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Synlett 2024; 35(18): 2101-2106
DOI: 10.1055/a-2290-0894
letter

Palladium-Catalyzed Asymmetric [3+2] Cycloaddition Reaction of Vinyl Cyclopropane with Electron-Deficient Dienes

Yun-Fan Li
a   Department of Chemistry, Shanghai Engineering Research Center of Organ Repair, Innovative Drug Research Center, Shanghai University, Shanghai 200444, P. R. of China
,
Cun Yang
a   Department of Chemistry, Shanghai Engineering Research Center of Organ Repair, Innovative Drug Research Center, Shanghai University, Shanghai 200444, P. R. of China
,
Yu-Ting Xi
a   Department of Chemistry, Shanghai Engineering Research Center of Organ Repair, Innovative Drug Research Center, Shanghai University, Shanghai 200444, P. R. of China
,
Qitao Tan
a   Department of Chemistry, Shanghai Engineering Research Center of Organ Repair, Innovative Drug Research Center, Shanghai University, Shanghai 200444, P. R. of China
,
Chang-Hua Ding∗
a   Department of Chemistry, Shanghai Engineering Research Center of Organ Repair, Innovative Drug Research Center, Shanghai University, Shanghai 200444, P. R. of China
,
Bin Xu∗
a   Department of Chemistry, Shanghai Engineering Research Center of Organ Repair, Innovative Drug Research Center, Shanghai University, Shanghai 200444, P. R. of China
b   State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032, P. R. of China
› Author AffiliationsWe thank the National Natural Science Foundation of China (No. 22071143, 22171178, 21971159) and Innovation Program of the Shanghai Municipal Education Commission (No. 2019-01-07-00-09-E00008) for financial support.
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Abstract

Palladium-catalyzed asymmetric [3+2] cycloaddition reaction of vinyl cyclopropane and electron-deficient dienes was realized. The cycloaddition reaction proceeded regioselectively on the distant C=C double bond of electron-deficient dienes, and was mainly controlled by the steric hindrance of the 5-substituent of electron-deficient dienes. Chiral multi-substituted cyclopentanes bearing three functional groups (monosubstituted alkene, conjugated ester, and cyano) and three continuous stereocenters were obtained in moderate to high yields, diastereoselectivities, and enantioselectivities.

Key words

palladium - [3+2] cycloaddition - vinyl cyclopropane - asymmetric catalysis - electron-deficient diene

Supporting Information

    Supporting information for this article is available online at https://doi.org/10.1055/a-2290-0894.
  • Supporting Information


Publication History

Received: 06 January 2024

Accepted after revision: 18 March 2024

Accepted Manuscript online:
18 March 2024

Article published online:
03 April 2024

© 2024. Thieme. All rights reserved

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  • References and Notes

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  • 13 Synthesis of Products 3; General Procedure: To a flame-dried Schlenk tube, Pd2(dba)3 (0.005 mmol, 4.28 mg), L4 (0.012 mmol, 7.33 mg), and anhydrous THF (2.0 mL) were added. The resulting mixture was allowed to stir for 30 min, then vinyl cyclopropane 1 (0.24 mmol) and 2,4-diene 2 (0.2 mmol) were added subsequently. The resulting reaction mixture was stirred at room temperature until the raw material disappeared (monitored by TLC). After the volatiles were removed in vacuo, the resulting residue was purified by flash chromatography on silica gel with petroleum ether and ethyl acetate as eluent to give the product 3. Compound 3a: Yield: 36.8 mg (61%); colorless oil; ee: 93%. HPLC (Chiralcel NQ(2), 4.6 mm × 250 mm, hexane/isopropanol = 98:2, 0.7 mL/min, 217 nm): t major = 32.79 min, t minor = 35.37 min. [α]D 19 +28.90 (c 1.0, CHCl3). 1H NMR (600 MHz, CDCl3): δ = 6.70 (d, J = 10.9 Hz, 1 H), 5.69 (ddd, J = 17.0, 10.3, 8.1 Hz, 1 H), 5.20–4.99 (m, 2 H), 3.83 (s, 3 H), 3.78 (s, 3 H), 3.23 (dq, J = 9.7, 8.2 Hz, 1 H), 2.96 (td, J = 10.8, 9.6 Hz, 1 H), 2.79 (dd, J = 13.9, 7.5 Hz, 1 H), 2.47 (dq, J = 10.7, 6.7 Hz, 1 H), 2.39 (dd, J = 13.9, 8.4 Hz, 1 H), 1.30 (d, J = 6.8 Hz, 3 H). 13C NMR (151 MHz, CDCl3): δ = 165.04, 163.63, 145.81, 134.60, 130.84, 118.48, 115.40, 114.05, 52.77, 52.72, 50.07, 47.83, 44.79, 42.46, 40.14, 14.20. IR (KBr): 3441, 2838, 2960, 2250, 1730, 1607, 1445, 1363, 1254, 1066, 930, 770, 536 cm–1. MS (DART): m/z = 303.1 [M + H]+. HRMS (DART): m/z [M + H]+ calcd for C16H19N2O4: 303.1339; found: 303.1336. Compound 3b: Yield: 26.1 mg (39%); colorless oil; ee: 65%. HPLC (Chiralcel ND(2), 4.6 mm × 250 mm, hexane/isopropanol = 98:2, 0.7 mL/min, 217 nm): t major = 20.96 min, t minor = 23.06 min. [α]D 19 +26.8 (c 1.0, CHCl3). 1H NMR (400 MHz, CDCl3): δ = 6.72 (d, J = 11.1 Hz, 1 H), 5.68 (ddd, J = 16.9, 10.3, 7.7 Hz, 1 H), 5.20–5.07 (m, 2 H), 3.84 (s, 3 H), 3.80 (s, 3 H), 3.27–3.14 (m, 1 H), 2.98 (dt, J = 11.1, 9.5 Hz, 1 H), 2.78 (dd, J = 13.7, 7.0 Hz, 1 H), 2.48–2.39 (m, 2 H), 1.76–1.61 (m, 2 H), 1.61–1.40 (m, 2 H), 0.97 (t, J = 7.1 Hz, 3 H). 13C NMR (101 MHz, CDCl3): δ = 165.15, 163.74, 146.86, 134.26, 130.09, 118.52, 116.10, 114.19, 54.81, 52.84, 52.78, 47.58, 45.37, 43.03, 38.49, 33.57, 20.98, 14.14. IR (KBr): 2955, 2832, 2718, 2321, 1724, 1605, 1437, 1363, 1250, 1069, 1069, 927, 776, 478 cm–1. MS (DART): m/z = 331.2 [M + H]+. HRMS (DART): m/z [M + H]+ calcd for C18H23N2O4: 331.1652; found: 331.1650. Compound 3c: Yield: 32.7 mg (42%); colorless oil; ee: 73%. HPLC (Chiralcel NQ(2), 4.6 mm × 250 mm, hexane/isopropanol = 98:2, 0.7 mL/min, 217 nm): t major = 18.23 min, t minor = 19.85 min. [α]D 19 +23.40 (c 1.0, CHCl3). 1H NMR (400 MHz, CDCl3): δ = 6.72 (d, J = 11.1 Hz, 1 H), 5.68 (ddd, J = 17.1, 10.3, 7.7 Hz, 1 H), 5.21–5.07 (m, 2 H), 3.84 (s, 3 H), 3.79 (s, 3 H), 3.21 (tt, J = 9.1, 7.6 Hz, 1 H), 2.98 (dt, J = 11.1, 9.4 Hz, 1 H), 2.77 (dd, J = 13.7, 7.0 Hz, 1 H), 2.48–2.38 (m, 2 H), 1.74–1.60 (m, 2 H), 1.54–1.38 (m, 2 H), 1.32–1.22 (m, 9 H), 0.90–0.80 (t, 3 H). 13C NMR (101 MHz, CDCl3): δ = 165.11, 163.71, 146.86, 134.25, 130.03, 118.46, 116.10, 114.19, 54.95, 52.80, 52.74, 47.59, 45.35, 43.01, 38.49, 31.74, 31.48, 29.53, 28.94, 27.54, 22.66, 14.14. IR (KBr): 3446, 2932, 2835, 2249, 1726, 1605, 1363, 1251, 1071, 988, 772 cm–1. MS (DART): m/z = 387.2 [M + H]+. HRMS (DART): m/z [M + H]+ calcd for C22H31N2O4: 387.2278; found: 387.2274. Compound 3d: Yield: 33.9 mg (47%); colorless oil; ee: 67%. HPLC (Chiralcel ND(2), 4.6 mm × 250 mm, hexane/isopropanol = 98:2, 0.7 mL/min, 217 nm): t major = 20.93 min, t minor = 22.33 min. [α]D 16 +16.70 (c 1.0, CHCl3). 1H NMR (400 MHz, CDCl3): δ = 6.72 (d, J = 11.1 Hz, 1 H), 5.68 (ddd, J = 17.0, 10.4, 7.7 Hz, 1 H), 5.23–5.03 (m, 2 H), 3.84 (s, 3 H), 3.79 (s, 3 H), 3.26–3.16 (m, 1 H), 2.98 (dt, J = 11.1, 9.4 Hz, 1 H), 2.77 (dd, J = 13.7, 6.9 Hz, 1 H), 2.47–2.36 (m, 2 H), 1.74–1.61 (m, 2 H), 1.57 (dt, J = 13.2, 6.6 Hz, 1 H), 1.44–1.27 (m, 2 H), 0.90 (d, J = 6.6, 0.9 Hz, 6 H). 13C NMR (126 MHz, CDCl3): δ = 165.11, 163.72, 146.77, 134.21, 130.06, 118.49, 116.15, 114.18, 55.14, 52.81, 52.73, 47.68, 45.37, 43.04, 38.52, 36.44, 29.38, 28.14, 22.48, 22.23. IR (KBr): 3443, 2956, 2865, 2250, 1728, 1606, 1443, 1365, 1254, 1129, 1070, 929, 743 cm–1. MS (DART): m/z = 359.2 [M + H]+. HRMS (DART): m/z [M + H]+ calcd for C20H27N2O4: 359.1965; found: 359.1964. Compound 3e: Yield: 37.5 mg (51%); colorless oil; ee: 91%. HPLC (Chiralcel NQ(2), 4.6 mm × 250 mm, hexane/isopropanol = 99:1, 0.7 mL/min, 217 nm): t major = 43.75 min, t minor = 52.15 min. [α]D 19 +28.90 (c 1.0, CHCl3). 1H NMR (500 MHz, CDCl3): δ = 6.72 (d, J = 11.1 Hz, 1 H), 5.68 (ddd, J = 17.0, 10.3, 7.7 Hz, 1 H), 5.48–5.40 (m, 1 H), 5.31–5.22 (m, 1 H), 5.21–5.07 (m, 2 H), 3.84 (s, 3 H), 3.80 (s, 3 H), 3.28–3.17 (m, 1 H), 3.01 (dt, J = 11.1, 9.5 Hz, 1 H), 2.78 (dd, J = 13.7, 6.9 Hz, 1 H), 2.50–2.39 (m, 2 H), 2.30–2.13 (m, 2 H), 2.03 (pd, J = 7.6, 1.7 Hz, 2 H), 1.85–1.66 (m, 2 H), 0.96 (t, J = 7.5 Hz, 3 H). 13C NMR (126 MHz, CDCl3): δ = 165.09, 163.69, 146.75, 134.21, 133.98, 130.15, 126.47, 118.56, 115.98, 114.19, 54.43, 52.81, 52.77, 47.58, 45.45, 43.02, 38.65, 31.61, 25.09, 20.72, 14.31. IR (KBr): 3441, 2959, 2250, 1728, 1606, 1444, 1365, 1252, 1068, 989, 928, 771, 729 cm–1. MS (DART): m/z = 371.2 [M + H]+. HRMS (DART): m/z [M + H]+ calcd for C21H27N2O4: 371.1965; found: 371.1963. Compound 3f: Yield: 30.6 mg (45%); colorless oil; ee: 78%. HPLC (Chiralcel NQ(2), 4.6 mm × 250 mm, hexane/isopropanol = 98:2, 0.7 mL/min, 217 nm): t major = 35.11 min, t minor = 37.16 min. [α]D 19 +16.60 (c 1.0, CHCl3). 1H NMR (500 MHz, CDCl3): δ = 6.77 (d, J = 11.1 Hz, 1 H), 5.67 (ddd, J = 17.0, 10.3, 7.9 Hz, 1 H), 5.22–5.06 (m, 2 H), 3.84 (s, 3 H), 3.79 (s, 3 H), 3.28–3.18 (m, 1 H), 3.03 (dt, J = 11.1, 9.7 Hz, 1 H), 2.79 (dd, J = 13.7, 7.0 Hz, 1 H), 2.72 (dt, J = 9.8, 7.1 Hz, 1 H), 2.48–2.37 (m, 3 H), 2.06 (t, J = 2.6 Hz, 1 H), 1.99 (dq, J = 14.3, 7.2 Hz, 1 H), 1.88 (dq, J = 14.1, 7.0 Hz, 1 H). 13C NMR (126 MHz, CDCl3): δ = 165.08, 163.59, 146.61, 134.09, 130.20, 118.67, 115.45, 114.03, 81.69, 70.88, 53.12, 52.82, 52.79, 46.91, 45.35, 42.91, 38.61, 29.85, 16.64. IR (KBr): 3292, 2835, 2250, 1701, 1617, 1363, 1256, 1078, 931, 785 cm–1. MS (ESI): m/z = 341.1 [M + H]+. HRMS (ESI): m/z [M + H]+ calcd for C19H21N2O4: 341.1496; found: 341.1491.