Highly Enantioselective Arylethylation Of Aldehydes With Deactivated Grignard Reagents Catalyzed By (S)-BINOL-Ti Complex

Grignard reagents are among the most important and traditional organometal reagents.Asymmetric addition of Grignard reagents to aldehydes is one of the most valuable carbon-carbon formation reactions,which can produce optically active sec-alcohols.However,this reaction has still been rather challenging and difficult to operate because of high reactivity of Grignard reagents.Until recently,two groups have showed the devclopments and prospects of this reaction.One was the transformation of full Grignard reagents into R₂Zn and then addition to aldehydes. Another was completely transformation of RMgBr into R-Ti(OⁱPr)₃ with large excess of Ti(OⁱPr)₄ and successive reaction with aldehydes.As those methods are costly,difficult to operate and less atom economy,our group have successfully demonstrated that the high reactive Grignard reagents could be partly deactivated by the additives BDMAEE(bis[2-(N,N'-dimethylamino)ethyl]ether) and Ti(OⁱPr)₄.The deactivated reagents could be smoothly added to aldehydes under mild conditions and achieved the highest enantioselectivity up to date.Addition of the Arylethyl Grignard reagents(ArCH₂CH₂MgBr) to aldehydes has ever been used to synthesize biologically interesting natural compounds.But it has not been disclosed that an asymmetric transformation was used to synthesize these chiral second alcohols under chiral catalysts.Using BDMAEE and Ti(Oⁱpr)₄ as effective deactivators,thc Arylethylmagnesium bromide highly enantioselectively react with aldehyes catalyzed by the complex of(S)-BINOL and Ti(Oⁱpr)₄ for the first time herein.Excellent enantioselectivities were obtained under very mild conditions for aliphatic and aromatic aldehydes,yield up to 89%,ee up to 97%.