A New Route toE‐Stilbenes through the Transition‐Metal‐Free KOtBu/DMF‐Promoted Direct Coupling of Alcohols with Phenyl Acetonitriles

Abstract

An alternative route to synthesise alkenes, based only on the KOtBu/DMF promoted activation and direct coupling of alcohols with phenyl acetonitriles, is reported. Various E‐stilbenes have thus been obtained directly from alcohols that are sustainable sources of carbon, which to our knowledge, is unprecedented in the absence of transition metal based catalysts. A variation allowing, through a Csp3−Csp3 bond formation, the selective synthesis of N‐Heteroarenes is also described. A mechanism for the olefination pathway proceeding via an original activation of alcohols under alkyl formates is provided.

Transition metal free C(sp3)–C(sp3) coupling between alcohols and N-heteroarenes via a dehydrogenative SET/HAT process

“…17 The conversion of alcohols and N-heteroarenes to E -alkenyl heteroarenes has recently been reported, often via transition metal catalyzed dehydrogenative coupling. 18 These methods constitute competitive alternatives to well-established olefination methods including Wittig, Julia or Peterson olefinations, Heck coupling and olefin metathesis. 19…”

Synthesis of Stilbenes by Cyanide/Base-Mediated Coupling of Benzylic Chlorides and Alcohols

“…26 However, DFT calculations have been performed on the elimination of 3 into 1 with potassium tert -butoxide in DMF. 13 The computations show that anion 19 is formed with an energy barrier of 14 kcal/mol and the following release of cyanide occurs rapidly with a barrier of only 9 kcal/mol. 13 The high KIE value may indicate that the deprotonation of 3 into 19 is the rate-determining step in the overall transformation.…”

“…13 The computations show that anion 19 is formed with an energy barrier of 14 kcal/mol and the following release of cyanide occurs rapidly with a barrier of only 9 kcal/mol. 13 The high KIE value may indicate that the deprotonation of 3 into 19 is the rate-determining step in the overall transformation. The last elimination reaction is then an example of an E1cB reaction 27 with a rate-determining carbanion formation.…”

“…11 An interesting organocatalytic protocol allows for the homocoupling of benzylic halides in the presence of phenyl seleneate as the catalyst with a stoichiometric amount of a base. 12 In addition, arylacetonitriles can be coupled with benzylic alcohols in the presence of either a base in DMF 13 or a nickel catalyst and a base (Scheme 1 ). 14 However, many of these previous stilbene syntheses suffer from either a poor E / Z selectivity or require special starting materials that are not commercially available.…”

“…These findings corroborate with the recent discoveries that the potassium tert -butoxide-mediated condensation between benzylic alcohols and arylacetonitriles primarily affords the α-alkylation product 2,3-diarylpropionitrile in refluxing toluene 16 while stilbenes are formed in the higher boiling solvents DMF and n -octane. 13 14 However, the drawback of these methods is the need for arylacetonitriles, which are usually not commercially available, but have to be synthesized from the corresponding benzylic halides by substitution with cyanide. This substitution is difficult in nonpolar solvents but is aided by cation-complexing agents.…”