Unexpected Vinyl Transfer in the Titanium-Mediated Cyclopropanation Reaction

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.

carbene - enols - esters - organometallic reagents - titanium

References and Notes

1 Kulinkovich OG. Chem. Rev.  2003,  103:  2597 

2 Lee J. Cha JK. Tetrahedron Lett.  1996,  37:  3663 

3 Sato F. Urabe H. Okamoto S. Synlett  2000,  753 

4 Urabe H. Mitsui K. Ohta S. Sato F. J. Am. Chem. Soc.  2003,  125:  6074 

5 Laroche C. Bertus P. Szymoniak J. Chem. Commun.  2005,  3030 

6 Lecornué F. Ollivier J. Org. Biomol. Chem.  2003,  1:  3600 

7 Methyl 2-(vinyloxy)benzoate (1a) was prepared from methyl salicylate according to the reported procedure: Blouin M. Frenette R. J. Org. Chem.  2001,  66:  9043 . ¹H NMR (360 MHz, CDCl₃): δ = 7.24-7.30 (m, 2 H), 7.09 (t, J = 7.5 Hz, 1 H), 7.00 (d, J = 8.1 Hz, 1 H), 6.60 (dd, J = 6.1, 13.7 Hz, 1 H), 4.69 (dd, J = 1.7, 13.7 Hz, 1 H), 4.41 (dd, J = 1.7, 6.1, Hz, 1 H), 3.70 (s, 3 H), 3.68 (s, 2 H). ¹³C NMR (75 MHz, CDCl₃): δ = 171.6, 154.5, 148.4, 131.0, 128.5, 124.6, 123.3, 116.7, 94.5, 51.7, 35.3. IR (neat): 2952, 1741, 1643, 1588 cm^-1. MS (EI): m/z (%) = 192 (20) [M⁺], 133 (48), 105 (100), 77 (49). HRMS: m/z calcd for C₁₁H₁₂O₃: 192.0781; found: 192.0773

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%).

10 Ouhamou N. Six Y. Org. Biomol. Chem.  2003,  1:  3007 

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.

12a Kulinkovich O. Eur. J. Org. Chem.  2004,  4517 

12b Casey CP. Stotman NA. J. Am. Chem. Soc.  2004,  126:  1699 

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.