One-Pot Synthesis of Difluorobicyclo[1.1.1]pentanes from α-Allyldiazoacetates

Abstract

Rapid access to 2,2-difluorobicylco[1.1.1]­pentanes is enabled from an α-allyldiazoacetate precursor in a one-pot process through cyclopropanation to afford a 3-aryl bicyclo[1.1.0]­butane, followed by reaction with difluorocarbene in the same reaction flask. The modular synthesis of these diazo compounds affords novel 2,2-difluorobicyclo[1.1.1]­pentanes that were inaccessible through previously reported methods. The reactions of chiral 2-arylbicyclo[1.1.0]­butanes in the same manner generate altogether different products with high asymmetric induction, methylene-difluorocyclobutanes. Larger ring systems including bicyclo[3.1.0]­hexanes are also rapidly furnished due to the modular nature of the diazo starting material.

(Bio)isosteres of ortho- and meta-substituted benzenes

“…More recently Davies and co-worker reported the one-pot synthesis of bridge difluorinated BCPs from α-allyldiazoacetates. In their reaction sequence, intramolecular cyclopropanation first forms the bicyclobutane which is then subjected to CF 2 carbene insertion to yield the BCP [ 76 ]. Another useful pathway to 1,2,3-BCPs is strain release functionalisation as was shown by Molander and co-workers [ 77 ].…”

Difluorocarbene in Cycloadditions and Annulations for the Synthesis of gem‐Difluorocarbocycles and gem‐Difluoroheterocycles

“…Differently, they proposed a stepwise ionic mechanism for the reaction of bicyclo[1.1.0]butanes and difluorocarbene depending upon the observation of byproducts of two different methyl 2,2difulorocyclobutanecarboxylates 15 and 16 (Scheme 3). [18] The big benefit is that the current strategy can be utilized to prepare methyl 3,4-disubstituted 2,2-bicyclo[1.1.1]pentane-1carboxylates 11, but in very low yields. 21), respectively, with treatments with tetrabutylammonium bromide (Bu 4 NBr, TBAB) or N-bromosuccimide (NBS) (Scheme 4).…”