Improvements on Reaction Logistics Reproducibility of Zn reagent More reactive towards CH2l2 Zn-Ag coup Denis, J. Girard, C; Conia, J. Synthesis, 1972, n-Cu couple TiCl4, acetyl chloride, and TMSCl accele CH2 Br2, additive Friedrich, E et al. J. Org. Chem, 1990, 2491 CH2N2, Znl Wittig, et al.: Angew. Chem., 1959, 71, 652 Rzn CH2l2 N.Tet.Lett.1966,28.3353 Furukawa's Breakthrough t2Zn, CH2l2 Solvent Time(h) Yield (%) benzene benzene 11 te retention of olefin geometry: ye cis-cyclopropanes and trans-olefins benzene Et2Zn, PhCHI2 benzene Furukawa, J ; Kawabata, N; Nishimura, J. Tetrahedron, 1968, 24, 53 Furukawa, J. Kawabata, N; Fujita, T. Tetrahedron, 1970, 26, 243 09B-043/299812:22PMImprovements on Reaction Logistics Furukawa, J.; Kawabata, C.; Nishimura, N. Tet. Lett., 1966, 28, 3353 Reproducibility of Zn reagent: Zn - Ag couple CH2I2 • More reactive towards CH2I2 • Higher yielding Denis, J.; Girard, C.; Conia, J. Synthesis, 1972, 549 Reaction Accelerators: Zn - Cu couple CH2Br2, additive • TiCl4, acetyl chloride, and TMSCl accelerate cyclopropanation dramatically (1 - 2 mol%) Friedrich, E. et al.; J. Org. Chem., 1990, 2491 New Zinc Source: CH2N2, ZnI2 Wittig, et al.; Angew. Chem., 1959, 71, 652 R2Zn CH2I2 Furukawa's Breakthrough Furukawa, J.; Kawabata, N.; Nishimura, J. Tetrahedron, 1968, 24, 53 O O O Cl Et2Zn, CH2I2 Solvent benzene benzene benzene benzene benzene ether 11 11 10 3 15 26 79 76 60 92 80 42 Substrate Solvent Time (h) Yield (%) • Electron-rich olefins react much faster than electron- poor ones. • Complete retention of olefin geometry: cis-olefins give cis-cyclopropanes and trans-olefins produce trans products. Ph Et2Zn, PhCHI2 ether, rt 69% syn : anti 94 : 6 Furukawa, J.; Kawabata, N.; Fujita, T. Tetrahedron, 1970, 26, 243 09B-04 3/29/98 12:22 PM