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Synlett 2006(13): 2114-2118  
DOI: 10.1055/s-2006-948187
LETTER
© Georg Thieme Verlag Stuttgart · New York

Synthesis of 4,5-trans-Substituted Cyclohexenones

E. Peter Kündig*, Manisankar Sau, Alejandro Perez-Luna
Department of Organic Chemistry, University of Geneva, 30 Quai Ernest Ansermet, 1211 Geneva 4, Switzerland
Fax: +41(22)3793215; e-Mail: Peter.Kundig@chiorg.unige.ch;
Further Information

Publication History

Received 8 May 2006
Publication Date:
09 August 2006 (online)

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Abstract

Dearomatization of anisole chromiumtricarbonyl by sequential regio- and diastereoselective addition of a C-nucleophile and a C-electrophile is problematic because of competitive ortho-deprotonation. A solution is offered by carrying out the reaction ­sequence with the bis ortho silylated complex. Decomplexation and acid work-up affords 4,5-trans-disubstituted cyclohexenones.

Key words

cyclohexenones - dearomatization - [Cr(arene)(CO)3] complexes - nucleophilic/electrophilic addition - C-C bond formation

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A React-IR spectrometer (Mettler Toledo, 1000 Optics Module) equipped with a silicon window was used for these measurements.

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Typical Experimental Procedures.
Synthesis of Compound 7c.
A freshly prepared solution of 2-lithio-1,3-dithiane [15] (1.25 mmol) in THF (5 mL) was added to a solution of [Cr(CO)3 (di-o-TMS-anisole)] (6, 0.39 g, 1.0 mmol) in THF (5 mL) at -78 °C. The magnetically stirred reaction mixture was allowed to warm to -55 °C over a period of 1 h and stirred at that temperature for another 1 h. The yellow-brown solution was recooled to -78 °C; DMPU (0.90 mL, 10.0 mmol) and allyl bromide (1.1 mL, 10.0 mmol) were added sequentially. Stirring was continued while the reaction mixture was allowed to warm to r.t. All volatiles were removed in vacuo and the residue was redissolved in THF (10 mL). Then, 2 N HCl (5 mL) was added and after stirring for 30 min THF was removed in vacuo and the product was extracted with Et2O. The organic layer was washed with sat. aq NaHCO3, brine and dried over MgSO4. Column purification of the crude product using silica, cyclohexane-EtOAc (9:1) gave 7c (0.167 g, 52%). IR (neat): 2901 (m), 1657 (s), 1595 (w) cm-1. 1H NMR (300 MHz, CDCl3): δ = 6.98 (d, J = 5.0 Hz, 1 H), 5.79-5.77 (m, 1 H), 5.18-5.14 (d, J = 8.0 Hz, 2 H), 4.34 (d, J = 9.0 Hz, 1 H), 2.90-2.87 (m, 4 H), 2.65-2.55 (m, 1 H), 2.47-2.35 (m, 2 H), 2.26-2.31 (m, 2 H), 2.09-2.14 (m, 2 H), 1.84-1.87 (m, 1 H), 0.13 (s, 9 H). 13C NMR (75 MHz, CDCl3): δ = 201.2, 160.4, 141.5, 134.9, 118.2, 51.6, 43.5, 39.7, 38.4, 36.5, 31.4, 31.1, 26.2, -1.3. HRMS: m/z calcd for C16H26OSiS2: 326.1194; found: 326.1218.
Synthesis of Compound 9b.
In a pressure-resistant Schlenk tube, freshly prepared 3-(trimethylsilyl)propargyl lithium [7] (3 mmol) in THF (5 mL) was added to complex (6, 0.39 g, 1.0 mmol) in THF (1.5 mL) at -78 °C. After stirring for 1 h at -78 °C, MeI (1.0 ml, 10 mmol) was added and the N2 atmosphere was exchanged for CO (3 bar). The reaction mixture was allowed to warm to r.t. Volatiles were removed in vacuo and the residue was taken up in THF (10 mL). Then, 2 N HCl (5 mL) was added and after stirring for 30 min THF was removed in vacuo and the aqueous layer was extracted with CHCl3 (10 mL). After stirring for 30 min at ambient temperature the two phases were separated. The aqueous phase was washed with CH2Cl2 and the combined organic portions were washed with H2O, brine and dried over Na2SO4. Column purification of the crude product using silica, pentane-Et2O (8:2) gave 9b (0.106 g, 41%). IR (neat): 2957 (w), 1708 (s), 1664 (s), 1588 (w) cm-1. 1H NMR (400 MHz, CDCl3): δ = 6.97 (s, 1 H), 2.63-2.77 (m, 2 H), 2.23-2.36 (m, 3 H), 2.20 (s, 3 H), 1.46 (s, 3 H), 0.15 (s, 9 H), 0.16 (s, 9 H). 13C NMR (100 MHz, CDCl3): δ = 207.7, 200.8, 158.2, 142.0, 104.1, 87.1, 53.4, 42.9, 39.2, 28.1, 23.9, 21.8, 0.04, -1.4. HRMS: m/z calcd for C18H31O2Si2 [M + H]+: 335.1872; found: 335.1865.