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
M. Shimizu et al., 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, B CHEM S J, 71(12), 1998, pp. 2903-2921
The treatment of tribromofluoromethane with BuLi in THF-Et2O (2: 1) at -130
degrees 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 stereosel
ectively to (E)-1-bromo- 1,2-difluoro olefin 5 via fluorination with Et2NSF
3, followed by dehydrobromination with lithium 2,2,6,6-tetramethylpiperidid
e, while (E)-1-bromo-1-fluoro olefin was obtained with high selectivity by
acetylation of 3, followed by reductive elimination using EtMgBr/(i-Pr)(2)N
H. Difluoro olefin 5 underwent a cross-coupling reaction with an aryl, alke
nyl, or alkynylmetal reagent to afford the corresponding fluoro olefin with
retention of configuration. On the other hand, the treatment of RCH[OCH2O(
CH2)(2)OCH3]CFBr2 with BuLi at -130 degrees C in the presence of 4-heptanon
e gave the corresponding adduct diastereoselectively. The stereochemical ou
tcome is explained in terms of chelation between lithium and oxygen atoms o
f the (2-methoxyethoxy)methyl group. Starting with 2-phenylpropanal, a prod
uct is obtained highly selectively containing three contiguous stereocenter
s including a -CFBr- moiety.