Stereoselective Electrocatalytic Cyclization of 4,4′-(Arylmethylene)bis(1H-pyrazol­-5-ols) to (5R*,6R*)-11-Aryl-4,10-dimethyl-2,8-diphenyl-2,3,8,9-tetraazadispiro[4.0.4.1]undeca-3,9-diene-1,7-diones

Abstract

Indirect electrochemical oxidation of 4,4¢-(arylmethylene)bis(1H-pyrazol-5-ols) in methanol in an undivided cell in the presence of sodium bromide results in highly efficient formation of the corresponding bis(spiro-2,4-dihydro-3H-pyrazol-3-one)cyclopropanes with 85-96% substance yields and 70-80% current efficiency. NMR and single crystal X-ray diffraction indicate that the products are formed exclusively as (R*,R*)-isomers. The application of this effective indirect electrochemical approach to the corresponding pharmacologically promising bis(spiro-2,4-dihydro-3H-pyrazol-3-one)cyclopropanes allows facile and convenient reaction conditions, and is valuable from the viewpoint of environmentally benign synthesis and large-scale processes.

Electrocatalytic stereoselective transformation of aldehydes and two molecules of pyrazolin-5-one into (R*,R*)-bis(spiro-2,4-dihydro-3H-pyrazol-3-one)cyclopropanes

“…18 Taking into consideration the above results and the data for the mechanisms of the electrocatalytic transformation of carbonyl compounds and CH-acids into substituted cyclopropanes [26][27][28] as well as the mechanism of the stereoselective electrocatalytic cyclization of 4,4′-IJarylmethylene)bis-IJ1H-pyrazol-5-ols) (1) into fused bispyrazolone cyclopropanes (2), 18 the following mechanism for the electrocatalytic transformation of aldehydes (3) and two equivalents of pyrazolin-5-one (4) into bispyrazolone cyclopropanes (2) is proposed. Nevertheless, in the NMR spectra of 2a-i, only a single set of signals were identified assuming stereoselective formation of individual diastereoisomers.…”

Recent Advances in the Electrochemical α‐C–H Bond Functionalization of Carbonyl Compounds

“…In 2011, Elinson and co‐workers demonstrated that this synthetic strategy could also be used to construct bis(spiro‐2,4‐dihydro‐3 H ‐pyrazol‐3‐one)cyclopropanes 58 from 4,4′‐(arylmethylene)bis(1 H ‐pyrazol‐5‐ols) 57 with NaBr as the mediator (Scheme ) …”

Electrochemical synthesis of cyclopropanes

“…42 The electrocatalytic cyclotrimerization of dimethyl malonate was carried out in an undivided cell with a Pt anode and a Fe cathode (Scheme 29). 43 Hexamethyl cyclopropanehexacarboxylate (38b) was synthesized in a yield of 70%.…”

“…Under analogous conditions, cyclotrimerization of ethyl cyanoacetate occurs stereosevectively giving the trans-isomer of triethyl 1,2,3-tricyanocyclopropane-1,2,3-tricarboxylate (42) in 85% yield (Scheme 30). 44 …”