Organocatalytic Packed-Bed Reactors for the Enantioselective Flow Synthesis of Quaternary Isotetronic Acids by Direct Aldol Reactions of Pyruvates
Lorenzo Poletti,
Carmela De Risi,
Daniele Ragno,
Graziano Di Carmine,
Riccardo Tassoni,
Alessandro Massi,
Paolo Dambruoso
Affiliations
Lorenzo Poletti
Department of Environmental and Prevention Sciences, University of Ferrara, Via L. Borsari, 46, 44121 Ferrara, Italy
Carmela De Risi
Department of Chemical, Pharmaceutical and Agricultural Sciences, University of Ferrara, Via L. Borsari, 46, 44121 Ferrara, Italy
Daniele Ragno
Department of Chemical, Pharmaceutical and Agricultural Sciences, University of Ferrara, Via L. Borsari, 46, 44121 Ferrara, Italy
Graziano Di Carmine
Department of Environmental and Prevention Sciences, University of Ferrara, Via L. Borsari, 46, 44121 Ferrara, Italy
Riccardo Tassoni
Institute for Organic Synthesis and Photoreactivity of the Italian National Research Council, Area della Ricerca di Bologna, Via P. Gobetti, 101, 40129 Bologna, Italy
Alessandro Massi
Department of Chemical, Pharmaceutical and Agricultural Sciences, University of Ferrara, Via L. Borsari, 46, 44121 Ferrara, Italy
Paolo Dambruoso
Institute for Organic Synthesis and Photoreactivity of the Italian National Research Council, Area della Ricerca di Bologna, Via P. Gobetti, 101, 40129 Bologna, Italy
The utilization of the homogeneous (S)-2-pyrrolidine-tetrazole organocatalyst (Ley catalyst) in the self-condensation of ethyl pyruvate and cross-aldol reactions of ethyl pyruvate donor with non-enolizable pyruvate acceptors, namely the sterically hindered ethyl 3-methyl-2-oxobutyrate or the highly electrophilic methyl 3,3,3-trifluoropyruvate, is described as the key enantioselective step toward the synthesis of the corresponding biologically relevant isotetronic acids featuring a quaternary carbon functionalized with ester and alkyl groups. The transition from homogeneous to heterogeneous flow conditions is also investigated, detailing the fabrication and operation of packed-bed reactors filled with a silica-supported version of the pyrrolidine-tetrazole catalyst (SBA-15 as the matrix).
