Manganese-catalyzed base-free addition of saturated nitriles to unsaturated nitriles by template catalysis

Abstract

The coupling of mononitriles into dinitriles is a desirable strategy, given the prevalence of nitrile compounds and the synthetic and industrial utility of dinitriles. Herein, we present an atom-economical approach for the heteroaddition of saturated nitriles to α,β- and β,γ-unsaturated mononitriles to generate glutaronitrile derivatives using a catalyst based on earth-abundant manganese. A broad range of such saturated and unsaturated nitriles were found to undergo facile heteroaddition with excellent functional group tolerance, in a reaction that proceeds under mild and base-free conditions using low catalyst loading. Mechanistic studies showed that this unique transformation takes place through a template-type pathway involving an enamido complex intermediate, which is generated by addition of a saturated nitrile to the catalyst, and acts as a nucleophile for Michael addition to unsaturated nitriles. This work represents a new application of template catalysis for C-C bond formation.

Scheme 1. Addition reactions involving nitriles promoted by manganese pincer complexes through template catalysis.

Scheme 2. Substrate scope of the manganese-catalyzed base-free heteroaddition of nitriles. ^aReaction conditions: saturated nitrile (0.3 mmol), unsaturated nitrile (0.3 mmol), THF (1 mL), Mn-1 (0.5 mol%), stirred at room temperature for 24 h. Reaction yields correspond to the pure isolated products. Values in parentheses are the conversions of the saturated nitrile substrates, as determined by GC analysis using mesitylene as internal standard. ^bReaction performed without solvent. ^c2 mol% of Mn-1 was used. ^dMn-1 (5 mol%), saturated aliphatic nitrile (1 mL) and unsaturated nitrile (0.3 mmol) were stirred at room temperature for 48 h. ^eThe value in parentheses is the conversion of the vinyl nitrile, as determined by GC analysis using mesitylene as internal standard. The diastereoisomeric ratios (d.r.) noted for the various products were determined by GC or NMR spectroscopic analysis.

Scheme 3. Mechanistic studies.

Scheme 4. Proposed mechanism of nitrile heteroaddition catalyzed by Mn-1.