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Synlett 2007(18): 2827-2828  
DOI: 10.1055/s-2007-991092
LETTER
© Georg Thieme Verlag Stuttgart · New York

Unexpected Vinyl Transfer in the Titanium-Mediated Cyclopropanation Reaction

Jean-Marc Garnier, Frédéric Lecornué, Florence Charnay-Pouget, Jean Ollivier*
Laboratoire de Synthèse Organique et de Méthodologie, UMR 8182, Institut de Chimie Moléculaire et des Matériaux d’Orsay, Université Paris-Sud XI, 91405 Orsay, France
Fax: +33(1)69156278; e-Mail: jollivie@icmo.u-psud.fr;
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Publication History

Received 6 September 2007
Publication Date:
12 October 2007 (online)

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Abstract

Simple cyclopropanols are obtained on addition of ethylmagnesium halides to esters in the presence of titanium isoprop­oxide. Alternatively, we have found that they may also be prepared in moderate to good yields through unexpected vinyl transfer from vinyl ethers via a titanium-promoted inter- or intramolecular reaction. On the basis of deuterium labeling experiments, a mechanism has been proposed.

Key words

carbene - enols - esters - organometallic reagents - titanium

    References and Notes

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8

2-[(1-Hydroxycyclopropyl)methyl]phenol (4): 1H NMR (250 MHz, CDCl3): δ = 7.95 (br s, 1 H), 7.16 (td, J = 1.7, 8.5 Hz, 1 H), 7.02 (dd, J = 1.7, 7.2 Hz, 1 H), 6.84-6.93 (m, 2 H), 3.81 (br s, 1 H), 2.90 (s, 2 H), 0.73-0.84 (m, 2 H), 0.62-0.73 (m, 2 H). 13C NMR (63 MHz, CDCl3): δ = 154.6, 131.5, 128.1, 125.7, 120.3, 116.5, 57.9, 40.1, 13.3. IR (neat): 3307, 2932, 1610, 1585 cm-1. MS (EI): m/z (%) = 164 (67) [M+], 131 (28), 108 (27), 107 (100), 57 (71). HRMS: m/z calcd for C10H1202: 164.0834; found: 164.0832.

9

Procedure for the Intermolecular Cyclopropanation: To a solution of methyl {2-[(trimethylsilyl)oxy]phenyl}acetate (5; 420 mg, 2 mmol), ethoxyethylene (0.96 mL, 10 mmol, 5 equiv) and titanium isopropoxide (0.6 mL, 2 mmol, 1 equiv) in anhyd THF (7 mL) was added dropwise at 20 °C under argon over a period of 4 h a solution of cyclohexylmagne-sium chloride (7 mL, 10 mmol, 5 equiv, 1.43 M in Et2O). After stirring for an additional hour at r.t., the solution was cooled to 0 °C and Et2O (20 mL) was added. The mixture was quenched by addition of a sat. NH4Cl solution (35 mL) and was stirred overnight at r.t. The organic phase was separated, washed with brine and dried over Na2SO4. After evaporation of the solvents, the residue was purified by flash chromatography (PE-Et2O, 93:7) to furnish the cyclopropane 4 (78 mg, 24%).

11

After distillation, the 1H NMR spectrum was taken in CDCl3 solution, and a 70% incorporation of deuterium was measured from the integration of the septuplet at δ = 4.51 ppm in comparison with a similar sample of Ti(Oi-Pr)4.

13

The 2H NMR spectrum of the compound measured in CHCl3 solution showed unambiguously a strong signal of deuterium in the range of cyclopropanic protons.