Sequential one-pot InBr(3)-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 InBr(3) 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 Me(3)SiCN to carbonyl compounds can be performed in one pot. With the optimized atom-efficient protocol, several polyfunctionalized alpha-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.
Bandini
Marco
M
Dipartimento di Chimica G. Ciamician, Università degli Studi di Bologna, via Selmi 2, 40126 Bologna, Italy.
Cozzi
Pier Giorgio
PG
Giacomini
Massimo
M
Melchiorre
Paolo
P
Selva
Simona
S
Umani-Ronchi
Achille
A