Sequential One-Pot InBr3-Catalyzed 1,4- then 1,2-Nucleophilic Addition to Enones

Abstract

Low sensitivity toward traces of moisture and high tolerance of different functional groups make indium tribromide suitable for carrying out multistep synthetic sequences. In particular, we have realized a 1,4-conjugated addition of indoles/thiols to α,β-unsaturated ketones mediated by a catalytic amount (10 mol %) of InBr₃ obtaining the desired β-substituted ketones in good yields. The Lewis acidity of indium salts was not affected by coordinating and acid nucleophiles; therefore, the subsequent catalytic 1,2-addition of Me₃SiCN to carbonyl compounds can be performed in one pot. With the optimized atom-efficient protocol, several polyfunctionalized α-silyloxy cyanohydrins were synthesized in good to excellent yields (up to 97%) and a notable level of simple 1,3-diastereoselection (up to 84:16) was recorded in the case of 2-cyclohexen-1-one 2c.