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

摘要

The treatment of tribromofluoromethane with BuLi in THF-Et_2O (2:1) at -130 ℃ generated dibromofluoromethyllithium, which was allowed to react smoothly with a coexisting aldehyde or ketone (RR'C = O) to give fluorinated alcohol RR'C (OH) CFBr_2 (3) in good yield. Alcohol 3 was converted stereoselectively to (E)-1-bromo-1, 2-difluoro olefin 5 via fluorination with Et_2NSF_3, 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 [OCH_2O (CH_2)_2OCH_3] CFBr_2 with BuLi at -130 ℃ 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.