Subscribe to RSS
Download PDF
DOI: 10.1055/s-2007-991092
Unexpected Vinyl Transfer in the Titanium-Mediated Cyclopropanation Reaction
Publication History
Publication Date:
12 October 2007 (online)
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
- 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 - 10
Ouhamou N.Six Y. Org. Biomol. Chem. 2003, 1: 3007 - 12a
Kulinkovich O. Eur. J. Org. Chem. 2004, 4517 - 12b
Casey CP.Stotman NA. J. Am. Chem. Soc. 2004, 126: 1699
References and Notes
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.
9Procedure 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%).
11After 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.
13The 2H NMR spectrum of the compound measured in CHCl3 solution showed unambiguously a strong signal of deuterium in the range of cyclopropanic protons.