Abstract
A novel organocatalytic multicomponent cyanovinylation of aldehydes was designed for the synthesis of conjugated cyanomethyl vinyl ethers. The reaction was implemented for the synthesis of a 3-substituted 3-(cyanomethoxy)acrylates, using aldehydes as substrates, acetone cyanohydrin as the cyanide anion source, and methyl propiolate as the source of the vinyl component. The multicomponent reaction is catalyzed by N-methyl morpholine (2.5 mol%) to deliver the 3-(cyanomethoxy)acrylates in excellent yields and with preponderance of the E-isomer. The multicomponent reaction manifold is highly tolerant to the structure and composition of the aldehyde (aliphatic, aromatic, heteroaromatics), and it is instrumentally simple (one batch, open atmospheres), economic (2.5 mol% catalyst, stoichiometric reagents), environmentally friendly (no toxic waste), and sustainable (easy scalability).
Highlights
When the vinyl moiety is endowed with electron withdrawing groups (e.g., 3), the cyanohydrin is directly converted into the conjugated cyanomethyl vinyl ether derivative by the amine-catalyzed Michael addition on the corresponding conjugated alkyne [6,7] (Scheme 1B)
We have shown that the organocatalytic multicomponent cyanovinylation of aldehydes is a powerful synthetic tool for the synthesis of conjugated cyanomethyl vinyl ethers
The power of this synthetic tool was demonstrated in the synthesis of an array of 3(cyanomethoxy)acrylates 7 endowed with a diverse substitution pattern at the position C-3
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. When the vinyl moiety is endowed with electron withdrawing groups (e.g., 3), the cyanohydrin is directly converted into the conjugated cyanomethyl vinyl ether derivative by the amine-catalyzed Michael addition on the corresponding conjugated alkyne [6,7] (Scheme 1B) In both protocols, the corresponding cyanohydrin has to be synthesized and isolated to be used in the following reaction step. A direct synthesis of CMVEs 1 from the parent aldehydes should be desirable in terms of synthetic efficiency and both labor and step economies With this idea in mind, we designed the three-component reaction (3CR) depicted in Scheme 1C, which implements a novel cyanovinylation of aldehydes to construct conjugated CMVEs 3.
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