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Multicatalytic Approach to One-Pot Stereoselective Synthesis of Secondary Benzylic Alcohols

Alessandra Casnati, Dawid Lichosyt, Bruno Lainer, Lukas Veth and Paweł Dydio*

*University of Strasbourg, CNRS, ISIS UMR 7006, 8 Alle Gaspard Monge, 67000 Strasbourg, France, Email: dydiounistra.fr

A. Casnati, D. Lichosyt, B. Lainer, L. Veth, P. Dydio, Org. Lett., 2021, 23, 3502-3506.

DOI: 10.1021/acs.orglett.1c00939


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Abstract

Multicatalytic protocols convert alkenes, unsaturated aliphatic alcohols, and aryl boronic acids into secondary benzylic alcohols with high stereoselectivities under sequential catalysis that integrates alkene cross-metathesis, isomerization, and nucleophilic addition.

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ligand

Multi-catalytic enantioselective conversion of alkenes to secondary benzylic alcohols - see article for details



General procedure: enantioselective isomerization-arylation of linear allylic alcohols

In a nitrogen-filled glovebox, an oven-dried 4 mL screw-cap scintillation vial equipped with an octagonal stir bar (2 mm x 5 mm) was charged with a stock solution of [Ir(cod)Cl]2 (0.21 mg, 1.25 x 10-4 equiv, 3.1 x 10-4 mmol) in anhydrous toluene (1 mL). Then, the appropriate allylic alcohol (1.0 equiv, 0.25 mmol), K2CO3 (35 mg, 1.0 equiv, 0.25 mmol), and degassed H2O (150 μL) were added. Next, the vial was sealed with a Teflon-lined screw cap, placed in a preheated aluminum block at 30 C, and allowed to stir at 800 rpm for 2 h. After that, the vial was removed from the heating block and let to cool to room temperature. (In the meantime, a stock solution of Ru-1 was prepared by allowing to stir a mixture of [Ru(p-cymene)Cl2]2 (4.6 mg, 0.030 equiv, 7.5 x 10-3 mmol) and Me-BIPAM (13 mg, 0.066 equiv, 1.65 x 10-2 mmol) in toluene (1 mL) for 1 h at rt). Then, the solution of Ru-1 and arylboronic acid (3.0 equiv, 0.75 mmol) were added to the reaction mixture. The vial was re-sealed with a Teflon-lined screw cap, removed from the glovebox, placed in a preheated aluminum block at 60 C, and allowed to stir at 800 rpm for 6 h. Next, the vial was removed from the heating block and let to cool to room temperature. The volatiles were removed under reduced pressure. The residue was subjected to column chromatography on silica gel (12 g), conducted with the aid of a Combiflash instrument, using a mixture of petroleum ether and ethyl acetate (usually with gradient of 100:0 - 80:20) as the eluent. Fractions containing the pure product (judged by TLC and/or GC analyses) were combined, and the solvent was evaporated, yielding the target product.


Key Words

benzylic alcohols


ID: J54-Y2021