Sequential one-pot InBr3-catalyzed 1,4-then 1,2-nucleophilic addition to enones

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 alpha,beta-unsaturated ketones mediated by a catalytic amount (10 mol %) of InBr3 obtaining the desired beta-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 alpha-silyloxy cyanchydrins 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.