Iron- and base-catalyzed C(α)-alkylation and one-pot sequential alkylation–hydroxylation of oxindoles with secondary alcohols

Abstract

The utilization of economical and environmentally benign transition metals in crucial catalytic processes is pivotal for sustainable advancement in synthetic organic chemistry. Iron, as the most abundant transition metal in the Earth's crust, has gained significant attention for this purpose. A combination of FeCl₂ (5 mol%) in the presence of phenanthroline (10 mol%) and NaO^tBu (1.5 equivalent) proved effective for the C(α)-alkylation of oxindole, employing challenging secondary alcohol as a non-hazardous alkylating agent. The C(α)-alkylation of oxindole was optimized in green solvent or under neat conditions. The substrate scope encompasses a broad array of substituted oxindoles with various secondary alcohols. Further post-functionalization of the C(α)-alkylated oxindole products demonstrated the practical utility of this catalytic alkylation. One-pot C–H hydroxylation of alkylated oxindoles yielded 3-alkyl-3-hydroxy-2-oxindoles using air as the most sustainable oxidant. Low E-factors (3.61 to 4.19) and good Eco-scale scores (74 to 76) of these sustainable catalytic protocols for the alkylation and one-pot sequential alkylation–hydroxylation of oxindoles demonstrated minimum waste generation. Plausible catalytic paths are proposed on the basis of past reports and control experiments, which suggested that a borrowing hydrogen pathway is involved in this alkylation.