Regioselective Synthesis of Spiro-oxindoles by Ruthenium Catalyzed Metathesis Reaction

Oxindoles are an important structural motifs found in various natural products and medicinal compounds. The spirocyclo-oxindole framework is the core structure of many pharmacological agents and biologically active molecules. Several functionalized spirocycloalkyloxindoles are also used as an active intermediate for the preparation of complex molecules of biological interest. This core moiety is the basic skeleton of various natural alkaloids including coerulescine, horsfiline, welwitindolinone A, spirotryprostatin A, elacomine, alstonisine, surugatoxin, etc. Due to the remarkable biological activity of spiro-oxindoles, significant effort has been paid towards the synthesis of substituted spirooxindole derivatives. On the other hand; ring-closing metathesis (RCM) reactions have been widely used as a synthetic tool for the construction of a great variety of carbo- and heterocyclic systems.

In this paper, the synthesis of 3^/-spiro pentacyclo-oxindole derivatives by the ring-closing metathesis of 3,3^/-diallyl oxindoles has been reported. The requisite starting materials 3,3^/-diallyl oxindoles were prepared by the simple alkylation of oxindoles with allyl bromide in the presence of NaH at room temperature. The ring-closing metathesis reaction of 3,3^/-diallyl oxindole proceeds with 2 mol% of Grubb’s catalyst-I in toluene at room temperature. The desired ring-closing products were obtained in good to excellent yields from the substituted 3,3^/-diallyl oxindoles under standard reaction conditions.