ORGN 594 |
| Previous studies in our laboratories have championed the use of equivalents of THF [anisole (A), p-methylanisole (p-MA) and p-chloroanisole (p-ClA)] and fractional equivalents of TMEDA [A and dimethylaniline (DMA)] for atom-economical preparation of the respective ortho-lithiated intermediates. These studies alone have demonstrated that there is not a single catalyzed-hydrocarbon-solution-fits-all system for these efficient metalations. Extending the application of these “deficiently catalyzed” hydrocarbon media to other arene substrates has prompted further modification. For the three dimethoxybenzenes, a system of 1.0 equivalent of THF, 0.1 equiv. of TMEDA in cyclohexane has afforded ca. 90% yield of each of the appropriate ortho-lithio intermediates. The p-haloanisoles presented a more difficult series to undertake. Although 1.0 equiv. THF in cyclohexane proved efficient for the ortho-lithiation of p-ClA, the same medium with n-BuLi provided halogen/lithium exchange for p-BrA and p-IA. For p-FA this medium generated the benzyne intermediate. A relatively clean inefficient metalation of p-FA ortho to the methoxy group can be attained by use of hydrocarbon media alone. ortho-Lithiation of p-BrA and p-IA has been accomplished in high yields utilizing a new metalation procedure which involves the use of o-LiDMA as the metalating agent. Hydrocarbon media, selectively catalyzed, promise greener, less hazardous systems for efficient application of organolithium reagents. |
|
Materials, Devices and Switches, Metal-Mediated Reactions, Asymmetric Reactions, Total Synthesis, Biologically-Related Molecules and Processes
7:00 PM-9:00 PM, Wednesday, April 9, 2008 Morial Convention Center -- La Louisiane, Blrm. C, Poster
Division of Organic Chemistry |