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Synlett 2011(19): 2799-2802  
DOI: 10.1055/s-0031-1289554
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

BF3×OEt2-Catalyzed Reaction of Donor-Acceptor Cyclobutanes with
Terminal Alkynes: Single-Step Access to 2,3-Dihydrooxepines

Ben P. Machin, Brian L. Pagenkopf*
Department of Chemistry, The University of Western Ontario, London, ON, N6A 5B7, Canada
Fax: +1(519)6613022; e-Mail: bpagenko@uwo.ca;
Further Information

Publication History

Received 5 August 2011
Publication Date:
25 October 2011 (online)

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Abstract

In the presence of BF3˙OEt2 cyclobutane-1,1-diesters undergo a reaction with terminal alkynes to quickly access dihydro­oxepines.

Key words

donor-acceptor cyclobutanes - oxepine - alkynes - Lewis acid - [4+2] cycloaddition

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Lewis acids screened included: Yb(OTf)3, Sc(OTf)3, Zn(OTf)2, ZnBr2, MgCl2, MgBr2, InBr3, TiCl4, Cu(OTf)2, and BiCl3 at temperatures ranging from 0 ˚C to refluxing and at ambient pressure to 1103 bar in a high-pressure reactor.

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Representative Procedure for the Preparation of 4a
To a solution of cyclobutane 1 (105 mg, 0.43 mmol, 1 equiv) and phenylacetylene (50 µL, 0.49 mmol, 1.1 equiv) in DCE (6 mL, 0.1 M) was added BF3˙OEt2 (55 µL, 0.43 mmol, 1 equiv). A reflux condenser was quickly attached, and the flask was placed in a preheated oil bath. After complete consumption of the cyclobutane as indicated by TLC (15 min), the reaction mixture was poured into a separatory funnel containing a half-saturated solution of NaHCO3. The aqueous phase was extracted with CH2Cl2 (3 × 5 mL), and the combined organic extracts were washed with brine, dried over MgSO4, filtered through a pad of Celite, and concentrated in vacuo. The crude reaction product was purified by flash column chromatography (hexanes-EtOAc = 4:1) to provide the corresponding addition-rearrangement product 4a (79 mg, 53%) as a yellow oil. R f = 0.49 (hexanes-EtOAc = 4:1). ¹H NMR (600 MHz, CDCl3): δ = 7.56-7.55 (m, 2 H), 7.31-7.29 (m, 2 H), 7.27-7.25 (m, 1 H), 5.72 (d, J = 8.8 Hz, 1 H), 5.53 (d, J = 8.8 Hz, 1 H), 4.32 (app t, J = 4.1 Hz, 2 H), 4.19 (q, J = 4.0 Hz, 4 H), 3.55 (t, J = 7.9 Hz, 1 H), 2.73 (d, J = 8.2 Hz, 2 H), 2.62 (app t, J = 4.1 Hz, 2 H), 1.25 (t, J = 7.0 Hz, 6 H). ¹³C NMR (100 MHz, CDCl3): δ = 169.0(2), 157.4, 137.5, 137.0, 128.3 (2), 128.1, 125.3 (2), 122.1, 99.1, 69.0, 61.5 (2), 51.0, 38.8, 37.1, 14.1 (2). HRMS: m/z calcd for C20H24O5: 344.1624; found: 344.1617.