Direct Asymmetric Addition Of Vinyl Grignard Reagents To Aldehydes Catalyzed By 3,3'-Dimethyl-BINOL-Mg Ate-complex

Grignard reagents are among the most commonly used and important organic metal reagents. Addition of Grignard reagents to aldehydes is one of most important methods for forming Carbon-Carbon bonds in organic synthesis. Catalytic asymmetric addition of Grignard reagents to aldehydes is an important method for forming chiral sec-alcohols. However, catalytic asymmetric addition of Grignard reagents to aldehydes is still difficulty and challenging because of the high reactivity of Grignard reagents.At present, the research of catalytic asymmetric addition of Grignard reagents to aldehydes have two methods. One was using chiral amine to complete catalytic asymmetric addition of Grignard reagents to aldehydes. Another was transforming Grignard reagent into other low reactivity organometal reagents such as R2Zn,R3Al and R-Ti, then catalytic asymmetric addition to aldehydes. Those two methods are difficult to operate, expensive and less atom economy, so realizing the direct asymmetric addition of Grignard reagents to aldehydes at mild conditions has very important value.Our group found that the complex of BDMAEE (bis [2-(N, N'-dimethylamino) ethyl] ether) could partly deactivate the reactivity of Grignard reagents. The deactivated Grignard reagents could asymmetrically add to aldehydes at mild conditions and achieve very good results.Because the particularity of vinyl Grignard reagents, related reports of asymmetric addition to aldehydes are scarce. That reports are transforming the vinyl Grignard reagents to vinyl zinc and vinyl bismuth, then asymmetrically add to aldehydes. Those methods are difficult to operate and less atom economy. At present, successful report of the direct asymmetric addition of vinyl Grignard reagent to aldehydes has not been reported by our knowledge. We used MTBE as a solvent and BINOL and its derivative as chiral ligand, deactivated vinyl Grignard reagents using BDMAEE or its analogues. The direct reaction of vinyl Grignard reagent and benzaldehyde reached enantiomeric excess up to 61%.