Generation of Organozinc Nucleophiles Based on the Biomass-Derived Platform Molecule 5-(Chloromethyl)furfural

Abstract

5-(Chloromethyl)furfural (CMF) is a cellulose derivative of increasing appeal as a renewable platform molecule. Although its role as an electrophile has been broadly studied, little is known about its potential utility as a carbon nucleophile. This work describes the preparation of organozinc reagents based on CMF by the insertion of zinc metal into the C−Cl bond. Reformatsky-type reactions are observed with a range of electrophiles under mild conditions in good to high yields. A kinetic study of zinc insertion shows the generation of this organometallic reagent from renewable furoate esters is a facile process. This method constitutes a practical tool in the synthetic repertory for the conversion of cellulosic biomass into useful organic molecules.

Electrochemical Incorporation of Electrophiles into the Biomass‐Derived Platform Molecule 5‐(Chloromethyl)furfural

“…This points to a reaction subsequent to the reduction of 2 that only takes place in the presence of CO 2 , supporting a two‐step reaction mechanism where 2 is first reduced to a furylogous enolate with the loss of chloride, followed by attack of the anion on carbon dioxide to give carboxylate anion 3 . In earlier work, we have reported the stabilizing influence of the furyl group on carbanions of 2 generated either by deprotonation or metalation of the methylene carbon [10,21] . To further support this mechanism, a test reaction was performed with platinum working electrode and aluminum counter electrode at a potential of −2.20 V, where no direct reduction of CO 2 takes place according to Figure 1a.…”

“…In earlier work, we have reported the stabilizing influence of the furyl group on carbanions of 2 generated either by deprotonation or metalation of the methylene carbon. [10,21] To further support this mechanism, a test reaction was performed with platinum working electrode and aluminum counter electrode at a potential of À 2.20 V, where no direct reduction of CO 2 takes place according to Figure 1a. Compound 3 was obtained under these conditions (Table 1, entry 1), albeit in a lower yield than when higher potentials were applied.…”

“…Performing the electrolysis in wet acetonitrile gave a less satisfactory result due to the generation of hydroxide in the course of the reaction. This reduction had been previously carried out by catalytic hydrogenation of 2 , [17] or metal‐halogen exchange followed by hydrolysis [21] …”

Furylogous Nucleophile Chemistry for the Preparation of Renewable Dyes

“…12 On the other hand, metalation of the halide led to Reformatskytype reactivity with a range of aldehydes. 14 In recent work, we have described the electrochemical fixation of the greenhouse gas carbon dioxide into ethyl 5-(chloromethyl)furan-2-carboxylate 2 to give, after esterification, ethyl 5-(carbethoxymethyl)furan-2-carboxylate 3. 15 Likewise, 2 can undergo nucleophilic substitution with cyanide to give analogue 4 (Scheme 1).…”

“…Thus, deprotonation of the furoate ester was observed to lead to Darzens-type reactivity, whereas the simple enolate of the dehalogenated furoate participated in classic carbon nucleophile reactions such as alkylation and addition to carbonyl compounds . On the other hand, metalation of the halide led to Reformatsky-type reactivity with a range of aldehydes …”