Synlett 2016; 27(10): 1541-1546
DOI: 10.1055/s-0035-1561401
letter
© Georg Thieme Verlag Stuttgart · New York

Al(OTf)3: An Efficient Lewis Acid Additive for Domino Addition–Elimination of Grignard Reagents to Activated Ketones

Tanya Pieterse
Department of Chemistry, University of the Free State, PO Box 339, Bloemfontein, 9300, South Africa   Email: bezuidbc@ufs.ac.za
,
Melanie Visser
Department of Chemistry, University of the Free State, PO Box 339, Bloemfontein, 9300, South Africa   Email: bezuidbc@ufs.ac.za
,
Charlene Marais
Department of Chemistry, University of the Free State, PO Box 339, Bloemfontein, 9300, South Africa   Email: bezuidbc@ufs.ac.za
,
Barend C. B. Bezuidenhoudt*
Department of Chemistry, University of the Free State, PO Box 339, Bloemfontein, 9300, South Africa   Email: bezuidbc@ufs.ac.za
› Author Affiliations
Further Information

Publication History

Received: 11 November 2015

Accepted after revision: 05 February 2016

Publication Date:
04 March 2016 (online)


Abstract

It has been demonstrated that aluminium triflate in either stoichiometric or catalytic quantities facilitates the addition–elimination of Grignard reagents to electron-rich ketones, such as methoxy substituted acetophenones, propiophenone and chromanone in a one-pot process, and that it has an enhancing effect on the addition of these reagents to the ketones. It has also been found that the reactions are highly stereoselective towards one regioisomer of the alkene in the case of oxygenated aryl-alkyl substituted substrates, but not when the elimination originates from a double benzylic alcohol intermediate.

Supporting Information

 
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  • 17 General Procedure: A solution of carbonyl compound in anhydrous CH2Cl2 (2–5 mL) was cooled to –30 °C. Al(OTf)3 (1.0 equiv) was added and the reaction mixture was stirred at –30 °C for 30 min under Ar. Grignard reagent (3.0 M in Et2O, 2.0 equiv) was subsequently added and the reaction mixture was allowed to warm to r.t. while being stirred. Once the reaction was deemed complete (TLC analysis), the reaction mixture was neutralised with aq NH4Cl and the product was extracted into EtOAc (3 × 50 mL). The organic layer was dried over Na2SO4, filtered and evaporated under reduced pressure. Purification by prep. TLC gave the corresponding alkenes or alcohols (Table 1). (Z)-2,4-Dimethoxy-α,β-dimethylstyrene (16): The general procedure with 2′,4′-dimethoxyacetophenone (3; 0.217 g, 1.22 mmol) and Al(OTf)3 (0.531 g, 1.12 mmol, 0.9 equiv) in CH2Cl2 (5 mL) and ethylmagnesium bromide (3 M, 0.7 mL, 1.7 equiv) yielded 16 (0.107 g, 46%) as a colourless oil. Rf = 0.61 (hexane–acetone, 8:2). 1H NMR (600 MHz, CDCl3): δ = 7.06 (d, J = 8.2 Hz, 1 H, H-6), 6.48 (d, J = 2.4 Hz, 1 H, H-3), 6.46 (dd, J = 8.2, 2.4 Hz, 1 H, H-5), 5.55 (qq, J = 6.7, 1.3 Hz, 1 H, H-β), 3.83 (s, 6 H, OMe), 2.00–1.98 (m, 3 H, α-CH 3 ), 1.80–1.78 (m, 3 H, β-CH3). 13C NMR (151 MHz, CDCl3): δ = 159.8 (C-2/4), 157.6 (C-2/4), 135.3 (C-1/α), 130.0 (C-6), 128.1 (C-1/α), 123.5 (C-β), 103.9 (C-5), 98.7 (C-3), 55.4 (-OMe), 17.0 (α-CH3), 14.0 (β-CH3). MS (EI, 70 eV): m/z (%) = 192.1 (100) [M]+. HRMS (AP+): m/z = 193.1233 [MH]+.
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