Regulation And Re-regulation Of Activity Of The Grignard Reagents: Highly Catalytic Asymmetric Arylation Of Aldehydes With Aryl Grignard Reagents

Enantioenriched diarylmethanols are important constituents of many biologically active compounds. As a result, the catalytic asymmetric arylation of aldehydes has generated an enormous amount of attention. However, catalytic asymmetric addition of organozinc reagents and organoboron reagents to aldehydes was the predominant method so far.Aryl Grignard reagents are easy-operation and low-cost, but due to the high activity, they were rarely used as addition reagent in the catalytic asymmetric reactions. However, the deactive aryl Grignard reagents by BDMAEE lead to low enantioselectivity because of the excessive low activity.And then, we added AICl3 as the activity-enhanced additive to improve the activity of deactivated aryl Grignard reagents by BDMAEE. Fortunately, AICl3 did the work and both of yields and ee of the products were extremely high, we even obtained the highest ee in compararation with those reported results in most cases.(ee>99%, yield up to 98%)The machenism of the system was also speculated. AICl3 facilitates the aryl group shifting between three different metal centers:magnesium-aluminum-titanium, then to aldehydes. BDMAEE as an inhibitor of magnesium salts suppressed the racemic background reaction which leads to a low ee.In addition, low-cost reagents, easy operation, complete mild condition, and feasible scale-up, an effective combination of all these advantageous features just in this single unique protocol will help it find its broad application or industrial interest.