Catalytic Enantioselective Arylation of Aldehydes by Using Functionalized Grignard Reagents Generated from Aryl Bromides

Abstract

An efficient catalytic method has been developed for the enantioselective synthesis of functionalized diarylmethanols starting from aryl bromides and aldehydes. In the presence of (R)-3-(3,5-diphenylphenyl)BINOL (2 mol%) and titanium tetraisopropoxide, functionalized aryl Grignard reagents (FGArMgCl; FG = 3-F₃C, 4-F₃C, 3-Br, 3-CN, 4-CN), prepared in situ by treatment of the bromides with i-PrMgCl˙LiCl, undergo addition to aldehydes to give the corresponding functionalized diarylmethanols in high enantioselectivities.

aldehydes - arylation - asymmetric catalysis - magnesium - titanium

References and Notes

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<A NAME="RU07011ST-11">11</A>

The mixed titanium reagent of 2-MeOC₆H₄MgBr and Ti(Oi-Pr)₄ also underwent nonenantioselective reaction to an aldehyde.^5c Intramolecular coordination of the ortho substituents to the titanium center might be responsible for the poor selectivities.