SN1-type reactions in the Presence of Water: Indium (III) Promoted Highly Enantioselective Organocatalytic Propargylation of Aldehydes

The use of alcohols in catalytic alkylation reactions has become a well-known and eco-sustainable reality.1 Moreover, the direct nucleophilic substitution of alcohols “in the presence of water” is possible because of the ability of water to form a hydrogen-bond network,2 and is driven by the stability of the generated carbocations. Recently we have reported an effective and very simple method to effect the enantioselective α-alkylation of aldehydes by SN1-type reaction with unfuctionalized alcohols,3 and we have found that InBr3 used in catalytic amount was able to induce alkylation of allylic alcohols by organocatalysis.3b On the basis of the electrophilicity parameters introduced by Mayr et al.,4 we decided to use reactive carbocations, generated from alcohols, for exploring a direct nucleophilic enantioselective substitution using enamines as suitable nucleophiles. Therefore, by using cooperative organocatalyst 1 and In(OTf)3 catalyst we report herein a practical and direct enantioselective propargylic alkylation of propargylic alcohols with aldehydes in the presence of water.