Improved Dimethylsulfoxonium Methylide Cyclopropanation Procedures, Including a Tandem Oxidation Variant

Abstract

A new procedure for the cyclopropanation of α,β-unsaturated carbonyl compounds and related systems is described which employs trimethylsulfoxonium iodide and an organic base in acetonitile to generate dimethylsulfoxonium methylide in situ; in addition, preliminary results are described in which activated alcohols are converted directly into cyclopropyl ketones by a one-pot tandem oxidation-cyclopropanation sequence.

cyclopropanes - cyclopropanations - tandem oxidation procedures - one-pot procedures

References and Notes

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All known products were characterised by NMR spectroscopy and comparison of key data with those published; novel products were fully characterised.

<A NAME="RD33306ST-10">10</A>

Representative Procedure for Cyclopropanation of α,β-Unsaturated Carbonyl Compounds.
To a stirred solution of trimethylsulfoxonium iodide (2b, 0.13 g, 0.6 mmol) and MTBD (6, 0.15 g, 1.0 mmol) in MeCN (4 mL) was added (E)-1,3-chalcone 3a (0.10 g, 0.5 mmol) in MeCN (1 mL). The reaction mixture was heated at 60 °C under nitrogen for 2.5 h. After this time the solvent was removed in vacuo and the residue purified by silica column chromatography (PE-EtOAc, 9:1) to afford cyclopropane 4a (0.095 g, 86%) as a white solid; R _f = 0.38 (PE-EtOAc, 3:1); mp 43-44 °C (lit.¹³ 42.0-43.5 °C), with spectroscopic data consistent with those reported.¹⁴

<A NAME="RD33306ST-11">11</A> (E)-1-Phenyl-3-pyridin-2-ylprop-2-en-1-ol was prepared by NaBH₄/CeCl₃ reduction of (E)-1-phenyl-3-(pyridin-2-yl)propenone, see: Bakó T. Bakó P. Keglevich G. Báthori N. Czugler M. Tatai J. Novák T. Parlagh G. Töke L. Tetrahedron: Asymmetry  2003,  14:  1917 

<A NAME="RD33306ST-12">12</A>

Representative Procedure for Tandem Oxidation-Cyclopropanation.
To a stirred solution of trimethylsulfoxonium iodide (0.13 g, 0.6 mmol) activated MnO₂ (Aldrich 21764-6, 0.44 g, 5.0 mmol) and MTBD (6, 0.15 g, 1.0 mmol) in MeCN (4 mL) was added (E)-1-phenyl-3-(pyridin-2-yl)prop-2-en-1-ol (0.10 g, 0.50 mmol) in MeCN (1 mL). The reaction mixture was heated at 60 °C under nitrogen for 2 h. After this time the reaction mixture was filtered through Celite^® and the residue washed with Et₂O. The solvent was removed in vacuo and the residue was purified by silica column chromatography (PE-EtOAc, 6:1) to afford cyclopropane 4b as a clear oil (0.078 g, 69%); R _f = 0.23 (PE-EtOAc, 3:1). IR (neat): ν_max = 1667, 1504, 1568, 1474 1339, 1222 cm^-1. ¹H NMR (400 MHz, CDCl₃): δ = 1.78-1.85 (2 H, m, CHH and CHH overlapping), 2.73-2.78 (1 H, ddd, J = 4.0, 6.0, 10.0 Hz, CH), 3.29-3.32 (1 H, ddd, J = 4.0, 5.5, 9.0 Hz, CH), 7.93 (1 H, ddd, 1.0, 5.0, 12.0 Hz, ArH), 7.26-7.29 (1 H, m, ArH), 7.44-7.48 (2 H, m, ArH), 7.54-7.60 (2 H, m, ArH), 8.03-8.05 (2 H, m, ArH), 8.49-8.51 (1 H, m, ArH). ¹³C NMR (100 MHz, CDCl₃): δ = 19.8 (CH₂), 28.4 (CH), 29.9 (CH), 121.4 (CH), 122.8 (CH), 128.3 (CH), 128.5 (CH), 133.0 (CH), 136.2 (CH), 137.7 (C) 149.6 (CH), 159.4 (C), 199.2 (CO). MS (CI): m/z (%) = 224 (100) [MH⁺], 206 (10), 118 (10), 105 (10). HRMS (CI): m/z calcd for C₁₅H₁₄NO: 224.1075 (2.1 ppm error); found: 224.107078 [MH⁺].

<A NAME="RD33306ST-13">13</A> Yanovskaya LA. Dombrovsky VA. Chizhov OS. Zolotarev BM. Subbotin OA. Kucherov VF. Tetrahedron  1972,  28:  1565 

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