A Bifunctional Copper Catalyst Enables Ester Reduction with H₂: Expanding the Reactivity Space of Nucleophilic Copper Hydrides

Abstract

Employing a bifunctional catalyst based on a copper­(I)/NHC complex and a guanidine organocatalyst, catalytic ester reductions to alcohols with H2 as terminal reducing agent are facilitated. The approach taken here enables the simultaneous activation of esters through hydrogen bonding and formation of nucleophilic copper­(I) hydrides from H2, resulting in a catalytic hydride transfer to esters. The reduction step is further facilitated by a proton shuttle mediated by the guanidinium subunit. This bifunctional approach to ester reductions for the first time shifts the reactivity of generally considered “soft” copper­(I) hydrides to previously unreactive “hard” ester electrophiles and paves the way for a replacement of stoichiometric reducing agents by a catalyst and H2.

Mechanochemical solid state synthesis of a bifunctional copper(I)/N-heterocyclic carbene complex and its catalytic activity in hydrogenative transformations

“…26 First, the silver(I)/NHC complex 5 had to be synthesized and isolated prior to transmetallation with copper(I) chloride. 19,20 The required formation of silver(I) complex 5 diminishes the overall yield of copper complex 6. As an additional disadvantage, the silver(I) byproducts have to be carefully removed in order to maintain reproducible results in the copper(I) catalysis.…”

“…Scheme 2 Published liquid state synthesis of 6 via silver complex 5 (Mes = Mesityl). 19,20 Synthesis via mechanochemical methods offers elegant and atomeconomic alternatives to liquid state synthesis approaches. 21,22 Very recently, the possibility of synthesizing copper(I)/NHC complexes in the ball mill has been disclosed (Scheme 1, e).…”

“…We have recently disclosed an unprecedented ester reduction with H 2 as terminal reducing agent utilizing bifunctional copper(I)/NHC complex 6 bearing a guanidine moiety as additional catalytic unit. 20 This catalysts acts by employing the copper(I)/NHC complex for H 2 activation on the one hand and by using the guanidine subunit for organocatalytic simultaneous activation of the ester on the other hand. Following a previously established synthetic pathway, 19 we have found that transmetallation via silver(I)/NHC complex 5 was the only viable entry point to this sophisticated bifunctional catalyst (Scheme 2).…”

“…As an additional disadvantage, the silver(I) byproducts have to be carefully removed in order to maintain reproducible results in the copper(I) catalysis. 20 We deemed this synthetic route unattractive with regards to sustainable synthesis due to the silver waste generated in the process and sought to replace the transmetallation route with a more atom economic approach to circumvent these problems.…”

“…27,28 We hypothesize that in the CO 2 adduct, the guanidine moiety is unavailable to perform its assisting part in catalysis through hydrogen-bonding interaction. 20 Since our attempts to establish direct synthetic routes to 6 in liquid state were not fruitful, we turned our attention to mechanochemical synthesis of bifunctional catalyst 6, based on two recent reports of preparation of copper(I)/NHC complexes in a ball mill. [23][24][25] However, with each of the two approaches, additional challenges associated with the bifunctional nature of complex 6 arose.…”