Highly Efficient And Regioselective Addition Of Grignard Reagents To 1,3-Diones Promoted By I-PrMgCl

Efficient synthesis of the tertiary alcohol is one of the most rapidly developing fields in organic chemistry.In chemical synthesis,chiral or racemic tertiary alcohols are important moieties of pharmaceutical intermediates,natural products and biologically active substances.Addition of organometallic reagents to ketones is one of the most direct and convenient method to provide tertiary alcohols.However,due to their strong alkalinity,these organic reagents often lead to the enolization of the substrates(i.e.ketones)or the generation of secondary alcohols by the transfer of beta-H and/then competitive reduction.It is due to the lack of good nucleophilic reagent and strong alkalinity of the organometallic reagent,there is great restriction to synthesize tertiary alcohols from ketones.Moreover,the synthesis of tertiary alcohols is always catalyzed by metal,even stoichiometrically,and the non-metal-catalyzed process of Grignard reagent to ketones to synthesize tertiary alcohols has always given very low yield.In this work,we found a cheap and readily available isopropyl magnesium chloride(iPrMgCl)can promote the addition of Grignard reagents to diones,and most adducts can be obtained in good to high yield.Furthermore,there is broad scope of both the Grignard reagents and substrates.The transformation of ketones can 'be carried out efficiently without any additive but only a simple Grignard reagent,and only the single carbonyl adduct instead of the dicarbonyl adduct can be obtained with good selectivity.Therefore,the reaction we developed can be performed in mild conditions,with low cost and easy operation.The range of the substrates is relatively wide,which has a definite implication for the research of the addition of the Grignard reagent to carbonyl compounds.