A Practical Route to Cyclobutanols and Fluorocyclobutanes

Vincent L Revil-Baudard (1) , Samir Z Zard (1)

1 DCSO - Laboratoire de synthèse organique

S-(1-Acetoxycyclobut-1-yl)-O-ethyl dithiocarbonate (xanthate) 7 was found to add to electronically unbiased alkene and to certain heteroarenes. In the latter case, this corresponds to a variant of the Minisci reaction and allows the late-stage modification of biologically active substances. Saponification of the acetate furnishes the corresponding cyclobutanol, which can be converted into fluorocyclobutanes by the action of DAST. Fluorocyclobutyl substituted aromatics and heteroaromatics are increasingly present in drug candidates. Finally, S-[1-(2',2',2'-trifluoroethoxy)cyclobut-1-yl]-O-ethyl dithiocarbonate 30 was obtained unexpectedly while optimizing the synthesis of xanthate 7 and found to be a very promising reagent for the introduction of the trifluoroethoxycyclobutyl motif.

Mots clés: radical addition; xanthates; cyclobutanols; fluorocyclobutenes; Minisci reaction

Domaines: Chimie organique

Vincent L Revil-Baudard, Samir Z Zard. A Practical Route to Cyclobutanols and Fluorocyclobutanes. Helvetica Chimica Acta, 2021, 104 (9), pp.e2100106. ⟨10.1002/hlca.202100106⟩. ⟨hal-03416880⟩