Green Synthesis of Electrophilic Alkenes Using a Magnesium Catalyst under Aqueous Conditions and Mechanistic Insights by Density Functional Theory

A green approach for the synthesis
of electrophilic alkenes has
been developed via Knoevenagel condensation between active methylene
compounds and carbonyl compounds using Mg powder under aqueous conditions.
In this strategy, Mg(OH)2 acts as a catalyst, which was
generated in situ by the reaction between metallic Mg (20 mol %) and
water. Mg was found to be an efficient, nontoxic, and inexpensive
metal catalyst system for producing a range of electrophilic alkenes
in excellent yields (≤98%). A gram-scale synthesis of electrophilic
alkenes has been developed, and Mg metal was recovered and recycled
up to three times without an appreciable loss of catalytic activity.
A catalytic cycle was proposed, and the reaction mechanism was investigated
using density functional theory. The key steps are enolization of
ethyl cyanoacetate, C–C bond formation, and then regeneration
of the catalyst via metathesis with H2O. The overall reaction
occurs easily with a maximum ΔG°⧧ value of 7.9 kcal/mol for the rate-determining C–C bond formation
step. Our protocol has several advantages and can be further extended
to one-pot sequential Knoevenagel condensation and Michael addition,
and one-pot sequential Knoevenagel condensation and chemoselective
reduction can be used for the synthesis of valuable precursors of
pharmaceutical products under green and aqueous conditions.