Aerobic/Room-Temperature-Compatible s-Block Organometallic Chemistry in Neat Conditions: A Missing Synthetic Tool for the Selective Conversion of Nitriles into Asymmetric Alcohols

Highly-efficient and selective one-pot/two-step modular double addition of different highly polar organometallic reagents (RLi/RMgX) to nitriles en route to asymmetric tertiary alcohols (without the need for isolation/purification of any halfway reaction intermediate) has been studied, for the first time, in the absence of external/additional organic solvents (neat conditions), at room temperature and under air/moisture (no protecting atmosphere is required), which are generally forbidden reaction conditions in the field of highly-reactive organolithium/organomagnesium reagents. The one-pot modular tandem protocol demonstrated high chemoselectivity with a broad range of nitriles, as no side reactions (Li/halogen exchange, ortho-lithiations or benzylic metalations) were detected. Finally, this protocol could be scaled up, thus proving that this environmentally friendly methodology is amenable for a possible applied synthesis of asymmetric tertiary alcohols under bench type reaction conditions and in the absence of external organic solvents.

Automated summary

This study investigated the synthesis of highly selective asymmetric tertiary alcohols under the absence of external organic solvents. It was found that the reaction can be carried out at room temperature and under air/moisture, without the need for a protecting atmosphere. The results showed high chemoselectivity and the possibility of scaling up the protocol.