[3+2] Annulation of Donor–Acceptor Cyclopropanes with Vinyl Azides

Abstract

A Sc(OTf)₃-catalyzed reaction of vinyl azides with donor–acceptor cyclopropanes affords highly functionalized azidocyclopentanes in a diastereoselective fashion. The resulting azidocyclopentanes could be transformed into various cyclic scaffolds.

Key words

vinyl azides - donor–acceptor cyclopropanes - cyclopentanes - [3+2] annulation - Lewis acids

• References and Notes


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The reactions of vinyl azide 1a with optically active cyclopropane (S)-2a (99% ee) gave [3+2]-annulation products in up to 93% ee, suggesting that the first C–C bond-forming process between 1a and 2a takes place predominantly in an S_N2-type manner (See the Supporting Information for the details). For relevant reports, see:
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• 13 The stereochemistry of the major isomer of 6aa (CCDC 1519381), 7aa (CCDC 1519383), 9aa (CCDC 1519478), and 9ca (CCDC 1519384) were secured by X-ray crystallographic analysis. The data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/getstructures.
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• 17 Procedure for the Synthesis of Cyclopentane 9aa To a stirred solution of cyclopropane 5a (218 mg, 0.493 mmol) and vinyl azide 1a (144 mg, 0.993 mmol) in CH₂Cl₂ (0.8 mL) and MeNO₂ (0.2 mL) was added Sc(OTf)₃ (37.6 mg, 0.0764 mmol) at 0 °C under an Ar atmosphere. The solution was stirred at 0 °C for 24 h and then quenched with sat. aq NaHCO₃. The mixture was extracted with CH₂Cl₂, and the combined extracts were washed with brine, dried over MgSO₄, and concentrated in vacuo. The resulting crude material was purified by flash column chromatography (hexane–Et₂O, 100:1 to 90:1) to yield cyclopentane 9aa (275 mg, 0.468 mmol) in 95% yield as a mixture of diastereomer (major/minor = 88:12, which was determined by ¹H NMR analysis). The major isomer could be recrystallized from CH₂Cl₂–hexane as a colorless crystal. Bis(2,6-dimethylbenzyl) (2S*,4R*)-2-azido-2,4-diphenylcyclopentane-1,1-dicarboxylate (9aa major) Mp 100–101 °C. ¹H NMR (400 MHz, CDCl₃): δ = 2.04 (6 H, s), 2.16 (6 H, s), 2.52 (1 H, dd, J = 6.8, 14.4 Hz), 2.79–2.91 (2 H, m), 3.03 (1 H, dd, J = 10.4, 14.4 Hz), 3.57–3.66 (1 H, m), 4.94 (1 H, d, J = 12.0 Hz), 5.08–5.14 (2 H, m), 5.29 (1 H, d, J = 12.0 Hz), 6.93 (2 H, d, J = 7.6 Hz), 6.99 (2 H, d, J = 7.6 Hz), 7.07–7.22 (6 H, m), 7.27–7.31 (4 H, m), 7.37 (2 H, d, J = 7.2 Hz). ¹³C NMR (100 MHz, CDCl₃): δ = 19.2, 19.3, 39.9, 43.2, 47.3, 62.2, 62.4, 69.8, 78.3, 126.4, 127.3, 127.4, 127.9, 128.09, 128.12 (overlapped), 128.2, 128.7, 128.8, 130.7, 131.1, 138.2, 138.4, 138.5, 144.4, 169.4, 170.1. ESI-HRMS: m/z calcd for C₃₇H₃₈NO₄ [M – N₂ + H]⁺: 560.2801; found: 560.2806.