Tandem Diels–Alder [4+2] Cycloadditions and Intramolecular [3+2] Cross-Cycloadditions of Dienylcyclopropane 1,1-Diesters

Abstract

A novel tandem reaction by combination of Diels–Alder [4+2] cycloaddition and [3+2] IMCC (intramolecular cross-cyclo­addition) of dienylcyclopropane 1,1-diesters has been successfully developed. In this reaction, three new rings and four new stereocenters were generated in one-pot. This supplies a strategy for rapid construction of 6,6- and 6,7-fused carbocyclic skeletons which are common cores in many biologically important natural products.

Key words

annulation - cyclopropane - cycloaddition - Diels–Alder reaction - domino reaction - natural products

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• 6 Other Lewis acids could also promote the [3+2] IMCC, among which Sc(OTf)₃ behaved as the optimal one.
• 7 CCDC 875497 (4a) contains the supplementary crystallographic data for this paper. These data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk /data_request/cif.
• 8 When dienylcyclopropane 1,1-diesters (1a or 1e) as a mixture of Z/E-isomers reacted with dienophiles, the ratio of Z/E-isomers increased as the reaction proceeded, which indicated that the E-isomers showed better reactivity than the Z-isomers.
• 9 Typical Procedure A; Two-Stage Process: In a 25-mL tube were added dienylcyclopropane 1,1-diester 1a (88 mg, 0.39 mmol), MVK (2b; 0.5 mL, 7.86 mmol), p-hydroquinone (10 mg, 0.091 mmol) and toluene (3 mL) under N₂. The tube was sealed and the reaction was carried out in an oil bath (120 °C). After complete consumption of 1a (monitored by TLC), the mixture was concentrated. Sc(OTf)₃ (19 mg, 0.0384 mmol, 20 mol%) and DCE (4 mL) were then added, and the mixture was stirred at r.t. under an atmosphere of nitrogen until the reaction was complete (monitored by TLC). The solvent was evaporated under vacuum and the residue was purified by silica gel column chromatography to afford 4b (35% yield based on 1a, dr = 5:1). ¹H NMR (400 MHz, CDCl₃): δ = 5.66 (dd, J = 7.5, 2.1 Hz, 1 H), 5.45–5.54 (m, 1 H), 4.47 (d, J = 7.4 Hz, 1 H), 3.78 (s, 3 H), 3.75 (s, 3 H), 2.79 (dd, J = 13.5, 7.9 Hz, 1 H), 2.45 (d, J = 13.5 Hz, 1 H), 2.12–2.21 (m, 1 H), 2.11–2.01 (m, 3 H), 1.77 (d, J = 1.5 Hz, 1 H), 1.57–1.68 (m, 2 H), 1.41–1.50 (m, 1 H), 1.34 (s, 3 H). ¹³C NMR (101 MHz, CDCl₃): δ = 172.51, 170.49, 130.05, 126.77, 86.68, 74.79, 68.14, 52.73, 52.61, 39.48, 38.09, 34.56, 29.06, 25.90, 20.10, 19.15. HRMS (ESI): m/z [M + Na]⁺ calcd for C₁₆H₂₂O₅: 317.1359; found: 317.1360.
• 10 Typical Procedure B; Domino Process: In a 25-mL tube were added dienylcyclopropane 1,1-diester 1f (102 mg, 0.39 mmol), MVK (2b; 0.5 mL, 7.86 mmol), p-hydroquinone (10 mg, 0.091 mmol) and toluene (3 mL) in N₂. The tube was sealed and the reaction was carried out in an oil bath (120 °C). After completion of the reaction (monitored by TLC), the solvent was evaporated under vacuum and the residue was purified by silica gel column chromatography to afford 4i (51% based on 1f, dr = 20:1). ¹H NMR (400 MHz, CDCl₃): δ = 7.28–7.35 (m, 4 H), 7.23 (dd, J = 5.2, 3.3 Hz, 1 H), 6.01 (d, J = 3.4 Hz, 1 H), 4.34–4.39 (m, 1 H), 3.80 (s, 3 H), 3.74 (s, 3 H), 2.39–2.56 (m, 4 H), 2.16–2.25 (m, 2 H), 1.65–1.79 (m, 2 H), 1.60 (s, 3 H). ¹³C NMR (101 MHz, CDCl₃): δ = 170.90, 140.27, 128.22, 126.78, 125.09, 124.93, 90.08, 81.41, 66.27, 52.64, 44.60, 41.70, 41.03, 25.13, 24.13, 14.72. HRMS (ESI): m/z [M + H]⁺ calcd for C₂₁H₂₄O₅: 357.1697; found: 357.1702.