Generation and Carbonyl Addition Reactions of Dibromofluoromethyllithium Derived from Tribromofluoromethane as Applied to the Stereoselective Synthesis of Fluoro Olefins and 2-Bromo-2-fluoro-1,3-alkanediols

The treatment of tribromofluoromethane with BuLi in THF–Et2O (2 : 1) at −130 °C generated dibromofluoromethyllithium, which was allowed to react smoothly with a coexisting aldehyde or ketone (RR′C=O) to give fluorinated alcohol RR′C(OH)CFBr2 (3) in good yield. Alcohol 3 was converted stereoselectively to (E)-1-bromo-1,2-difluoro olefin 5 via fluorination with Et2NSF3, followed by dehydrobromination with lithium 2,2,6,6-tetramethylpiperidide, while (E)-1-bromo-1-fluoro olefin was obtained with high selectivity by acetylation of 3, followed by reductive elimination using EtMgBr/(i-Pr)2NH. Difluoro olefin 5 underwent a cross-coupling reaction with an aryl, alkenyl, or alkynylmetal reagent to afford the corresponding fluoro olefin with retention of configuration. On the other hand, the treatment of RCH[OCH2O(CH2)2OCH3]CFBr2 with BuLi at −130 °C in the presence of 4-heptanone gave the corresponding adduct diastereoselectively. The stereochemical outcome is explained in terms of chelation between lithium and oxygen atoms of the (2-methoxyethoxy)methyl group. Starting with 2-phenylpropanal, a product is obtained highly selectively containing three contiguous stereocenters including a –CFBr– moiety.