Direct Coupling of Arylacetonitriles and Primary Alcohols to α‐Alkylated Arylacetamides with Complete Atom Economy Catalyzed by a Rhodium Complex–Triphenylphosphine– Potassium Hydroxide System

Abstract

Ad irect synthesis of a-alkylated arylacetamides from arylacetonitriles andp rimary alcohols has been accomplished for the first time.I nt he presence of the rhodium complex [Rh(cod)Cl] 2 /triphenylphosphine/potassium hydroxide system,t he desired a-alkylated arylacetamides were obtained in 74-92% yield under microwave conditions.T he experimental results in this paper are in sharp contrast with previous reports, where the coupling of arylacetonitriles and primary alcoholsp roduced the a-alkylated arylacetonitriles.M echanistic investigations show that arylacetonitriles are first a-alkylated with primary alcohols to produce a-alkylateda rylacetonitriles, which are further hydrated with the water resulting from the a-alkylation step to produce a-alkylated arylacetamides.M orei mportantly,t his research shows the potentialo fd eveloping completelya tomeconomical reactions that involve the hydrogenautotransfer (or hydrogenborrowing) process.

C‐Alkylation of Ketones and Related Compounds by Alcohols: Transition‐Metal‐Catalyzed Dehydrogenation

“…[58] Direct coupling of arylacetonitriles with primary alcohols by [{Rh(cod)Cl} 2 ]/PPh 3 /KOH was performed under microwave conditions,thus leading to a-alkylated arylacetamides in 74-92 %y ields. [59] Mechanistic studies revealed that arylacetonitriles are first a-alkylated with primary alcohols to produce a-alkylated arylacetonitriles,w hich are further hydrated with water, formed from the a-alkylation step,t o give the target products.Inthe case of using acetonitrile,both [{Ir(OH)(cod)} 2 ]/PPh 3 [60] and [RuHCl(PPh 3 ) 3 (CO)] [61] could effect its reaction with primary or secondary alcohols in the presence of ab ase [Eq. (13)].…”

Atmosphere‐Controlled Chemoselectivity: Rhodium‐Catalyzed Alkylation and Olefination of Alkylnitriles with Alcohols

“…Nitriles are useful buildingb locks in organic synthesis. [8] With watera st he only by-product,t he alkylation of alkylnitriles with alcohols through hydrogen borrowing provides a" green" route for the synthesis of new nitrile compounds.T ransition-metal catalysts, including Ru, [3,9] Os, [10] Ir, [11] Rh, [12] and Pd, [13] have been employed for this reaction. The olefination of alkylnitriles with alcohols could afford a,b-unsaturated nitriles, which are also valuable intermediates in organic synthesis.…”

Ru(II)‐PBTNNXN complex bearing functional 2‐(pyridin‐2‐yl)benzo[d]thiazole ligand catalyzed α‐alkylation of nitriles with alcohols

“…Since 1981, when Grigg and co‐workers first used RuH 2 (PPh 3 ) 4 as a catalyst in the alkylation of nitriles with alcohol, a lot of effort has been devoted to exploring various catalysts, including Ru, Rh, Ir, Pd, Os, Fe, and Mn. Of these, Ru complexes are the most reported, for example Gunanathan's group reported that Ru(PNP) (PNP = bis(2‐(diphenylphosphino)‐ethyl)amine) pincer complex showed good activity for α ‐alkylated reaction of arylmethyl nitriles .…”