hexane/i-PrOH (V/ V=97/3), flow rate 1.0 mL/min, T=40 °C, λ=254 nm, tR1=11.5 min (minor), tR2=13.4 min (major), 78.5∶21.5 er.
Diisopropyl (E)-1-styryl-1,3-dihydro-2H-indene-2,2-di- carboxylate (3aa): Pale yellow solid (25.2 mg, 64% yield). m.p. 88.3~89.6 °C; 1H NMR (600 MHz, CDCl3) δ: 7.35~7.30 (m, 2H), 7.30~7.26 (m, 2H), 7.24~7.22 (m, 1H), 7.22~7.16 (m, 4H), 6.60 (d, J=15.7 Hz, 1H), 6.11 (dd, J=9.6, 15.7 Hz, 1H), 5.05 (p, J=6.3 Hz, 1H), 4.97 (p, J=6.3 Hz, 1H), 4.76 (d, J=9.5 Hz, 1H), 3.94 (d, J=16.7 Hz, 1H), 3.35 (d, J=16.7 Hz, 1H), 1.24 (d, J=6.2 Hz, 6H), 1.19 (d, J=6.3 Hz, 3H), 1.07 (d, J=6.2 Hz, 3H); 13C NMR (150 MHz, CDCl3) δ: 171.0, 169.4, 143.2, 139.6, 137.0, 132.7, 128.6, 127.58, 127.56, 127.3, 126.5, 125.0, 124.4, 69.20, 69.16, 65.3, 54.6, 39.6, 21.9, 21.7, 21.6. HRMS (ESI) calcd for C25H28O4 [M+Na]+ 415.1885, found 415.1888. Optical rotation: [α]20 D–97.6 (c 1.0, CHCl3). HPLC (Chiralpak IM): n-Hexane/i-PrOH (V/V=97/3), flow rate 1.0 mL/min, T=40 °C, λ=254 nm, tR1=15.1 min (major), tR2=21.3 min (minor), 24:76 er.
Dimethyl 1-phenethyl-1,3-dihydro-2H-indene-2,2-dicar- boxylate (4a): Pale yellow solid (33.8 mg, 100% yield). m.p. 58.0~58.9 °C; 1H NMR (400 MHz, CDCl3) δ: 7.25~7.21 (m, 3H), 7.20~7.16 (m, 3H), 7.16~7.07 (m, 3H), 3.96 (dd, J=5.5, 8.6 Hz, 1H), 3.82 (d, J=16.5 Hz, 1H), 3.73 (s, 3H), 3.67 (s, 3H), 3.33 (d, J=16.5 Hz, 1H), 2.82~2.70 (m, 1H), 2.70~2.58 (m, 1H), 1.86~1.68 (m, 2H); 13C NMR (100 MHz, CDCl3) δ: 172.2, 170.6, 144.0, 142.0, 139.2, 128.52, 128.46, 127.3, 126.9, 126.0, 124.8, 124.6, 65.6, 53.0, 52.7, 49.9, 39.3, 33.6, 33.1. HRMS (ESI) calcd for C21H22O4 [M+Na]+ 361.1414, found 361.1416. Optical rotation: [α]20 D–55.6 (c 1.0, CHCl3). HPLC (Chiralpak AD-H): n-Hexane/i-PrOH (V/V=97/3), flow rate 1.0 mL/ min, T=40 °C, λ=254 nm, tR1=10.7 min (minor), tR2=11.5 min (major), 19.5:80.5 er.
(E)-(1-Styryl-2,3-dihydro-1H-indene-2,2-diyl)dimetha-nol (4b): Pale yellow solid (19.7 mg, 70% yield). m.p. 127.5~128.5 °C; 1H NMR (400 MHz, CDCl3) δ: 7.39~7.34 (m, 2H), 7.34~7.28 (m, 2H), 7.26~7.22 (m, 2H), 7.22~7.13 (m, 3H), 6.54 (d, J=15.7 Hz, 1H), 6.28 (dd, J=9.4, 15.7 Hz, 1H), 3.95 (d, J=11.0 Hz, 1H), 3.88 (d, J=9.4 Hz, 1H), 3.86~3.73 (m, 3H), 3.00 (d, J=16.2 Hz, 1H), 2.83 (d, J=16.2 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ: 144.3, 141.3, 137.0, 132.3, 129.0, 128.8, 127.7, 127.4, 126.9, 126.5, 125.5, 125.3, 69.8, 67.3, 53.7, 53.3, 37.5. HRMS (ESI) calcd for C19H20O2 [M+Na]+ 303.1361, found 303.1360. Optical rotation: [α]20 D–99.1 (c 1.0, CHCl3). HPLC (Chiralpak AD-H): n-Hexane/i-PrOH (V/V=97/3), flow rate 1.0 mL/min, T=40 °C, λ=254 nm, tR1=18.3 min (major), tR2=23.6 min (minor), 85.5∶14.5 er.
(E)-1-Styryl-2,3-dihydro-1H-indene-2-carboxylic acid (4c): Pale yellow solid (23.7 mg, 90% yield). m.p. 131.0~131.8 °C; 1H NMR (500 MHz, CDCl3) δ: 7.41 (d, J=7.5 Hz, 1H), 7.35~7.28 (m, 2H), 7.28~7.15 (m, 6H), 6.63 (d, J=15.8 Hz, 0.57H), 6.49 (d, J=15.7 Hz, 0.45H), 6.28~6.17 (m, 1H), 4.27 (q, J=8.4 Hz, 1H), 3.66~3.56 (m, 0.47H), 3.48~3.39 (m, 0.47H), 3.35~3.24 (m, 1H), 3.23~3.16 (m, 0.66H),3.13~3.05 (m, 0.47H); 13C NMR (125 MHz, CDCl3) δ: 180.4, 178.7, 143.8, 143.5, 141.5, 141.0, 137.2, 137.1, 132.6, 132.0, 130.5, 128.7, 128.6, 128.0, 127.64, 127.61, 127.55, 127.52, 127.11, 127.08, 126.6, 126.5, 125.1, 124.8, 124.7, 124.6, 52.5, 51.5, 51.4, 49.4, 35.7, 33.7. Attempts to determine the er value of compound 4c by chiral HPLC were unsuccessful.
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(Li, L.)